Journal articles on the topic 'Royal free hospital global assessment'

BackgroundThe hepatitis C virus is one of the main causes of liver disease worldwide and may develop nutritional deficiencies.ObjectiveThe objective of this study was to assess and compare different nutritional status methods of adult patients with chronic hepatitis C virus, and to describe inadequacies in dietary intake.MethodsA cross-sectional study was conducted with adult outpatients with hepatitis C virus at a Brazilian hospital. Nutritional assessment included the 24-hour dietary recall, anthropometry (body weight, height, body mass index, triceps skinfold, mid-upper arm circumference, mid-arm muscle circumference, mid-upper arm muscle area, adductor policis muscle), Subjective Global Assessment, Royal Free Hospital Global Assessment and handgrip strength.ResultsA total of 94 outpatients (ages 30 to 76 years), was included, 46 were men. The prevalence of malnutrition as measured by the different methods was 6.4% (body mass index); 60.6% (handgrip strength), and 53.2% (Royal Free Hospital Global Assessment). There was correlation between mid-upper arm circumference and mid-arm muscle circumference (r=0.821), mid-upper arm circumference and triceps skinfold (r=0.575) and mid-upper arm circumference and mid-upper arm muscle area (r=0.781). Energy and protein intakes were below recommended levels in 49 (52.1%) and 44 (46.8%) of patients, respectively. Inadequate calcium, potassium, zinc and vitamin C intakes occurred in 92.6%, 97.9%, 63.8% and 60.6% of patients. There was an association between dietary energy and protein intake with Royal Free Hospital Global Assessment (P<0.001) and a tendency for them to be associated with handgrip strength (P=0.076 and P=0.054).ConclusionMalnutrition is frequently in hepatitis C virus patients. They have high prevalence of inadequate energy, protein and micronutrients intake, even in the absence of cirrhosis.

Background: Childhood epilepsy has increased in global incidence. Children with epilepsy require immediate healthcare evaluation and monitoring. Waiting times between first seizure onset and pediatric neurology assessment may impact seizure outcome at follow-up. Quality of medical care for children with first seizure onset will be assessed and the impact of pediatric neurology clinic waiting times on seizure outcomes will be determined Methods: This retrospective study, based on chart review, includes patients with first seizure evaluation at the Royal University Hospital in Saskatoon between January 2012 and December 2015. The interim period before first assessment and other factors were studied in relation to seizure outcome on follow-up. Results: 1158 patients were assessed. 378 (32.6%) patients had first seizure clinic assessment. 197 (52%) had epileptic events. 181 (48%) had non-epileptic events. The mean age of patients was 8.8 years. The mean waiting time for assessment by a pediatric neurologist was 4.33 months. The mean duration of follow-up was 20.9 months. At the last seizure assessment, 132 patients were free of seizures and 65 patients had a recurrence of seizures. Conclusions: First seizure assessment is crucial for management of children with epilepsy. Waiting time and other factors may influence seizure outcome, representing opportunities to improve standard medical care.

AbstractMalnutrition risk screening in cirrhotic patients is crucial, as poor nutritional status negatively affects disease prognosis and survival. Given that a variety of malnutrition screening tools is usually used in routine clinical practice, the effectiveness of eight screening tools in detecting malnutrition risk in cirrhotic patients was sought. A total of 170 patients (57·1 % male, 59·4 (sd 10·5) years, 50·6 % decompensated ones) with cirrhosis of various aetiologies were enrolled. Nutritional screening was performed using the Malnutrition Universal Screening Tool, Nutritional Risk Index, Malnutrition Screening Tool, Nutritional Risk Screening (NRS-2002), Birmingham Nutritional Risk Score, Short Nutritional Assessment Questionnaire, Royal Free Hospital Nutritional Prioritizing Tool (RFH-NPT) and Liver Disease Undernutrition Screening Tool (LDUST). Malnutrition diagnosis was defined using the Subjective Global Assessment (SGA). Data on 1-year survival were available for 145 patients. The prevalence of malnutrition risk varied according to the screening tools used, with a range of 13·5–54·1 %. RFH-NPT and LDUST were the most accurate in detecting malnutrition (AUC = 0·885 and 0·892, respectively) with a high sensitivity (97·4 and 94·9 %, respectively) and fair specificity (73·3 and 58 %, respectively). Malnutrition according to SGA was an independent prognostic factor of within 1-year mortality (relative risk was 2·17 (95 % CI 1·0, 4·7), P = 0·049) after adjustment for sex, age, disease aetiology and Model for End-stage Liver Disease score, whereas nutrition risk according to RFH-NPT, LDUST and NRS-2002 showed no association. RFH-NPT and LDUST were the only screening tools that proved to be accurate in detecting malnutrition in cirrhotic patients.

Guyana is a low-middle income country on the northern coast of South America between Venezuela and Suriname. Guyana has relatively high child mortality and a notable gap in health care provision. As of 2011, there were no paediatricians in the public sector where approximately 90% of the population seek care. In response to this unmet need, Guyanese diaspora living in Canada, in partnership with Canadian paediatricians and the main teaching hospital, Georgetown Public Hospital Corporation (GPHC), developed a Master’s program in paediatrics. The postgraduate program was designed with adapted training objectives from the Royal College of Physicians and Surgeons of Canada and the American Board of Paediatrics. Innovative strategies to overcome the lack of qualified paediatric faculty in Guyana included web-conferencing and a volunteer North American paediatric faculty presence at GPHC with a goal of 1-2 weeks every month. By November 2016, 10 graduates will have passed through a rigorous program of assessment including a two-day final examination with an objective structured clinical examination (OSCE) component.

Introduction. The schizophrenics are frequently disinterested and resistant to standard care. Case report. We presented clinical observations of group art therapy of two schizophrenic patients during integrative therapy in Day Hospital. We modified the original ?Synallactic collective image technique? (Vassiliou G, Vassiliou V.). The group is open, heterogeneous, meets once a week and discusses on exhibited drawings, drawn by free associations. The patients' drawings and group protocols showed clinical improvement by lowering depressive themes, more human figures and self-confidence. The obvious severity of markedly impairment on Clinical Global Impression (CGI) and Global Assessment of Functioning (GAF) scales on admission with minimal improvement at discharge was rated. Conclusion. Group art therapy enables visual expression of emotions, perceptions and cognitions, develops creative potentials and support within the group, thus facilitating the integrative therapeutic process of schizophrenics. It may be useful adjunctive therapy for schizoprenic patients.

PURPOSE: Several management options are available to patients with stage I seminoma, including adjuvant radiotherapy, surveillance, and adjuvant chemotherapy. We performed a pooled analysis of patients from the four largest surveillance studies to better delineate prognostic factors associated with disease progression. PATIENTS AND METHODS: Individual patient data were obtained from each center (Princess Margaret Hospital, Danish Testicular Cancer Study Group, Royal Marsden Hospital, and Royal London Hospital) for 638 patients. Tumor characteristics (size, histologic subtype, invasion of rete testis, and tumor invasion into small vessels [SVI]) as well as age at diagnosis were analyzed for prognostic importance for relapse. RESULTS: With a median follow-up of 7.0 years (range, 0.02 to 17.5 years), 121 relapses were observed for an actuarial 5-year relapse-free rate (RFR) of 82.3%. On univariate analysis, tumor size (RFR: ≤ 4 cm, 87%; > 4 cm, 76%; P = .003), rete testis invasion (RFR: 86% [absent] v 77% [present], P = .003), and the presence of SVI (RFR: 86% [absent] v 77% [present], P = .038) were predictive of relapse. On multivariate analysis, tumor size (≤ 4 cm v > 4 cm, hazard ratio 2.0; 95% confidence interval [CI], 1.3 to 3.2) and invasion of the rete testis (hazard ratio 1.7; 95% CI, 1.1 to 2.6) remained as important predictors for relapse. CONCLUSION: We have identified size of primary tumor and rete testis invasion as important prognostic factors for relapse in patients with stage I seminoma managed with surveillance. This information will allow patients and clinicians to choose management based on a more accurate assessment of an individual patient’s risk of relapse. In addition, it will allow clinicians to tailor follow-up protocols based on risk of occult disease.

Background: Few studies have explored the effects of anti-epileptic drugs (AEDs) on electroencephalograph (EEG) findings during the assessment of seizure management. Although a patient may reach seizure freedom, EEG results may continue to be abnormal. Further information is required to understand the trend of EEG findings during seizure treatment. Methods: This is a retrospective study based on chart reviews. Patients who had epilepsy evaluations at the Royal University Hospital in Saskatoon between January 2012 and December 2015, were selected. The relationships among time of initiating AEDs, EEG findings, and seizure outcome on follow-ups, have been evaluated. Results: 151 patients had first seizure clinic assessments, in which 75 patients had an EEG before starting AEDs. Among the 75 patients, 54 (72%) had abnormal EEGs. From those, 38 (70.3%) patient’s EEGs became normal and 16 (29.7%) patients continued to have abnormal EEGs after the introduction of AEDs. The seizure freedom was 81.5% among those who had normal EEG on follow-up, and 43.7% of those who continued to have abnormal EEGs. Conclusions: Although patients with normal EEGs after starting AEDs may encounter a higher chance of seizure freedom, the seizure free patients with abnormal EEGs indicate that EEG is not completely sufficient in predicting seizure status.

Malnutrition in liver cirrhosis is frequently underestimated. To determine if a patient is at risk of malnutrition, several screening tools have been established. However, most of them are not validated for patients with liver cirrhosis. Therefore, we compared the RFH-NPT (Royal Free Hospital Nutritional Prioritizing Tool) as the validated gold standard for malnutrition screening in cirrhosis patients with GMS (Graz Malnutrition Screening), NRS-2002 (Nutritional Risk Screening) and MNA-SF (Mini Nutritional Assessment-Short Form). Based on common validity criteria for screening tools, only the MNA-SF showed fair correlation (12/15 points) with the RFH-NPT, whereas NRS-2002 and GMS performed worse (6/15 points). Taken together, our results suggest that NRS-2002 and GMS are not suitable for screening of malnutrition in cirrhosis patients. A cirrhosis-specific screening tool like RFH-NPT should be used to assess malnutrition and to identify those at risk of malnutrition.

Introduction: Malnutrition is one of the most common complications of liver cirrhosis. Yet, little attention is paid in evaluating nutrition in this group of patients. This study aims to assess malnutrition among cirrhotic patients using a nutrition screening tool and anthropometry. Methods: This was a prospective, observational study of admitted patients with liver cirrhosis. In the study duration of 3months, 50 patients met the inclusion criteria and were included. Nutritional assessment was performed using the Royal Free Hospital Nutritional Prioritizing Tool (RFH-NPT), BMI and standard anthropometry including TSF,MUAC and MAMC. Results: The mean age was 51.56 ± 11.50 with a Male to Female ratio of 3:2. Chronic alcohol consumption (72%) was the most common etiology while management of tense as cites (40%) was the most common reason for hospital admission. 58% had Child Pugh Class C cirrhosis while the remaining 42% were Class B. The average MELD Nascore was 19.64 ± 6. Significant differences in anthropometric measurements including BMI, MUAC, TSF and MAMC were found between Child B and C cirrhosis. Similarly, those patients who had low, moderate and high-risk of malnutrition by the RFH-NPT had significant differences in anthropometric measurements between them. Conclusion: A significant number of patients had moderate to severe risk of malnutrition that correlated well with anthropometric measurements. The degree of malnutrition is parallel with the severity of liver disease among these patients. Both the RFH-NPT and anthropometry are relatively easy to perform and effective. Hence, they can be used as a practical means for identifying malnutrition among cirrhotic patients in routine clinical practice.

IntroductionHigh prevalence of impaired sexual function in patients with schizophrenia has been reported by several studies. Various factors were incriminated including the disease itself, the low level of social competence and treatmentside effects.ObjectiveTo compare sexual function in drug free schizophrenic patients and six months after initializing antipsychotic treatment.MethodsA consecutive sample of 109 patients meeting DSM-IV criteria of schizophrenia was constituted in psychiatry department of Farhat Hached hospital (Sousse, Tunisia), during a twenty four months period. They were drug naïve or drug free for at least three months. Assessment was performed at two time points:T0: During an acute phase of the disease as defined by a BPRS global score ≥ 40 T1: six months after antipsychotic treatment.Assessment of sexual function used the Arizona Sexual Experience Scale (ASEX).ResultsSexual function was impaired under antipsychotic treatment. In fact, we noticed lower global score of asex (p = 0.03) and lower subscores of drive (p = 0.015), arousal (p = 0.006), erection or vaginal lubrication (p= 0.010), orgasm (p= 0.001) and satisfaction (p= 0.005).ConclusionSexual function was impaired in patients under antipsychotic drugs, according to global score and to diffrent sexual dimensions subscores. This results seem to, prospectively, confirm the implication of treatment in sexual dysfunction occurence among schizophrenic patients.

Abstract With demand for endocrine tests steadily increasing year-on-year, we examined thyroid function test (TFT) frequencies in patients on levothyroxine replacement therapy to assess the effect of initial TFT results and request source on TFT re-testing interval. All TFTs performed by the Clinical Biochemistry Departments at the Salford Royal Hospital (2009–2012; 288 263 requests from 139 793 patients) and University Hospital of North Midlands (2011–2014; 579 156 requests from 193 035 patients) were extracted from the laboratory computer systems. Of these, 54 894 tests were on 13 297 patients confirmed to be on levothyroxine therapy in the test cohort (Salford) and 67 298 requests on 11 971 patients in the confirmatory cohort (North Midlands). In the test cohort, median TFT re-testing interval in the total group was 19.1 weeks (IQR 9.1–37.7 weeks), with clearly defined peaks in TFT re-testing evident at 6 and 12 months and a prominent broad peak at 1–3 months. Median re-test interval was much lower than recommended (52 weeks) for those with normal TFTs at 31.3 weeks (30.6 weeks for the confirmatory cohort). Where thyroid-stimulating hormone (TSH) was elevated and free thyroxine (fT4) was below the reference range, re-test interval was much longer than is recommended (8 weeks) at 13.4–17.6 weeks (7.1–23.4 weeks in the confirmatory cohort), as was the interval when TSH was below and fT4 was above the normal range, at 16.7–25.6 weeks (27.5–31.9 weeks in the confirmatory cohort). Our findings show that the majority of TFT requests are requested outside recommended intervals and within-practice variability is high. A new approach to ensuring optimum monitoring frequency is required. Direct requesting from the clinical laboratory may provide one such solution.

Liver cirrhosis is an increasing public health threat worldwide. Malnutrition is a serious complication of cirrhosis and is associated with worse outcomes. With this review, we aim to describe the prevalence of malnutrition, pathophysiological mechanisms, diagnostic tools and therapeutic targets to treat malnutrition. Malnutrition is frequently underdiagnosed and occurs—depending on the screening methods used and patient populations studied—in 5–92% of patients. Decreased energy and protein intake, inflammation, malabsorption, altered nutrient metabolism, hypermetabolism, hormonal disturbances and gut microbiome dysbiosis can contribute to malnutrition. The stepwise diagnostic approach includes a rapid prescreen, the use of a specific screening tool, such as the Royal Free Hospital Nutritional Prioritizing Tool and a nutritional assessment by dieticians. General dietary measures—especially the timing of meals—oral nutritional supplements, micronutrient supplementation and the role of amino acids are discussed. In summary malnutrition in cirrhosis is common and needs more attention by health care professionals involved in the care of patients with cirrhosis. Screening and assessment for malnutrition should be carried out regularly in cirrhotic patients, ideally by a multidisciplinary team. Further research is needed to better clarify pathogenic mechanisms such as the role of the gut-liver-axis and to develop targeted therapeutic strategies.

Background/Aims Restrictions to clinical practice necessitated by the COVID-19 global pandemic exerted pressures on staff, families and patients within the paediatric intensive care unit of the Royal Hospital for Children in Glasgow. The authors sought to explore parents' experiences during this pandemic. Methods A single centre study was performed using a questionnaire distributed to parents of patients in the 22-bed paediatric intensive care unit. The key areas targeted were visiting restrictions, ward round changes, facilities closures and the need to wear personal protective equipment. Free text responses were reviewed by two authors independently and common themes identified. Results The findings offer insight into family perceptions that illustrate the negative repercussions of the restrictions to parents. Understanding on the part of the parents was demonstrated throughout; however, restrictions and pandemic interventions also resulted in isolation, distress, exclusion and anxiety. Conclusions There are no current studies exploring parental perceptions of COVID-19 interventions within paediatric intensive care units. These findings offer insights that illustrate the unique challenges faced by those who strive to deliver family-centred care, and the additional stress that this can put upon parents. The authors propose adaptive strategies to enhance family-centred care at paediatric intensive care units.

Abstract Background Awake craniotomies require exceptional intra-operative communication between the multidisciplinary team. This is difficult with traditional operating microscopes, where the operative field cannot be visualised by all parties. The Synaptive Modus V is a hands-free, robotic, extracorporeal telescope (exoscope), allowing images to be viewed on multiple large monitors. The Royal London Hospital is the first United Kingdom installation of this device and the first unit in Europe to apply it to awake craniotomies for low-grade glioma. Methods Two consecutive patients with low grade glioma underwent awake craniotomy using the Modus V. Qualitative feedback (semi-structured interview) was received from the MDT including surgeons, occupational/ speech and language/ physio-therapists, neurophysiologists, anaesthetists and scrub team. Optimal device positioning is described. Results Both female patients (38 and 52 years old) underwent surgery between December 2018 and February 2019. Lesions were located in right perisylvian and posterior inferior frontal gyrus locations respectively. Surgical resection was satisfactory. Patient 1 developed a wrist-drop intra-operatively. Patient 2 had transient mild word finding difficulties. Surgeons reported easier surgical flow with hands-free positioning, larger working area and improved ergonomics. Adapting to non-stereoscopic vision increased operating times. Multi-disciplinary team members reported an better communication with the operating surgeon during patient assessment and a more involved educational experience. Conclusion Hands-free exoscopes may provide improved surgical flow and efficiency for awake craniotomy whilst simultaneously improving multidisciplinary communication and education. There is an, as yet, unidentified learning curve for its use that requires learning curve data generation.

In a previous clinical study, a probiotic formulation (PF) consisting ofLactobacillus helveticusR0052 andBifidobacterium longumR0175 (PF) decreased stress-induced gastrointestinal discomfort. Emerging evidence of a role for gut microbiota on central nervous system functions therefore suggests that oral intake of probiotics may have beneficial consequences on mood and psychological distress. The aim of the present study was to investigate the anxiolytic-like activity of PF in rats, and its possible effects on anxiety, depression, stress and coping strategies in healthy human volunteers. In the preclinical study, rats were daily administered PF for 2 weeks and subsequently tested in the conditioned defensive burying test, a screening model for anti-anxiety agents. In the clinical trial, volunteers participated in a double-blind, placebo-controlled, randomised parallel group study with PF administered for 30 d and assessed with the Hopkins Symptom Checklist (HSCL-90), the Hospital Anxiety and Depression Scale (HADS), the Perceived Stress Scale, the Coping Checklist (CCL) and 24 h urinary free cortisol (UFC). Daily subchronic administration of PF significantly reduced anxiety-like behaviour in rats (P < 0·05) and alleviated psychological distress in volunteers, as measured particularly by the HSCL-90 scale (global severity index,P < 0·05; somatisation,P < 0·05; depression,P < 0·05; and anger–hostility,P < 0·05), the HADS (HADS global score,P < 0·05; and HADS-anxiety,P < 0·06), and by the CCL (problem solving,P < 0·05) and the UFC level (P < 0·05).L. helveticusR0052 andB. longumR0175 taken in combination display anxiolytic-like activity in rats and beneficial psychological effects in healthy human volunteers.

Objectives There is a high rate of false-positive arterial Thoracic Outlet Syndrome (ATOS) diagnoses due to limited research into the optimal use of ultrasound. To improve future diagnostic efficiency, we aimed to characterise the haemodynamic effects of different provocative positions and estimate the prevalence of compression in the healthy population. Design In this cross-sectional, observational study, the effect of varying degrees of arm abduction on discomfort levels and/or changes in subclavian artery Doppler waveform was analysed in the healthy population; the peak systolic velocity (PSV), systolic rise time (SRT), phasicity and extent of turbulence were recorded. Setting Department of the Vascular Studies, Royal Free Hospital. Participants 19 participants (11 females, 27.4 ± 5.2 years) were recruited for bilateral scans. Main outcome measures Seven positions were investigated; the primary outcome was an occlusion or monophasic waveform indicating significant compression and this was compared with the secondary outcome; any physiological discomfort. Results 28.9% experienced significant arterial compression in at least one position; 120° abduction was the position with the greatest level of abduction that did not result in significant waveform changes or symptoms. The PSV and SRT were difficult to accurately measure and bore no correlation to the level of compression. Conclusion Ultrasound testing in isolation would result in a false indication of TOS in almost 30% of our normal population. With further research, the 120° abduction position may have a lower false-positive rate. The PSV and SRT must be interpreted with caution due to their variability even within the healthy population.

79 Background: The cancer multidisciplinary team (MDT) meeting is regarded as the best platform to reduce unwarranted variation in cancer care through evidence-compliant management. However, MDT meetings are often overburdened with many different agendas, and hence struggle to achieve their full potential. Methods: We have developed an interactive computer system called MATE to facilitate explicit, evidence-based decision-making in MDT meetings for breast cancer care. MATE provides prognostication and risk assessment and also flags up patients eligible for recruiting into ongoing research trials. We describe the system; share our experience of implementing MATE and report initial audit and survey results. MATE was used to record the proceedings of breast MDT meetings between 2008-2009 to gather 1,295 cases discussed in the MDMs during this period and to audit the MDT decisions and MATE recommendations against NICE, NHSBSP, and NCCN guidelines. Results: MATE identified 61% more patients who were eligible for recruitment into clinical trials than the MDT and its recommendations demonstrated high concordance with MDT decisions (93.2 %). MATE is in routine use in breast MDT meetings at Royal Free Hospital, London, and deployment of the system in other NHS trusts is being explored. Conclusions: Sophisticated decision support systems can enhance the conduct of MDT meetings in a way that is acceptable to and valued by the clinical team. Further rigorous evaluations are required to examine cost-effectiveness, measure the impact on patient outcomes and test the generalizability of the system in different hospital setups and in different cancers.

ObjectivesTo compare situation awareness (SA), visual attention (VA) and protocol adherence in simulated neonatal resuscitations using two different monitor positions.DesignRandomised controlled simulation study.SettingsSimulation lab at the Royal Alexandra Hospital, Edmonton, Canada.ParticipantsHealthcare providers (HCPs) with Neonatal Resuscitation Program (NRP) certification within the last 2 years and trained in neonatal endotracheal intubations.InterventionHCPs were randomised to either central (eye-level on the radiant warmer) or peripheral (above eye-level, wall-mounted) monitor positions. Each led a complex resuscitation with a high-fidelity mannequin and a standardised assistant. To measure SA, situation awareness global assessment tool (SAGAT) was used, where simulations were paused at three predetermined points, with five questions asked each pause. Videos were analysed for SAGAT and adherence to a NRP checklist. Eye-tracking glasses recorded participants’ VA.Main outcome measureThe main outcome was SA as measured by composite SAGAT score. Secondary outcomes included VA and adherence to NRP checklist.ResultsThirty simulations were performed; 29 were completed per protocol and analysed. Twenty-two eye-tracking recordings were of sufficient quality and analysed. Median composite SAGAT was 11.5/15 central versus 11/15 peripheral, p=0.56. Checklist scores 46/50 central versus 46/50 peripheral, p=0.75. Most VA was directed at the mannequin (30.6% central vs 34.1% peripheral, p=0.76), and the monitor (28.7% central vs 20.5% peripheral, p=0.06).ConclusionsSimulation, SAGAT and eye-tracking can be used to evaluate human factors of neonatal resuscitation. During simulated neonatal resuscitation, monitor position did not affect SA, VA or protocol adherence.

66 Background: Cancer of Unknown Primary (CUP) is the 4th most common cause of cancer death in England and Wales. [(Office for National Statistics, Mortality Statistics: Deaths registered in England and Wales. http://www.ons.gov.uk/ons/search/index.html?newquery=series+dr (accessed 1/7/14).] Patients with CUP have poor outcomes secondary to delayed, inappropriate investigations and poor treatment response. In line with NICE guidance [(NICE guidelines: CG 104 (July 2010).]. Metastatic malignant disease of unknown primary: diagnosis and management of metastatic malignant disease of unknown primary.) a CUP service was set-up at the Royal Free in June 2012. This analysis assessed its impact on patients diagnosed with metastatic cancer who were not fit for active treatment. Methods: Clinical notes were reviewed for all admissions with an imaging-based diagnosis of metastatic cancer. A retrospective analysis (January-April 2009) was compared to prospective data following the launch of the CUP service (June-December 2012). Results: The notes of 9 patients (2009) and 15 patients (2012) were compared (see table). Age and length of stay (LOS) were analysed using t-test, other data were compared using chi-squared test. All patients were reviewed by Oncology and Palliative Care teams. There was a significant reduction in mean LOS (6.7 days, 18.6 days p<0.004) and the number who died in hospital (7%, 67% p<0.002) with only one patient not dying in his preferred place. Conclusions: Prompt assessment by the CUP service facilitates early input from Oncology and Palliative Care teams resulting in reduced LOS and fewer deaths in hospital in keeping with the agenda of the End of Life Care Strategy [(End of Life Care Strategy: Promoting high quality care for all adults at the end of life (July 2008). DOH (England).]. [Table: see text]

Objectives To evaluate the influence of initial nutritional status on continuous ambulatory peritoneal dialysis (CAPD) patient survival and to identify factors determining initial nutritional status and patient mortality. Design Prospective single-center study. Setting Kidney Center, Soon Chun Hyang University Hospital. Patients A total of 91 consecutive CAPD patients, who underwent initial nutritional assessment at Soon Chun Hyang University Hospital, Seoul, Korea, between September 1994 and January 1999, was included in this study. All patients were assessed at a mean of 7 days after beginning CAPD (range 3 – 24 days). Forty-eight patients were male, 50 were diabetics, and their mean age was 53.9 years (range 22 – 76 years). Methods Nutritional status was assessed by subjective global assessment (SGA), biochemical and anthropometric measurements, fat-free edema-free (FFEF) body mass by creatinine kinetics, urea kinetic studies, and calculation of the normalized protein equivalent of total nitrogen appearance (nPNA). Results By SGA, 55% were classified as having normal nutrition while 45% had signs of malnutrition; 61% of female and 31% of male patients, and 54% of diabetics and 34% of nondiabetics were classified as malnourished. Initial FFEF body mass, blood urea nitrogen (BUN), serum albumin (sAlb), residual renal function (RRF), and weekly total creatinine clearance were significantly lower in the malnourished patients than in the patients with normal nutrition. On multiple regression analysis, only FFEF body mass was an independent determinant of SGA score. On 31 January 1999, 41 patients were still on CAPD, 15 patients had died, and 27 patients had been transferred to hemodialysis. Those who died during observation were older and had lower initial FFEF body mass, % lean body mass, BUN, sAlb, RRF, and SGA score. The 2-year patient survival rate was significantly lower in the malnourished than in normal patients (67.1% vs 91.7%, p = 0.02). On Cox proportional hazards analysis, initial age, malnutrition assessed by SGA, and FFEF body mass were identified as factors determining death. Conclusion Malnutrition was present in 45% of patients commencing CAPD when assessed by SGA. Initial FFEF body mass was a determinant of SGA score and predicted death. Malnutrition as assessed by SGA was also an independent predictor of death. Initial nutritional status, therefore, appears to exert a powerful influence on CAPD patient survival.

IntroductionAn integrated program (Institutional Psychiatric Open Light Treatment) for psychosis and personality disorder was enriched with audiovisual functions provided through a dedicated website.The aim of the present study was to observe how and if these added functions support the patients in their daily living, influencing the quality of the recovery process.Recent studies highlighted how telemental health services are effective to provide access, improve basic outcome, facilitate empowerment of patients and be well-accepted (Hilty, 2013; Hailey, 2008) and how integrated community-based treatment, such as Community-Based Psychodynamic Treatment Program (Chiesa and Fonagy, 2009) or Assertive Community Treatment (Veldhuizen and Bahler, 2013) are effective in SMI.Telemental health services may become factors improving real-life functioning, integrating community-based treatment for psychosis and bettering social cognition, functional capacity, resilience, internalized stigma and engagement with mental health services, so positively affecting outcomes of psychosis treatment.MethodsAll patients admitted (May 2010–April 2015) were included. Aged between 18 and 65, with schizophrenia, psychosis, schizoaffective disorder, bipolar disorder, personality disorder.Some troubles with the website use (Voice2Voice) led to a second version, more friendly and simple to use (app2gether).App2gether provided several functions: audio/video conference rooms for patients or family (synchronous virtual space to interact, at scheduled time, with a psychologist, a psychiatrist or a peer support worker, in free groups); chat (asynchronous virtual space for any question or information).We considered primary outcomes proposed by Cochrane Collaboration (Shek, 2010): hospital admissions, days of hospitalization, day-hospital admissions, day-program attendance (e.g. weekly), treatment compliance (voluntary discharge or missing scheduled date).We considered, as secondary outcomes, variables closely associated with real-life functioning (Galderisi, 2015): global functioning (Italian translation of Global Assessment of Functioning Scale), quality of life (Short Form 36 item), social relationships (Personal and Social Performance), internalized stigma (Internalized Stigma Mental Illness Inventory), empowerment (Empowerment Scale).Patients were divided into four cohorts:– 1-using “app2gether” functions in the follow-up, attending day treatment program (n = 35);– 2-attending day treatment program (n = 52);– 3-attending transitional day-hospital program (n = 171);– 4-not included in the IPOLT-program (n = 188).Patients were included in the first group only based on their basic computer skills and fast Internet availability.ResultsAt first, we compared (2) and (3) with (4), as control group. For each patient, we considered an identical observation period before and after day-hospital admission (ANOVA, P < 0.05).We found a significant improvement in primary outcomes and global functioning, but not in other secondary outcomes, for the groups (2) and (3) compared with (4).Over 6-months observation, patients using “app2gether” functions in the follow-up showed:– a significantly decrease in hospital admissions and hospitalization length, compared to non-IPOLT-program group;– a reduction in day-hospital admissions and day-hospital attendance, compared to (2) and (3) groups;– a notable effect on secondary outcomes, compared to all other groups.ConclusionA dedicated website in the IPOLT-program supports patients in their living's place, does not interfere with daily activities, decreases social costs, encourages community integration and reduces stigma.Synchronous telepsychiatry allow a professionally modulated intervention in “here and now”; asynchronous contacts with specialists combine professional intervention with chances of autonomy and autoregulation. These services reduce costs, in terms of FTE (Full Time Equivalent), but not the efficacy.Future advances in the websites should be designed, simplifying the contact surface with the treating-team and reducing the social impact of therapeutic practice.A better understanding of the complex variables influencing real-life functioning and new sensitive tools to detect it are needed.Disclosure of interestThe authors have not supplied their declaration of competing interest.

IntroductionCT is the primary imaging option for acute abdominal pain in adults. Intravenous (IV) contrast media use improves CT quality but may cause post-contrast acute kidney injury (PC-AKI). Retrospective studies show no association between reduced baseline renal function and IV contrast CT, but, to our knowledge, no data from randomised controlled trials exist.Methods and analysisThe INCARO (INtravenous Contrast computed tomography versus native computed tomography in patients with acute Abdomen and impaired Renal functiOn) trial is a multicentre, open-label, parallel group, superiority, individually randomised controlled trial comparing IV contrast-enhanced CT to native CT in patients requiring emergency abdominal or body CT with impaired renal function defined as an estimated glomerular filtration rate (eGFR) of 15 to 45 mL/min/1.73 m2. The primary outcome is a composite of all-cause mortality or renal replacement therapy (RRT) within 90 days from CT. Secondary outcomes are AKI measured by KDIGO (The Kidney Disease: Improving Global Outcomes) criteria within 72 hours from CT, organ dysfunction defined by mSOFA (modified Sequential Organ Failure Assessment) criteria after 48 hours from CT, alive and hospital-free days within 90 days after CT, and time from imaging to definitive treatment. All-cause mortality, need for RRT and renal transplant in long-term follow-up are also measured. The calculated sample size is 994 patients. Patient recruitment is estimated to take 3 years.Ethics and disseminationThe Ethics Committee of Helsinki University Hospital approved the study. The findings will be disseminated in peer-reviewed academic journals.Trial registration numberNCT04196244

Abstract Background: Radiotherapy for muscle invasive bladder cancer (MIBC) aims to offer organ preservation without oncological compromise. Neo-adjuvant chemotherapy provides survival advantage; response may guide patient selection for bladder preservation and identify those most likely to have favourable result with radiotherapy. Methods: Ninety-four successive patients with T2-T4aN0M0 bladder cancer treated between January 2000 and June 2011 were analysed at the Royal Marsden Hospital. Patients received platinum-based chemotherapy following transurethral resection of bladder tumour; repeat cystoscopy (±biopsy) was performed to guide subsequent management. Responders were treated with radiotherapy. Poor responders were recommended radical cystectomy. Progression-free survival (PFS), disease-specific survival (DSS) and overall survival (OS) were estimated using Kaplan–Meier method; univariate and multivariate analyses were performed using the Cox proportional hazard regression model. Results: Response assessment was performed in 89 patients. Seventy-eight (88%) demonstrated response; 53 (60%) achieved complete response (CR); 74 responders had radiotherapy; 4 opted for cystectomy. Eleven (12%) demonstrated poor response, 10 received cystectomy. Median survival for CR was 90 months (95% CI 64.7, 115.9) compared with 16 months (95% CI 5.4, 27.4; P<0.001) poor responders. On multivariate analysis, only response was associated with significantly improved PFS, OS and DSS. After a median follow-up of 39 months (range 4–127 months), 14 patients (16%) required salvage cystectomy (8 for non-muscle invasive disease, 5 for invasive recurrence, 1 for radiotherapy related toxicity). In all, 82% had an intact bladder at last follow-up after radiotherapy; 67% had an intact bladder at last follow-up or death. Our study is limited by its retrospective nature. Conclusions: Response to neo-adjuvant chemotherapy is a favourable prognostic indicator and can be used to select patients for radiotherapy allowing bladder preservation in >80% of the selected patients.

Abstract Deficiency of clotting factors VIII (Hemophilia A) and IX (Hemophilia B) represent one of the most debilitating inherited groups of bleeding disorders. According to the most recent survey report from the World Hemophilia Federation, an estimated 178,500 patients suffer from hemophilia globally (143,000 Hemophilia A, 28,000 with Hemophilia B approximately). By most recent estimates from 2014 India has surpassed every country in the global database with a total of 17,470 patients with hemophilia ahead of USA with its 17,131 reported cases. Infectious disease and perinatal mortality take precedence for resource allocation in evolving economies like India, presenting an ongoing challenge for "rare" diseases like hemophilia. This study assesses the quality of hemophilia care at the SMS Medical School which is the flagship medical care center in the northwestern Indian city of Jaipur, the capital of the largest Indian state with an area of 0.34 million square kilometers and population of 68.55 million. Since the introduction of the free factor distribution in the fall of 2012, the program grew from a modest patient population size of 60 patients to a robust 700 plus patients within 4 years aided by the World Hemophilia Twinning program grant. A standardized self-administered questionnaire was administered to all the hemophilia patients seen at the outpatient comprehensive hemophilia program (CHP) at the SMS Medical College between February 1, 2016 and May 5, 2016. Two hundred patients met the inclusion criteria and participated in the study. One hundred eighty-seven (94%) and 13 (6) patients were diagnosed with hemophilia A and B respectively; 126 (63) had severe disease while 65 (33) had moderate and 9 (5) had mild hemophilia. In an expected male predominant sample (n=198 males [99.5]), the median age at the time of study was 12 years (range=1-53 years), and 144 (72) patients were from rural outskirts of the resource poor state visiting the tertiary care center for hemophilia care. Contrary to popular belief, only a minority 11% and 1% of patients identified themselves of the Muslim and Sindhi faith respectively, versus a majority 87% who followed Hinduism. Tenets of consanguinity and family size have often led to misunderstanding and stigmatization of the disease in the Asian subcontinent prior to this study thus far. Despite a majority 63% patients suffering from severe hemophilia, nearly half (44%) reported a delay of more than 6 months in diagnosis time from the first bleed. Remarkably, 96 % reported to know their diagnosis fully and 93% reported understanding that hemophilia is a genetically transmitted disorder but approximately 82.5 % did not know if they ever underwent testing for viral infections (H.I.V, Hepatitis B, C ) since their diagnosis . Nearly 45 % were offered genetic counseling services at some point during their care, a remarkable feat for a hemophilia program in a resource strapped environment. Inpatient stay for bleeds and complications in this predominantly severe mix of patients was encouragingly less than 1-5 days in 93% of the patients but despite free drug delivery program 79% families reported an out of pocket expense of more than 10,000 Indian rupees (INR; approximately 147 USD) during the hospital stay. This in a state where 65% of patients reported per capital household income less than 100,000 INR (1,485 USD) was particularly concerning. Nearly 18 % of the respondents identified themselves as below poverty (BPL) and enjoyed the benefits of free transportation under the governmental subsidies through a BPL card. Household income and below poverty status were not associated with hemophilia care outcomes (p-values <0.1). Reported favorable patient satisfaction (86%) and continued access to free factor infusion services irrespective of socio economic status as demonstrated by this study, for a resource limited setting caring for over 600 hemophilia patients should be considered a success. New epidemiologic insights from this study will help researchers and clinicians alike to design care delivery models for hemophilia. Not only does this study reflect the power of international collaborations in remarkably improving services for such ignored debilitating diseases in the resource limited nations but also presents as a unique first quality assessment tool for the nation with the largest number of identified hemophilia patients in the world. Disclosures Parnes: Pfizer: Consultancy; Baxalta: Research Funding. Neufeld:Pfizer: Consultancy; baxalta: Consultancy, Research Funding.

Abstract Background Schizophrenia is a complex disorder typically defined by the presence of positive symptoms that include hallucinations, delusions, and disorganisation in speech and behaviour, negative symptoms of avolition and social withdrawal, and a decline in functioning. Despite an ability to treat clinical symptoms, functional recovery in schizophrenia remains poor. The Recovery Day Program at the Royal Ottawa Mental Health Centre is a multi-disciplinary intervention tailored to help people living with schizophrenia attain recovery goals, lead more satisfying lives, engage in activities, develop a social network and assist in community reintegration. Eligibility criteria are: 18 years of age or older, meet DSM V criteria for Schizophrenia Spectrum illness, have clinical needs that cannot be met in the community, have housing, require intensive recovery support/integration into community, be able to engage in day hospital programming and develop recovery goals. Maximum number of day clients in Day Program is 20. Client admissions began in June 2016. As of November 2019, there have been 50 admissions with 29 discharges. Age range of clients was 20–60 years (mean 36.5). Clients were invited to provide feedback on their experience with the Day Program for program evaluation and improvement of service. Methods A qualitative and quantitative evaluation of functional outcomes and patient satisfaction was conducted. Measures were administered at admission and discharge: The Illness Management and Recovery Scale (IMRS), a custom-generated activity and goal attainment scale, Quality of Life Scale, The World Health Organization Disability Assessment Schedule 2.0, the Modified Global Assessment of Functioning Scale and the Clinical Global Impression Scale. The Ontario Perception of Care Survey for Mental Health and Addictions (OPOC) was administered during a two month period from January 2019. Results Discharge results were available for 29 individuals out of 50 admissions. Clients identified goals in areas including vocational, social, educational, symptom management, optimizing independence, minimizing substance use, managing finances and stable housing; group and individual interventions targeted these areas. Interventions occur at the hospital and in the community. Results of the activity summary identify significant change in community integration in the following areas: employment (admission 5% and discharge 47%), unpaid/volunteer work (admission 11% and discharge 42%), course or study (admission 0% and discharge 32%), social/recreation/group activities (admission 63% and discharge 100%). Results show a significant increase in IMRS scores over time. Goal achievement was statistically significant according to the goal attainment scale (mean at intake 3.4 and at discharge 8.6). Results show that goal importance did not change over time. Open ended questions about day programming were added to the OPOC. Of 15 respondents, the average length of time in the Program was 16 months. Majority of respondents attended as much as they liked, while those unable to attend as much as they wanted, identified that increased attendance may have been helpful to achieving their goals. Discussion Overall, clients were very satisfied with services provided. There were significant achievements in goal attainment over time with targeted interventions provided in functional domains including employment, unpaid/volunteer work, course of study and social/recreation activities. Our data suggest that a medium term, intensive day program increases functional outcomes and personal satisfaction for individuals with a Schizophrenia Spectrum disorder. Further study would be important to assess how these changes are sustained over time.

Abstract Bone marrow transplantation (BMT) is known to be both a physically and emotionally stressful procedure, due to the significant associated risk of developing life-threatening complications, and because of behavioural treatment related factors such as the post-transplant isolation period. BMT recipients have therefore been found to be at increased risk of experiencing a variety of psychosocial difficulties and factors that impact negatively on their quality of life. Identified factors include anxiety, depression, sexual difficulties, fatigue, interpersonal stressors and sleep disturbance. Psychosocial difficulties have been identified throughout the transplant process and into the recovery phase of treatment. Even disease-free BMT survivors report significantly disrupted cognitive, occupational and interpersonal functioning. Reported prevalence of psychosocial difficulties varies between 28% and 41% depending on the adopted diagnostic criteria and stage of transplant. Problems such as anxiety and depression are known often to go unrecognised in hospital settings. Unrecognised, or untreated psychosocial difficulties in the context of BMT are known to interfere with medical treatment and have been associated with reduced survival. It is therefore important that psychosocial difficulties in this patient group are identified at the earliest opportunity, and pro-actively addressed. In the BMT Unit at Glasgow Royal Infirmary, a nurse-led psychosocial screening programme has been established under the supervision of a clinical psychologist. All BMT recipients are now interviewed using a semi-structured interview prior to their transplant, to screen for psychological predictors of poor psychosocial outcome. Psychometric measures are also taken at this time. Measures comprise the Hospital Anxiety Depression Scale, The Brief Symptom Iventory-18, and the National Cancer Comprehensive Network ‘distress thermometer’, which assesses domains associated with quality of life. Repeat assessment is performed at day +14 and +100 post-transplant, in order to monitor potential change in presentation. Data collected from the first twenty-six consecutive BMT recipients are presented. Clinically significant psychological morbidity was identified in 43% of this sample. Levels of anxiety and depression were generally high and stable, before, during and after the transplant process. Formal contact with a clinical psychologist was required by 53% of the sample. Data from the measure of distress revealed that emotional and physical problems were most commonly reported and most highly rated. Consistent themes that emerged through interview included overt anticipatory fear regarding the transplant process, systemic family issues, the importance of family support, and the prospect of financial difficulties post-transplant. Many patients held unrealistically positive views regarding post-transplant quality of life, or were relying on positive thoughts to help them through the process. In conclusion, the prevalence of psychological morbidity in this population of BMT recipients was found to be high and stable. A psychosocial screening programme has aided the identification and treatment of ‘at risk’ cases. This highlights the need for continued awareness of psychosocial issues in this population, and the importance of ongoing formal, psychosocial support services for BMT recipients. Screening programmes are recommended for initial and ongoing assessment of psychosocial difficulties in this population.

Protein-calorie malnutrition is very frequent in cancer patients and is associated with an increase in morbidity and mortality. Recently, the Global Leadership Initiative on Malnutrition (GLIM) criteria were proposed to standardize the diagnosis of malnutrition. Nevertheless, these criteria were not validated in prospective studies. Our objective is to determine the prevalence of malnutrition in cancer inpatients using different diagnostic classifications, including GLIM criteria, and to establish their association with length of stay and mortality. Hence, we designed a prospective study. Within the first 24 hours of admission to the Inpatient Oncology Unit, subjective global assessment (SGA) was carried out, and anthropometric data (body mass index (BMI), mid-arm circumference (MAC), arm muscle circumference (AMC), fat-free mass index (FFMI)) and hand grip strength (HGS) were obtained to assess the reduction of muscle mass according to GLIM criteria. Length of stay, biomarkers (albumin, prealbumin, C-reactive protein (CRP)), and in-hospital and six-month mortality were evaluated. Regarding the 282 patients evaluated, their mean age was 60.4 ± 12.6 years, 55.7% of them were male, and 92.9% had an advanced-stage tumor (17.7% stage III, 75.2% stage IV). According to SGA, 81.6% of the patients suffered from malnutrition (25.5% moderate malnutrition, and 56.1% severe malnutrition), and, based on GLIM criteria, malnutrition rate was between 72.2 and 80.0% depending on the used tool. Malnourished patients (regardless of the tool used) showed significantly worse values concerning BMI, length of stay, and levels of CRP/albumin, albumin, and prealbumin than normally nourished patients. In logistic regression, adjusted for confounding variables, the odds ratio of death at six months was significantly associated with malnutrition by SGA (odds ratio 2.73, confidence interval (CI) 1.35–5.52, p = 0.002), and by GLIM criteria calculating muscle mass with HGS (odds ratio 2.72, CI 1.37–5.40, p = 0.004) and FFMI (odds ratio 1.87, CI 1.01–3.48, p = 0.047), but not by MAC or AMC. The prevalence of malnutrition in advanced-stage cancer inpatients is very high. SGA and GLIM criteria, especially with HGS, are useful tools to diagnose malnutrition and have a similar predictive value regarding six-month mortality in cancer inpatients.

582 Background: Guidelines for cardiac scanning in adjuvant Trastuzumab (T) trials were developed due to clinical concerns regarding cardiotoxicity, and these same guidelines are now used in clinical practice. This was a retrospective audit to assess adherence to these guidelines and characterise the nature and timescale of problems experienced with adjuvant T in clinical practice. Methods: A retrospective review of MUGA/ECHO results was conducted in patients who received adjuvant T for breast cancer. Data was compiled from five UK cancer centres: Glasgow, Manchester, Cardiff, The Royal Free hospital and Newcastle. Results: A total of 424 patients received at least one dose of adjuvant T between September 2005 and January 2008, using a HERA trial schedule. There were 262 with detailed information regarding treatment delays/withdrawals for cardiac reasons. 12% (32/262 pts) were withdrawn from adjuvant trastuzumab treatment for cardiac reasons, with another 11% (29/262 pts) experiencing at least 1 delay in treatment. Analysis of cardiac scan results for the remaining 162 pts suggested a total cardiac delay/withdrawal percentage of 14.4% (61/424 pts). There was no age effect with 15% (50/338) of <65 year olds experiencing cardiac delays/withdrawals compared to 18% (9/50) of ≥65 year olds. Preherceptin cardiac scan results did appear to be predictive of subsequent problems, with 29% (38/132 pts) who had an ejection fraction (EF) of 40–59% experiencing cardiac delays/withdrawals compared to 10% (19/183 pts) with an EF of 60–69% and 4% (4/98 pts) with an EF ≥ 70%. Pretreatment with Doxorubicin was associated with an approximate doubling of cardiac problems (6/20 pts; 30%) compared to pretreatment with Epirubicin containing chemotherapy regimens. No temporal relationship existed between timing of cardiac delays/withdrawals and stage of T treatment. Conclusions: Significant numbers of patients are experiencing delays/withdrawals during adjuvant T treatment. In routine practice the withdrawal rates are more than twice those reported in the HERA trial population. There is a clear role for a re-assessment of the trial-derived cardiac management guidelines, which should be prospectively audited. [Table: see text]

Objectives To assess the nutritional status of Korean peritoneal dialysis (PD) patients and to compare with data from Western literature, and to elucidate independent factors determining nutritional status and death. Design Cross-sectional single-center study. Setting Kidney Center, Soon Chun Hyang University Hospital. Materials Ninety-eight CAPD patients were included. Of these, 54 patients were male, 32 patients were diabetic, mean age was 47.9 :i: 13.1 years, and mean duration of CAPD was 22.3 :i: 21.6 months. The patients were followed until death, transfer to hemodialysis (HD) or other units, transplantation, or until 3 years had elapsed after the first evaluation. Methods Nutritional status was assessed by subjective global assessment (SGA), biochemical and anthropometric measurements, fat-free edema-free (FFEF) body mass by creatinine (Cr) kinetics, protein equivalent of total nitrogen appearance (PNA), and urea kinetic studies. Results By SGA score, 53.1% of patients were classified as normal, 44.9% with mild-to-moderate malnutrition, and 2% with severe malnutrition. Patients with malnutrition were significantly older and had higher peritonitis rates, lower serum albumin (Alb), blood urea nitrogen (BUN), serum Cr, FFEF body mass, mid arm muscle circumference, and PNA (p < 0.05). On stepwise multiple regression analysis, the SGA score was negatively correlated with age and peritonitis rate (p < 0.01). At the end of the 3-year follow-up period, 11 patients were still on CAPD, 26 had died, 51 had transferred to HD and 5 to other units, 3 patients had been transplanted, and 2 patients were lost to follow-up. Patients who died during follow-up were older and had higher peritonitis rates and lower total serum protein, Alb, Cr, and FFEF body mass when compared to those who survived (p < 0.05). Independent predictors of death were age, peritonitis rate, and serum Alb (p < 0.01). Conclusion Malnutrition was as common in Korean PD patients as reported in the Western literature. Our data suggests that, to prevent malnutrition and early death, it is important to reduce the peritonitis rate, to improve protein intake, and to prescribe an adequate dose of peritoneal dialysis.

Background:Rheumatoid arthritis (RA) is associated with higher cardiovascular disease (CVD) risk due to the underlying inflammation (1). It is uncertain if the excess CV risk could be reduced by effective suppression of inflammation using the treat-to-target (T2T) approach in patients with early RA (ERA).Objectives:This study compared the 5-year cardiovascular event (CVE) rate among ERA patients managed by a T2T strategy with a CV risk factor-matched non-RA population.Methods:This was an observational study using the Hong Kong Hospital Authority population-based hospital database known as the Clinical Data Analysis and Reporting System (CDARS) and the Clinical Rheumatology Systematic Treat-to-target in Asia Leadership (CRYSTAL) registry. ERA subjects from the registry with baseline disease duration less than 2 years were recruited between 2012-2016. All patients received a tight control, T2T treatment strategy aiming at remission and had been followed for at least 5 years. Each ERA subject was matched to 3 non-RA controls according to age, gender, smoking status, and the presence of diabetes mellitus (DM), hypertension (HT) and hyperlipidaemia (HL). All subjects on antiplatelet agents, with pre-existing CVD or chronic kidney disease were excluded. All subjects were analysed up to 5 years from baseline. The primary end point was the first occurence of a CVE, namely ischaemic cerebrovascular disease, ischaemic heart disease and heart failure.Results:The study identified 261 ERA subjects and 783 matched controls. Their characteristics were shown on Table 1. The mean age was 60+/-12 years, 78% were female, 18% were smokers, 8%, 25% and 22% had DM, HT and HL respectively.Table 1.Characteristics of ERA subjects and the matched controlsERA (n=261)Controls (n=783)p-valueAge (mean +/- SD)60.2 +/- 1260.3 +/- 120.99Total cholesterol (mean +/- SD)4.8 +/- 0.944.9 +/- 1.000.34High density lipoprotein-cholesterol (median, IQR)1.4 (1.2-1.6)1.4 (1.2-1.7)0.612Low density lipoprotein-cholesterol (mean +/- SD)2.8 +/- 0.82.6 +/- 0.80.27Triglyceride (median, IQR)0.96 (0.7-1.3)1.2 (0.8-1.7)0.00Atherogenic index# (mean +/- SD)-0.07 +/-0.29-0.15 +/- 0.280.48RA disease characteristicsBaselinelast visitSeropositivity89.3%Disease duration (median days, IQR)177 (96-299)2026 (1818-2126)Erythrocyte sedimentation rate (mean +/- SD)55.7 +/- 3432.6 +/- 21.3C-reactive protein (median, IQR)7.9 (3.5-22.2)2.1 (1.0-5.0)Swollen joint count (median, IQR)3 (2-6)0 (0-1)Tender joint count (median, IQR)6 (3-10)0 (0-1)Patient’s global assessment (mean mm +/- SD)50.7 +/- 26.816.0 +/- 18.3DAS28-ESR (mean +/- SD)5.2 +/- 1.32.4 +/- 1.8DAS28-CRP (mean +/- SD)4.4 +/- 1.31.8 +/- 1.5Health assessment questionnaire (mean +/- SD)0.77 +/- 0.740.38 +/- 0.51# Atherogenic index = log10 (triglyceride/HDL-cholesterol)SD: standard deviation, IQR: interquartile range, DAS28: disease activity score-28CVEs occurred in 2.3% ERA subjects and in 3.3% controls. The difference was statistically insignificant. The CVE-free survival was shown in Figure 1.Figure 1.CVE-free survival curves of ERA subjects & matched controlsIn the ERA cohort, after adjusting for baseline age and atherogenic index, cox-regression analysis showed that i) a longer DAS28 remission duration was protective for CVE with an adjusted hazard ratio (AHR) of 0.46 (95% CI 0.23-0.93), while ii) poor baseline function as reflected by a higher health assessment questionnaire (HAQ) score was predictive of CVE with an AHR of 5.2 (95% CI 1.2-23).Conclusion:ERA patients treated by a T2T strategy did not develop excess CVE compared to CV risk factor-matched controls over 5 years. A longer disease remission duration was protective while a higher baseline HAQ was associated with a higher CVE risk.References:[1]Agca R et al. EULAR recommendations for cardiovascular disease risk management in patients with rheumatoid arthritis and other forms of inflammatory joint disorders: 2015/2016 update. Annals of the Rheumatic Diseases.Disclosure of Interests:None declared

Abstract In the majority of low-middle-income countries (LMIC) worldwide, cancer care is limited by lack of patients' access to care and/or unaffordable cost of treatment. In contrast with many other LMIC, Cuban government provides cancer therapy to every citizen. Therefore, any standard treatment for acute leukemias, including BMT, is available for free. However, because of limited financial resources laboratories do not always provide immunophenotypic, cytogenetic or molecular tests to support the diagnosis or the management of leukemias, and only standard chemotherapy protocols are available. In this retrospective study we analyzed the results of BMT in adult acute leukemia patients transplanted at the Hermanos Ameijeiras Hospital in Havana (Cuba) from June 1986 to January 2016. A total of 101 consecutive cases (83 acute myeloid leukemia [AML] and 18 acute lymphoblastic leukemia [ALL]) were transplanted. Eligibility criteria for BMT included: age >16 and <60; achievement of morphologic complete remission after induction and consolidation chemotherapy and no severe comorbidities according to standard BMT criteria. Because of lack of access to international donor registries, only patients who had an HLA matched related donor (MRD) received an allogeneic BMT, whereas the others received a further consolidation with an autologous BMT. Stem cell source was fresh bone marrow in 80% of patients, fresh G-CSF mobilized peripheral blood (PBSC) in 19%, and only 1 cord blood transplant was attempted in a patient without a MRD. Of 83 AML patients, 36 received an allogeneic (AML-allo) and 47 an autologous (AML-auto) stem cell transplant. Median age in AML-allo and AML-auto groups was 37 (range:22-54) and 36 (range: 18-58) years, respectively. Median follow-up was 50.4 months (range:1-288) in AML-allo and 50.7 months (range: 1-324) in AML-auto. This is in part due to the policy that patients from outside Havana return to their primary hematologist within 1-2 years after transplant. In addition, some patients left Cuba soon after transplant. Of 36 AML-allo 36% died of transplant-related-mortality (TRM) and 25% of relapse. On the contrary, of 47 AML-auto 17% died of TRM and 40% of relapse. Overall survival (OS) was 38% in AML-allo and 42% in AML-auto. Of 18 ALL patients, 7 received an allogeneic (ALL-allo) and 11 and autologous (ALL-auto) transplant. Median age in the two groups was 36 (range: 18-47) and 27 (range:17-34) years, respectively. Of 7 ALL-allo cases, 1 died of TRM and 3 of relapse (OS 43%). Of 11 ALL-auto cases 4 patients died, all due to relapse (OS 64%). In conclusion, BMT is available for acute leukemia patients in Cuba. Despite limited resources, we envision that through an active collaboration with UIC the BMT program at the Hermanos Ameijeiras Hospital may rapidly expand its activity by developing disease risk assessment through cytogenetic and molecular technologies, implementing cryopreservation of stem cells from PBSC, introducing haploidentical transplantation for patients without a MRD, offering reduced intensity conditioning regimens to patients >60 years old. Support of training and development of research infrastructures remain of key importance in global health cancer care and global BMT. Disclosures No relevant conflicts of interest to declare.

Abstract Abstract 4626 The management of menorrhagia presents a challenge in women with severe bleeding disorders. Conservative medical management is the first line treatment and most women with severe bleeding disorder require combination treatment. Surgical intervention may ultimately be offered to women in whom medical management has failed and whom no longer desire fertility. Women with low factor levels are at risk of perioperative bleeding complications and may require haemostatic support. A total of 50 women with severe factor deficiencies (less than 20iu/dL) were included in this study. 46 women were registered at the Haemophilia Centre at the Royal Free Hospital in London. Four cases were also included from the Rhine-Ruhr Haemophilia Centre in Duisburg, Germany. We reviewed the occurrence of menorrhagia and the management options that were offered. In those that required surgical intervention, the incidence of postoperative bleeding complications and the requirement for factor concentration was also reviewed. The bleeding disorders in these women were 34 (68%) with severe factor XI deficiency, 10 (20%) with severe type 1 and type 3 von Willebrand's disease, 4 (8%) with factor VII deficiency, 2 (4%) had factor V or X deficiencies and one (2%) had a combination of factor VI and VIII deficiency. The ISTH/SSC joint working group bleeding assessment tool was used to assess the severity and frequency of bleeding symptoms among this cohort of women. The bleeding scores ranged from −2 to 30 with a median score of 9.5. In total, 32 out of 50 (64%) women with severe factor deficiency required medical attention for menorrhagia. Medical treatment included hormonal preparations (combined oral contraceptive pill or levonorgestrel intrauterine device), which was used as a first line treatment in 15 out of 32 (46.8%) women. Haemostatic treatment included antifibrinolytic medication such as tranexamic acid, which was used in combination with hormonal therapy. One women required intranasal DDAVP, von Willebrand factor concentrate and tranexamic acid. Failure to control menstrual bleeding occurred in 14 (43.7%) women and surgical intervention was required. 7 out of 14 (50%) women required hysterectomy and the remaining 7 women underwent endometrial ablation. Prophylaxis with factor concentration to cover surgical intervention was given in 8 out of 14 women (64.2%). The remainder received tranexamic acid for 24–48 hours following surgery. Postoperative bleeding occurred in 7 women that had surgical intervention, despite two women receiving prophylaxis. This study highlights the complexity involved in the management of menorrhagia in women with severe bleeding disorders and the high risk of postoperative bleeding. Disclosures: No relevant conflicts of interest to declare.

Background:The rapid global spread of COVID-19 required swift action to provide people with rheumatic and musculoskeletal diseases (RMDs) with reliable information. Important issues included the risk of infection and severe illness, (continued) use of medication, temporary closure of clinics, and organization of (semi-) virtual care. People with limited health literacy are a particularly vulnerable group that might have difficulty accessing, understanding, and applying health information.Objectives:To evaluate (a) key aspects of crisis communication and (b) explicit consideration of people’s health literacy needs in communication to people with RMDs during the first wave of COVID-19 in the Netherlands.Methods:We conducted an explorative qualitative study including seven interviews in May and June 2020 with representatives of organisations (a mixed regional/academic hospital, the association for RMD professionals and two patient organisations) responsible for information provision to people with RMDs in the Netherlands. Interviewees were asked about preparedness (1) and strategy (2) for crisis communication, and content (3) and reach (4) of communication, considering principles of good crisis communication and health literacy. In addition, through systematic screening of websites, social media and emails, we identified and analysed 13 written communications provided to people with RMDs by these organisations during the first three months of the COVID-19 pandemic. We assessed comprehensibility and applicability with the Dutch adapted version of the Patient Education Materials Assessment tool (PEMAT), the outcome being a percentage of adherence to 24 criteria. We assessed difficulty level using an online assessment application (Figure 1), with Common European Framework of Reference for Languages (CEFR) level B1 being the highest acceptable level.Figure 1.Example of textual assessment using the application. Note: Dutch-language text was used for analysis; the English translation is provided as a reference only and might be of different difficulty.Results:While admittedly being underprepared, respondents generally perceived their crisis communication as adequate. They quickly adapted to people’s needs and changing circumstances and attempted to adapt written and verbal communication to people with limited health literacy. Respondents reported challenges related to the scientific uncertainty, lack of reach, difficulty simplifying information, and being unsure if their communication approach was adequate. Textual assessment showed great variation in applicability (range 60-100%) and comprehensibility (range 58-100%) of these texts, and 69% of communications were more difficult than B1-level. Considering principles of crisis communication and health literacy, we propose several lessons to be learned for future crises (Table 1 Table 1.Recommendations for improvement of crisis communicationPreparedness:Use current experience to establish a future crisis communication planTrain staff and management in crisis communication and health literate communicationStrategy:Collaborate with relevant organisations to ensure consistency in messagesInform people early and frequentlyRemain transparent about uncertaintyContent:Adapt information to different people’s needs, considering e.g. age, cultural backgroundCheck difficulty level of written information (aim at B1) and adapt accordinglyAsk your audience for feedbackMake sure information is directly applicable in practiceCombat fake news through acknowledgement and counterargumentsReach:Use multiple channelsUse diverse outreach strategies to cater to a diverse audienceOverall:Consider people’s health literacy throughout).Conclusion:The rheumatology organisations mostly adhered to principles of crisis communication, and made efforts to adapt information to their audience’s needs, including health literacy needs. Nevertheless, important recommendations were drawn which are potentially also relevant for other clinical fields.Acknowledgements:We thank Mr. Tigran Spaan for providing free access to the online language assessment application.Disclosure of Interests:None declared.

Abstract Abstract 1680 We studied BCR-ABL1 transcript levels in patients with CML in chronic phase at 3, 6 and 12 months after starting imatinib to identify molecular milestones that would predict for overall survival and other outcomes more reliably than serial marrow cytogenetics. We analyzed 282 patients with CML-CP who received imatinib 400 mg/day as first line therapy followed by dasatinib or nilotinib if they failed imatinib. The median age was 46.3 years (range 13–86.4), 157 (55.7%) patients were male. The Sokal risk distribution was: 31.8% low, 40.1% intermediate and 28.1% high. The median follow-up was 69 months (range 17–131). BCR-ABL1 transcripts were analyzed in the peripheral blood at 12 week intervals using RQ-PCR. Results were expressed as percentage ratios relative to an ABL internal control and converted to the international scale. Complete molecular response (CMR) was defined as two consecutive samples with no detectable transcripts with the ABL1 control >40,000 copies (the median ABL control in the CMR samples was 84,000). We employed a ROC curve to identify the cut-offs in transcript levels at 3, 6 and 12 months that would best predict patient outcome. Patients with transcript levels >9.84% (n=68) at 3 months had significantly lower 8-year probabilities of overall survival (OS) (56.9% vs 93.3%, p<0.0001), progression-free survival, cumulative incidence of CCyR and CMR than those with higher transcript levels. Similarly transcript levels >1.67% (n=87) at 6 months and >0.53% (n=93) at 12 months identified poor risk patients. However transcript levels at 3 months were the most strongly predictive for the various outcomes. When we compared OS for the groups defined molecularly at 6 and 12 months with use of the usual cytogenetic milestones, categorization by transcript numbers was the only independent predictor for OS (RR= 0.207, p<0.0001 and RR=0.158, p<0.0001). We validated our results by classifying 95 patients treated with imatinib first line at the Royal Liverpool University Hospital according to their transcript levels at 3, 6 and 12 months after converting their local their RQ-PCR results to the international scale. At each time point the high risk patients had significantly poorer OS, namely 69.1% vs 98.3% (p=0.003); 98.1% vs 71.2% (p=0.009) and 98.0% vs 74.4 (p= 0.016) than the good risk patients. The various transcript cut-offs could be refined in order to better identify those patients more likely to achieve CMR. The 57 patients who had a 3-month transcript ratio ≤0.61% had a 8-year CI of CMR of 84.7%, while the 222 patients with a ratio >0.61% had a CI of CMR of only 1.5% (p<0.0001). Similar thresholds with high predictive power could be identified for 6 and 12 months. We also tried to identify levels of transcripts at 6 and 12 months above which patients in CCyR were destined to fare worse than those with lower values. At 6 months and 12 months, 23 of the 109 and 20 of the 166 patients who were in CCyR had a transcript level higher than 0.53% (the value that we had previously identified as defining the 12 months high risk group); these patients had significantly worse OS (65.8% vs 95.9%, p=0.0002 and 81.5% vs 94.9%, p=0.01) than the 104 and 140 patients with lower transcript levels. During follow-up 118 patients failed imatinib and required alternative therapy. In order to explore further the impact of early measurements of transcript levels on outcome irrespective of the use of subsequent rescue treatment, we calculated the ‘current CCyR survival’ (c-CCyRS, i.e. the probability of being alive and in CCyR at a given time point). The 8-year c-CCyRS for the whole population was 76.6%. High risk patients had a significantly worse 8-year probability of c-CCyRS than good risk patients, namely 47.0% vs 91.1% at 3 months (p=0.0002) and 53.1% vs 91.3% (p=0.0001) at 6 months (Figure 1). These findings indicate that the prognostic value of early measurement of the residual leukemia burden retains its value even for patients requiring treatment with second generation tyrosine kinase inhibitors. In conclusion, a single measurement of BCR-ABL1 transcripts performed at 3 months is the best way to identify patients destined to fare poorly, thereby allowing early clinical intervention.Figure 1Figure 1. Disclosures: No relevant conflicts of interest to declare.

Abstract Introduction: Median age of Chronic Lymphocytic Leukemia (CLL) patients is 72 years with 40% older than 75 and 22.8% over 80 years. Important therapeutic progresses have been made, including chemo-immunotherapy as well as the recent use of targeted therapies, leading to progression-free-survival (PFS) and overall survival (OS) improvements. Although the elderly represents the largest subgroup of CLL patients, they are underrepresented in clinical studies and little is known about their clinical characteristics, treatment and outcome. Consequently, results from trials cannot be directly translated into clinical practice for these patients. Bairey et al (Ann Hematol, 2011) reported a series of 214 patients (80 years or older) diagnosed in Israel between 1979 and 2009 with a mean age of 84. However, in this cohort, 56% of the patients had a Rai stage 0 and only 53 received treatment. Median survival was 56 months. Methods: We performed a retrospective study of CLL patients aged 80 or more at initiation of first line therapy. Patients were treated between 2003 and 2013, in 17 hospitals affiliated to the French Innovative Leukemia Organisation (FILO). We report here a cohort of 201 such CLL patients, and describe their clinical and biological characteristics, treatment options and outcome. Results: Patients' median age was 83.4 years (80-92), 29% were older than 85 years, and the sex ratio was 60% male/40% female. Performance status (97%≤ 2) and nutritional status (median Corporal Mass Index of 25.3 kg/m²) were preserved. The median Cumulative Index Rating Scale (CIRS) comorbidity score was 5. More precisely in term of fitness, 57.8% patients were characterized as "go-go" with a CIRS ≤ 6 and organ comorbidities <3. The median creatinine clearance was 48 mL/min (Cockroft formula). Most patients lived at home (89.5%), often with familial or professional help (72%). A complete geriatric assessment was performed for 6.1% of them. Diagnosis relied on a Royal Marsden Hospital (RMH) score > 3, and CD38 was positive in 43,4% of the 129 cases tested (64%). Cytogenetic data were available for 42% of the patients. Isolated abnormalities were deletion 13q (38.1%), trisomy 12 (21.4%), deletion 17q (10.7%) or deletion 11q (7.1%). Besides, associated chromosomic abnormalities were detected, mainly by fluorescence in situ hybridization (FISH) and complex karyotypes (1.2%). At treatment initiation, Binet stage was either A (27.2%), B (28.7%) or C (41.5%). Therapies consisted mainly in Chlorambucil (65.5%), Bendamustine (10.5%) and Rituximab (44.3%). Indeed, therapy regimens were composed of Chlorambucil alone (45.3%) or chemo-immunotherapy (48.3%) including Rituximab+Chlorambucil (22.7%), Rituximab+Bendamustine (10.4%), Rituximab+Cyclophosphamide+Dexamethasone (5.5%) or Rituximab+Fludarabine+Cyclophosphamide (5.5%). In term of tolerance, 20.2% of the patients required hospitalization and 10% of these cases were febrile neutropenia. Finally, 31.8% required a dose reduction of chemotherapy. The Overall Response Rate was 65.9% with 31.4% of clinical complete remission. The median OS and PFS (from treatment initiation) were 48.6 and 18 months, respectively (cf. Survival curves). Afterwards, an important number of patients (41.3%) remained fit enough to receive a second line treatment. In univariate analysis, only comorbidities evaluated by the CIRS had a significant impact on survival (p=0.03). Indeed patients identified as fit by a CIRS score ≤ 6 and no organ comorbidity > 3 had a better outcome. Conclusion: We report a large series of elderly CLL patients, who received first line treatment at a median age of 83. Median OS was about 4 years, which is less than normal population of the same age. Our results suggest that treatment (including immunochemotherapy) is feasible, even in this very old population. Different bias are possible in this retrospective study including the selection of only fit patients, the low percentage of geriatric evaluation, and the possible undertreatment of this population since chlorambucil was the most frequent treatment. In the future, prospective trials should target this population. Oncogeriatric evaluation and new targeted therapies should be part of such future trials. Figure 1. Survival curve 1: Overall Survival Figure 1. Survival curve 1: Overall Survival Figure 2. Survival curve 2: Progression Free Survival Figure 2. Survival curve 2: Progression Free Survival Disclosures Dupuis: ROCHE: Speakers Bureau; ABBVIE: Membership on an entity's Board of Directors or advisory committees. Aurran-Schleinitz:CSLBehring: Honoraria; Janssen: Honoraria. Cymbalista:Karyopharm: Honoraria; Gilead: Honoraria; Roche: Honoraria; Janssen: Honoraria, Research Funding. Dilhuydy:Roche: Honoraria, Other: Travel reimbursement; Janssen: Honoraria, Other: Travel reimbursement; Mundipharma: Honoraria. Cazin:GILEAD,: Honoraria; ROCHE: Consultancy; MUNDIPHARMA: Honoraria, Research Funding; NOVARTIS: Honoraria. Leblond:Roche: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses, Speakers Bureau; GSK: Consultancy, Honoraria, Speakers Bureau; Mundipharma: Honoraria; Gilead: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau. Cartron:Sanofi: Honoraria; Gilead: Honoraria; Celgene: Honoraria; GSK: Honoraria; Roche: Consultancy, Honoraria.

AimTo reduce the average length of stay (LoS) of paediatric inpatients requiring discharge medication (TTO’s) on the short stay pathway (Comet).MethodsA paediatric multi-disciplinary team (MDT) used the model for improvement to identify stakeholders and key drivers for change. The Comet patient journey was mapped from A&E to discharge. Plan-Do-Study-Act (PDSA) cycles were used to reduce LoS, targeting the addition of a paediatric pharmacist to the morning ward round and use of over- label packs to facilitate nurse-led discharge for simple TTO’s required within 2 hours. Data was collected over a two week period in summer; PDSA 1 baseline data, one week prior to change; PDSA 2, one week after implementation. Baseline measurements included time taken to write, screen and dispense TTO and the average LoS. Data was collected via the electronic prescribing system (Lastword). Patients eligible for the Comet pathway were included for analysis. Results were analysed using Microsoft Excel. Ethics approval was not required for this study.ResultsPDSA one; 15 patients admitted onto the Comet pathway. 67% patients were admitted outside working hours. Six patients needed TTOs, 33% were written out of hours and all dispensed by pharmacy. Average time to writing TTO 14.6 hours (16minutes-44hhours); time to pharmacist clinical screen 19.4 hours (6 minutes – 21 hours); average time for pharmacy to dispense TTO after screening 2 hours (69–203 minutes); average LoS for all Comet patients 17.6 hours (8–44) and 26 hours (14–44) for those needing TTO’s. Post implementation 12 patients were eligible for the Comet pathway. 83% patients were admitted outside of hours. Six patients needed TTO’s, 16% were written out of hours and 33% were dispensed by the nursing team. Average time to writing TTO increased to 20.2 hours (14–26), average time to pharmacist clinical screen was reduced to 10 minutes (1–98) and average time for pharmacy to dispense TTO reduced to 57 minutes (47–74). Average LoS for Comet patients was similar to PDSA 1 at 17.7 hours (3–27) but reduced to 20.8 h0urs (5–27) for those needing TTO’s.ConclusionIncreasing patient-facing time of pharmacists to improve outcomes is recommended by the Carter report.(1)Pressures in emergency-care to free up beds for patients means we need to look for creative solutions. (2) This study found the addition of a paediatric pharmacist to the ward round increased efficiency of writing, screening and dispensing TTO’s - dramatically reducing time to screening TTO’s; and the average LoS by 5 hours. The pharmacist was aware of Comet discharges at the time of decision to discharge and was on hand to resolve medication related issues. New doctors in August could explain the increased time to writing TTO’s in the second week. Promotion of nurse-led discharge via over-label packs reduced the number of TTO’s sent to pharmacy. Limitations include2 weeks of data over summer were analysed and non-paediatric hospital activity would impact pharmacy dispensing time. Future work will test how pharmacist transcribing TTO’s on the ward round affect Los and to review pharmacist clinical interventions to assess impact on outcomes.ReferencesDepartment of Health. Carter report: Unwarranted variation: A review of operational productivity and performance in English NHS acute hospitals. 5thFebruary 2016.Royal College of Paediatrics and Child Health. Standards for Short-Stay Paediatric Assessment Units (SSPAU). March 2017.

Abstract Several studies have found fatigue to be the most common, persistent, and disabling symptom affecting patients with AML. Effective measures to prevent or treat fatigue have yet to be found. Cytokines, biological markers of inflammation, may represent one potential intervention target, but data on the fatigue-cytokine relationship in AML are limited to one small published study. We examined this relationship in patients age 50 or older with AML, fluent in English, within one year of AML diagnosis, and free of any other active malignancy. Fatigue was measured using the Functional Assessment of Cancer Therapy (FACT) Fatigue subscale and a single-item global fatigue scale. Quality of life (QOL) and depression were assessed using the European Organization for the Research and Treatment of Cancer (EORTC) core questionnaire (QLQ-C30) and the Hospital Anxiety and Depression Scale (HADS), respectively. Blood was simultaneously drawn for quantitative measurement of a panel of cytokines. Patients were reassessed 4–6 weeks later, and the same set of questionnaires were administered and a second blood sample drawn. Pearson’s correlation was used to examine relationships between individual cytokines and fatigue scores. Variables were transformed as necessary. For patients with data at two time points, changes in fatigue scores were correlated with changes in cytokines. At the time of submission, 31 patients (20 males; 11 females) have been enrolled (mean age 67 y; range 52–84). 32% had not started active chemotherapy or were receiving best supportive care, while the remainder were undergoing active chemotherapy. At the first time point (t1), no moderate or strong correlations were observed with any of the cytokines and at least one fatigue score. Weak correlations (0.30<r<0.50) were seen with interleukin(IL)-5, IL-6, IL-8, and IL-10 with at least one fatigue measure. No correlations (r<0.30) were observed with any of the other cytokines tested (interferon (IFN)-γ, IL-1β, IL-2, IL-4, IL-12, interferon-inducible protein (IP)-10, monocyte chemotactic protein (MCP)-1, monokine induced by gamma-IFN (MiG), and tumour necrosis factor (TNF)-α). Among patients with follow-up data, a moderate correlation (0.50<r<0.70) was noted between changes in IL-6 level and fatigue scores. Changes in concentrations of IFN-γ, IL-1β, IL-2, IL-5, IL-8, IL-10, IP-10, and MiG showed weak correlation with changes in at least one fatigue measure. A moderate correlation was observed between age and IL-1β but no age relationship was noted for any of the other cytokines. There was no correlation between fatigue and age but there were moderate to strong correlations between fatigue and depression. Based on these data, the most consistent relationships between concentrations of cytokines and fatigue were noted with IL-5, IL-6, and IL-8, and these show the most promise for future studies. Our study bore two notable limitations: the first was the small sample size, and the second was the recruitment of patients at differing time points during their treatment course. Further patient enrolment and data collection are underway to validate our findings and clarify the significance of these preliminary results.

Abstract INTRODUCTION: Although specific prognostic models for Chronic Myelomonocytic Leukemia (CMML) exist, few are based on large series of patients. Since its publication in 2002, the MD Anderson prognostic score (MDAPS) has been the most powerful prognostic tool for CMML. Due to the recent emergence of the CMML-specific prognostic scoring system (CPSS) and the Mayo prognostic model, we compared the three scores to assess their usefulness in our series. These three indexes, and not those based on clinical and molecular variables (Mayo Molecular Model and GFM prognostic score), were selected as the most easy-to-apply in normal clinical practice. AIM: 1) To assess the prognostic impact on overall survival (OS) and leukemia-free survival (LFS) of the variables composing the scores: MDAPS, CPSS and Mayo prognostic model; 2) To test the capability of the scores to detect the high-risk CMML patients; 3) To detect the index with the best predictive value for mortality and leukemia transformation, and 4) To implement a new score after selecting the best variables of the three indexes in terms of OS prognostic information. PATIENTS AND METHODS: From January 1997 to August 2013 a retrospective analysis including 146 patients diagnosed with CMML was performed in Hospital Clínic of Barcelona (n=134) and Hospital Germans Trias i Pujol (n=12). The median age was 76 years (range 27-96 years) and 63% were males. One-hundred and twenty-nine (88%) had a CMML-1, 17 (12%) a CMML-2, 102 (70%) a CMML-MD and 44 (30%) a CMML-MP. The median follow-up for surviving patients was 24.5 months and the median OS was 20 months (range 0-159 months). The prognostic impact in terms of OS and LFS of each of the variables that compose the indexes were studied by a univariate survival analysis (Kaplan-Meier; Log-Rank). A multivariate analysis (Cox model) was performed to assess the independent impact of the variables that showed significance in the univariate analysis in order to select the ones with the best prognostic information. The global prognostic scores were analyzed by univariate and multivariate analyses. In addition, ROC curves and the concordance index (C-index) were implemented to select the score with the best predictive power for mortality or leukemia transformation. RESULTS: All the variables that compose the MDAPS (hemoglobin level < 12 g/dl, absolute lymphocyte count > 2.5 x 109/L, presence of circulating immature myeloid cells (IMCs) and BM blasts ≥ 10%), the CPSS (CMML-MD vs. CMML-MP, CMML-1 vs. CMML-2, RBC transfusion dependency and the Spanish cytogenetic risk classification) and the Mayo prognostic model (absolute monocyte count > 10x109/L, presence of IMCs, hemoglobin < 10 g/dl and platelet count < 100 x 109/L) showed prognostic value on OS with the exception of circulating IMCs. Regarding LFS, only CPSS variables, BM blast ≥ 10% and an absolute monocyte count > 10x109/L had an impact. When the scores were applied, all showed an impact on OS and retained their significance in multivariate analysis. By using ROC curves and C-index, CPSS (ROC area: 0.80, CI 95%: 0.72-0.88; C-index: 0.73) showed a slightly better predictive value for mortality. Variables composing the three indexes were compared in a multivariate analysis and only CPSS parameters and platelets < 100 x 109/L retained their significance. Based on these findings, by adding platelet count information to CPSS, a new score was implemented (CPSS-P) showing the best risk stratification in our series (Figure 1). CONCLUSIONS: The present study reinforces the validity of CPSS, the MDAPS and the Mayo prognostic model for the assessment of CMML patients. Moreover, by including the platelet count information to the CPSS improved the prediction capacity for OS and LFS in our series. It is of importance to remark that platelet count information could help to better stratify CMML patients, being of special value in the subset of patients with normal karyotype. Figure 1. Associations Between Genetic Mutations and Clinical or Demographic Parameters Figure 1. Associations Between Genetic Mutations and Clinical or Demographic Parameters Disclosures No relevant conflicts of interest to declare.

Abstract Advances in novel agents and treatment combinations have improved prognosis and increased disease-free and overall survival for patients (pts) with multiple myeloma (MM). However, currently available data on disease presentation, treatment patterns, and outcomes for real-world MM pts at the global level are limited. This is due to several factors, including the overrepresentation of medically fit pts in clinical trials making generalization of outcomes challenging, the large number of treatment combinations, and varying global access/practice patterns. INSIGHT-MM (NCT02761187) is a global, prospective, non-interventional, observational study which aims to further understand disease and pt characteristics at presentation, treatment and clinical outcomes of real-world MM pts, as well as the association of treatment with tolerability, effectiveness, health-related quality of life (HRQoL), and healthcare resource utilization (HRU), on both a country-specific and global basis. As this is an observational study, no formal hypothesis will be tested. The INSIGHT-MM objectives are summarized in the Table. At least 5000 pts aged ≥18 yrs with newly diagnosed or relapsed/refractory MM will be enrolled over a 3-yr period and followed prospectively for ≥5 yrs, until death or end of study, whichever comes first. Pts not available for data collection for >9 mos will have follow-up for survival. No study drug or medications will be provided; no modification of standard of care pt management will be assigned per protocol. Choice of therapy for all pts will be decided by the treating healthcare provider independent of study participation. Baseline pt and MM-specific characteristics, diagnosis, comorbidities, and prior therapies will be recorded based on review of hospital/clinic records. MM management, disease status and safety data will be obtained as part of routine office visits and recorded quarterly by each site in electronic case report forms. Quarterly assessment of MM management will be done based on prior and current treatment and recorded reason for treatment changes. Effectiveness of therapy will be assessed based on response, progression status, time to next therapy, vital status, and date and cause of death. Treatment tolerability will be assessed based on serious and non-serious adverse events leading to treatment discontinuation or dose modification. Incidence of second primary malignancies will be recorded. HRQoL, a specific type of patient reported outcome (PRO), will be collected at study entry and at predefined intervals following initiation of therapy using a secure electronic data collection system. HRQoL will be collected using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and the MM module (EORTC QLQ-MY20). To capture pt satisfaction with MM-directed therapy, including the dimension of convenience, the 9-item Treatment Satisfaction Questionnaire for Medication will be used. The 5-dimension, 5-level EuroQol (EQ-5D-5L) PRO instrument will capture self-reported preference-based measures of health status suitable for calculating quality-adjusted life year (QALY) data to inform health economic evaluations. Frailty will be assessed using the Charlson Comorbidity Index, the Katz Index of Independence in Activities of Daily Living, and the Lawton Instrumental Activities of Daily Living. HRU will be evaluated using inpatient and intensive care unit admissions, length of stay, outpatient clinic visits, and emergency room visits. Data for all participating pts will be extracted by healthcare professionals at the site level and entered into a central database; descriptive statistical analyses will be done to address the study objectives. Interim analyses are planned after 1000 and 5000 pts have been enrolled and a final analysis will be conducted within 1 year after the last pt entered has completed ≥5 yrs follow-up. Data will be analyzed biannually to address emerging clinical questions identified by investigators to increase understanding of real-world treatment patterns. INSIGHT-MM aims to promote better understanding of contemporary demographics, patterns of care, and outcomes for real-world MM pts to inform treatment practice, supportive care, and pt outcomes. The study is currently ongoing and recruiting pts; further details regarding study rationale and protocol will be provided. Table 1 Table 1. Disclosures Davies: Takeda: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. Palumbo:Janssen Cilag: Honoraria; Takeda: Employment, Honoraria. Zonder:Bristol Myers Squibb: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Prothena: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Pharmacyclics: Other: DSMC membership. Girnius:Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Speakers Bureau. Costello:Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Usmani:Array: Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Amgen: Consultancy, Research Funding, Speakers Bureau; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Millenium: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Onyx: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; BioPharma: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Pharmacyclics: Research Funding; Britsol-Myers Squibb: Consultancy, Research Funding; Skyline: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Speakers Bureau. Berdeja:Abbvie, Acetylon, Amgen, Bluebird, BMS, Calithera, Celgene, Constellation, Curis, Epizyme, Janssen, Karyopharm, Kesios, Novartis, Onyx, Takeda, Tragara: Research Funding. Omel:Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Member of Takeda's "Patient Leadership Council". Token payment. Thompson:Celgene: Membership on an entity's Board of Directors or advisory committees, Other: MDS/AML Registry; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees; AIM Specialty Health: Membership on an entity's Board of Directors or advisory committees; VIA Oncology: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees, Other: Multiple Myeloma International Registry; Doximity: Equity Ownership, Membership on an entity's Board of Directors or advisory committees. Shah:Array: Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Honoraria, Research Funding; Bristol-Myers Squibb: Research Funding; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Schwartz:Bayer: Consultancy; Blue Cross and Blue Shield Associations: Consultancy; Pfizer: Consultancy; Takeda: Consultancy. Hajek:Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. Terpos:Amgen: Consultancy, Honoraria, Research Funding; Celgene: Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria; Genesis: Consultancy, Honoraria, Research Funding; Novartis: Honoraria. Hungria:Takeda: Consultancy; Roche: Consultancy; International Myeloma Foundation Latin America: Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Speakers Bureau; Bristol: Consultancy; Amgen: Consultancy. Mateos:Takeda: Honoraria; Amgen: Honoraria; Janssen: Honoraria; Celgene: Honoraria. Cook:Bristol-Myers Squibb: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Takeda: Consultancy, Honoraria, Research Funding, Speakers Bureau; Glycomimetics: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Sanofi: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau. Leleu:Novartis: Honoraria; LeoPharma: Honoraria; Pierre Fabre: Honoraria; Amgen: Honoraria; Bristol-Myers Squibb: Honoraria; Takeda: Honoraria; Celgene: Honoraria; Janssen: Honoraria; TEVA: Membership on an entity's Board of Directors or advisory committees. Goldschmidt:Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Chugai: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Millennium: Membership on an entity's Board of Directors or advisory committees, Research Funding; Onyx: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees. Seal:Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment, Equity Ownership. Pashos:Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment. Stull:Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment. Romanus:Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment. Cacioppo:Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment. Bell:Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment, Equity Ownership. Yu:Takeda Restricted Stock Unit (RSU), a publicly traded company: Equity Ownership; Takeda Development Center Americas, Inc., Deerfield, IL, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment. Luptakova:Takeda Oncology: Employment. Niculescu:Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment. Noga:Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment, Equity Ownership. Skacel:Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment. Chari:Array Biopharma: Consultancy, Research Funding; Amgen Inc.: Honoraria, Research Funding; Celgene: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Pharmacyclics: Research Funding; Novartis: Consultancy, Research Funding; Janssen: Consultancy, Research Funding.

Abstract Abstract 4001 Introduction Serum free light chain (FLC) measurements are used routinely to identify monoclonal immunoglobulin (M-Ig) production in patients. In addition, summated kappa + lambda concentrations have recently been shown to have prognostic value in chronic lymphocytic leukaemia (CLL), Hodgkins lymphoma and HIV patients; presumably reflecting immune stimulation. A recently developed companion assay to FLC testing measures intact immunoglobulin heavy chain/light chain (HLC) pairs in serum calculating Ig'κ/Ig'λ ratios as a reflection of clonality. Here we report on a computational approach combining FLC and HLC measurements to identify clonal disease, hyper- and hypo-gammaglobulinemia, and as markers of immune dysfunction. Furthermore, we comment on the potential of such an algorithm to risk stratify haematological and non-haematological malignancies. Patients, Materials and Methods 1468 patients referred to the Royal Wolverhampton Hospital for haematological evaluation were enrolled on to the study. Median patient age was 64 years, with a slight female preponderance (60%). Patient sera were analysed at presentation using routine electrophoresis tests (serum protein electrophoresis, SPEP and immunofixation, IFE). FLC and HLC (IgG, IgA and IgM) were measured by nephelometric immunoassay. Each immunoassay result was assessed with respect to individual normal ranges (FLCκ = 3.3–19.4mg/L, FLCλ = 5.71–26.30mg/L, IgGκ = 4.03–9.78g/L, IgGλ = 1.97–5.71g/L, IgAκ = 0.48–2.82g/L, IgAλ = 0.36–1.98, IgMκ = 0.29–1.82g/L, IgMλ = 0.17–0.94g/L) and ratios (FLCκ/FLCλ = 0.26–1.65, Gκ/Gλ = 0.98–2.75, Aκ/Aλ = 0.8–2.04, Mκ/Mλ = 0.96–2.3). The results were used to create an algorithm which assessed the degree of abnormality individually and with respect to the other results generated. Diagnosis was recorded ∼3 months after the analysis and patients were followed for up to 3 years. Results 293/1468 (19%) samples had an abnormal SPEP of which 95/293 were confirmed by IFE including: 10 intact immunoglobulin Multiple Myeloma (MM, 6 IgGκ, 1 IgGλ, 2 IgAκ, 1 IgAλ), 6 light chain MM (LCMM, 4 FLCκ, 2 FLCλ), 2 Waldenstrom macroglobulinemia (2 IgMκ), 1 IgMκ cryoglobulinemia, 3 CLL, 1 mantle cell lymphoma, 3 other lymphoma, 1 IgGκ plasmacytoma, and 68 MGUS patients, 26/68 were confirmed MGUS (1 FLCκ, 13 IgGκ, 4 IgGλ, 4 IgAκ, 2 IgMκ, 2 IgMλ), 42 were laboratory findings requiring follow up (1FLCκ, 3 FLCλ, 19 IgGκ, 5 IgGλ, 4 IgAκ, 1 IgAλ, 8 IgMκ, 1 IgMλ). FLC/HLC algorithm identified 85/95 IFE positive patients; of the 10 patients reported not identified by the algorithm, 3 had oligoclonal banding indicative of infection and 7 had monoclonal bands secondary to other diagnoses (including 2 colon cancer patients and 2 rheumatoid arthritis patients). In addition the algorithm identified 15 IFE negative patients with M-Ig production including: 2 AL amyloid patients, 1 asymptomatic LCMM, 1 patient with ∼1g/L FLCκ (lost to follow up), 1 follicular lymphoma patient and 1 CLL; diagnosis was not available for 9/15 patients. Furthermore, the algorithm identified 205/1468 patients as having elevated polyclonal FLC (cFLC) >50mg/L without evidence of clonal production. In a subset analysis comparing matched numbers of patients with elevated or normal cFLC concentrations, cFLC >50mg/L predicted all cause mortality (logistic regression odds ratio 9.96, 95% CI 4.72–21.0, p<0.001), and was associated with poorer overall survival (Kaplan Meier p<0.001, Cox regression hazard ratio 8.73, 95% CI 4.47–17.02). Discussion MM presents with disparate and vague symptoms pervasive in an elderly population. Current guidelines recommend SPEP and FLC analysis reflexing to IFE for confirmation in the event of abnormality. However, SPEP and IFE require interpretation making the assessment variable. Standardised immunoassays (FLC+HLC) may obviate the need for interpretation and in this study identified additional haematological malignancies. Furthermore, standard assessments can be used to identify M-Ig, but in the absence of this finding may offer little information pertaining to the symptoms that prompted referral. By contrast this algorithm identified patients with elevated cFLC which in agreement with other reports was associated with increased risk of mortality. Further work is required to assess the algorithm, and determine if cFLC measurements should be used as a prompt for additional diagnostic investigations. Disclosures: Faint: The Binding Site Group, Ltd.: Employment. Harding:The Binding Site Group Ltd.: Membership on an entity's Board of Directors or advisory committees. Mirbahai:The Binding Site Group, Ltd: Employment.

Background: Umbralisib is an oral, once-daily, dual inhibitor of phosphatidylinositol-3-kinase-delta (PI3Kδ) and casein kinase-1ε (CK1ε) that exhibits improved selectivity for the delta isoform of PI3K. The UNITY-NHL trial (NCT02793583) is a multicenter, open-label, registration directed Phase 2 study designed to evaluate the safety and efficacy of umbralisib in previously treated NHL patients (pts). Previously reported results in pts with relapsed/refractory (R/R) marginal zone lymphoma (MZL) demonstrated that umbralisib was active with a manageable safety profile. In contrast with other PI3K inhibitors, there was a low incidence of immune-mediated toxicities with umbralisib, possibly attributable to enhanced selectivity for the PI3Kδ isoform as well as inhibition of CK1ε. Herein, we present results from the final analysis of the iNHL population treated with single agent umbralisib. Methods: Eligible pts had histologically confirmed iNHL: MZL (splenic, nodal, extranodal), follicular lymphoma (FL; Gr 1, 2, 3a), or small lymphocytic lymphoma (SLL). MZL pts were R/R to ≥1 prior lines of treatment, which must have included an anti-CD20, while FL and SLL pts were R/R to ≥2 prior lines, which had to include an anti-CD20 and an alkylating agent. Umbralisib was administered orally at 800 mg once-daily in 28-day treatment cycles until disease progression or unacceptable tolerability. The primary endpoint of the study was overall response rate (ORR) as assessed by an independent review committee (IRC), according to the revised IWG criteria (Cheson 2007). Secondary endpoints included duration of response (DoR), progression-free survival (PFS), time to response (TTR), and safety. Pneumocystis jiroveci pneumonia (PCP) and anti-viral prophylaxis were mandated for all pts. Results: 208 iNHL pts received at least 1 dose of umbralisib, including 69 MZL, 117 FL, and 22 SLL pts. The median duration of exposure was 8.4 mos (range 0.2 - 27.0), median age was 66, and 56.7% were male. Pts had received a median of 2 prior regimens (range 1 - 10) with 46.1% having received ≥ 3 regimens. FL patients had a median of 3 prior regimens. With a median follow up of 27.8 mos, MZL pts had an ORR of 49.3% (95% CI 37.0% - 61.6%) with 15.9% achieving a complete response (CR), and a Disease Control Rate (DCR: CR+PR+SD) of 82.6%. ORR was consistent amongst MZL subtypes. The median TTR was 2.8 months (95% CI 2.7 - 2.9). The median profession-free survival (PFS) was not reached (95% CI 12.1 mos - not evaluable [NE]) with an estimated 12-month PFS rate of 64.2%. The median DoR was not reached (95% CI 10.3 mos - NE), and no pts who achieved CR have experienced disease progression to date. With a median follow up of 27.5 mos, FL pts had an ORR of 45.3% (95% CI 36.1% - 54.8%) with 5.1% achieving a CR, and a DCR of 79.5%. The median TTR was 4.6 mos (95% CI 3.0 - 5.6). The median PFS was 10.6 mos (95% CI 7.2 - 13.7) with an estimated 12-month PFS rate of 45.9%. The median DoR was 11.1 mos (95% CI 8.3 - 15.6). With a median follow up of 29.3 mos, SLL pts had an ORR of 50.0% (95% CI 28.2 - 71.8) with 4.5% achieving a CR, and a DCR of 86.4%. The median TTR was 2.7 mos (95% CI 2.4 - 2.8). The median PFS was 20.9 mos (95% CI 7.4 - 24.1) with an estimated 12-month PFS rate of 62.6%. The median DoR was 18.3 mos (95% CI 2.4 - NE). Best % change in target lesions form baseline for pts with at least one post-baseline assessment is shown in the figure. At the data cut-off, 60 pts (26 MZL, 27 FL, 7 SLL) remained on treatment. The most common ≥G3 AEs were neutropenia (11.5%), diarrhea (10.1%) and increased ALT/AST (7.2%). Other AEs of interest included pneumonitis (All G 1.4%; ≥G3 1.0%), and colitis (All G 1.4%; ≥G3 0.5%). Serious AEs were reported in 28.1% of pts, with 24.6% ≥G3. One patient with SLL had a fatal myocardial infarction (unrelated to umbralisib); there were no other G5 AEs. A total of 31 pts (14.9%) discontinued due a treatment-related adverse event (AE). Treatment-related AEs leading to dose reductions occurred in 20 (9.6%) pts. Conclusions: In the Phase 2 UNITY-NHL study, umbralisib achieved meaningful clinical activity in a heavily pretreated iNHL population. The safety profile was manageable, with a relatively low incidence of immune-mediated toxicities and AE-related discontinuations. These results suggest umbralisib has a favorable benefit-risk profile in this patient population and further development is ongoing. Figure Disclosures Zinzani: Kirin Kyowa: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kyowa Kirin: Consultancy, Speakers Bureau; MSD: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ADC Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Immune Design: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Portola: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Eusapharma: Consultancy, Speakers Bureau; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; TG Therapeutics, Inc.: Honoraria, Speakers Bureau; Servier: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Immune Design: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Verastem: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen-Cilag: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; EUSA Pharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sandoz: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celltrion: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Jurczak:Sandoz-Novartis: Consultancy; Afimed: Research Funding; Acerta: Consultancy, Research Funding; Pharmacyclics: Research Funding; Bayer: Research Funding; Maria Sklodowska-Curie National Research Institute of Oncology, Krakow, Poland: Current Employment; TG Therapeutics, Inc.: Research Funding; Celgene: Research Funding; Servier: Research Funding; Takeda: Research Funding; Roche: Research Funding; Merck: Research Funding; MEI Pharma: Research Funding; Janssen China R&D: Consultancy, Research Funding; BeiGene: Consultancy, Research Funding; AstraZeneca: Consultancy; European Medicines Agency,: Consultancy; Jagiellonian University, Krakow, Poland: Ended employment in the past 24 months; Epizyme: Consultancy; Gilead Sciences: Research Funding; MorphoSys: Research Funding; Nordic Nanovector: Research Funding. Ghosh:Kite/Gilead: Consultancy, Speakers Bureau; Juno/Celgene/Bristol-Myers Squibb: Consultancy, Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding, Speakers Bureau; SGN: Consultancy, Research Funding, Speakers Bureau; TG Therapeutics: Consultancy, Research Funding; Roche/Genentech: Research Funding; Karyopharm: Consultancy; Genmab: Consultancy, Speakers Bureau; AbbVie: Speakers Bureau; AstraZeneca: Speakers Bureau; Celgene/Bristol-Myers Squibb: Speakers Bureau; Forty Seven Inc: Consultancy, Other: Research Bureau, Research Funding; Janssen: Consultancy, Research Funding, Speakers Bureau. Derenzini:TG Therapeutics, Inc.: Research Funding. Cheah:Celgene, F. Hoffmann-La Roche, MSD, Janssen, Gilead, Ascentage Pharma, Acerta, Loxo Oncology, TG therapeutics: Honoraria; Celgene, F. Hoffmann-La Roche, Abbvie, MSD: Research Funding. Phillips:Karyopharm: Consultancy; Beigene: Consultancy; Seattle Genetics: Consultancy; BMS: Consultancy; Abbvie: Consultancy, Research Funding; AstraZeneca: Consultancy; Incyte: Consultancy, Other: travel expenses; Cardinal Health: Consultancy; Bayer: Consultancy, Research Funding; Pharmacyclics: Consultancy. Lech-Marańda:Roche, Amgen, Gilead: Speakers Bureau; Roche, Novartis, Takeda, Janssen-Cilag, Amgen, Gilead, AbbVie, Sanofi: Consultancy. Cheson:Abbvie: Consultancy, Research Funding; Kite: Consultancy; TG Therapeutics: Speakers Bureau; Morphosys: Consultancy; Symbio: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Consultancy, Research Funding; Jannsen: Consultancy; Parexel: Consultancy; Trillium: Research Funding; GSK: Membership on an entity's Board of Directors or advisory committees. Caimi:Verastem: Other: Advisory Board; Celgene: Speakers Bureau; Amgen: Other: Advisory Board; Bayer: Other: Advisory Board; Kite Pharma: Other: Advisory Board; ADC Therapeutics: Other: Advisory Board, Research Funding. Leslie:BeiGene: Honoraria, Speakers Bureau; KitePharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Speakers Bureau; Celgene: Speakers Bureau; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; TG Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; ADC therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bayer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Honoraria, Speakers Bureau; Epizyme: Honoraria, Speakers Bureau; AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Chavez:Karyopharm: Consultancy; BeiGene: Speakers Bureau; Bayer: Consultancy; Merck: Research Funding; AbbVie: Consultancy; Genentech: Speakers Bureau; Epizyme: Speakers Bureau; Gilead: Consultancy; Novartis: Consultancy; Kite, a Gilead Company: Consultancy, Speakers Bureau; Celgene: Consultancy; Morphosys: Consultancy, Speakers Bureau; AstraZeneca: Speakers Bureau; Verastem: Consultancy; Pfizer: Consultancy. Fonseca:Bristol-Myers Squibb Company: Speakers Bureau. Babu:Merck: Research Funding; Syndax: Research Funding; AbbVie: Research Funding; Janssen Oncology: Research Funding; TG Therapeutics: Research Funding; Amgen: Research Funding; Sanofi: Research Funding; Lutheran Hospital: Other; Argenx: Consultancy, Research Funding; Nektar: Research Funding; Novartis: Research Funding; Bayer: Honoraria; Lilly: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Alexion Pharmaceuticals: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Fort Wayne Medical Oncology & Hematology: Current Employment, Current equity holder in publicly-traded company; AstraZeneca/MedImmune: Research Funding; AstraZeneca: Consultancy, Honoraria; Genentech, Inc./ F. Hoffmann-La Roche: Research Funding; Boehringer Ingelheim: Consultancy. Hodson:Gilead Sciences: Research Funding. Burke:Bristol Myers Squibb: Consultancy; Verastem: Consultancy; Bayer: Consultancy; Astra Zeneca: Consultancy; Gilead: Consultancy; Seattle Genetics: Speakers Bureau; AbbVie: Consultancy; Morphosys: Consultancy; Adaptive: Consultancy; Epizyme: Consultancy; Kura: Consultancy; Celgene: Consultancy; Adaptive Biotechnologies: Consultancy; Roche: Consultancy. Sharman:TG Therapeutics: Consultancy, Research Funding; Bristol Meyers Squibb: Consultancy, Research Funding; BeiGene: Research Funding; Genentech: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding; Acerta: Consultancy, Research Funding; Roche: Consultancy, Research Funding; Celgene: Consultancy, Research Funding. O'Connor:Kymera Therapeutics: Current equity holder in private company, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Other: Data Safety Monitoring Committee, Research Funding; TG Therapeutics: Current Employment, Current equity holder in publicly-traded company; Servier: Consultancy; Mundipharma: Other: Consulting; Nomocan: Membership on an entity's Board of Directors or advisory committees; Merck: Research Funding; Astex Pharmaceuticals: Honoraria, Research Funding. Miskin:TG Therapeutics, Inc.: Current Employment, Current equity holder in publicly-traded company. Sportelli:TG Therapeutics, Inc.: Current Employment, Current equity holder in publicly-traded company. Weiss:TG Therapeutics, Inc.: Current Employment, Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees. Fowler:Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Research Funding; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding.

Abstract Despite the introduction of modern therapeutics, overall survival (OS) in metastatic breast cancer (MBC) has not changed in 20 ys. In the 1990s a major effort was made to improve the situation through the use of high dose chemotherapy with autologous stem cell transplantation (HD-ASCT). Although OS was not affected in randomized trials, which led to near abandonment of this therapy, some studies suggested that progression-free survival (PFS) can be improved with HD-ASCT. To identify distinct transplant-, disease- and patient-related characteristics predictive of survival in patients with MBC who received HD-ASCT, we reviewed records of all patients in the bone marrow transplant registry at UCSD treated with HD-ASCT for MBC between 1989 and 2000. METHODS: Age, race, stage at diagnosis, histology, estrogen receptor (ER) and menopausal status, body mass index (BMI) in kg/m2, time to transplant and death, site of metastasis, disease status prior to and after transplant, and days in hospital were extracted from medical records. Brookmeyer & Crowley’s 95% confidence intervals were used for median survival times, Cox models for predictors of a time-to-event variable and Schoenfeld tests for proportional hazard assumptions, respectively. RESULTS: Of 96 patients with MBC 21, 43, 23, 8 and 1 had stage I, II, III, IV or unknown disease at diagnosis, respectively. Histologies were: infiltrating ductal, lobular, inflammatory or unknown in 79, 10, 6 and 1 of the cases, respectively. ER status was positive in 59.4% of patients and 29.2% of patients were post-menopausal. 84.4%, 4.2% and 11.5 % of patients were of caucasian, black or other ethnicity, respectively. Mean ages at diagnosis and at transplant were 43.7 ys (SD 8.6) and 47.4 ys (SD 8.7), respectively, with a median time to transplant of 29 months (range 3.8–180.8). When progression of disease (PD) was diagnosed, primary sites were visceral (39.6%), bone (29.2%), local (16.7%) or nodal (14.6%). Mean BMI at transplant was 26 (SD 5.9); 24% of patients were obese (BMI ≥ 30). Mean length of hospitalization after transplant was 17 days (SD 9.5 days); 33% of patients were hospitalized ≥ 18 days. Pre-transplant, 30.2% of patients were in complete remission; after HD-ASCT, this percentage increased to 41.7%. Median PFS and OS were 3.9 ys (CI 2.9–5.4) and 5.6 ys (CI 4.1–7.4) after initial diagnosis and 0.6 ys (CI 0.5–0.8) and 1.7 ys (CI 1.36–2.07) after transplant, respectively. As opposed to ER+ patients the rate of death events in ER− patients slowed down substantially after 5 ys from diagnosis. Although not statistically significant, at 12 ys, survival after HD-ASCT was 18.5% in ER− patients and 2.6% in ER+ patients. Stratified by ER status, stage at diagnosis was an independent predictor of length of PFS and OS. At diagnosis, stage I patients were at lowest risk of death when compared to stage II–IV patients with HRs of 2.7 (II vs I CI 1.4–5.2), 4.6 (III vs I CI 2.1–10) and 17 (IV vs I CI 6.1–47.8) disease; lower risk of death persisted for patients with initial stage I after PD was diagnosed with HRs of 2.4 (II vs I CI 1.3–4.6), 2.8 (III vs I CI 1.3–5.7) and 3.9 (IV vs I CI 1.6–9.9). Death risks were increased with infiltrating lobular carcinoma when compared with infiltrating ductal carcinoma (HR 2.5; CI 1.1–5.38) or when BMI was ≥ 30 (HR 3.1; CI 1.8–5.4); PFS in patients with a BMI ≥ 30 was significantly shorter after PD was diagnosed (death HR 3.1 [CI 1.8–5.5] when compared to BMI &lt; 30). Visceral when compared to bone metastasis was a negative predictor of OS (HR 2.3; CI 1.3–4.1). Hospitalization ≥ 18 days after HD-ASCT was the strongest predictor of time to death after transplant (HR 2.2; CI 1.4–3.6). DISCUSSION: The survival rate at 12 ys after HD-ASCT was 8.2% for patients with MBC. Survival was higher for ER- compared to ER+ patients. Negative prognostic factors for OS and PFS were higher stages of disease at initial diagnosis, but also once PD was diagnosed, infiltrating lobular histology and obesity. Since all transplants were carried out prior to routine assessment of Her-2 neu receptor status, this information was not part of our analysis. At PD, visceral metastasis translated into poorer OS and after HD-ASCT, length of hospitalization became the most important outcome predictor. Although HD-ASCT in MBC has lost favor because of no improvement in global OS, our analysis may provide a rationale for selection criteria to determine which patients could benefit from future trials of HD-ASCT.

Abstract Introduction Vitamin D deficiency is common in the general population. Approximately 25-50% of adult patients seen at routine visits in the United States are found to have an insufficient vitamin D level. Vitamin D has been shown to be prognostic in several types of cancers including breast, prostate and colon cancer. Vitamin D activates a nuclear transcription factor that regulates the expression of almost 200 genes which modulate a variety of cellular processes including angiogenesis, differentiation, proliferation, and apoptosis. Recent research has shown that vitamin D levels may have a prognostic effect in patients with chronic lymphocytic leukemia (CLL), where 25-OH vitamin D insufficiency was associated with shortened time to treatment and poorer overall survival. A centrally important unanswered question relates to causation: does vitamin D insufficiency yield more aggressive cancer disease biology, or do intrinsically progressive cases of CLL cause vitamin D insufficiency? We hypothesized that vitamin D insufficiency alters CLL cell biology and favors a more aggressive disease phenotype. Methods Untreated patients within 12 months of initial diagnosis of CLL from Duke University Hospital and the Durham VA were studied. Serum samples from 185 patients were assayed for the 25-OH vitamin D level (immunochemiluminometric assay). A multivariate analysis was performed using: age, race, gender, Rai stage, CD38, Zap70, hierarchical FISH, IGHV, and season of diagnosis to determine whether vitamin D levels are a significant predictor of OS and TTT in this group. Global mRNA expression from 23 patients was analyzed using Affymetrix U133 Plus 2.0 arrays as a function of vitamin D level and gene list generated for those with p values < 10-5. rtPCR was performed on samples from an additional 50 patients to validate the findings from the mRNA expression analysis. Linear regression analysis was conducted to evaluate for significant associations between genes and 25-OH vitamin D levels. An in vitro assessment of 1,25-di-OH vitamin D effects on CLL cell viability in serum free media was evaluated using an MTS assay. Results The mean vitamin D level amongst the group of 185 patients was 25.6± 9.7 ng/mL. Eighty-nine patients had a vitamin D level less than 25 and 96 had a level above 25, which we used as our cutoff, as prior reports have used this level to define insufficiency in CLL. Thirty-one of 95 (33%) of the sufficient vitamin D group were treated versus 39 of 89 (44%) of the insufficient vitamin D group (p=0.12). Among those requiring treatment, the mean TTT was approximately the same between the two groups: 4.7±0.3 yrs for the higher vitamin D group vs. 4.6±0.4 yrs for the insufficient group (p=0.126). OS for the higher vitamin D group was 8.3±0.3 vs. 7.0±0.2 years for the lower vitamin D group (p=0.935). Multivariable analysis showed that IGHV mutation (HR = 0.386; p=0.0159) and Rai stage 0 or 1 (HR = 0.174; p=0.0002) predicted TTT, while age and race influenced OS, with age>62 conferring greater risk of death (p=0.0191) and African Americans having decreased survival (p=0.0110). Preliminary studies of gene expression data identified eight probes that were differentially expressed as a function of vitamin D level. rtPCR was then performed on GPR82, MPZL3, FBXW4, ROR1, and CXCL11 to validate these results. Linear regression confirmed that ROR1 and FBXW4 gene expression correlated with vitamin D level (p=0.0065; r2=0.144 and p=0.0185; r2=0.110, respectively). High levels of ROR1 are observed in B-CLL. FBXW4 has been shown to be mutated or under-expressed in a variety of human cancer cell lines. Early in vitro cytotoxicity of 1,25 di-OH vitamin D in CLL (n = 5 patient derived samples) showed an IC50 = 334 nM. Discussion Our results show that the basal level of vitamin D is not significantly correlated with either OS or TTT in CLL in contrast to previous studies. No interaction between vitamin D levels and race, age, gender, Rai stage, IGHV mutation, season of diagnosis was observed. However, ongoing in vitro experiments show that 1,25 vitamin D is cytotoxic to CLL, raising the intriguing possibility that intermittent bolus dosing could potentially be used therapeutically. Further, we have identified specific genes where quantitative gene expression is correlated with basal vitamin D levels. These findings expand our understanding of the interaction between vitamin D and B cell malignancies. Disclosures: No relevant conflicts of interest to declare.

Background: Acalabrutinib (acala) is a next-generation, highly selective, covalent Bruton tyrosine kinase (BTK) inhibitor approved for patients (pts) with mantle cell lymphoma (MCL) who have received ≥1 prior therapy. The efficacy and safety of acala in relapsed/refractory (R/R) MCL pts was demonstrated in a single-arm phase 2 study (ACE-LY-004; NCT02213926) after a median follow-up of 26 mo (Wang M, et al. Leukemia. 2019;33:2762-6). Here, we present results after an additional year of follow-up. Methods: Adults with MCL and ECOG PS ≤2 who had relapsed or were refractory to 1-5 prior therapies, had no prior BTK/BCL-2 inhibitor exposure, and did not require warfarin/vitamin K antagonists, received oral acala 100 mg twice daily until progressive disease (PD) or toxicity. Overall response rate (ORR; investigator-assessed partial response [PR] or better per Lugano classification), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety were assessed. Minimal residual disease (MRD) was analyzed in formalin-fixed, paraffin-embedded samples and peripheral blood by next-generation sequencing (5x10-6) in pts with available paired samples. Results: 124 pts were included (median age, 68 [range: 42-90] y; ECOG PS ≤1, 93%; bulky lymph nodes ≥10 cm, 8%; extranodal involvement, 72%; intermediate-/high-risk simplified MCL International Prognostic Index score, 44%/17%; median number of prior therapies, 2 [range: 1-5]; refractory disease, 24%). After a median follow-up of 38.1 mo (range: 0.3-59.5), 24 (19%) pts remain on treatment and an additional 31 pts (55 total; 44%) remain in follow-up for survival. Of the 31 pts in post-acala follow-up, 6 remain PD-free (4 received post-acala treatment: anticancer treatment combinations and allogeneic stem cell transplant [n=3]; radiotherapy [n=1]). ORR was 81% (95% CI: 74, 88); 48% (95% CI: 39, 57) achieved complete response (CR). Median DOR was 28.6 mo (95% CI: 17.5, 39.1) and the estimated 36-mo DOR rate was 41.9% (95% CI: 31.7, 51.8). Median PFS was 22.0 mo (95% CI: 16.6, 33.3; Figure); estimated 36-mo PFS rate was 37.2% (95% CI: 28.2, 46.1). ORR and PFS were not significantly different between subgroups divided by Ki-67 index (≤50%, &gt;50%); PFS also did not differ significantly by prior treatment regimen (bendamustine/rituximab [BR]-based, non-BR) or prior therapy line (1, 2, ≥3). Median OS was not reached; estimated 36-mo OS rate was 60.5% (95% CI: 51.1, 68.7). Of 30 MRD-evaluable pts, 6 (20%) achieved CR and undetectable MRD (uMRD) and maintained uMRD at last assessment. The adverse event (AE) profile was largely unchanged with an additional year of follow-up. The most frequent AEs (≥20%) of headache (39%), diarrhea (37%), fatigue (30%), cough (23%), myalgia (22%), and nausea (22%) were primarily grade 1/2. Grade 3/4 AEs (≥5%) were neutropenia (11%), anemia (10%), and pneumonia (6%). Overall, 16 pts (13%) had cardiac AEs (11 with prior cardiac risk factors); 3 of the 16 pts had cardiac AEs in the last year of follow-up (grade 3/4: n=2). Overall, 6 pts (5%) had grade 3/4 cardiac AEs (acute coronary syndrome, acute myocardial infarction, complete atrioventricular block, cardiac failure, cardiorespiratory arrest, coronary artery disease, sinus arrest; n=1 each). One pt had grade 3/4 hypertension in the last year (total any grade, n=5 [4%]; total grade 3/4, n=2 [2%]). Five pts had bleeding AEs in the last year (n=46 [37%] total) including 2 with grade 3/4 AEs of gastrointestinal hemorrhage (n=2 total) and 1 with grade 3/4 subdural hematoma (n=1 total). Three pts had grade 3/4 infections in the last year (n=21 [17%] total). Treatment discontinuation was primarily due to PD (n=74; 60%) and AEs (n=14; 11%). Seventeen AEs led to discontinuation in 14 pts; each AE occurred in only 1 pt. There were 57 deaths (46%), most commonly due to PD (n=38; 31%) or AEs (n=6; 5%); 14 deaths (11%) occurred in the last year of follow-up (PD, n=9; other, n=1; unknown, n=4). There were 6 deaths due to AEs (bilateral pulmonary embolism, critical aortic stenosis, myelodysplastic syndrome, pneumonia, suicide, non-small cell lung cancer); none were related to acala. Conclusion: Extended follow-up demonstrates no emerging safety concerns for acala in R/R MCL pts. After a median of 38.1 mo, 19% of pts remain on acala. Overall, an estimated one-third of pts remain progression free at 36 mo, with median OS not yet reached. These data support long-term use of acala in R/R MCL pts. Disclosures Wang: Dava Oncology: Honoraria; Verastem: Research Funding; Loxo Oncology: Consultancy, Research Funding; Pulse Biosciences: Consultancy; OncLive: Honoraria; Molecular Templates: Research Funding; AstraZeneca: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding; Beijing Medical Award Foundation: Honoraria; BioInvent: Research Funding; Acerta Pharma: Research Funding; VelosBio: Research Funding; Targeted Oncology: Honoraria; Lu Daopei Medical Group: Honoraria; OMI: Honoraria, Other: Travel, accommodation, expenses; MoreHealth: Consultancy; Juno: Consultancy, Research Funding; Pharmacyclics: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding; Guidepoint Global: Consultancy; Nobel Insights: Consultancy; Janssen: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding; Kite Pharma: Consultancy, Other: Travel, accommodation, expenses, Research Funding; Celgene: Consultancy, Other: Travel, accommodation, expenses, Research Funding; InnoCare: Consultancy; Oncternal: Consultancy, Research Funding. Rule:Celgene: Consultancy; Celltrion: Consultancy; Roche Pharma AG: Consultancy, Research Funding; Janssen Oncology: Consultancy, Research Funding, Speakers Bureau; AstraZeneca: Consultancy. Zinzani:ADC Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; TG Therapeutics, Inc.: Honoraria, Speakers Bureau; Kirin Kyowa: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen-Cilag: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MSD: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Portola: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celltrion: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Verastem: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sandoz: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Servier: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Eusapharma: Consultancy, Speakers Bureau; EUSA Pharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Immune Design: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Immune Design: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kyowa Kirin: Consultancy, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau. Goy:Kite, a Gilead Company: Consultancy, Current equity holder in publicly-traded company, Honoraria, Other: leadership role, Research Funding; MD Anderson: Research Funding; Celgene: Honoraria, Research Funding; CALBG: Research Funding; Janssen: Consultancy, Honoraria, Other: leadership role, Research Funding; Hackensack UMC and University of Nebraska: Research Funding; Karyopharm: Research Funding; Xcenda: Consultancy; Regional Cancer Care Associates/OMI: Current Employment; COTA: Consultancy, Current equity holder in publicly-traded company, Other: leadership role; Acerta: Consultancy, Honoraria, Other: leadership role, Research Funding; RCCA/OMI: Current Employment; PracticeUpdate Oncology: Consultancy; Infinity Verastem: Research Funding; AbbVie: Research Funding; Morphosys: Research Funding; Genentech/Roche: Research Funding; AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: leadership role, Research Funding; Bayer: Research Funding; Infinity: Research Funding; Constellation: Research Funding. Casasnovas:Abbvie: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Gilead: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Roche: Consultancy, Honoraria, Other: travel, accomodations, expenses, Research Funding; MSD: Consultancy, Honoraria; Amgen: Consultancy, Honoraria. Smith:Ignyta: Research Funding; Genentech: Research Funding; Bayer: Research Funding; AstraZeneca: Research Funding; Merck: Research Funding; De Novo Biopharma: Research Funding; Bristol Meyers Squibb: Research Funding; Ayala: Research Funding; Pharmacyclics: Research Funding; Millenium/Takeda: Consultancy; Acerta Pharma BV: Research Funding; Incyte: Research Funding; Karyopharm: Consultancy; Seattle Genetics: Research Funding; AstraZeneca: Consultancy; Portola: Research Funding; Beigene: Consultancy. Doorduijn:Roche: Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company). Morschhauser:Celgene: Membership on an entity's Board of Directors or advisory committees; Servier: Consultancy; Epizyme: Membership on an entity's Board of Directors or advisory committees; Genentech, Inc.: Consultancy; Abbvie: Membership on an entity's Board of Directors or advisory committees; F. Hoffmann-La Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Honoraria; Gilead: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Panizo:Bristol-Myers Squibb, Kyowa Kirin: Speakers Bureau; Clínica Universidad de Navarra: Current Employment; Janssen, Roche: Membership on an entity's Board of Directors or advisory committees. Shah:Kite/Gilead, Celgene/Juno/BMS, Novartis, Pfizer, Amgen, Spectrum/Acrotech, Precision Biosciences, Beigene, AstraZeneca, Pharmacyclics/Jansen, Adaptive: Honoraria; NCCN: Vice-Chair, Acute Lymphoblastic Leukemia Working Group: Membership on an entity's Board of Directors or advisory committees; Kite/Gilead, Jazz, Incyte: Research Funding; Moffitt Cancer Center: Current Employment; Kite/Gilead, Precision Biosciences, Novartis, AstraZeneca: Other: TRAVEL, ACCOMMODATIONS, EXPENSES. Davies:Celegene, Roche, Kite Pharma, Celegene: Honoraria; Roche: Other: TRAVEL, ACCOMMODATIONS, EXPENSES; Roche, Celgene, Kite Pharma, Acerta, Karyopharma, Regeneron, Incyte: Consultancy; Roche, Acerta Pharma, AstraZeneca, Celgene, Gilead, ADC Therapeutics, Gilead: Research Funding. Dupuis:Henri Mondor University Hospital Creteil France: Current Employment. Jacobsen:Merck, Pharmacyclics, F. Hoffmann-LaRoche, Novartis: Research Funding; Takeda: Honoraria; Acerta, AstraZeneca, Merck: Consultancy. Kater:Roche: Research Funding; Celgene: Research Funding; Genentech: Research Funding; Abbvie: Research Funding; Janssen: Research Funding. Le Gouill:Roche Genentech, Janssen-Cilag and Abbvie, Celgene, Jazz pharmaceutical, Gilead-kite, Loxo, Daiichi-Sankyo and Servier: Honoraria; Loxo Oncology at Lilly: Consultancy. Oberic:Roche, Janssen: Consultancy; Roche: Honoraria; Roche, Janssen: Other: Travel, Accommodations, Expenses. Robak:Sandoz: Consultancy, Honoraria; Octapharma: Honoraria; AbbVie: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Janssen: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; UCB: Honoraria, Research Funding; Pharmacyclics LLC, an AbbVie Company: Honoraria, Research Funding; Acerta: Research Funding; Roche: Consultancy, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Medical University of Lodz: Current Employment; GSK: Research Funding; Novartis: Honoraria, Research Funding; AstraZeneca: Honoraria, Research Funding; UTX-TGR: Research Funding; Takeda: Consultancy; Morphosys: Research Funding; BioGene: Honoraria, Research Funding; Bristol Meyers Squibb: Research Funding; Pfizer: Research Funding; Momenta: Consultancy. Brock:Jazz Pharmaceuticals Inc: Current Employment; Acerta Pharmaceuticals: Ended employment in the past 24 months; Astra Zeneca: Current equity holder in publicly-traded company. Patel:AstraZeneca: Current Employment, Current equity holder in publicly-traded company. Tao:Clindata Insight inc: Ended employment in the past 24 months; Acerta Pharma, LLC: Current Employment.

The pandemic of COVID-19 has afflicted every individual and has initiated a cascade of directly or indirectly involved events in precipitating mental health issues. The human species is a wanderer and hunter-gatherer by nature, and physical social distancing and nationwide lockdown have confined an individual to physical isolation. The present review article was conceived to address psychosocial and other issues and their aetiology related to the current pandemic of COVID-19. The elderly age group has most suffered the wrath of SARS-CoV-2, and social isolation as a preventive measure may further induce mental health issues. Animal model studies have demonstrated an inappropriate interacting endogenous neurotransmitter milieu of dopamine, serotonin, glutamate, and opioids, induced by social isolation that could probably lead to observable phenomena of deviant psychosocial behavior. Conflicting and manipulated information related to COVID-19 on social media has also been recognized as a global threat. Psychological stress during the current pandemic in frontline health care workers, migrant workers, children, and adolescents is also a serious concern. Mental health issues in the current situation could also be induced by being quarantined, uncertainty in business, jobs, economy, hampered academic activities, increased screen time on social media, and domestic violence incidences. The gravity of mental health issues associated with the pandemic of COVID-19 should be identified at the earliest. Mental health organization dedicated to current and future pandemics should be established along with Government policies addressing psychological issues to prevent and treat mental health issues need to be developed. References World Health Organization (WHO) Coronavirus Disease (COVID-19) Dashboard. 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Introduction: MAVORIC was an open-label, multicenter, randomized phase 3 study evaluating the safety and efficacy of mogamulizumab (moga) compared to vorinostat (vori) in patients with mycosis fungoides (MF) or Sézary syndrome (SS) who had failed at least one prior course of systemic therapy (NCT01728805). Primary results have been reported (Kim et al. Lancet Oncol 2018) and were based on a data cutoff date of December 31, 2016. The primary endpoint was progression-free survival (PFS); patients in the moga treatment arm experienced significantly longer PFS compared to patients in the vori treatment arm (median 7.7 months vs 3.1 months; p<0.0001). The most common treatment-emergent adverse events (TEAEs) of any cause or grade reported in patients randomized to moga were: infusion-related reaction (33.2%), drug eruption (ie, skin rash attributed to moga [23.9%]), diarrhea (23.4%), and fatigue (23.4%). This report provides the final safety results of MAVORIC as of the data available on January 3, 2019. Methods: Patients were randomized 1:1 to moga 1.0 mg/kg administered intravenously on Days 1, 8, 15, and 22 of the first cycle and on Days 1 and 15 of subsequent cycles or vori 400 mg administered orally once daily. Patients randomized to vori were allowed to cross over to moga upon progression or intolerable toxicity. Safety was assessed by reported adverse events (AEs), changes in physical examinations, vital sign measurements, electrocardiograms, and laboratory analyses. Results: In total, 372 patients were randomized (moga, 186; vori, 186), of whom 370 received study drug and were included in the safety analysis (moga, 184; vori, 186). For the final safety analysis, median duration of follow-up was 34.5 months (range, 0.13-70.0) in the randomized part of the study. Median treatment exposure was 170 days (range, 1-1813) for moga and 84 days (4-1230) for vori, which represent the same median values but broader ranges compared to the primary analysis (primary analysis, 170 days [1-1379] for moga and 84 days [4-1058] for vori). The type and frequency of AEs in either the moga or vori treatment groups (Table) were consistent with those reported in the primary analysis. TEAEs, regardless of causality, that were reported at similar rates in the two treatment groups included constipation, peripheral edema, headache, and anemia. TEAEs (all causality) that occurred at higher frequency in the moga vs vori arm included infusion-related reaction (33.2% vs 0.5%) and drug eruption (25.0% vs 1.1%); the majority of these events were grade 1 or 2 (Table). The types and frequencies of AEs attributable to moga (per Investigator assessment) included infusion-related reaction (33.2% [61/184]), drug eruption (23.9% [44/184]), and fatigue (18.5% [34/184]), and for vori, diarrhea (55.4% [103/186]), nausea (38.2% [71/186]), and fatigue (33.3% [62/186]). In patients who crossed over from the vori to moga arm and received study drug (n=135), the most frequently reported AEs attributable to moga were infusion-related reaction (37.8% [51/135]), drug eruption (24.4% [33/135]), fatigue (7.4% [10/135]), increased alanine aminotransferase (7.4% [10/135]), and increased aspartate aminotransferase (7.4% [10/135]). Discontinuation rates due to AEs were similar between treatment arms and in crossover patients (moga, 21.7% [40/184]; vori, 23.7% [44/186]; crossover, 25.9% [35/135]). The most common AEs leading to discontinuation were drug eruption in the moga arm (7.1% [13/184]) and fatigue in the vori arm (4.3% [8/186]). Overall, the rates of drug-related serious TEAEs were similar between treatment arms and in crossover patients (moga, 19.6% [36/184]; vori, 16.7% [31/186]; crossover, 11.9% [16/135]). After the data cutoff for the primary analysis, 1 additional patient randomized to moga (decreased appetite, general physical health deterioration, hypoalbuminemia) and 1 crossover patient (cerebral hemorrhage) experienced TEAEs with an outcome of death, all considered unrelated to study treatment per Investigator. Conclusions: This final safety analysis from the MAVORIC study in patients with previously treated MF and SS demonstrates that moga was generally well tolerated. Longer follow-up and treatment exposure did not identify any new safety signals. The type and incidence of treatment-related AEs among patients receiving moga after crossover were similar to those observed for patients initially randomized to moga. Disclosures Kim: Merck: Research Funding; Portola Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Horizon: Research Funding; Corvus: Honoraria, Membership on an entity's Board of Directors or advisory committees; Galderma: Research Funding; Elorac: Research Funding; Soligenix: Research Funding; Kyowa Hakko Kirin: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Eisai: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Forty Seven Inc: Research Funding; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Medivir: Honoraria, Membership on an entity's Board of Directors or advisory committees; Innate Pharma: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Trillium: Research Funding; Neumedicine: Research Funding; miRagen: Research Funding. Bagot:Innate Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Zinzani:MSD: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Eusapharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Consultancy; Celltrion: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Servier: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sandoz: Membership on an entity's Board of Directors or advisory committees; Immune Design: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Portola: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kyowa Kirin: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; TG Therapeutics: Honoraria, Speakers Bureau; Verastem: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Duvic:Seattle Genetics: Consultancy, Honoraria, Research Funding; Eisai: Research Funding; Shape: Research Funding; UT MD Anderson Cancer Center: Employment; USCLC Registry: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Secretary/treasurer of Item h; Spatz Foundation: Research Funding; Tetralogic: Research Funding; Millennium (formerly Takeda): Research Funding; Mallinckrodt Pharmaceuticals (formeraly Therakos, Inc): Research Funding; Kyowa Hakko Kirin Co., Ltd.: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Forty Seven Inc: Membership on an entity's Board of Directors or advisory committees; Cutaneous Lymphoma Foundation: Membership on an entity's Board of Directors or advisory committees; PleXus Communications: Speakers Bureau; Guidepoint Global: Consultancy; Evidera, Inc.: Consultancy; Cell Medica Inc.: Consultancy; Allos: Research Funding; Rhizen Pharma: Research Funding; Oncoceuticals: Research Funding; Soligenetics: Research Funding; Cell Medica Ltd.: Honoraria; Therakos: Speakers Bureau; Jonathan Wood & Assoc.: Speakers Bureau; Hawaiian Dermatology Society: Speakers Bureau; Hemedicus: Speakers Bureau; Janssen Pharmaceuticals (div of Johnson & Johnson): Speakers Bureau. Morris:Guys Hospital: Employment. Kim:Medimmune: Research Funding; Soligenix: Research Funding; Kyowa Kirin: Research Funding; Galderma: Consultancy, Research Funding; Actelion: Consultancy, Research Funding. Musiek:Menlo: Other: Investigator; Helsinn: Membership on an entity's Board of Directors or advisory committees; Soligenix: Other: Investigator; Pfizer: Other: Investigator; Elorac: Other: Investigator; Kyowa: Honoraria, Other: Above honoraria: for Ad Board; miRagen: Other: Investigator. Ortiz-Romero:Actelion: Consultancy, Membership on an entity's Board of Directors or advisory committees; Kyowa: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; PLCG1: Patents & Royalties; miRagen: Membership on an entity's Board of Directors or advisory committees; MEDA: Research Funding; Innate Pharma: Membership on an entity's Board of Directors or advisory committees; 4SC: Membership on an entity's Board of Directors or advisory committees. Eradat:Kyowa: Research Funding; Kite: Research Funding; Pharmacyclics: Consultancy, Honoraria, Research Funding, Speakers Bureau; Roche: Research Funding; Genentech: Consultancy, Honoraria, Research Funding, Speakers Bureau; AbbVie: Consultancy, Honoraria, Research Funding, Speakers Bureau; Gilead: Research Funding. Magnolo:University Hospital of Muenster, Center of Innovative Dermatology: Employment. Scarisbrick:Kyowa Kirin: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Recordat: Consultancy; 4SC: Consultancy, Membership on an entity's Board of Directors or advisory committees; Innate Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees; Helsinn: Consultancy, Membership on an entity's Board of Directors or advisory committees. Dalle:Kyowa: Other: Principal Investigator in clinical trials promoted by Kyowa. Fisher:Kyowa Kirin: Consultancy. Poligone:Stemline Therapeutics: Consultancy, Speakers Bureau; Regeneron: Consultancy, Speakers Bureau; Actelion: Consultancy, Speakers Bureau; Astex Pharmaceuticals: Research Funding; Bioniz: Research Funding; Celgene: Consultancy; Helsinn: Research Funding, Speakers Bureau; Innate Pharma: Research Funding; Kyowa Hakko Kirin: Consultancy, Honoraria, Research Funding, Speakers Bureau; miRagen: Research Funding; Soligenix: Research Funding. Pro:Takeda: Consultancy, Honoraria, Other: Travel Expenses; Celgene: Consultancy, Honoraria; Kyowa Hakka Kirin: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria, Other: Travel Expenses, Research Funding. Quaglino:Actelion: Honoraria, Other: Advisory Board; Innate Pharma: Honoraria, Other: Advisory Board; Takeda: Honoraria, Other: Advisory Board; Kyowa Kirin: Honoraria, Other: Advisory Board; Helsinn: Honoraria, Other: Advisory Board; Therakos: Honoraria, Other: Advisory Board. Reddy:AbbVie: Honoraria; Janssen: Honoraria; KITE: Honoraria; Merck: Research Funding; Celgene: Honoraria, Speakers Bureau. Geskin:Merck: Other: Supported/Contracted Research; UpToDate: Patents & Royalties: Royalty, Receipt of Intellectual Property Rights / Patent Holder; Actelion: Other: Supported/Contracted Research; Helsinn: Consultancy, Honoraria, Other: Supported/Contracted Research; Stratpharma: Other: Supported/Contracted Research; Mallinckrodt: Consultancy, Honoraria, Other: Supported/Contracted Research; Medscape: Speakers Bureau; Medivir: Consultancy, Honoraria. Halwani:Amgen: Other: Investigator; Takeda: Other: PI; Seattle Genetics: Other: PI; Pharmacyclics: Other: Investigator; miRagen: Other: PI; Kyowa Hakko Kirin: Other: PI; Immune Design: Other: PI; Genentech, Inc.: Other: Investigator; Bristol-Myers Squibb: Other: PI; AbbVie: Other: PI. Khot:Peter MacCallum Cancer Centre: Employment; Amgen: Consultancy, Speakers Bureau; Celgene: Consultancy; Janssen: Consultancy; Kyowa Hakko Kirin: Consultancy. Korman:Genentech: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Dermira: Research Funding; Glaxo: Honoraria, Membership on an entity's Board of Directors or advisory committees; Immune Pharma: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Kyowa: Research Funding; Leo: Research Funding; Menlo: Research Funding; Merck: Research Funding; Novartis: Consultancy, Honoraria, Speakers Bureau; Pfizer: Research Funding; Principia: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Prothena: Research Funding; Regeneron: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Rhizen: Research Funding; Sun: Honoraria, Membership on an entity's Board of Directors or advisory committees; Syntimmune: Research Funding; UCB: Research Funding; Valeant: Honoraria, Membership on an entity's Board of Directors or advisory committees; Eli Lilly: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Research Funding; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Horwitz:Seattle Genetics: Consultancy, Research Funding; Affimed: Consultancy; Astex: Consultancy; Portola: Consultancy; ADCT Therapeutics: Research Funding; Kyowa Hakko Kirin: Consultancy; Infinity/Verastem: Consultancy, Research Funding; Miragen: Consultancy; Seattle Genetics: Consultancy, Research Funding; Forty-Seven: Research Funding; Celgene: Consultancy, Research Funding; Millennium/Takeda: Consultancy, Research Funding; Miragen: Consultancy; Innate Pharma: Consultancy; Kura: Consultancy; Corvus Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Miragen: Consultancy; Infinity/Verastem: Consultancy, Research Funding; Millennium/Takeda: Consultancy, Research Funding; Portola: Consultancy; Kura: Consultancy; Celgene: Consultancy, Research Funding; Kura: Consultancy; Kyowa Hakko Kirin: Consultancy; Infinity/Verastem: Consultancy, Research Funding; Forty-Seven: Research Funding; Trillium: Research Funding; Corvus Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Research Funding; Astex: Consultancy; Affimed: Consultancy; ADCT Therapeutics: Research Funding; Aileron: Research Funding; Corvus Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Kyowa Hakko Kirin: Consultancy; Trillium: Research Funding; Millennium/Takeda: Consultancy, Research Funding; Mundipharma: Consultancy; Millennium/Takeda: Consultancy, Research Funding; Kyowa Hakko Kirin: Consultancy; Portola: Consultancy; Aileron: Research Funding; Mundipharma: Consultancy; Celgene: Consultancy, Research Funding; Mundipharma: Consultancy; Seattle Genetics: Consultancy, Research Funding; ADCT Therapeutics: Research Funding; Portola: Consultancy; Kura: Consultancy; ADCT Therapeutics: Research Funding; Corvus Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Infinity/Verastem: Consultancy, Research Funding; Aileron: Research Funding; Affimed: Consultancy; Trillium: Research Funding; Innate Pharma: Consultancy; Affimed: Consultancy; Astex: Consultancy; Mundipharma: Consultancy; Aileron: Research Funding; Miragen: Consultancy; Trillium: Research Funding; Innate Pharma: Consultancy; Forty-Seven: Research Funding; Forty-Seven: Research Funding; Innate Pharma: Consultancy; Astex: Consultancy; Seattle Genetics: Consultancy, Research Funding. Lamar:Seattle Genetics: Consultancy; Kyowa: Consultancy, Membership on an entity's Board of Directors or advisory committees. Moskowitz:Cell Medica: Consultancy; ADC Therapeutics: Consultancy; Merck: Research Funding; Erytech Pharma: Consultancy; Takeda Pharmaceuticals: Consultancy; Erytech Pharma: Consultancy; Merck: Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Erytech Pharma: Consultancy; Incyte: Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Merck: Research Funding; Erytech Pharma: Consultancy; ADC Therapeutics: Consultancy; ADC Therapeutics: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Erytech Pharma: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Takeda Pharmaceuticals: Consultancy; Seattle Genetics: Consultancy, Honoraria, Research Funding; Cell Medica: Consultancy; Erytech Pharma: Consultancy; Seattle Genetics: Consultancy, Honoraria, Research Funding; Cell Medica: Consultancy; Merck: Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; ADC Therapeutics: Consultancy; Merck: Research Funding; Cell Medica: Consultancy; Cell Medica: Consultancy; ADC Therapeutics: Consultancy; Incyte: Research Funding; Takeda Pharmaceuticals: Consultancy; Seattle Genetics: Consultancy, Honoraria, Research Funding; Cell Medica: Consultancy; Cell Medica: Consultancy; miRagen Therapeutics Inc: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; Erytech Pharma: Consultancy; miRagen Therapeutics Inc: Consultancy, Research Funding; Incyte: Research Funding; Incyte: Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Merck: Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; ADC Therapeutics: Consultancy; Merck: Research Funding; ADC Therapeutics: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Merck: Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Cell Medica: Consultancy; Seattle Genetics: Consultancy, Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Incyte: Research Funding; Takeda Pharmaceuticals: Consultancy; Takeda Pharmaceuticals: Consultancy; Cell Medica: Consultancy; Cell Medica: Consultancy; Cell Medica: Consultancy; Incyte: Research Funding; Incyte: Research Funding; Erytech Pharma: Consultancy; ADC Therapeutics: Consultancy; Erytech Pharma: Consultancy; Erytech Pharma: Consultancy; Erytech Pharma: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Erytech Pharma: Consultancy; Erytech Pharma: Consultancy; Seattle Genetics: Consultancy, Honoraria, Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Merck: Research Funding; Takeda Pharmaceuticals: Consultancy; Merck: Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Merck: Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; Incyte: Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Merck: Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; ADC Therapeutics: Consultancy; miRagen Therapeutics Inc: Consultancy, Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Takeda Pharmaceuticals: Consultancy; Takeda Pharmaceuticals: Consultancy; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Takeda Pharmaceuticals: Consultancy; ADC Therapeutics: Consultancy; ADC Therapeutics: Consultancy; Incyte: Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; ADC Therapeutics: Consultancy; Incyte: Research Funding; Cell Medica: Consultancy; Incyte: Research Funding; Takeda Pharmaceuticals: Consultancy; Incyte: Research Funding; Takeda Pharmaceuticals: Consultancy; Takeda Pharmaceuticals: Consultancy; Takeda Pharmaceuticals: Consultancy; Cell Medica: Consultancy; Cell Medica: Consultancy; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Cell Medica: Consultancy; miRagen Therapeutics Inc: Consultancy, Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; Takeda Pharmaceuticals: Consultancy; Incyte: Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; Erytech Pharma: Consultancy; miRagen Therapeutics Inc: Consultancy, Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Merck: Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; Incyte: Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; Incyte: Research Funding; Takeda Pharmaceuticals: Consultancy; ADC Therapeutics: Consultancy; ADC Therapeutics: Consultancy; ADC Therapeutics: Consultancy; Erytech Pharma: Consultancy; Seattle Genetics: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Merck: Research Funding; Merck: Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding. Wells:Takeda Pharmaceuticals Australia Pty Limited: Membership on an entity's Board of Directors or advisory committees; MSD Australia: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Akilov:Trillium Therapeutics: Consultancy, Other: PI on the clinical trials, Research Funding; Pfizer: Research Funding. Cowan:Kyowa Kirin: Consultancy. Dummer:Merck Sharp & Dohme: Other: Intermittent, project focused consulting and/or advisory relationships; Novartis: Other: Intermittent, project focused consulting and/or advisory relationships; Bristol-Myers Squibb: Other: Intermittent, project focused consulting and/or advisory relationships; Roche: Other: Intermittent, project focused consulting and/or advisory relationships; Amgen: Other: Intermittent, project focused consulting and/or advisory relationships; Takeda: Other: Intermittent, project focused consulting and/or advisory relationships; Pierre Fabre: Other: Intermittent, project focused consulting and/or advisory relationships; Sun Pharma: Other: Intermittent, project focused consulting and/or advisory relationships; Sanofi: Other: Intermittent, project focused consulting and/or advisory relationships; Catalym: Other: Intermittent, project focused consulting and/or advisory relationships; Second Genome: Other: Intermittent, project focused consulting and/or advisory relationships. Lechowicz:Kyowa Kirin Inc: Consultancy; Spectrum: Consultancy. Foss:Eisai: Consultancy; Seattle Genetics: Consultancy, Other: fees for non-CME/CE services ; miRagen: Consultancy; Acrotech: Consultancy; Mallinckrodt: Consultancy; Spectrum: Other: fees for non-CME/CE services . Wilcox:University of Michigan: Employment. Porcu:Innate Pharma: Honoraria, Other: Scientific Board, Research Funding; Viracta: Honoraria, Other: Scientific Board, Research Funding; BeiGene: Other: Scientific Board, Research Funding; Incyte: Research Funding; Daiichi: Research Funding; Kyowa: Honoraria, Other: Scientific Board, Research Funding; ADCT: Research Funding; Spectrum: Consultancy. Vermeer:Kyowa: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding. Abhyankar:Therakos: Other: Consulting, Speakers Bureau; Incyte: Speakers Bureau. Pacheco:University of Colorado: Employment. William:Techspert: Consultancy; Guidepoint Global: Consultancy; Defined Health: Consultancy; Celgene Corporation: Consultancy; Kyowa Kirin, Inc.: Consultancy. Fukuhara:Kyowa-Hakko Kirin: Honoraria; Bayer: Research Funding; Mundi: Honoraria; Janssen Pharma: Honoraria; Mochida: Honoraria; Ono Pharmaceutical Co., Ltd.: Honoraria; Takeda Pharmaceutical Co., Ltd.: Honoraria, Research Funding; Chugai Pharmaceutical Co., Ltd.: Honoraria; Eisai: Honoraria, Research Funding; Celgene Corporation: Honoraria, Research Funding; Nippon Shinkyaku: Honoraria; Zenyaku: Honoraria; AbbVie: Research Funding; Gilead: Research Funding; Solasia Pharma: Research Funding. Munoz:Pharmacyclics /Janssen: Consultancy, Research Funding, Speakers Bureau; Bayer: Consultancy, Speakers Bureau; Merck: Consultancy; Kyowa: Consultancy, Honoraria, Speakers Bureau; Seattle Genetics: Consultancy, Honoraria, Research Funding, Speakers Bureau; Celgene/Juno: Consultancy, Research Funding; Genentech: Consultancy, Research Funding, Speakers Bureau; Fosunkite: Speakers Bureau; AstraZeneca: Speakers Bureau; Portola: Research Funding; Incyte: Research Funding; Kite/Gilead: Consultancy, Research Funding, Speakers Bureau; Bristol-Myers Squibb: Consultancy; Alexion: Consultancy; Pfizer: Consultancy. Querfeld:Elorac: Other: Investigator, Research Funding; Trillium: Consultancy, Other: Investigator, Research Funding; Medivir: Consultancy; miRagen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Investigator; Helsinn: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Investigator; Soligenix: Other: Investigator; City of Hope Cancer Center and Beckman Research Institute: Employment; Celgene: Other: Investigator, Research Funding; Kyowa: Membership on an entity's Board of Directors or advisory committees, Other: Investigator; Eisai: Other: Investigator; Bioniz: Membership on an entity's Board of Directors or advisory committees, Other: Investigator. Uhara:Kyowa Kirin Co., Ltd: Honoraria, Research Funding. Huen:Innate Pharmaceuticals: Research Funding; Galderma Inc: Research Funding; Rhizen Pharmaceuticals: Research Funding; Glaxo Smith Kline Inc: Research Funding. Tobinai:Meiji Seika: Honoraria; Takeda Pharmaceutical: Consultancy, Honoraria, Research Funding; Daiichi Sankyo: Consultancy, Honoraria; Janssen Pharmaceutical: Honoraria, Research Funding; Kyowa Kirin: Honoraria, Research Funding; Ono Pharmaceutical: Consultancy, Honoraria, Research Funding; Zenyaku Kogyo: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Mundi Pharma: Consultancy, Honoraria, Research Funding; Eisai: Honoraria, Research Funding; HUYA Bioscience: Consultancy, Honoraria; Bristol-Myers Squibb: Honoraria; AbbVie: Research Funding; Verastem: Honoraria; Chugai Pharmaceutical: Honoraria, Research Funding; Yakult: Honoraria; Solasia: Honoraria. Tokura:Kyowa Kirin Pharmaceutical Development, Inc.: Honoraria. Boh:Actelion: Other: Principal Investigator; Tulane University School of Medicine: Employment; Celgene: Other: Principal Investigator, Speaker, Grants; Sun: Other: Speaker; Janssen: Other: Principal Investigator, Speaker, Grants; Novartis: Other: Principal Investigator, Speaker, Grants; Soligenix: Other: Principal Investigator; Incyte: Other: Principal Investigator; Regeneron: Other: Principal Investigator, Grants; Ortho Dermatologics: Other: Speaker, Grants; Pfizer: Other: Principal Investigator; UCB: Other: Speaker, Grants; Elorac: Other: Principal Investigator; Abbvie: Other: Principal Investigator. Nicolay:Teva Pharmaceutical Industries: Honoraria, Other: Conference participation fees; Novartis AG: Consultancy, Honoraria; Biogen GmbH: Consultancy, Honoraria; Almirall Hermal AG: Consultancy, Honoraria; Actelion Pharmaceuticals: Consultancy, Honoraria; Innate Pharma: Consultancy; Kyowa Hakko Kirin: Consultancy, Honoraria; Takeda Pharmaceuticals: Consultancy. Leoni:Kyowa Kirin Pharmaceutical Development, Inc.: Employment. Ito:Kyowa Kirin Pharmaceutical Development, Inc.: Employment. Herr:Kyowa Kirin, Inc.: Employment. Sokol:EUSA: Consultancy.

Background: Malnutrition in cirrhosis has a significant negative impact on morbidity and mortality. There is no agreed gold standard of the screening tool. Study comparing the diagnostic properties of nutritional assessment tools in cirrhotic patients is limited. The Subjective Global Assessment (SGA) is one of the global assessment tools. It is used to assess nutritional status in different patient populations. Objective: To evaluate the diagnostic properties of different nutritional screening tools compared with SGA in cirrhotic patients. Materials and Methods: A cross-sectional study was conducted at the HRH Princess Maha Chakri Sirindhorn Medical Center. All cirrhotic patients were enrolled. The nutritional status was evaluated by the SGA, the Royal Free Hospital Subjective Global Assessment (RFH-SGA), the Royal Free Hospital-Nutritional Prioritizing tool (RFH-NPT), the Liver Disease Undernutrition Screening Tool (LDUST), the Malnutrition Universal Screening Tool (MUST), the Prognostic Nutritional Index (PNI-O), the Nutritional Risk Index (NRI), the Spanish Society of Parenteral, the Enteral Nutrition (SENPE), and the Controlling Nutritional Status (CONUT). Sensitivity, specificity, positive predictive value, and negative predictive value were calculated to evaluate RFH-SGA, RFH-NPT, LDUST, MUST, PNI-O, NRI, SENPE, and CONUT compared with SGA. Results: Ninety-four cirrhotic patients were included. The mean age was 60.82 (SD 10.11) years. Patients with cirrhosis Child Turcotte Pugh (CTP) A, B, and C were 62, 21, and 11, respectively. Twenty-five patients (28.7%) were malnourished according to SGA, five with CTP A cirrhosis, twelve with CTP B cirrhosis, and ten with CTP C cirrhosis. The present study also showed that NRI had the highest sensitivity (100%) and LDUST had the highest specificity (94%). Conclusion: NRI is an effective tool with high sensitivity for identifying malnutrition in early stage of cirrhosis. Keywords: Nutritional screening; Cirrhosis; Subjective Global Assessment; SGA; Nutritional Risk Index; NRI

Abstract Background Ebstein's anomaly (EA) is a right ventricular myopathy with failure of tricuspid valve (TV) delamination. While conventional echocardiographic measurements of ventricular function such as tricuspid annular plane systolic excursion (TAPSE), tissue Doppler imaging RV systolic velocity (s'), fractional area change (FAC) and left ventricle ejection fraction (LV EF) are load dependent measures of systolic function and may not reflect true myocardial function, speckle tracking echocardiography (STE) evaluates more subtle myocardial deformation on a regional level. However, the role of STE for the biventricular assessments in an adult cohort of EA before and after tricuspid valve repair/replacement (TVR) is not fully elucidated. Purposes To assess biventricular function by conventional echocardiographic parameters and global and regional longitudinal strain (GLS, RLS) using speckle tracking echocardiography in adult patients with EA pre- and post-TVR. Methods 47 patients with EA (57% women, age at operation 37±16 years) who had TV repair/replacement (17/30) between 2005 and 2019 were retrospectively identified from Echo database. 2D conventional echocardiographic parameters (TAPSE, s', FAC and LV EF) and biventricular GLS and RLS were assessed pre-TVR, at 1-, 2- and 5-year post-TVR. RV and LV segments were visually graded for STE feasibility assessment (Figure 1). Results TAPSE and s' declined after TVR with no further changes over 5 years (both p&lt;0.0001); FAC decreased after TVR (p=0.005) with some amelioration but remaining impaired at 5 years. RV GLS deteriorated at 1 year post-TVR with improvements at 2 and 5 years (p&lt;0.0001, Table 1). LV EF remained preserved (p=0.2), however, LV GLS was low pre-TVR and decreased at 1 year with improvements at 2 and 5 years (p=0.004). Least feasible segments were RV mid (pre-TVR and 1y and 5y post-TVR) and apical free wall (both pre- and post-operative) and LV apical lateral (pre-TVR and 2y post-TVR) all with median score of 1. Conclusions Despite the TV regurgitation reduction, TV surgeries have led to RV dysfunction with only some amelioration of RV longitudinal strain and all conventional echocardiographic parameters after 5 years. The segmental analysis showed that the basal septal segment was the most negatively affected. LV strain was reduced before and after surgery despite preserved ejection fraction. Hence, speckle tracking echocardiography is a feasible and a sensitive method in detecting myocardial dysfunction in patients with Ebstein's anomaly. Feasibility assessment Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Royal Brompton Hospital; Imperial College

Abstract Background Patients with native or post-surgical right ventricular outflow tract (RVOT) dysfunction often require several re-interventions. Percutaneous pulmonary valve implantation (PPVI) has recently been proposed as an attractive alternative to surgery, but there is still lack of data on long-term results. Aim To determine the long-term outcome after PPVI and to investigate whether clinical benefit and cardiac performance improvement is achieved after the procedure. Methods and results Seventy-eight patients (mean age 31.75±11.7) undergoing PPVI between April 2007 and July 2017 at Royal Brompton Hospital were retrospectively included in the study. The median follow-up was 6.1 years (2.1–11.2). Overall survival was 90.8%±4.1 at 6 years and 85%±5.9 at 11 years with freedom from valve failure (defined as either severe stenosis or regurgitation) of 87.6%±5 at 6 years of follow-up. Annual reintervention rate was 3.2% (95% CI 1.6–5.5). Infective endocarditis was a major concern with annual incidence rate of 1.6% (95% CI 0.5–3.4) and 50% of adverse outcome. Male sex (HR 3.2, 95% CI 1.3–7.9, p=0.013), age at procedure&gt;50 years (HR 4.7, 95% CI 1.5–15.1, p=0.01) and residual mean gradient&gt;25 mmHg at immediate postprocedural echo (HR 4.6, 95% CI 1.6–13.5%, p=0.006) were independently associated to the composite endpoint (including death, re-intervention, valve failure and arrhythmia). At latest follow-up, significant NYHA class (Pre Vs 6.1yrs Post p&lt;0.0001) and cardiopulmonary test results improvement (peakVO2 p=0.01) and arrhythmic burden reduction (p=0.002) were found. Both cardiovascular magnetic resonance (CMR) and serial echocardiograms showed biventricular reverse remodeling (Pre Vs 1.3yrs Post CMR: RVEDVi p=0.0002, RVESVi p=0.0012, LVEDVi p=0.028). Furthermore, speckle tracking assessments demonstrated significant improvement of RV free wall GLS (Pre Vs 6.4yrs Post p=0.03) and LV GLS (p=0.01) at long-term. Moreover, concomitant improvement of RV relaxation properties was suggested by echo evidence of right atrial (RA) reverse remodeling (Pre Vs 6.4yrs Post RA area p=0.0001), increased RA strain (p=0.0005) and reduction of the patients with restrictive RV physiology (p&lt;0.0001). Conclusion PPVI is a reliable alternative to surgery with long-lasting favourable clinical effects associated with significant and persistent structural biventricular reverse remodeling and global systolic and diastolic functional improvement. Valve failure and infective endocarditis remain major complications during follow-up. Older and male patients and those with residual transvalvular gradients immediately post procedure are at higher risk of adverse clinical events, thus suggesting that re-intervention should be anticipated and that complete relief of RVOT obstruction should be pursued. Kaplan-Meier curves for survival free from VF Funding Acknowledgement Type of funding source: None