Journal articles: '571.978 37'

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Watson, C. B. "ANCIENT RHETORIC - E. Gunderson (ed.) The Cambridge Companion to Ancient Rhetoric. Pp. x + 355. Cambridge: Cambridge University Press, 2009. Paper, £20.99, US$37 (Cased, £58, US$90). ISBN: 978-0-521-67786-8 (978-0-521-86054-3 hbk)." Classical Review 63, no. 1 (March 1, 2013): 46–48. http://dx.doi.org/10.1017/s0009840x12002284.

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Kerr, Betsy. "C. Schnedecker and A. Theissen (eds), Topicalisation et partition. Cahiers de praxématique, 37. Montpellier: Université de Montpellier III, 2001, 200 pp. 978 284269 511 9." Journal of French Language Studies 19, no. 3 (September 28, 2009): 416–18. http://dx.doi.org/10.1017/s0959269509990305.

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Ip, Andrew, Shuo Wang, Divya Cheruku, Kanchi Krishnamurthy, Melinda Weber, Brittany Sinclaire, Elli Gourna Paleoudis, et al. "Late immune-related adverse events with immune checkpoint inhibitors." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): 2635. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.2635.

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2635 Background: Immune Checkpoint Inhibitors (ICIs) are associated with unique immune-related adverse events (irAEs). IrAEs can occur at any timepoint of ICI treatment. Late irAEs are not well reported in the literature. Herein, we attempt to characterize irAEs that occur 6-month, one year and two years after ICI treatment initiation. Methods: We identified patients treated with ICIs (anti-CTLA-4, anti-PD(L)-1 either alone or in combination or with chemotherapy) across Hackensack Meridian Health hospital and MedStar Georgetown University Health systems from 12011 to 4/2018. Patients' baseline demographics, treatment history, and irAEs were collected from EHR. CTCAE V4.03 was used to grade irAEs. Results: We identified 1332 patients treated with 1443 unique ICIs. The ICI therapies were nivolumab 38% (543), pembrolizumab 23% (332), ipilimumab plus nivolumab 12% (180), ipilimumab 11% (161), Atezolizumab 3% (47) and others 13% (180). Tumor types were lung cancer 34% (496), melanoma 27% (389), GI cancers 6% (92), kidney cancer 6% (87), and other cancers 26% (379). The median age was 66 (21-87), age >75 37% (541), Caucasian 67% (970). We identified a total of 911 any grade irAEs among 37% (552) therapies. Among, 911 irAEs, grade 1-2, grade ≥3 and unknown grade irAEs were 39% (572), 12% (182) and 11% (157), respectively. The most common any grade irAEs were skin rash 22% (202), colitis 13% (120), and hepatitis 12% (108). 84% of all irAEs and 85% of ≥ Grade 3 irAEs occurred within 6 months of treatment initiation. Of the 350, patients on active treatment at six months, 37 % (132) and 7% (26) developed any grade and grade ≥3 irAEs, respectively. irAEs that had > 10% of their occurrences after six months were skin rash and colitis 14% each. Other common irAEs were hypothyroidism, hepatitis, joint pain, pruritis and pneumonitis at 7% each. Among 170 patients on active treatment at one year, 37% (62) and 7% (12) developed any grade and grade ≥3 irAEs respectively. irAEs with >10% incidence after one year of treatment were rash 19% and hepatitis 13%. Conclusions: Our RWE findings suggest although 85% irAEs occurs within the first six months of treatment, late irAEs can occur with ICI treatment. The incidence and pattern of late irAEs appears similar to early irAEs, (e.g., skin rash, colitis, hypothyroidism and hepatitis) with pneumonitis being a notable exception. It is uncertain if these results will be influenced by changing patterns of ICI use (e.g. different diseases and/or regimens) over time.[Table: see text]

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WHALAN, MARK. "Celeste-Marie Bernier , Suffering and Sunset: World War I in the Art and Life of Horace Pippin (Philadelphia: Temple University Press, 2015, $39.95). Pp. 517. isbn 978 1439 9127 37." Journal of American Studies 51, no. 4 (October 10, 2017): 1286–88. http://dx.doi.org/10.1017/s0021875817001049.

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Bianchini, Monica L., Rachel M. Kenney, Robyn Lentz, Marcus Zervos, Manu Malhotra, and Susan L. Davis. "Discharge Delays and Costs Associated With Outpatient Parenteral Antimicrobial Therapy for High-Priced Antibiotics." Clinical Infectious Diseases 71, no. 7 (October 31, 2019): e88-e93. http://dx.doi.org/10.1093/cid/ciz1076.

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Abstract Background Outpatient parenteral antimicrobial therapy (OPAT) is a widely used, safe, and cost-effective treatment. Most public and private insurance providers require prior authorization (PA) for OPAT, yet the impact of the inpatient PA process is not known. Our aim was to characterize discharge barriers and PA delays associated with high-priced OPAT antibiotics. Methods This was an institutional review board–approved study of adult patients discharged with daptomycin, ceftaroline, ertapenem, and novel beta-lactam-beta-lactamase inhibitor combinations from January 2017 to December 2017. Patients with an OPAT PA delay were compared with patients without a delay. The primary endpoint was total direct hospital costs from the start of treatment. Results Two-hundred patients were included: 141 (71%) no OPAT delay vs 59 (30%) OPAT delay. More patients with a PA delay were discharged to a subacute care facility compared with an outpatient setting: 37 (63%) vs 52 (37%), P = .001. Discharge delays and median total direct hospital costs were higher for patients with OPAT delays: 31 (53%) vs 21 (15%), P < .001 and $19 576 (interquartile range [IQR], 10 056–37 038) vs $7770 (IQR, 3031–13 974), P < .001. In multiple variable regression, discharge to a subacute care facility was associated with an increased odds of discharge delay, age >64 years was associated with a decreased odds of discharge delay. Conclusions OPAT with high-priced antibiotics requires significant care coordination. PA delays are common and contribute to discharge delays. OPAT transitions of care represent an opportunity to improve patient care and address access barriers.

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O, Uchendu J., Nwachokor N. F, and Ijomone A. E. "Audit of medico legal death in metropolitan city of Warri, Nigeria." International Journal of Forensic Medical Investigation 3, no. 1 (July 17, 2017): 29. http://dx.doi.org/10.21816/ijfmi.v3i1.49.

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Aim: To describe the various medico legal autopsy cases with respect to sex, age, cause and manner of death. Material and Methods: This is a descriptive retrospective study of 972 medico-legal autopsy cases studied in Warri Metropolis from 1st Jan. 2003 to 31th December 2016. The relevant information was extracted and subsequently analyzed statistically using SPSS version 22. Results: A total of 972 cases of medico legal autopsies of 843 males against 129 females were studied. Their ages of victims ranged from 0.4 years to 85 years, with a mean of 34.45 years and a peak age group in their 3rd decade. Homicidal, accidental, sudden natural, suicidal, and indeterminate cases accounted for 55.7% (541), 24.7% (240), 17.3% (168), 1.4% (14) and 0.9% (9) of the cases respectively. Firearm injuries, sharp weapon and blunt injuries, accounting for 374 (69.1%), 122(22.6%) and 37(6.8%) of homicide cases. Road traffic accident, drowning, burns injury and electrocution accounted for 119(49.6%), 34(14.2%), 26(10.8%) and 19(7.9%) of accidental cases respectively. Cardiovascular, Central nervous system-related and infectious diseases are responsible for 79(47.0%), 21(12.5%) and 15(8.9%) of sudden natural deaths observed in this study. Hanging and corrossive chemical ingestion accounted for 10(71.4%) and 4(28.6%) respectively of the suicide cases, and together representing a MFR of 3.7:1. Conclusion: Our study showed that firearm injuries, road traffic accident and sharp weapons injuries are the leading cause of unnatural death while cardiovascular diseases account for most cases of sudden natural deaths

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Vene, Nina, Barbara Salobir, Miran Šebeštjen, Mišo Šabovic, Irena Keber, and Borut Jug. "Prognostic impact of haemostatic derangements in chronic heart failure." Thrombosis and Haemostasis 102, no. 08 (2009): 314–20. http://dx.doi.org/10.1160/th08-11-0721.

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SummaryHeart failure is characterised by activation of haemostasis. We sought to explore the prognostic impact of deranged haemostasis in chronic heart failure. In stable, optimally managed outpatients with chronic heart failure, baseline levels of prothrombin fragment F1+2, D-dimer, and tPA and PAI-1 antigens were determined. Clinical follow-up was obtained and the rate of events (heart failure related deaths or hospitalisations) was recorded. We included 195 patients [32.3% female, NYHA class II (66.2%) or III (33.8%), mean age 71 years]. During a median follow up of 693 (interquartile range [IQR] 574–788) days, 63 (30.9%) patients experienced an event; those with an event had higher levels of tPA antigen (median 11.8 [IQR 8.7–14.0] vs. 9.4 [7.9–12.1] µg/l; p=0.033) and D-dimer (938 [485–1269] vs. 620 [37–1076] µg/l; p=0.018). However, on Cox multivariate analysis, only tPA levels above optimal cut-off value of 10.2 µg/l (but not D-dimer) emerged as an independent predictor of prognosis (HRadjusted 2.695, 95% confidence interval 1.233–5.363; p=0.017). Our findings suggest that elevated tPA antigen levels are an independent prognostic predictor in patients with chronic stable heart failure.

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Morrison, Nicole, Sherrie Bryden, and Andreu F. Costa. "Split vs. Single Bolus CT Urography: Comparison of Scan Time, Image Quality and Radiation Dose." Tomography 7, no. 2 (May 20, 2021): 210–18. http://dx.doi.org/10.3390/tomography7020019.

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The purpose of this study was to compare the scan time, image quality and radiation dose of CT urograms (CTU) using a split vs. single bolus contrast media injection technique. A total of 241 consecutive CTUs performed between August 2019-February 2020 were retrospectively reviewed. There were three study groups: Group 1, <50 years old, 50/80 cc split-bolus administered at 0 and 700 s post initiation of injection, with combined nephrographic and excretory phases; group 2, ≥50 years old, same split-bolus protocol; and group 3, ≥50 years old, 130 cc single bolus injection, with nephrographic and excretory phases acquired at 100 s and 460 s post injection initiation. The recorded data elements were scan time, number of excretory phases, imaging quality based on opacification of the urinary collecting system (<50%, 50–75%, 75–100%), and dose-length product (DLP). Associations between group and categorical variables were assessed (Chi-square); mean scan time and DLP were compared (one-way ANOVA). Following analysis, proportionally fewer CTUs required a repeat excretory phase in group 3 (32/112, 28.6%) than in groups 1 (25/48, 52.1%) and 2 (37/80, 46.3%) (p = 0.006). Mean scan time was significantly lower in group 3 (678 s) than in groups 1 (1046 s) and 2 (978 s) (p < 0.0001). There was no association between groups and image quality (p = 0.13). DLP was higher in group 3 (1422 ± 837 mGy·cm) than in groups 1 (1041 ± 531 mGy·cm) and 2 (1137 ± 646 mGy·cm) (p = 0.003). In conclusion, single bolus CTU resulted in significantly fewer repeat phases and faster scan time at the expense of a slightly higher radiation dose.

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Fowden, Garth. "The Parthenon between antiquity, barbarism and Europe - ANTHONY KALDELLIS, THE CHRISTIAN PARTHENON. CLASSICISM AND PILGRIMAGE IN BYZANTINE ATHENS (Cambridge University Press2009). Pp. xvi + 252, figs. 37. ISBN 978-0-521-88228-6. $99/£55." Journal of Roman Archaeology 23 (2010): 802–10. http://dx.doi.org/10.1017/s1047759400003196.

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Kompa, Andrzej. "John Tzetzes, Allegories of the “Iliad”, trans. Adam J. Goldwyn and Dimitra Kokkini. (Dumbarton Oaks Medieval Library 37.) Cambridge, MA: Harvard University Press, 2015. Pp. xxiv, 577. $29.95. ISBN: 978-0-674-96785-4." Speculum 92, no. 2 (April 2017): 593–95. http://dx.doi.org/10.1086/690814.

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Dickerson, Josie, Brian Kelly, Bridget Lockyer, Sally Bridges, Christopher Cartwright, Kathryn Willan, Katy Shire, et al. "Experiences of lockdown during the Covid-19 pandemic: descriptive findings from a survey of families in the Born in Bradford study." Wellcome Open Research 5 (October 2, 2020): 228. http://dx.doi.org/10.12688/wellcomeopenres.16317.1.

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Background: Lockdown measures implemented to contain the Covid-19 virus may be increasing health inequalities, with families from deprived and ethnically diverse backgrounds most likely to be adversely affected. This paper presents findings of the experiences of the Covid-19 lockdown on families living in the multi-ethnic and deprived city of Bradford, England. Methods: Questionnaire surveys were sent during the Covid-19 UK lockdown (10th April to 30th June 2020) to parents in two prospective birth cohort studies. Cross tabulations explored variation by ethnicity and employment status. Text from open questions were analysed using thematic analysis. Results: Of 7,652 families invited, 2,144 (28%) participated. Ethnicity of respondents was: 957 (47%) Pakistani heritage, 715 (35%) White British and 356 (18%) other. 971 (46%) live in the most deprived decile of material deprivation in England. 2,043 (95%) were mothers and 101 were partners. The results summarised below are based on the mothers’ responses. Many families live in poor quality (N=574, 28%), and overcrowded (N=364, 19%) housing; this was more common in families of Pakistani heritage and other ethnicities. Financial (N=738 (37%), food (N=396, 20%), employment (N=728, 37%) and housing (N=204, 10%) insecurities were common, particularly in those who were furloughed, self-employed not working or unemployed. Clinically significant depression and anxiety symptoms were reported by 372 (19%) and 318 (16%) of the mothers and were more common in White British mothers and those with economic insecurity. Open text responses corroborated these findings and highlighted high levels of anxiety about becoming ill or dying from Covid-19. Conclusions: The experiences of the Covid-19 lockdown in this ethnically diverse and deprived population highlight a large number of families living in poor housing conditions, suffering from economic insecurity and poor mental health. There is a need for policy makers and commissioners to better support these families.

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Dickerson, Josie, Brian Kelly, Bridget Lockyer, Sally Bridges, Christopher Cartwright, Kathryn Willan, Katy Shire, et al. "Experiences of lockdown during the Covid-19 pandemic: descriptive findings from a survey of families in the Born in Bradford study." Wellcome Open Research 5 (February 26, 2021): 228. http://dx.doi.org/10.12688/wellcomeopenres.16317.2.

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Background: Lockdown measures implemented to contain the Covid-19 virus have increased health inequalities, with families from deprived and ethnically diverse backgrounds most likely to be adversely affected. This paper describes the experiences of families living in the multi-ethnic and deprived city of Bradford, England.Methods: A wave of survey data collection using a combination of email, text and phone with postal follow-up during the first Covid-19 UK lockdown (10th April to 30thJune 2020) with parents participating in two longitudinal studies. Cross tabulations explored variation by ethnicity and financial insecurity. Text from open questions was analysed using thematic analysis.Results: Of 7,652 families invited, 2,144 (28%) participated. The results presented are based on the 2,043 (95%) mothers’ responses: 957 (47%) of whom were of Pakistani heritage, 715 (35%) White British and 356 (18%) other ethnicity 971 (46%) lived in the most deprived decile of material deprivation in England. and 738 (37%) were financially insecure.Many families lived in poor quality (N=574, 28%), overcrowded (N=364, 19%) housing. Food (N=396, 20%), employment (N=728, 37%) and housing (N=204, 10%) insecurities were common, particularly in those who were furloughed, self-employed not working or unemployed. Clinically important depression and anxiety were reported by 372 (19%) and 318 (16%) mothers. Ethnic minority and financially insecure families had a worse experience during the lockdown across all domains, with the exception of mental health which appeared worse in White British mothers. Open text responses corroborated these findings and highlighted high levels of anxiety and fear about Covid-19.Conclusions: There is a need for policy makers and commissioners to better support vulnerable families during and after the pandemic. Future work will use longitudinal data from before the pandemic, and from future surveys during the pandemic, to describe trajectories and the long-term consequences of the pandemic on vulnerable populations.

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Sternal, Marta, Barbara Kwiatkowska, Krzysztof Borysławski, and Agnieszka Tomaszewska. "The influence of neonatal infections on the development of cerebral palsy." Anthropological Review 84, no. 1 (March 1, 2021): 37–49. http://dx.doi.org/10.2478/anre-2021-0007.

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Abstract One of the most significant biological factors predisposing to cerebral palsy (CP) are infections. The paper aims to analyze neonatal infections’ influence in the risk of CP development with consideration of all significant risk factors including single, twin, full-term and pre-term pregnancies. 278 children with CP attending the chosen school-educational centers in Poland were included in the questionnaire. The control group included data obtained from the medical documentation of 435 children born in Limanowa County Hospital, Poland. Socio-economic factors, factors connected with pregnancy, and the coexisting disorders and diseases in children were taken into consideration. Constructed models of logistic regression were applied in the statistical analysis. Neonatal infections increase the risk of CP development in all children (odds ratio (OR) 5.1, 95% confidence interval (CI) 2.6–9.8), children from single pregnancies (OR 5.8, 95% CI: 3.0–11.29), full-term (OR 6.2, 95% CI: 3.2–12.3), and single full-term pregnancies (OR 6.0, 95% CI: 3.0–12.0). The influence of neonatal infections in the risk of CP development in children from pre-term and single premature pregnancies was not indicated. Neonatal infections are an independent risk factor for CP development in newborns from full-term pregnancy (>37 weeks of pregnancy). The patho-mechanism of CP is different in children from full-term and premature pregnancy and results from interrelating factors are discussed in this paper.

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Brice, Lee L. "The Roman Republican narrative breaks down, again - CHRISTOPHER S. MACKAY, THE BREAKDOWN OF THE ROMAN REPUBLIC: FROM OLIGARCHY TO EMPIRE (Cambridge University Press2009). Pp. ix + 445, figs. 37, maps 5. ISBN 978-0-521-51819-2. $98." Journal of Roman Archaeology 24 (2011): 540–41. http://dx.doi.org/10.1017/s1047759400003561.

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Singhal, Siddharth, Pushpa Gupta, Sanjay Chaturvedi, and Mayank Singhal. "Awareness of Thalassemia in Medical Students in a Medical School of Delhi." Blood 108, no. 11 (November 16, 2006): 3827. http://dx.doi.org/10.1182/blood.v108.11.3827.3827.

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Abstract Awareness of thalassemia in medical students. Thalassemia affects 200 million people worldwide. In Southeast Asia, it is a major public health problem. In India, 10 000 cases are born per year. Thalassemia has until recently, received little attention and is not widely understood by health professionals. There is lack of proper awareness of Thalassemia. Thus. This study was done in 203 medical students at Delhi to assess their awareness about Thalassemia. A preformed proforma was used for this purpose. All the students present on a day in a particular batch were included. MS EXCEL and SPSS were used for analysis. P-value was calculated to assess the statistic significance. Concepts like hematological, genetic & non-infective were well known as opposed to symptoms like fatigue, muscular weakness, abnormal bleeding, jaundice, protruding abdomen, fits, dark urine, bone pain, abnormal facial bones, and susceptibility to infections. Diagnostic and treatment modalities like electromyography, vitamins, antibiotics, cryoprecipitates, spleenectomy, bone marrow transplant and umbilical cord were also much less known. Awareness of preventive interventions like genetic counseling, consanguity, fetal blood sampling was less. Thus, a continuous education model for medical staff is required. Although programs for increasing community awareness are underway in many countries; interventions to raise thalassemia awareness in medical professionals are also required. General & Symptoms 2nd sem n=39 4th sem n=47 6th sem n=59 8th sem n=58 ’p’ value(X2) aware of thalassemia 38(97.4%) 47(100%) 59(100%) 58(100%) 0.238 not infectious disease 38(97.4%) 46(97.8%) 57(96.6) 57(98.3) 0.861 disorder of blood 37(94.9) 47(100%) 57(96.6) 58(100%) 0.267 genetic 37(94.9) 46(97.8%) 54(91.5) 57(98.3) 0.378 fatigue 28(71.8) 45(95.7) 51(86.4) 51(86.4) 0.009 muscular weakness 16(41) 21(44.7) 23(38.9) 24(40.6) 0.01 abnormal bleeding 21(53.8) 11(23.4) 24(40.7) 28(47.5) 0 jaundice 13(33.3) 42(89.4) 38(64.4) 40(67.8) 0 protruding abdomen 2(5.1) 13(27.6) 21(35.6) 25(42.4) 0 fits 7(17.9) 5(10.6) 7(11.9) 12(20.3) 0 dark urine 7(17.9) 33(70.2) 25(42.4) 0 bone pain 10(25.6) 35(74.5) 42(71.2) 40(68.9) 0 abnormal facial bones 5(12.8) 37(78.7) 50(84.7) 44(75.9) 0 susceptibility to infections 14(35.9) 27(57.4) 42(71.2) 41(70.7) 0 Investigations, Treatment & Prevention 2nd sem n=39 4th sem n=47 6th sem n=59 8th sem n=58 ’p’ value(X2) CBC & ferretin 22(56.4) 21(44.7) 26(44) 32(55.1) 0 radiography 0 6(12.7) 11(18.6) 25(42.4) 0 Hb electrophoresis 12(30.7) 34(72.3) 40(67.8) 35(60.3) 0 vitamins 0 12(25.5) 18(30.5) 21(36.2) 0 antibotic 1(2.5) 18(38.3) 21(35.6) 26(44.8) 0 transfusion 30(76.9) 35(74.5) 43(72.9) 39(67.2) 0.121 cryoprecipitate 13(33.3) 20(42.5) 23(38.9) 25(42.4) 0.001 spleenectomy 1(2.5) 27(57.4) 20(33.9) 32(55.1) 0 BM transplant 22(56.4) 34(72.3) 35(59.3) 32(55.1) 0.005 umbilical cord 3(7.6) 22(46.8) 22(37.3) 28(48.3) 0 penatal diagnosis 23(59) 27(57.4) 37(62.7) 41(70.7) 0.5 genetic counselling 12(30.8) 29(61.7) 43(72.9) 38(65.5) 0 gene therapy 19(48.7) 18(38.3) 29(49.1) 38(65.5) 0.044 consanguity 4(10.2) 15(31.9) 17(28.8) 33(55.9) 0 fetal blood 5(12.8) 17(36.1) 22(37.3) 30(50.8) 0.002

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Qiu, Hongxia, Hanxin Wu, Songwen Ju, Wei Xu, Ji Xu, Xin Lv, Jinzhang Shao, and Ri Zhang. "Analysis of Clinical Features and Survival in 42 Cases of Acute Monocytic Leukemia." Blood 112, no. 11 (November 16, 2008): 3992. http://dx.doi.org/10.1182/blood.v112.11.3992.3992.

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Abstract Background: Acute monocytic leukemia (M5) is a distinct subtype of acute myeloid leukemia (AML) with characteristic biologic and clinical features. This study was designed to analyze the clinical and laboratory features, and management and survival of newly diagnosed patients at with M5. Methods: The white blood counts, immunophenotype and karyotypes were retrospectively analyzed in 42 patients (pts) with M5. The overall survival(OS)was estimated by Kaplan-Meier analysis, and the different groups were compared using log-rank test. Results: Of the 42 pts, 7 had M5a and 35 had M5b. The incidence rates of M5 in newly diagnosed patients with acute leukemia and acute myelocytic leukemia were 13.7% and 22%, respectively. 28(66.7%) pts with M5 had a higher white blood counts more than 25×109/L. 36 pts obtained the outcomes of karyotype, 14(39%) pts with an abnormal cytogenetic clone, seven (19.4%) of these patients had trisomy 8 as the sole or accompanied complex cytogenetic aberration, 5(13.8%) had a translocation involving 11q23. An immunophenotype consistent with acute monocytic leukemia (CD14) was seen in 24(57.1%) of 42 pts. 16 pts (38.1%) gave up the chemotherapy at diagnosis and the complete remission rate was 73.1% for 26 pts who received induction chemotherapy. The OS for all M5 pts was 90 days (95%CI, 51.3~128.7) and the median survival for all M5 pts was 137.5 days. The median OS for the 19 CR pts was 273 days (95% CI, 226~320.1) and 85 days (95% CI, 72.2~97.8) for the 16 NR pts (95% CI, 72.2~97.8). For 16 pts who didn’t receive chemotherapy, the median OS was 35 days (95% CI, 33~37)(P<0.0001). M5 presents hyperleukocytosis, 86.1% pts of M5 has a normal clone or trisomy 8 or a translocation involving 11q23. The overall survival of M5 pts with currently available therapy is poor.

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Abdelraheem, Mohamed, El-Tigani Ali, Rania Osman, Rashid Ellidir, Amna Bushara, Rasha Hussein, Shiraz Elgailany, et al. "Outcome of Acute Kidney Injury in Sudanese Children — An Experience from a Sub-Saharan African Unit." Peritoneal Dialysis International: Journal of the International Society for Peritoneal Dialysis 34, no. 5 (July 2014): 526–33. http://dx.doi.org/10.3747/pdi.2013.00082.

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BackgroundAcute Kidney Injury (AKI) is an important cause of morbidity and mortality in developing countries. Although continuous renal replacement therapy is gaining more popularity worldwide, peritoneal dialysis (PD) in children remains an appropriate therapy for AKI in children for all age groups including neonates.MethodologyWe retrospectively reviewed all children who have been admitted with AKI at the pediatric nephrology unit, Soba University Hospital, Khartoum, during the period from January 2005 to December 2011.ResultsOver 7 years we recorded 659 children of whom 362 (54.9%) were male. The spectrum of age was variable with the majority being neonates, 178 (27.1%). The average patient admission rate was 94 patients per year, with an estimated incidence of 9.8 patients/million population/year. Common causes of AKI were sepsis 202 (30.8%), acute glomerulonephritis 75 (11.5%) and obstructive uropathy due to stones 56 (8.5%). The most common dialysis modality used was PD, 343 (52.4%), and peritonitis was reported in 53 (15.4%) patients. Recovery from AKI was achieved in 450 (68.9%) children, 37 (5.7%) went into chronic kidney disease (CKD), 33 (5.1%) referred to the pediatric surgery and 194 (29.7%) died.ConclusionIn the setting of developing countries where AKI is a common cause of morbidity and mortality, reasonably equipped renal units with adequately trained medical staff may save many lives. International funding programs for communicable diseases and charity organizations should include AKI management in their programs. Acute PD remains the treatment modality of choice for AKI in developing countries.

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Suryana, Dadan, Fitriana Sari Khairma, Novi Engla Sari, Lina, Farida Mayar, and Sri Satria. "Star of The Week Programs Based on Peer Relationship for Children Social Emotional Development." JPUD - Jurnal Pendidikan Usia Dini 14, no. 2 (November 30, 2020): 288–302. http://dx.doi.org/10.21009/jpud.142.07.

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The influence of family, school and peers on students' emotional social development is very important as a starting point for the design of school activities that will also improve student development in an integral way. The Star of the Week program was developed with the aim of helping students apply the knowledge, attitudes, and skills needed to socialize and understand and manage emotions. This study uses the Thiagarajan model stages, namely define, design, develop, and disseminate (4D). The results of the validity test from the experts show that this program has workable value with 91.1% material aspects, 90% emotional development aspects and 92% presentation aspects. For the practicality test results through teacher questionnaires obtained scores of 90%, and 88.67% through teacher observations of children who are in the high practical category. The results of the program effectiveness test showed a value of 89.08% on children's social-emotional development, because it showed an increase in values before and after the intervention. The implication of further research is that it is hoped that various kinds of learning methods will develop aspects of child development based on cooperation and peer relationships. Keywords: Early Childhood, Peer Relationships, Star of the Week Program, Social Emotional References Acar, I. H., Hong, S. Y., & Wu, C. R. (2017). Examining the role of teacher presence and scaffolding in preschoolers’ peer interactions. European Early Childhood Education Research Journal, 25(6), 866–884. https://doi.org/10.1080/1350293X.2017.1380884 Acar, I. H., Rudasill, K. M., Molfese, V., Torquati, J., & Prokasky, A. (2015). Temperament and preschool children’s peer interactions. Early Education and Development, 26(4), 479–495. https://doi.org/10.1080/10409289.2015.1000718 Akhir, K., & Wisz, M. S. (2018). Sustainostic Nusantara : Managing marine plastic debris for sustainable tourism in the ‘ New Bali ’ of Indonesia (4.0). https://doi.org/https://doi.org/10.7287/peerj.preprints.26747v1 | Alwaely, S. A., Yousif, N. B. A., & Mikhaylov, A. (2020). Emotional development in preschoolers and socialization. Early Child Development and Care, 0(0), 1–10. https://doi.org/10.1080/03004430.2020.1717480 Asher, S. R., & Parker, J. G. (1989). Significance of Peer Relationship Problems in Childhood. In Social Competence in Developmental Perspective, 5–23. https://doi.org/https://doi.org/10.1007/978-94-009-2442-0_1 Beazidou, E., & Botsoglou, K. (2016). Peer acceptance and friendship in early childhood: the conceptual distinctions between them. Early Child Development and Care, 186(10), 1615–1631. https://doi.org/10.1080/03004430.2015.1117077 Blazevic, I. (2016). Family, Peer and School Influence on Children’s Social Development. World Journal of Education, 6(2), 42–49. https://doi.org/10.5430/wje.v6n2p42 Chung, K. K. H., Lam, C. B., & Liew, J. (2020). Studying Children’s Social-Emotional Development in School and at Home through a Cultural Lens. Early Education and Development, 31(6), 927–929. https://doi.org/10.1080/10409289.2020.1782860 Coelho, L., Torres, N., Fernandes, C., & Santos, A. J. (2017). Quality of play, social acceptance and reciprocal friendship in preschool children. European Early Childhood Education Research Journal, 25(6), 812–823. https://doi.org/10.1080/1350293X.2017.1380879 Conti-Ramsden, G., Mok, P., Durkin, K., Pickles, A., Toseeb, U., & Botting, N. (2019). Do emotional difficulties and peer problems occur together from childhood to adolescence? The case of children with a history of developmental language disorder (DLD). European Child and Adolescent Psychiatry, 28(7), 993–1004. https://doi.org/10.1007/s00787-018-1261-6 Di Maggio, R., Zappulla, C., Pace, U., & Izard, C. E. (2017). Adopting the Emotions Course in the Italian Context: A Pilot Study to Test Effects on Social-Emotional Competence in Preschool Children. Child Indicators Research, 10(2), 571–590. https://doi.org/10.1007/s12187-016-9387-x Domitrovich, C. E., Staley, K. C., Durlak, J. A., & Weissberg, R. P. (2017). Social-Emotional Competence : An Essential Factor for Promoting Positive Adjustment and Reducing Risk in School Children Social-Emotional Competence : An Essential Factor for Promoting Positive Adjustment and Reducing Risk in School Children. Child Development, 1–9. Durlak, J. A., Weissberg, R. P., Dymnicki, A. B., Taylor, R. D., & Schellinger, K. B. (2011). The Impact of Enhancing Students’ Social and Emotional Learning: A Meta-Analysis of School-Based Universal Interventions. Child Development, 82(1), 405–432. https://doi.org/10.1111/j.1467-8624.2010.01564.x Elias, M. J., & Haynes, N. M. (2008). Social Competence, Social Support, and Academic Achievement in Minority, Low-Income, Urban Elementary School Children. School Psychology Quarterly, 23(4), 474–495. https://doi.org/10.1037/1045-3830.23.4.474 Fajriyah, L. (2018). Pengembangan Literasi Emergen Pada Anak Usia Dini. Proceedings of the ICECRS, 165–172. https://doi.org/https://doi.org/10.21070/picecrs.v1i3.1394 Forrest, C. L., Gibson, J. L., Halligan, S. L., & St Clair, M. C. (2018). A longitudinal analysis of early language difficulty and peer problems on later emotional difficulties in adolescence: Evidence from the Millennium Cohort Study. Autism & Developmental Language Impairments, 3, 239694151879539. https://doi.org/10.1177/2396941518795392 Hartup, W. W. (1992). Peer Relations in Early and Middle Childhood. https://doi.org/https://doi.org/10.1007/978-1-4899-0694-6_11 Hernández, Y. C. U., Núñez, E. F. D., Inga-Arias, M., & Lozada, O. R. (2020). Early stimulation and emotional intelligence and its incidence in communication learning at the initial level. International Journal of Early Childhood Special Education,12(1), 433–441. https://doi.org/10.9756/INT-JECSE/V12I1.201023 Khoiruddin, M. A. (2018). Perkembangan Anak Ditinjau dari Kemampuan Sosial Emosional. Jurnal Pemikiran Keislaman, 29(2), 425–438. https://doi.org/https://doi.org/10.33367/tribakti.v29i2.624 Kim, J., & Cicchetti, D. (2010). Longitudinal pathways linking child maltreatment, emotion regulation. J Child Psychol Psychiatry, 51(6), 706–716. https://doi.org/10.1111/j.1469-7610.2009.02202.x.Longitudinal Kompri. (2016). Motivasi Pembelajaran Perspektif Guru dan Siswa. PT Remaja Rosdakarya. Krauthamer Ewing, E. S., Herres, J., Dilks, K. E., Rahim, F., & Trentacosta, C. J. (2019). Understanding of Emotions and Empathy: Predictors of Positive Parenting with Preschoolers in Economically Stressed Families. 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Districtwide Initiative to Improve Tier 1 With Evidence-Based Classroom Lessons. Professional School Counseling, 22(1b), 2156759X1983443. https://doi.org/10.1177/2156759x19834438 Moberly, D. A., Waddle, J. L., & Duff, R. E. (2014). Journal of Early Childhood Teacher Education The use of rewards and punishment in early childhood classrooms The use of rewards and punishment in early childhood classrooms. Journal of Early Childhood Teacher Education, 37–41. https://doi.org/10.1080/1090102050250410 Moore, J. E., Cooper, B. R., Domitrovich, C. E., Morgan, N. R., Cleveland, M. J., Shah, H., Jacobson, L., & Greenberg, M. T. (2015). The effects of exposure to an enhanced preschool program on the social-emotional functioning of at-risk children. Early Childhood Research Quarterly, 32, 127–138. https://doi.org/10.1016/j.ecresq.2015.03.004 Morris, A. S., & Williamson, A. C. (2019). Building early social and emotional relationships with infants and toddlers: Integrating research and practice. 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Kaneda, H., K. Nakagawa, H. Saito, T. Kashii, Y. Iwamoto, N. Katakami, T. Nakano, T. Kurata, and M. Fukuoka. "Randomized phase II study of carboplatin and paclitaxel (CP) versus gemcitabine and vinorelbine (GV) in performance status (PS) 2 patients with advanced non-small cell lung cancer (NSCLC): Preliminary results of West Japan Thoracic Oncology Group 0004." Journal of Clinical Oncology 24, no. 18_suppl (June 20, 2006): 7151. http://dx.doi.org/10.1200/jco.2006.24.18_suppl.7151.

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7151 Background: A platinum-based chemotherapy is a standard treatment in PS 0–1 patients with advanced NSCLC and a non-platinum doublet is an alternative option. However, the role of combination chemotherapy remains to be defined in PS 2 patients with advanced NSCLC. We have conducted a randomized phase II study to compare the efficacy and safety of CP versus GV in PS 2 patients with NSCLC. Methods: Chemotherapy-naive ECOG PS 2 patients with stage IIIB (malignant effusion) or IV NSCLC were enrolled in this study. Patients were randomized to carboplatin AUC 6 and paclitaxel 200 mg/m2 day 1 every 3 weeks or gemcitabine 1,000 mg/ m2 and vinorelbine 25mg/m2 day 1, 8 every 3 weeks. The primary endpoint was 1-year survival rate and secondary endpoint were response rate, toxicity, time to progression and quality of life. Results: A total of 89 patients were enrolled and 86 were eligible: 42 patients (median age 64 years, male/female 31/11, stage IIIB/IV 7/35) in CP and 44 patients (median age 67 years, male/female 33/11, stage IIIB/IV 7/37) in GV. Of 84 patients evaluable for response, one complete response and 11 partial responses were obtained in CP (29.3%) and 9 partial responses in GV (20.9%). As of 12/05, toxicity data were available in 80 patients. Grade 3/4 toxicity in CP and GV included neutropenia 65.8% vs 63.4%, anemia 13.2% vs 31.7%, thrombocytopenia 7.9% vs 12.2%, liver dysfunction 2.6% vs 9.8%, febrile neutropenia 15.4% vs 12.2%, infection 30.8% vs 22%, nausea/vomiting 15.4% vs 2.4%, constipation 23.1% vs 7.3% pulmonary infiltrates 5.1% vs 12.2% and neuropathy 5.1% vs 0%. Conclusions: CP and GV were feasible and effective in PS 2 patients with advanced NSCLC. GV caused more anemia, thrombocytopenia, liver dysfunction and pulmonary infiltrates, while CP produced more nausea/vomiting, constipation and neuropathy. Response and toxicity data in all pts in each arm will be presented at the meeting. No significant financial relationships to disclose.

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Kuznetsov, Vyacheslav A., Petr O. Kushchev, Irina V. Ostankova, Alexander Yu Pulver, Natalia A. Pulver, Stanislav V. Pavlovich, and Rimma A. Poltavtseva. "Modern Approaches to the Medical Use of pH- and Temperature-Sensitive Copolymer Hydrogels (Review)." Kondensirovannye sredy i mezhfaznye granitsy = Condensed Matter and Interphases 22, no. 4 (December 15, 2020): 417–29. http://dx.doi.org/10.17308/kcmf.2020.22/3113.

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This article provides the review of the medical use of pH- and temperature-sensitive polymer hydrogels. Such polymers are characterised by their thermal and pH sensitivity in aqueous solutions at the functioning temperature of living organisms and can react to the slightest changes in environmental conditions. Due to these properties, they are called stimuli-sensitive polymers. This response to an external stimulus occurs due to the amphiphilicity (diphilicity) of these (co)polymers. The term hydrogels includes several concepts of macrogels and microgels. Microgels, unlike macrogels, are polymer particles dispersed in a liquid and are nano- or micro-objects. The review presents studies reflecting the main methods of obtainingsuch polymeric materials, including precipitation polymerisation, as the main, simplest, and most accessible method for mini-emulsion polymerisation, microfluidics, and layer-by-layer adsorption of polyelectrolytes. Such systems will undoubtedly be promising for use in biotechnology and medicine due to the fact that they are liquid-swollen particles capable of binding and carrying various low to high molecular weight substances. It is also important that slight heating and cooling or a slight change in the pH of the medium shifts the system from a homogeneous to a heterogeneous state and vice versa. This providesthe opportunity to use these polymers as a means of targeted drug delivery, thereby reducing the negative effect of toxic substances used for treatment on the entire body and directing the action to a specific point. In addition, such polymers can be used to create smart coatings of implanted materials, as well as an artificial matrix for cell and tissue regeneration, contributing to a significant increase in the survival rate and regeneration rate of cells and tissues. References 1. Gisser K. R. C., Geselbracht M. J., Cappellari A.,Hunsberger L., Ellis A. B., Perepezko J., et al. 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Gastroenterology.2012;143(3): 582–588. DOI: https://doi.org/10.1053/j.gastro.2012.04.05044. Ebihara G., Sato M., Yamato M., Mitani G.,Kutsuna T., Nagai T., et al. Cartilage repair intransplanted scaffold-free chondrocyte sheets usinga minipig model. Biomaterials. 2012;33(15): 3846–3851. DOI: https://doi.org/10.1016/j.biomaterials.2012.01.05645. Sato M., Yamato M., Hamahashi K., Okano T.,Mochida J. Articular cartilage regeneration using cellsheet technology. The Anatomical Record. 2014;297(1):36–43. DOI: https://doi.org/10.1002/ar.2282946. Kuramoto G., Takagi S., Ishitani K., Shimizu T.,Okano T., Matsui H. Preventive effect of oral mucosalepithelial cell sheets on intrauterine adhesions. HumanReproduction. 2014;30(2): 406–416. DOI: https://doi.org/10.1093/humrep/deu32647. Yamamoto K., Yamato M., Morino T.,Sugiyama H., Takagi R., Yaguchi Y., et al. Middle earmucosal regeneration by tissue-engineered cell sheettransplantation. NPJ Regenerative Medicine. 2017;2(1):6. DOI: https://doi.org/10.1038/s41536-017-0010-748. Gan D., Lyon L. A. Synthesis and Proteinadsorption resistance of PEG-modified poly(Nisopropylacrylamide) core/shell microgels.Macromolecules. 2002;35(26): 9634–9639. DOI: https://doi.org/10.1021/ma021186k49. Veronese F. M., Mero A. The impact ofPEGylation on biological therapies. BioDrugs.2008;22(5): 315–329. DOI: https://doi.org/10.2165/00063030-200822050-0000450. Sahay G., Alakhova D. Y., Kabanov A. V.Endocytosis of nanomedicines. Journal of ControlledRelease. 2010;145(3): 182–195. DOI: https://doi.org/10.1016/j.jconrel.2010.01.03651. Nolan C. M., Reyes C. D., Debord J. D.,García A. J., Lyon L. A. Phase transition behavior,protein adsorption, and cell adhesion resistance ofpoly(ethylene glycol) cross-linked microgel particles.Biomacromolecules. 2005;6(4): 2032–2039. DOI:https://doi.org/10.1021/bm050008752. Scott E. A., Nichols M. D., Cordova L. H., GeorgeB. J., Jun Y.-S., Elbert D. L. Protein adsorption and celladhesion on nanoscale bioactive coatings formed frompoly(ethylene glycol) and albumin microgels.Biomaterials. 2008;29(34): 4481–4493. DOI: https://doi.org/10.1016/j.biomaterials.2008.08.00353. South A. B., Whitmire R. E., García A. J.,Lyon L. A. Centrifugal deposition of microgels for therapid assembly of nonfouling thin films. ACS AppliedMaterials & Interfaces. 2009;1(12): 2747–2754. DOI:https://doi.org/10.1021/am900543554. Wang Q., Uzunoglu E., Wu Y., Libera M. Selfassembledpoly(ethylene glycol)-co-acrylic acidmicrogels to inhibit bacterial colonization of syntheticsurfaces. ACS Applied Materials & Interfaces. 2012;4(5):2498–2506. DOI: https://doi.org/10.1021/am300197m55. Wang Q., Libera M. Microgel-modified surfacesenhance short-term osteoblast response. Colloids andSurfaces B: Biointerfaces. 2014;118: 202–209. DOI:https://doi.org/10.1016/j.colsurfb.2014.04.00256. Tsai H.-Y., Vats K., Yates M. Z., Benoit D. S. W.Two-dimensional patterns of poly(N-isopropylacrylamide)microgels to spatially control fibroblastadhesion and temperature-responsive detachment.Langmuir. 2013;29(39): 12183–12193. DOI: https://doi.org/10.1021/la400971g57. Lynch I. , Miller I. , Gallagher W. M. ,Dawson K. A. Novel method to prepare morphologicallyrich polymeric surfaces for biomedical applicationsvia phase separation and arrest of microgel particles.The Journal of Physical Chemistry B. 2006;110(30):14581–14589. DOI: https://doi.org/10.1021/jp061166a58. Li Y., Chen P., Wang Y., Yan S., Feng X., Du W.,et al. Rapid assembly of heterogeneous 3D cellmicroenvironments in a microgel array. AdvancedMaterials. 2016;28(18): 3543–3548. DOI: https://doi.org/10.1002/adma.20160024759. Bridges A. W., Singh N., Burns K. L., BabenseeJ. E., Andrew Lyon L., García A. J. Reduced acuteinflammatory responses to microgel conformalcoatings. Biomaterials. 2008;29(35): 4605–4615. DOI:https://doi.org/10.1016/j.biomaterials.2008.08.01560. Bridges A. W., Whitmire R. E., Singh N.,Templeman K. L., Babensee J. E., Lyon L. A., et al.Chronic inflammatory responses to microgel-basedimplant coatings. Journal of Biomedical Materials Research Part A. 2010;94A(1): 252–258. DOI: https://doi.org/10.1002/jbm.a.3266961. Gutowski S. M., Templeman K. L., South A. B.,Gaulding J. C., Shoemaker J. T., LaPlaca M. C., et al.Host response to microgel coatings on neuralelectrodes implanted in the brain. Journal of BiomedicalMaterials Research Part A. 2014;102(5): 1486–1499.DOI: https://doi.org/10.1002/jbm.a.3479962. da Silva R. M. P., Mano J. F., Reis R. L. Smartthermoresponsive coatings and surfaces for tissueengineering: switching cell-material boundaries.Trends in Biotechnology. 2007;25(12): 577–583. DOI:https://doi.org/10.1016/j.tibtech.2007.08.01463. Schmidt S., Zeiser M., Hellweg T., Duschl C.,Fery A., Möhwald H. Adhesion and mechanicalproperties of PNIPAM microgel films and theirpotential use as switchable cell culture substrates.Advanced Functional Materials. 2010;20(19): 3235–3243. DOI: https://doi.org/10.1002/adfm.20100073064. Uhlig K., Wegener T., He J., Zeiser M., BookholdJ., Dewald I., et al. Patterned thermoresponsivemicrogel coatings for noninvasive processing ofadherent cells. Biomacromolecules. 2016;17(3): 1110–1116. DOI: https://doi.org/10.1021/acs.biomac.5b01728

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Normand, A. C., P. Becker, F. Gabriel, C. Cassagne, I. Accoceberry, M. Gari-Toussaint, L. Hasseine, et al. "Validation of a New Web Application for Identification of Fungi by Use of Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry." Journal of Clinical Microbiology 55, no. 9 (June 21, 2017): 2661–70. http://dx.doi.org/10.1128/jcm.00263-17.

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ABSTRACT Matrix-assisted laser desorption ionization–time of flight (MALDI-TOF) mass spectrometry has emerged as a reliable technique to identify molds involved in human diseases, including dermatophytes, provided that exhaustive reference databases are available. This study assessed an online identification application based on original algorithms and an extensive in-house reference database comprising 11,851 spectra (938 fungal species and 246 fungal genera). Validation criteria were established using an initial panel of 422 molds, including dermatophytes, previously identified via DNA sequencing (126 species). The application was further assessed using a separate panel of 501 cultured clinical isolates (88 mold taxa including dermatophytes) derived from five hospital laboratories. A total of 438 (87.35%) isolates were correctly identified at the species level, while 26 (5.22%) were assigned to the correct genus but the wrong species and 37 (7.43%) were not identified, since the defined threshold of 20 was not reached. The use of the Bruker Daltonics database included in the MALDI Biotyper software resulted in a much higher rate of unidentified isolates (39.76 and 74.30% using the score thresholds 1.7 and 2.0, respectively). Moreover, the identification delay of the online application remained compatible with real-time online queries (0.15 s per spectrum), and the application was faster than identifications using the MALDI Biotyper software. This is the first study to assess an online identification system based on MALDI-TOF spectrum analysis. We have successfully applied this approach to identify molds, including dermatophytes, for which diversity is insufficiently represented in commercial databases. This free-access application is available to medical mycologists to improve fungal identification.

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Vogl, T. J., N. Naguib, S. Zangos, K. Eichler, and T. Gruber. "Repeated transarterial chemoperfusion and -embolization (TACE) in primary hepatic cholangiocarcinoma (CCC): Local tumor control and survival rate." Journal of Clinical Oncology 27, no. 15_suppl (May 20, 2009): e15595-e15595. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.e15595.

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e15595 Background: To evaluate local tumor control and survival data in the palliative and symptomatic treatment of hepatic cholangiocarcinoma (CCC) using repeated transarterial chemoperfusion and -embolization (TACE) with two different chemotherapy protocols. Methods: 41 patients with primary cholangiocarcinoma (CCC) were repeatedly treated with transarterial chemoembolization (TACE) in 4-week intervals. In total, 291 TACE sessions were performed with a mean of 7.1 sessions per patient (mean age: 57.1 years; range, 37–80 years). 22 patients had multiple tumors, 6 showed 1 lesion, 5 had 2 lesions and 8 presented 3 to 4 lesions. The local chemotherapy protocol consisted of Mitomycin C alone (n=20), or in combination with gemcitabine (n=18). Embolization was performed with lipiodol and starch microspheres for vessel occlusion. Tumor response was evaluated by magnetic resonance imaging (MRI) in 3-month intervals. Results: Evaluation of local tumor control according to the RECIST criteria was as follows: partial response 9.8%, stable disease 43.6%, and progressive disease 46.6%. The 1-year survival rate after TACE was 58%, the 2-year survival rate was 21%. The mean survival time from the date of diagnosis of liver involvement was 34.1 months (according to Kaplan-Meier), after first TACE treatment 16.7 months. The median survival time of the palliative group was 14.5 months and of the symptomatic group 6 months. Conclusions: Our data indicated that repeated TACE using the protocols is well tolerated and yields respectable results in patients with unresectable liver lesions from CCC. No significant financial relationships to disclose.

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Even, Yael. "Mitchell B. Merback, ed. Beyond the Yellow Badge: Anti-Judaism and Antisemitism in Medieval and Early Modern Culture. Brill's Series in Jewish Studies 37. Leiden: Brill, 2008. xxiv + 574 pp. index. illus. bibl. $143. ISBN: 978–90–04–15165–9." Renaissance Quarterly 62, no. 2 (2009): 549–50. http://dx.doi.org/10.1086/599912.

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Levine, R. J., P. D. Chantler, R. W. Kensler, and J. L. Woodhead. "Effects of phosphorylation by myosin light chain kinase on the structure of Limulus thick filaments." Journal of Cell Biology 113, no. 3 (May 1, 1991): 563–72. http://dx.doi.org/10.1083/jcb.113.3.563.

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The results discussed in the preceding paper (Levine, R. J. C., J. L. Woodhead, and H. A. King. 1991. J. Cell Biol. 113:563-572.) indicate that A-band shortening in Limulus muscle is a thick filament response to activation that occurs largely by fragmentation of filament ends. To assess the effect of biochemical changes directly associated with activation on the length and structure of thick filaments from Limulus telson muscle, a dually regulated tissue (Lehman, W., J. Kendrick-Jones, and A. G. Szent Gyorgyi. 1973. Cold Spring Harbor Symp. Quant. Biol. 37:319-330.) we have examined the thick filament response to phosphorylation of myosin regulatory light chains. In agreement with the previous work of J. Sellers (1981. J. Biol. Chem. 256:9274-9278), Limulus myosin, incubated with partially purified chicken gizzard myosin light chain kinase (MLCK) and [gamma 32P]-ATP, binds 2 mol phosphate/mole protein. On autoradiographs of SDS-PAGE, the label is restricted to the two regulatory light chains, LC1 and LC2. Incubation of long (greater than or equal to 4.0 microns) thick filaments, separated from Limulus telson muscle under relaxing conditions, with either intact MLCK in the presence of Ca2+ and calmodulin, or Ca2(+)-independent MLCK obtained by brief chymotryptic digestion (Walsh, M. P., R. Dabrowska, S. Hinkins, and D. J. Hartshorne. 1982. Biochemistry. 21:1919-1925), causes significant changes in their structure. These include: disordering of the helical surface arrangement of myosin heads as they move away from the filament backbone; the presence of distal bends and breaks, with loss of some surface myosin molecules, in each polar filament half; and the production of shorter filaments and end-fragments. The latter structures are similar to those produced by Ca2(+)-activation of skinned fibers (Levine, R. J. C., J. L. Woodhead, and H. A. King. J. Cell Biol. 113:563-572). Rinsing experimental filament preparations with relaxing solution before staining restores some degree of order of the helical surface array, but not filament length. We propose that outward movement of myosin heads and thick filament shortening in Limulus muscle are responses to activation that are dependent on phosphorylation of regulatory myosin light chains. Filament shortening may be due, in large part, to breakage at the filament ends.

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Tigchelaar, Eibert. "Qumrân Grotte 4 XXVII: Textes araméens deuxième partie: 4Q550-4Q575a, 4Q580-4Q587 et appendices. By Émile Puech. (Discoveries in the Judaean Desert 37). Oxford: Clarendon Press, 2009. Pp. xxvi, 561, plates. Cloth with dusk jacket. £ 110.00. ISBN 978-0-19-955004-3." Journal for the Study of Judaism 41, no. 1 (2010): 131–34. http://dx.doi.org/10.1163/004722110x12580098290838.

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Bitaraf, Mohammad Ali, Mazdak Alikhani, Pouya Tahsili-Fahadan, Rouzbeh Motiei-Langroudi, Alireza Zahiri, Mahmoud Allahverdi, and Soraya Salmanian. "Radiosurgery for glomus jugulare tumors: experience treating 16 patients in Iran." Journal of Neurosurgery 105, Supplement (December 2006): 168–74. http://dx.doi.org/10.3171/sup.2006.105.7.168.

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ObjectGlomus jugulare tumors (GJT) have traditionally been treated by surgery or fractionated external-beam radiotherapy. The aim of this retrospective study was to determine the tumor control rate, clinical outcome, and short-term complications of stereotactic radiosurgery in subsets of patients who are poor candidates for these procedures, based on age, medical problems, tumor size, or prior treatment failure.MethodsThe Leksell Gamma Knife was used to treat 16 patients harboring symptomatic, residual, recurrent, or unresectable GJTs. The age of the patients ranged from 12 to 77 years (median 46.5 years). Gamma Knife surgery (GKS) was performed as primary treatment in five patients (31.3%). Microsurgery preceded radiosurgery in 10 patients (62.5%) and fractionated radiotherapy in three patients (18.8%). The median tumor volume was 9.8 cm3 (range 1.7–20.6 cm3). The median marginal dose applied to a mean isodose volume of 50% (range 37–70%) was 18 Gy (range 14–20 Gy).Neurological follow-up examinations revealed improved clinical status in 10 patients (62.5%), a stable neurological status in six (37.5%), and no complications. After radiosurgery, follow-up imaging was conducted in 14 patients; the median interval from GKS to the last follow up was 18.5 months (range 4–28 months). Tumor size had decreased in six patients (42.9%), and the volume remained unchanged in the remaining eight (57.1%). None of the tumors increased in volume during the observation period.Conclusions According to the authors' experience, GKS represents a useful therapeutic option to control symptoms and may be safely conducted in patients with primary or recurrent GJTs with no death and no acute morbidity. Because of the tumor's naturally slow growth rate, however, long-term follow-up data are needed to establish a cure rate after radiosurgery.

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Harari, Colin, Adam Burr, H. Ian Robins, and Steven Howard. "RTHP-35. RE-IRRADIATION USING PULSED REDUCED DOSE RATE RADIATION THERAPY IN PATIENTS WITH GRADE 2 GLIOMAS." Neuro-Oncology 21, Supplement_6 (November 2019): vi217. http://dx.doi.org/10.1093/neuonc/noz175.906.

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Abstract BACKGROUND The time course of progressive grade 2 glioma can span nearly a decade. However, much less is known about re-irradiation in this cohort than in high grade patients. Pulsed reduced dose rate (PRDR) radiation therapy is a method of radiation delivery, which may spare normal tissues by slowing the rate of radiation delivery to allow repair. METHODS We identified consecutive patients from an institutional database initially diagnosed with grade 2 glioma from 2001 to 2017 who underwent pulsed reduced dose rate radiation therapy. Radiation was delivered in 20 cGy pulses every three minutes, most commonly with a 3D conformal, three field technique, encompassing gross disease with a 1–2 cm margin. Kaplan Meier method was utilized to analyze patient outcomes. RESULTS 35 patients with grade 2 glioma were identified. The median survival from the date of the first surgery was 103 months (95% CI 78–129 mo). 71% underwent at least a second resection and 86% of patients receiving chemotherapy. 80% of patients underwent transformation to grade 3 (51%) or grade 4 (29%) glioma. Overall survival from PRDR was 9.8 months (95% CI 4.5–14.5mo) and progression free survival was 6.2 months (95% CI 5.1–7.4) in all patients. Overall response rate was 37%. In patients who remained grade 2 histology, overall survival was 13.3 months and two patients remain disease free at 83 and 34 months with overall response of 71%. Four seizures were documented, otherwise treatment was well tolerated. CONCLUSIONS Progressive grade 2 glioma can progress and evolve over nearly the course of a decade. This study demonstrates the efficacy of re-irradiation in prolonging survival in these patients by delaying progression. In patients who remain with grade 2 disease, prolonged salvage of their disease appears possible.

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Colombet, Isabelle, Colette Saguez, Marie-José Sanson-Le Pors, Benoît Coudert, Gilles Chatellier, and Pierre Espinoza. "Diagnosis of Tetanus Immunization Status: Multicenter Assessment of a Rapid Biological Test." Clinical Diagnostic Laboratory Immunology 12, no. 9 (September 2005): 1057–62. http://dx.doi.org/10.1128/cdli.12.9.1057-1062.2005.

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ABSTRACT Diagnosis of tetanus immunization status by medical interview of patients with wounds is poor. Many protected patients receive unnecessary vaccine or immunoglobulin, and unprotected patients may receive nothing. The aim of this study is to evaluate the feasibility and accuracy of the Tetanos Quick Stick (TQS) rapid finger prick stick test in the emergency department for determining immunization status. We designed a prospective multicenter study for blinded comparison of TQS with an enzyme-linked immunosorbent assay (ELISA). Adults referred for open wounds in 37 French hospital emergency departments had the TQS after receiving standard care (emergency-TQS). TQS was also performed in the hospital laboratory on total blood (blood/lab-TQS) and serum (serum/lab-TQS). ELISA was performed with the same blood sample at a central laboratory. We assessed concordance between emergency-TQS and blood/lab-TQS by the kappa test and the diagnostic accuracy (likelihood ratios) of medical interview, emergency-TQS, and lab-TQS. ELISA was positive in 94.6% of the 988 patients included. Concordance between blood/emergency-TQS and blood/lab-TQS results was moderate (κ = 0.6), with a high proportion of inconclusive blood/emergency-TQS tests (9.8%). Likelihood ratios for immunization were 3.0 (95% confidence interval [CI], 1.8 to 5.1), 36.6 (95% CI, 5.3 to 255.3), 89.1 (95% CI, 5.6 to 1,405.0), and 92.7 (95% CI, 5.9 to 1,462.0) for medical interview, blood/emergency-TQS, blood/lab-TQS, and serum/lab-TQS, respectively. The sensitivity of the blood/emergency-TQS was 76.7%, and the specificity was 98% by reference to the ELISA. TQS use in the emergency room could make tetanus prevention more accurate if its technical feasibility were improved, and our assessment will be supplemented by a cost effectiveness study.

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Berger-Tal, Oded. "Conservation Biology. By Bradley J. Cardinale, Richard B. Primack, and James D. Murdoch. Oxford and New York: Oxford University Press (Sinauer Associates). $114.95. xvii + 584 p.; ill.; G-1 - G-13; R-1 - R-37; I-1 - I-15 (index). ISBN: 978-1-6053-5714-0. 2020." Quarterly Review of Biology 96, no. 2 (June 1, 2021): 152–53. http://dx.doi.org/10.1086/714471.

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Rhodes, Samhita S., Amadou K. S. Camara, James S. Heisner, Matthias L. Riess, Mohammed Aldakkak, and David F. Stowe. "Reduced mitochondrial Ca2+ loading and improved functional recovery after ischemia-reperfusion injury in old vs. young guinea pig hearts." American Journal of Physiology-Heart and Circulatory Physiology 302, no. 3 (February 2012): H855—H863. http://dx.doi.org/10.1152/ajpheart.00533.2011.

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Oxidative damage and impaired cytosolic Ca2+ concentration ([Ca2+]cyto) handling are associated with mitochondrial [Ca2+] ([Ca2+]mito) overload and depressed functional recovery after cardiac ischemia-reperfusion (I/R) injury. We hypothesized that hearts from old guinea pigs would demonstrate impaired [Ca2+]mito handling, poor functional recovery, and a more oxidized state after I/R injury compared with hearts from young guinea pigs. Hearts from young (∼4 wk) and old (>52 wk) guinea pigs were isolated and perfused with Krebs-Ringer solution (2.1 mM Ca2+ concentration at 37°C). Left ventricular pressure (LVP, mmHg) was measured with a balloon, and NADH, [Ca2+]mito (nM), and [Ca2+]cyto (nM) were measured by fluorescence with a fiber optic probe placed against the left ventricular free wall. After baseline (BL) measurements, hearts were subjected to 30 min global ischemia and 120 min reperfusion (REP). In old vs. young hearts we found: 1) percent infarct size was lower (27 ± 9 vs. 57 ± 2); 2) developed LVP (systolic-diastolic) was higher at 10 min (57 ± 11 vs. 29 ± 2) and 60 min (55 ± 10 vs. 32 ± 2) REP; 3) diastolic LVP was lower at 10 and 60 min REP (6 ± 3 vs. 29 ± 4 and 3 ± 3 vs. 21 ± 4 mmHg); 4) mean [Ca2+]cyto was higher during ischemia (837 ± 39 vs. 541 ± 39), but [Ca2+]mito was lower (545 ± 62 vs. 975 ± 38); 5) [Ca2+]mito was lower at 10 and 60 min REP (129 ± 2 vs. 293 ± 23 and 122 ± 2 vs. 234 ± 15); 6) reduced inotropic responses to dopamine and digoxin; and 7) NADH was elevated during ischemia in both groups and lower than BL during REP. Contrary to our stated hypotheses, old hearts showed reduced [Ca2+]mito, decreased infarction, and improved basal mechanical function after I/R injury compared with young hearts; no differences were noted in redox state due to age. In this model, aging-associated protection may be linked to limited [Ca2+]mito loading after I/R injury despite higher [Ca2+]cyto load during ischemia in old vs. young hearts.

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Beilin, Elaine V. "Elizabeth Cooke Hoby Russell. The Writings of an English Sappho. Ed., Patricia Phillippy. Trans. Jaime Goodrich. The Other Voice in Early Modern Europe: The Toronto Series, 14. Toronto: Iter Inc. and Centre for Reformation and Renaissance Studies, 2011. xvi + 541 pp. $37. ISBN: 978–0–7727–2112–9." Renaissance Quarterly 65, no. 3 (2012): 1014–15. http://dx.doi.org/10.1086/668398.

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Wibring, Kristoffer, Johan Herlitz, Markus Lingman, and Angela Bång. "PP13 Predicting high-risk conditions among ems patients with chest pain." Emergency Medicine Journal 37, no. 10 (September 25, 2020): e7-e7. http://dx.doi.org/10.1136/emermed-2020-999abs.13.

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BackgroundChest pain is a common cause for contacting the EMS, representing 10–15% of all EMS missions. Within this group only 15% suffer from a high-risk condition. It is an important, but challenging, task to identify these patients in need of prompt hospital care.ObjectiveTo identify prehospital predictors of high-risk conditions among EMS patients with chest pain.MethodsWe prospectively included 2917 consecutive EMS missions concerning patients with chest pain. Data regarding, medical history, symptoms, vital parameters and troponin were collected. All patients were classified as having high-risk condition or not. High-risk condition was defined as a time-sensitive diagnose with high mortality rates in need of immediate care (based on diagnose on hospital discharge).ResultsIn total 16% of included missions concerned a patient with a high-risk condition. In total 24 factors showed significantly increased odds of having a high-risk condition (table 1). Several factors also predicted lowered odds of high-risk condition.Abstract PP13 Table 1Factors predicting high-risk conditions, sorted by confidence interval (CI)Total with variable% (n)Patients with high-risk condition% (n)Patients without high-risk condition% (n)High-risk vs without high-risk, p-value*Odds RatioCI 95%All 100.0 (2917) 16.0 (467) 84.0 (2450) - - - ECG - ST-Elevation 6.1 (164) 22.9 (102) 2.8 (62) < 0.001 8.337 5.520–12.593 Prehospital Troponin T >50 ng/L 11.2 (168) 35.2 (90) 6.3 (78) < 0.001 6.382 4.469–9.115 ECG - ST-Depression 7.6 (204) 23.8 (106) 4.4 (98) < 0.001 4.629 3.225–6.646 Age ≥65 years 65.2 (1902) 76.7 (358) 63.0 (1544) < 0.001 3.866 2.608–5.740 NRS ≥9 5.1 (127) 10.0 (41) 4.1 (86) < 0.001 3.245 2.169–4.854 Pain in right arm 8.4 (145) 16.4 (48) 6.8 (97) < 0.001 2.886 1.967–4.235 Pale 16.4 (386) 29.1 (111) 14.0 (275) < 0.001 2.411 1.858–3.128 Age 51–64 years 18.5 (539) 17.1 (80) 18.7 (459) < 0.001 2.780 1.779–4.344 Male sex 50.2 (1465) 63.8 (298) 47.6 (1167) < 0.001 2.090 1.699–2.573 Debut during activity 22.1 (479) 32.8 (116) 20.0 (363) < 0.001 2.113 1.632–2.735 Pain between scapulars 2.2 (37) 4.1 (12) 1.8 (25) 0.003 2.980 1.449–6.132 Pain in left arm 24.0 (412) 33.6 (98) 22.0 (314) < 0.001 1.861 1.406–2.462 Central pain 53.4 (1215) 64.5 (240) 51.2 (975) < 0.001 1.746 1.381–2.207 NRS ≥6 32.1 (803) 38.9 (159) 30.8 (644) < 0.001 1.607 1.283–2.014 Constant pain 55.5 (1212) 61.8 (235) 49.9 (977) < 0.001 1.625 1.277–2.068 Clammy 8.7 (204) 14.4 (55) 7.6 (149) < 0.001 1.512 1.275–1.794 Pain in jaw 5.3 (92) 7.5 (22) 4.9 (70) 0.014 1.907 1.142–3.184 Breathing rate ≥25 breaths/min 10.2 (297) 14.7 (68) 9.4 (229) 0.007 1.505 1.118–2.026 Band-shaped pain 3.3 (58) 5.2 (15) 3.0 (43) 0.031 1.974 1.064–3.662 Quick debut, within minutes 35.2 (718) 42.7 (149) 33.6 (569) 0.004 1.194 1.059–1.346 ECG - Premature Atrial Contractions, PAC 3.5 (94) 6.1 (27) 3.0 (67) 0.034 1.799 1.046–3.095 Pain in right shoulder 4.2 (72) 6.2 (18) 3.8 (54) 0.035 1.830 1.042–3.213 Oxygen saturation ≤91% 3.8 (110) 6.4 (30) 3.3 (80) 0.046 1.571 1.007–2.452 ECG - T-wave Inversion 14.5 (388) 22.7 (101) 12.8 (287) 0.046 1.412 1.007–1.980 *Logistic regression, adjusted for age and sexConclusionsSeveral factors available in the prehospital setting seem to be suitable for risk assessment of patients with chest pain. Combing these factors in a scoring tool might be a feasible way to improve prehospital risk assessment.

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Vlachopoulos, D., A. R. Barker, C. A. Williams, and L. Gracia-Marco. "How Different Loading Sports and a 9-Month Plyometric Intervention Programme Affect Bone Turnover Markers During Adolescence: The PRO-BONE Study." Proceedings 25, no. 1 (September 20, 2019): 38. http://dx.doi.org/10.3390/proceedings2019025038.

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Aim: The purpose of the present study was to (1) investigate the cross-sectional (baseline) and longitudinal (12 months) effects of football (weight-bearing sport), swimming and cycling (non-weight-bearing sports), and an active control group on bone turnover markers in adolescent males and (2) examine the effect of a 9-month progressive jumping intervention programme on bone turnover in the sports groups of adolescent males. Materials & Methods: A total of 105 adolescent males (30 footballers, 37 swimmers, 26 cyclists, and 12 active controls), aged 12 to 14 years at baseline, were measured at baseline (T0), after 1 year of sport-specific training (T1) and following a 9-month progressive jumping intervention programme (T2). Bone turnover was measured using serum N-terminal propeptide of procollagen type I (PINP) as bone formation marker and isomer of the carboxy-terminal telopeptide of type 1 collagen (CTX-I) as bone resorption marker. Bone turnover rate and balance were estimated using the multiple of medians logarithmic equations of PINP and CTX-I. Results: At T0 there were no significant differences between groups in any of the biochemical markers. At T1 PINP was significantly higher in footballers than swimmers (3.3%) and cyclists (6.0%). Cyclists had significantly lower PINP (5.1%) and CTX-I (14.8%) than controls. In swimmers, there was a significant decrease in PINP (5.8%) and a significant increase in CTX-I (9.8%) from T0 to T1. In cyclists, PINP significantly decreased (7.2%) and CTX-I non-significantly increased (4.3%) from T0 to T1. At T2, PINP was reduced in all non-intervention sport groups (4.4% in swimmers, 3.3% in footballers, and 4.2% in cyclists). CTX-I was reduced by 3.8% in swimmers and cyclists who did not perform the intervention. Conclusions: The present study showed that at baseline there were no differences between groups in bone turnover, but after 1 year of sport-specific training bone turnover was significantly improved in footballers and controls compared to swimmers and cyclists. Following the 9-month jumping intervention bone turnover significant declined in the intervention groups of cycling and swimming. By contrast, bone formation significantly decreased in footballers and the control groups, and bone resorption significantly decreased in the non-intervention groups of cycling and swimming.

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Mahajan, V. "Lymphadenectomy in carcinoma stomach: Experience from a regional cancer centre." Journal of Clinical Oncology 24, no. 18_suppl (June 20, 2006): 14121. http://dx.doi.org/10.1200/jco.2006.24.18_suppl.14121.

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14121 Background: Carcinoma stomach is the most common cancer in males in chennai city. Lot of controversy exists regarding the need for extended lymphadenectomy because of the morbidity and mortality associated. Methods: A retrospective analysis was done to assess the benefit of extended lymphadenectomy. The records of all the patients operated at Cancer Institute from 1991 to 2004 were analysed. Out of 5050 cases of carcinoma stomach seen, only 570 cases were taken up for some form of treatment. 400 cases underwent resection, of which 366 patients records were retreived from the tumor registry for analysis. Followup ranged from 1 year to 10 years. Results: Male to female ratio was 3:1, most patients were in 40 - 60 year age group (60%). 60% patients had antral tumors and the rest were evenly distributed. 79 patients (21%) underwent conventional gastrectomy (D1), 243 patients (66%) underwent extended lymphadenectomy and 44 patients (12%)underwent palliative gastrectomy. 280 patients underwent subtotal gastrectomy, 54 patients total gastrectomy, 28 esophago gastrectomy and 5 had transhiatal esophagectomies. Stage wise distribution was IA 4.9%, IB 9.8%, II 21%, IIIA 29.4%, IIIB 12.8%, IV 22.1%. The total number of nodes dissected in the Extended nodal dissection group was less than or equal to 15 in 12% patients, 15 to 30 nodes in 48% patients and >30 nodes in 40% patients. 72% patients had node positive disease. Overall Survival at 5years was 38.9% for all the cases. 5year ovarall survival for conventional gastrectomy group was 37% and was 48% for the extended lymphadenectomy group which was statistically significant(p =0.06) .On substratification for T status and stage, the difference in survival between conventional and extended lymphadenectomy arms was not found to be significant.However,there was a trend towards improved survival in the lymphadenectomy arm.There were 7 post operative deaths in the lymphadenectomy arm,5 of which were in the first year of starting extended lymphadenectomies, which points to the learning curve for these procedures. Conclusions: Larger trials may be required to prove the advantage of extended lymphadenectomies in Gastric cancer. In addition neoadjuvant chemotherapy and Intraoperative radiotherapy may need to be studied to improve survival in gastric cancer. No significant financial relationships to disclose.

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Saridaki, Z., M. Tzardi, C. Papadaki, M. Sfakianaki, F. Pega, A. Kalikaki, E. Tsakalaki, D. Mavroudis, V. Georgoulias, and I. Sougklakos. "Impact of KRAS, BRAF, and PIK3CA mutations, PTEN, AREG, and EREG expression, and skin rash in metastatic colorectal cancer patients treated with cetuximab-containing salvage treatment." Journal of Clinical Oncology 29, no. 4_suppl (February 1, 2011): 445. http://dx.doi.org/10.1200/jco.2011.29.4_suppl.445.

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445 Background: To investigate the predictive significance of KRAS exon 2, BRAF V600E, PIK3CA exon 9 and 20 mutational status, AREG- EREG mRNA expression, PTEN protein expression and skin rash in patients with metastatic colorectal cancer (mCRC) treated with cetuximab containing salvage chemotherapy. Methods: Primary tumors from 112 mCRC patients were analyzed. The worst skin toxicity during treatment was recorded. Results: KRAS, BRAF and PIK3CA mutations were present in 37 (33%), 8 (7.2%) and 11 (9.8%) cases, respectively, PTEN was lost in 21 (19.8%) cases, AREG and EREG were overexpressed in 48 (45%) and 51 (49%) cases. In the whole study population, time to tumor progression (TTP) and overall survival (OS) was significantly lower in patients with KRAS (p=0.001 and p=0.026, respectively) or BRAF (p=0.001 and p<0.0001, respectively) mutant tumors, downregulation of AREG (p=0.018 and p=0.013, respectively) or EREG (p=0.002 and p=0.004, respectively) and in those with grade 0-1 skin rash (p<0.0001 and p<0.0001, respectively). In KRAS wt patients TTP and OS was significantly lower in patients with BRAF (p=0.0001 and p<0.0001, respectively) mutant tumors, downregulation of AREG (p=0.021 and p=0.004, respectively) or EREG (p=0.0001 and p<0.0001, respectively) and grade 0-1 skin rash (p<0.0001 and p<0.0001, respectively). TTP was significantly lower in patients with PIK3CA mutations (p=0.01) or lost PTEN (p=0.002). Multivariate analysis revealed KRAS (hazard ratio [HR] 4.3, p<0.0001), BRAF mutation (HR: 5.1, p<0.0001), EREG low mRNA expression (HR: 1.6, p=0.021) and absence of severe/moderate skin rash (HR: 4.0, p<0.0001) as independent prognostic factors for decreased TTP. Similarly, KRAS (HR 2.9, p=0.01), BRAF mutation (HR: 3.0, p=0.001), EREG low mRNA expression (HR: 1.7, p=0.021), absecence of severe/moderate skin rash (HR: 3.7, p<0.0001) and the presence of undifferantited tumours (HR: 2.2, p=0.001) were revealed as independent prognostic factors for decreased OS. Conclusions: These results underscore the potential of advanced CRCs genetic profiling in order to identify patients with different treatment response. No significant financial relationships to disclose.

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Khan, Saad A., Maneka Puligandla, Suzanne Eleanor Dahlberg, Gregory A. Masters, Corey J. Langer, Julie R. Brahmer, Nasser H. Hanna, et al. "Impact of prior radiation on survival in metastatic lung cancer ECOG-ACRIN trials." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): 9051. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.9051.

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9051 Background: Up to 50% of advanced NSCLC patients receive radiation therapy at some point in their course. We sought to determine whether patients with prior radiation demonstrate altered outcomes on subsequent metastatic clinical trials. Methods: We reviewed 8 ECOG-ACRIN advanced non-small cell lung cancer studies conducted between 1993 and 2011 in which information was collected about receipt of prior radiation. Whether radiotherapy was given with curative or palliative intent, or to specific sites was not recorded. Median follow-up among all trials was 66 months. We used the log-rank, Wilcoxon and Fisher’s exact tests to compare patients, and Cox Model and Kaplan-Meier method to calculate survival. Results: 574/3041 (18.9%) patients had received prior radiation. These patients were more likely to be male (64% vs 58%), have squamous histology (20% vs 14%) and have had prior surgery (48% vs 33%) compared to those with no prior radiation. At registration, prior radiation patients were more likely to have an ECOG PS of 1 (66% vs 58%), while they were less likely to have a PS of 0 (24% vs 36%) or have a pleural effusion (23% vs 37%). Patients who received radiation were more likely to have been registered on to studies between 1993-1999 than 2000-2011 (69% vs 31%) (all p < 0.001). Median Overall Survival (OS) for patients with prior radiation was 7.6 months (range 7-8.3) vs 9.5 (9.1-9.8) for those without (p < 0.001). Median Progression Free Survival (PFS) for those with prior radiation was 3.5 months (3-3.9) vs 4.2 (4.1-4.4) for those without (p < 0.001). In multivariable analysis controlling for stage IIIB/IV, sex, PS, histology, and prior surgery, the impact of prior radiation on overall survival remained significant (p = 0.042, HR (95% CI) = 1.11 (1.00, 1.22)). Conclusions: Almost one-fifth of lung cancer patients on systemic therapy trials for advanced disease previously received radiation. They are more likely to be male, have squamous histology, have an ECOG PS of 1 and have had prior surgery. Prior radiation is significantly associated with inferior OS and PFS. For advanced NSCLC clinical trials, documentation of whether curative intent/palliative intent radiation was given and stratification by prior radiation exposure should be considered.

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Hummler, Madeleine. "Children - Mary E. Lewis The Bioarchaeology of Children: Perspectives from Biological and Forensic Anthropology. x+256 pages, 37 illustrations, 15 tables. 2006. Cambridge: Cambridge University Press; 978-0-521-83602-9 hardback £70 & $130. - Traci Ardren & Scott R. Hutson (ed.). The Social Experience of Childhood in Ancient Mesoamerica. xxii+310 pages, 73 illustrations, 11 tables. 2006. Boulder (CO): University Press of Colorado; 978-0-87081-827-1 hardback $45." Antiquity 81, no. 313 (September 1, 2007): 818–19. http://dx.doi.org/10.1017/s0003598x00095922.

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Klepin, Heidi D., Leslie Renee Ellis, Denise Levitan, and Bayard Powell. "Feasibility of Inpatient Geriatric Assessment for Older Adults with Newly Diagnosed Acute Myelogenous Leukemia." Blood 112, no. 11 (November 16, 2008): 3996. http://dx.doi.org/10.1182/blood.v112.11.3996.3996.

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Abstract Background: Acute myelogenous leukemia (AML) is a disease which largely affects older adults, for whom optimal therapy is unclear. Evidence based strategies are lacking to identify those older adults who may tolerate and benefit from standard therapies. Objective: Test the feasibility of pre-treatment, inpatient geriatric assessment (GA) in older adults hospitalized with newly diagnosed AML. Methods: Prospective evaluation of consecutive patients ≥60 years of age with newly diagnosed AML and planned induction chemotherapy admitted to a single institution from 6/2007–6/2008. Bedside GA was performed within 72 hours of diagnosis. In addition to demographics and routine labs, the GA measures obtained by a trained nurse included Mini-Mental Status Exam (MMSE), Center for Epidemiologic Studies Depression Scale (CES-D), Charlson Comorbidity Index (CCI), Vulnerable Elders Survey-13 (VES-13), Short Physical Performance Battery (SPPB, includes timed 4 meter walk, chair stands, standing balance), and grip strength. Measures to assess feasibility included: recruitment; time to complete the assessment, and proportion completing entire GA battery. Results: Among 22 eligible inpatients, 11 enrolled (50%). The median age was 71 (range 63–78) and 72.7% were female. Poor risk cytogenetics were present in 27.3%. Laboratory measures included white blood cell count (mean=24.6×103/mm3, SD 26.2×103), hemoglobin (mean=8.5 g/dl, SD 1.6), platelet count (mean=60.3×103/mm3, SD=38.4×103), lactate dehydrogenase (LDH) (mean=340.0 U/L, SD=235.1), and albumin (mean=3.2 g/dl, SD=0.36). 66.6% of participants completed the entire GA battery; the remainder completed only self-report measures. Mean time for completion of the GA was 36.8 minutes (SD 9.8). Mean scores for survey measures included: MMSE=26.1 (range 21–30, SD 3.2), CCI=1.6 (range 0–4, SD 1.1), CES-D=22.9 (range 8–37, SD 11.0), VES-13 survey=5.0 (range 1–8, SD 2.5). A wide range of objective physical performance was demonstrated including mean SPPB total score=7.4 (range 5–10; SD 2.1), mean timed 4 meter walk=12.9 seconds (range 6.6–22.1; SD 5.1), and mean grip strength=29.3 (range 12–62; SD 16.8). Conclusions: Inpatient GA including physical performance assessment is feasible in older adults hospitalized for AML and our preliminary findings demonstrate significant variability in cognitive, emotional and physical status. These measures may represent valuable candidate predictors of outcomes, and ongoing studies will identify which measures are most predictive of treatment morbidity and response.

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Di Giuseppe, D., H. Bower, B. Delcoigne, T. Frisell, K. Chatzidionysiou, U. Lindström, C. Sjowall, E. Lindqvist, and J. Askling. "POS0601 DIFFERENCES IN DRUG SURVIVAL BETWEEN ORIGINATOR AND BIOSIMILAR PRODUCTS AMONG FIRST USERS OF EACH MOLECULE." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 535.2–535. http://dx.doi.org/10.1136/annrheumdis-2021-eular.977.

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Background:Biosimilar products of biological disease-modifying antirheumatic drugs (bDMARDs) entered the Swedish market in 2015, with regulatory approvals based on head to head trials of limited duration. Longer-term comparative drug survival, in clinical practice, remains less well documented.Objectives:To compare survival on drug between biosimilars and their originator products among first starters of etanercept, infliximab, adalimumab and rituximab.Methods:Data from the Swedish Rheumatology Quality register (SRQ) was used to identify and follow patients who started a first ever treatment with etanercept since April 2015 (originator=ETA,biosimilar= SB4), infliximab since March 2014 (originator=IFX,biosimilar= CT-P13), adalimumab since January 2018 (originator=ADA biosimilars=SB5, ABP501), or rituximab since January 2018 (originator=RIT,biosimilar= GP2013), through December 31st, 2019, date of first discontinuation of the drug, or death. Discontinuation was defined as lack of effectiveness or adverse events, while other reasons for interruption of the drug (including non-medical switch) were considered censoring events. Descriptive characteristics were collected from the SRQ and tabulated. Hazard ratios (HR) of discontinuation were estimated using Cox regression, with each drug analyzed separately, adjusted for age,sex,indication,line of treatment,disease duration,year of treatment start,region and concomitant use of csDMARD.Results:9274 patients started etanercept(49% SB4), 3609 started infliximab(64% CT-P13), 3117 started adalimumab(27% SB5, 14% ABP 501), and 763 started rituximab(39% GP2013), Table 1. Patients starting CT-P13 and GP2013 were less likely to be biologics-naïve compared to those starting the originator product. Initiators of SB5,ABP501 and GP2013 were more likely,and those starting CT-P13 were less likely,to be on concomitant csDMARDs compared to those starting the originator products. Patients characteristics of ETA and SB4 were similar.The introduction of a biosimilar was typically followed by a decrease in the uptake of the originator, but for ETA a change in pricing in 2018 later led to a reversal of this pattern (Figure 1).For IFX,ADA,and RIT, survival on drug was similar for the originator and its biosimilar(s). For ETA,risk of discontinuation was somewhat lower for the biosimilar than for the originator(adjusted HR:0.87,95% confidence interval:0.79-0.95), Table 1.Table 1.Hazard ratios of discontinuation and descriptive characteristics of biosimilar vs. originator among first starters of each molecule, until 31st December 2019.EtanerceptInfliximabAdalimumabRituximabOriginatorSB4OriginatorCT-P13OriginatorSB5ABP 501OriginatorGP2013N47214553130823011834852431465298Discontinuation12891236582878399139805726Adjusted hazard ratios*Ref0.87 (0.79-0.95)Ref1.14 (0.99-1.31)Ref1.02 (0.83-1.26)1.16 (0.88-1.52)Ref1.12 (0.68-1.85)Age, mean years (std)51 (16)51 (15)49 (16)49 (16)48 (15)52 (15)51 (15)59 (15)60 (15)Female, %67%65%61%64%62%64%65%75%76%RA, %46%48%39%35%33%42%43%61%76%Bionaïve, %72%72%76%69%45%52%43%53%38%Disease duration, mean years (std)11 (12)11 (11)11 (11)11 (11)12 (13)12 (11)14 (15)14 (19)15 (11)DAS28, mean4.0 (1.3)4.0 (1.4)4.1 (1.4)4.1 (1.4)3.7 (1.4)3.8 (1.3)4.0 (1.3)4.5 (1.4)4.7 (1.4)Concomitant csDMARDs, %45%47%57%48%37%49%42%36%43%Abbreviations: RA=rheumatoid arthritis. csDMARDs=conventional synthetic DMARD, std=standard deviation.Figure 1.Number of starts of biosimilars compared to the originator during the follow-up time, by moleculeConclusion:Despite their identical indications and therapeutic positioning, there are some differences in the baseline characteristics between patients who start ADA, IFX and RIT and their biosimilars. There are no differences in drug survival between originator and biosimilar with the possible exception of etanercept although the observed difference should be interpreted in light of possible unmeasured or residual channeling.Disclosure of Interests:Daniela Di Giuseppe: None declared, Hannah Bower: None declared, Bénédicte Delcoigne: None declared, Thomas Frisell: None declared, Katerina Chatzidionysiou Consultant of: Eli Lilly, AbbVie and Pfizer, Ulf Lindström: None declared, Christopher Sjowall: None declared, Elisabet Lindqvist: None declared, Johan Askling Grant/research support from: Abbvie, Astra-Zeneca, BMS, Eli Lilly, MSD, Pfizer, Roche, Samsung Bioepis, Sanofi, and UCB,

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Begna, Kebede H., Amro Abdelatif, Susan M. Schwager, Curtis A. Hanson, Animesh Pardanani, and Ayalew Tefferi. "Busulfan for the Treatment of Myeloproliferative Neoplasms: The Mayo Clinic Experience." Blood 126, no. 23 (December 3, 2015): 4078. http://dx.doi.org/10.1182/blood.v126.23.4078.4078.

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Abstract Background: The cytoreductive treatment options for myeloproliferative neoplasms, in those who have indications, may be limited to hydroxyurea and interferon. Busulfan has been reported to have some activity, but used less frequently in the management of BCR/ABL negative MPNs (Haanen CM et al Br J Cancer 1981; Brodsky American J of clinical oncology 1998). One study has shown significant JAK2V617F allele burden reduction with busulfan (Kuriakose ET et al; Haematologica 2013). Ruxolitinib was approved by the FDA for intermediate and high risk myelofibrosis; and as second line therapy for polycythemia vera in those who are intolerant or develop side effect to hydroxyurea. Objective: To assess the utility of busulfan, an old drug, in patients with myeloproliferative neoplasms who are intolerant to other forms of therapy. Methods: The mayo clinic data base from 1970 to 2014 was interrogated using the terms myeloproliferative disorder, polycythemia vera (PV), essential thrombocythemia (ET), myelofibrosis (MF) and busulfan. Patients' follow up information was collected till July 2015. Results : Seventy five patients with full demographic, diagnostic and therapeutic information were identified, and those included 37 patients with ET, 22 with PV, 12 with MF, and 4 with myeloproliferative neoplasms unclassifiable. The median age was 64 (range 31-91) years. After a median follow up of 17 years, 40 patients (53 %) died, and leukemic transformation was documented in 4 (5%). The median time for leukemic transformation was 86 months (12-229). 1. Essential Thrombocytopenia (n=37): Twenty nine (79%) were females, and the median (range) age was 67 (33-90) years. At diagnosis the median (range) hemoglobin (Hgb) (gm/dL), white blood cell count (WBC) (X109/L), and platelet count (X109/L) were 13.6 (9.8-16.9), 10.2 (5-231), 1113 (593-2062) respectively. After a median follow up time of 230 months, 15 patients (41%) died, and leukemic transformation was documented in 1 patient who was also treated with radioactive phosphorous (P32). Leukemic transformation was documented 230 months from date of diagnosis. Follow up complete blood count was available in 20 patients and the median (range) Hgb, WBC and platelet count was 12 (9.9-16), 7.4 (3.1-25), and 267 (126-573) respectively. 2. Polycythemia Vera (n=22): Fourteen (61%) were females, and the median (range) age was 64 (46-91) years. At diagnosis the median (range) Hgb, WBC, and platelet count were 17.5 (15.1-20.8), 11.5 (1.2-26.6), and 669 (185-2370) respectively. After a median follow up time of 188 months 13 (57%) patients died, and leukemic transformation was documented in 2 patients and one of them was given P32. Follow up complete blood count was available in 21 patients and their median (range) Hgb, WBC and platelet count was 12.9 (10-15.2), 7.2 (2.8-20), and 303 (124-833) respectively. 3. Myelofibrosis (Primary and Post-PV and Post-ET myelofibrosis) (n=12) : The median age was 52 (31-75) and 5 were females. The median Hgb, WBC, and platelet count were 13.6, 14.5, and 472. Six (50 %) patients did have splenomegaly (and 5 of them have splenic size reduction after busulfan), 3 underwent splenectomy, and 3 have no palpable spleen. At a median follow up of 208 months, and 39 months (range 78-401) from the start of busulfan, 10 (84%) patients died and no leukemic transformation was documented. Conclusion: Busulfan should be considered as alternative therapy in myeloproliferative neoplasms especially in ET and PV that are intolerant to other forms of cytoreductive therapy. Busulfan may be given as pulse therapy in controlling cell counts. Disclosures Off Label Use: Busulfan as alternative therapy in myeloproliferative neoplasms.

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Strangfeld, A., B. Manger, M. Worsch, T. Schmeiser, A. Zink, and M. Schaefer. "OP0116 ELDERLY PATIENTS ARE NOT AT INCREASED RISK OF SERIOUS INFECTIONS WHEN RECEIVING BDMARDS OR JAK INHIBITORS COMPARED TO CSDMARD TREATMENT." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 64.2–65. http://dx.doi.org/10.1136/annrheumdis-2021-eular.763.

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Background:Elderly rheumatoid arthritis (RA) patients are generally at increased risk of serious infections (SI). At the same time, treatment with bDMARDs has been associated with a higher SI risk than treatment with csDMARDs (1). However, long-term use of bDMARDs did not increase the risk of SI in a small group of elderly patients over 65 (2). The extent to which elderly patients are exposed to a higher SI risk when treated with JAK inhibitors (JAKi) is an open question.Objectives:To assess the effects of bDMARDs and specifically JAKi on the risk of SI in elderly patients with RA.Methods:The German register RABBIT is a prospective, longitudinally followed cohort of RA patients enrolled with a new start of a DMARD after at least one csDMARD failure. This analysis comprises patients over 70 years of age who were enrolled between 01/2007 and 04/2020 and had at least one follow-up.Results:Of 13,491 patients followed-up in RABBIT, 2274 with an age > 70 years were included in the analysis. 626 SI were observed in 425 of these patients. Baseline characteristics at start of the respective DMARD are shown in Table 1. In most characteristics, patients on JAKi were more comparable to patients under bDMARDs than to those on csDMARDs. JAKi patients received glucocorticoids (GC) less frequently than patients on other treatments. The HR for SI was lower than 1 in patients receiving bDMARDs or JAKi compared to csDMARDs, but without statistical significance (Figure 1). GC use (HR 1.6, 95% CI: 1.2 – 2.2 for ≤ 10 mg/d), higher DAS28-ESR values (HR 1.1, 95% CI: 1.0 – 1.2 per 1 point increase), COPD or pulmonary fibrosis (HR 1. 8, 95% CI: 1.3 – 2.4), chronic kidney disease (HR 1.5, 95% CI: 1.2 – 1.9) and diabetes mellitus (HR 1.3, 95% CI: 1.0 – 1.7) were associated with an increased risk of SI. Better physical capacity was associated with a decreased risk of SI (HR 0.9, 95% CI: 0.88 – 0.98 for a 10 point increase).Table 1.Patient characteristics by treatment at baselineParametercsDMARDsTNFiRTXABAIL-6iJAKiN=758N=840N=209N=147N=212N=108Age (years)75.9 (3.9)75.5 (3.6)74.8 (3.6)76.1 (3.9)75.9 (3.7)76.7 (3.7)Male sex184 (24.3)220 (26.2)50 (23.9)36 (24.5)46 (21.7)28 (25.9)Ever smoker249 (32.8)287 (34.2)77 (36.8)50 (34)73 (34.4)39 (36.1)Disease duration (years)7.9 (8.8)12.3 (11.4)17 (11.1)12.8 (10)13.8 (11.7)11.9 (10.9)Seropositivity487 (64.3)671 (79.9)201 (96.2)126 (85.4)182 (85.8)79 (73.5)Number of previous DMARDs1.4 (0.7)2.5 (1.3)4.2 (1.8)3.6 (1.9)3.3 (1.8)2.6 (1.5)DAS28-ESR4.6 (1.2)5.1 (1.2)5.4 (1.3)5.3 (1.3)5.3 (1.3)5 (1.2)Proportion of full physical function64.8 (23.1)57.1 (23.6)50.4 (23.7)52.9 (23.5)55.3 (24.1)55.2 (23.7)Number of comorbidities3.1 (2.5)3.8 (2.6)4.2 (2.6)4.6 (2.9)3.6 (2.4)3.8 (2.2)No comorbidity52 (6.9)29 (3.5)4 (1.9)4 (2.7)9 (4.2)5 (4.6)Three and more comorbidities385 (50.8)528 (62.9)147 (70.3)107 (72.8)131 (61.8)76 (70.4)COPD or pulmonary fibrosis69 (9.1)89 (10.6)29 (13.9)26 (17.7)12 (5.7)11 (10.2)Chronic kidney disease94 (12.4)151 (18)28 (13.4)21 (14.3)39 (18.4)22 (20.4)Diabetes mellitus151 (19.9)172 (20.5)31 (14.8)23 (15.6)42 (19.8)25 (23.1)GCs (last 6 months)347 (45.8)526 (62.6)143 (68.8)82 (56.2)127 (59.9)44 (40.7)GCs (<5mg)447 (58.9)384 (45.7)101 (48.2)88 (60)118 (55.8)72 (66.7)GCs (5-9mg)252 (33.3)375 (44.6)81 (38.7)43 (29)72 (34.2)27 (25.1)GCs (>=10mg)59 (7.8)82 (9.8)274 (13.1)16 (11)21 (10)9 (8.2)Results are presented as mean ± SD for continuous variables and number (percentage) for discrete variables.Figure 1.Hazard ratios for serious infections with 95% confidence intervalsConclusion:Treatment with JAKi as well as treatment with bDMARDs was not associated with an increased risk of SI in elderly patients above 70 years of age. Key comorbidities such as diabetes mellitus, chronic pulmonary and kidney diseases were associated with increased risk, as was concomitant GC use and higher disease activity.References:[1] Listing J et al., Rheumatology 2013; 52 (1): 53-61.[2] Kawashima H. et al., Rheum. Intern. 2017; 37: 369-376.Acknowledgements:RABBIT is supported by a joint, unconditional grant from AbbVie, Amgen, BMS, Celltrion, Fresenius-Kabi, Gilead, Hexal, Lilly, MSD, Pfizer, Roche, Samsung Bioepis, Sanofi-Aventis, UCB, and Viatris.Disclosure of Interests:None declared

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Chiassai, Silvia, Claudia Francalanci, Fabio Ferretti, and Rosalba Mattei. "Presenza di una possibile correlazione tra la scelta del corso di laurea e un pre-esistente o probabile rischio di DCA." RIVISTA DI PSICOTERAPIA RELAZIONALE, no. 27 (March 2009): 63–77. http://dx.doi.org/10.3280/pr2008-027004.

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- In the last years, in the occidental world, was developed an increase of the incidence in behavioural eating disorders, mostly by young people with a middle-high social status. There are many studies based on the nutritional habitudes of the adolescent, but we know less things about an eventually correlation between the eating disorder and the decision to follow an particular university course. Our purpose is to extend the pilot study made in the academic year 2005/2006 based on the questionnaire EDI-2 completed by the students that follows the University for Nutrition (I-II-III year of study), Obstetrician, Dental Hygienists, Sanitary Assistant, to valuate if the selection of the courses could be influenced by an pre-existent attitude more or less pathologic towards the food. The study was represented during the academic year 2006/2007, with the new students from the same courses. The considerable extension of the sample has permitted to obtain significant statistical results. The study is based on the test EDI-2 completed by the students between 16 and 49 years: 224 students, 187 females and 37 males (middle age 22,08 ds 4,72) The test EDI-2 (Eating disorder inventory-2) is the first and probably the most utilized method for individualizing the nutritional disorders, which can be utilized up the age of 11. The test are composed of 91 items, the first 64 represent the 8 primary scores while the last 27 represent the 3 additionals scores. The analysis of the dates shows that the nutritionists presents significant high scores in many scales. They have in particular important problems in the scale of bulimia compared with the other students. Comparing the scores M vs F, shows that sex can be an element which can influence the probability to be on risk or to present a behavioural eating disorder. Particular, the females shows high scores compared to the males on the scale Drive for thinnes (F=6,12; M=1,11). In the entire sample of study, the percents of female on risk is higher compared to the males, with higher values mostly in the scale Drive for thinnes (P<0.000; FM=5,7 vs MM=2,5), and in Body Dissatisfaction (P<0.000; FM=9,8 vs MM=5,1). Based on the results, it can be supposed that the choice of the course in nutrition is, for many students, conditioned by the pre-existent problematic rapport with the food. In particular it seems a higher probability among students following an Academic Nutrition course to have some bulimic problems, with a higher risk in the female group. Key words: behavioural eating disorders, mental anorexia, mental bulimia, binge eating disorders, university course, Eating Disorder Inventory-2.

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Ibarguengoitia, O., I. Calvo, D. Montero, L. Vega, C. García, O. Fernandez, I. Torre, et al. "AB0151 FOLLOW-UP IN A MULTIDISCIPLINARY UNIT IMPROVES PREGNANCY OUTCOME IN INFLAMMATORY ARTHROPATIES ON BIOLOGICAL THERAPY." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 1103.2–1103. http://dx.doi.org/10.1136/annrheumdis-2021-eular.715.

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Background:Women with inflammatory arthropaties have fertility problems and complications during pregnancy and frequently biological therapy (BT) is required for the disease control.Objectives:To evaluate pregnancy in women with inflammatory arthropaties in a multidisciplinary unit composed of Rheumatologists and Obstetricians: describe disease evolution, complications and treatment used (including BT).Methods:Retrospective and descriptive study of the evolution of pregnancy in patients withinflammatory diseases (Rheumatoid Arthritis (RA), Spondyloarthritis (SpA) and Juvenile Idiopathic Arthritis (JIA)) and follow-up in a multidisciplinary unit for more than 15 years (until December 2020). Demographics, maternal disease, time until conception, previous abortions and presence of antibodies were collected. In addition, during follow-up, treatment, abortions, Caesarean sections (C-section), preterm births, disease activity and maternal/fetal complications were collected.Results:We registered 41 pregnancies (32 women): 20 RA (62.5%), 9 SpA (28.1%) and 3 JIA (9.4%). Maternal average age at diagnosis was 27.1±6.6 years and average age at childbirth/abortion was 34.9±5.1 years.It took an average time of 9.6±8.5 months to conceive. 9.8% received fertility treatment with in vitro fertilization techniques.AntiRo antibodies were registered in 7.3% of patients and 34.1% had at least 1 antiphospholipid antibody.At the time of gestational desire/gestation 17 women (12 RA, 4 SpA, 2 JIA) were receiving BT: 7 certolizumab (CZP), 7 adalimumab (ADA), 3 etanercept (ETN). 1 patient was being treated with baricitinib. Due to pregnancy, ADA was changed to CZP in 3 women and BT was stopped in 6 cases (3 ETN, 2 ADA, 1 CZP) as well as baricitinib. In 2 cases, ADA was stopped at week 17 of pregnancy (medical indication). Pregnancy was completed with BT (CZP) in 9 cases.9 abortions were registered prior to follow-up in the unit (0.28 abortions/mother) and 3 during follow-up (0.09 abortions/mother): 2 of them in women with CZP.C-section was performed in 26.8% of cases.Preterm birth (<37 weeks) happened in 9.7% (n: 4) of the pregnancies: 1 case in a woman with CZP.A total of 17 different fetal/maternal complications were registered during follow-up: 6 in the BT group (35.3%) compared to 11 (64.7%) in the group without BT, being Intrauterine Growth Restriction (IUGR) more frequent among women with BT. Infections were not more common in patients with BT. Complications are listed in Table 1.Table 1.COMPLICATIONSWITH BT (n, %) n: 11WITHOUT BT (n, %) n: 30IUGR3 (27.3%)1 (3.3%)LOW BIRTH WEIGHT2 (18.2%)2 (6.6%)INFECTION1 (9.1%)4 (13.3%)CHOLESTASIS0 (0%)2 (6.6%)PREECLAMPSIA0 (0%)1 (3.3%)DIABETES MELLITUS0 (0%)1 (3.3%)HIGH BLOOD PRESSURE0 (0%)0 (0%)NEPHROPATY0 (0%)0 (0%)NEONATAL LUPUS0 (0%)0 (0%)HEART BLOCK (0%)0 (0%)MALFORMATION0 (0%)0 (0%)HELLP SYNDROME0/0%)0 (0%)TOTAL6 (54.6%)11 (36.4%)Regarding concomitant treatment, low dose prednisone was used in 48.8% of pregnancies, hydroxychloroquine in 51.2%, sulfasalazine in 9.8% and acetylsalicylic acid in 51.2%. We didn´t find differences in the use of these treatments between the two groups.Median DAS28 among RA patients and available data was under 2.6 throughout pregnancy as well as previously and posteriorly. No differences in median DAS28 were found between women with BT and without BT. SpA patients had BASDAI lower than 4 in both groups during pregnancy and previously.Conclusion:In our series, as described in the literature, women with inflammatory arthropaties are older and are more likely to have preterm births compared to general population. Fewer abortions were registered during follow-up in the multidisciplinary unit. Appropriate disease control was maintained during pregnancy, also previously and afterwards. We registered more IUGR and low birth weight among women with BT but given the low number of patients with BT no statistically significant conclusions about complications can be drawn. Therefore, more studies among pregnant women with BT are necessary.Disclosure of Interests:None declared

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Anderlini, Paolo, Sandra Acholonu, Grace-Julia Okoroji, Sergio A. Giralt, Roy Jones, Chitra M. Hosing, Muzaffar H. Qazilbash, et al. "Donor Leukocyte Infusions (DLIs) for Recurrent Hodgkin Lymphoma (HL) Following Allogeneic Stem Cell Transplantation (allo-SCT): Ten-Year Experience at the M.D. Anderson Cancer Center." Blood 118, no. 21 (November 18, 2011): 4460. http://dx.doi.org/10.1182/blood.v118.21.4460.4460.

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Abstract Abstract 4460 Background: The role of DLIs in the management of recurrent HL following allo-SCT is not well established. Response rates in the 30–50% range have been reported (as high as 79% in a recent report), but their durability and impact on patient survival are not always clear (Peggs et al, BJH 2008; 143:468 and JCO 2011; 29: 971). We wish to update our initial report on this issue (Anderlini et al, BMT 2004; 34: 511). For more details on response criteria definitions, please refer to our original report. Patients and Methods: Between 1999 and 2010, 27 consecutive patients with relapsed/refractory HL following unmanipulated allo-SCT received a total of 55 DLIs as immunotherapy for treatment of progressive disease (PD). Their median age was 30 years (19–60; M/F 19/8), and 21/27 (78%) had a history of prior autologous SCT. Seventeen patients received more than one DLI (range 2–5). Seventeen had a matched sibling/parent donor and ten a matched unrelated donor. In all but two cases the conditioning regimen included fludarabine plus cyclophosphamide or melphalan plus/minus antithymocyte globulin. The median time to PD after allo-SCT was 5 months (range 1–21). In ten patients (37%) prior salvage chemotherapy was administered prior to at least one of their DLIs. The pre-DLI chimerism status was 2/27 mixed and 25/27 full donor. Results: Ten of 27 (37%) patients had a complete/partial response (CR/PR) following at least one of their DLIs. Six of 27 patients (22%) achieved CR/CRU (complete response, unknown), and four of 27(15%) achieved a PR. The median response duration was 7.5 months (range 0.5–20). Of all these ten responders, 100% developed graft-vs-host disease (GVHD) and half of them (50%) had received concomitant chemotherapy. Of the ten patients who received only one DLI, two (20%) had chemotherapy prior to their DLIs. One (10%) had a CRU and the other had stable disease (SD) (10%). Of the remaining eight that did not have chemo prior to DLI, 2 (20%) had CRU, 3 (30%) had PR, 2 (20%) had SD and 1 (10%) had PD. The median CD3+ cell dose administered was 49.8 × 10E6/ kg (range 0.05–285). GVHD developed (or flared) following the DLI in 45/55 cases (82%). After the DLI mixed chimerism (n=2) was converted to complete (or near-complete) donor chimerism. At the latest follow-up (March 2011), five patients (18%) are alive (two in CR). For these five survivors, the follow-up after the 1st DLI is 42 months (range 4–63). Four of them (80%) did not receive chemotherapy with their DLI(s), while one did. Twenty-two patients expired. Their median survival after the 1st DLI was 14 months (range 4–64). Causes of death included PD (n=15; 68%) and non-relapse mortality (n=7; 32%). Conclusions: Despite the limitations related to the small sample size, patient heterogeneity and concomitant chemotherapy administration, these data suggest that (a) DLIs for immunotherapy of recurrent HL following allo-SCT have significant (albeit not always durable) activity, and a subset of patients become long-term survivors (b) administration of multiple DLIs is feasible in selected patients (c) responses are associated with the development of GVHD (d) the role (if any) of concomitant chemotherapy is unclear and, lastly (e) PD remains the main cause of mortality following DLIs. The role of DLIs should be reassessed in the contest of new and effective agents now available in the salvage setting (SGN-35, panobinostat, etc). Disclosures: Off Label Use: Fludarabine, cyclophosphamide and melphalan as part of conditioning regimen for allogeneic stem cell transplantation.

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Rousselot, Philippe, Hyacinthe Johnson-Ansah, Françoise Huguet, Laurence Legros, Martine Escoffre-Barbe, Martine Gardembas, Pascale Cony-Makhoul, et al. "Personalized Daily Doses of Imatinib By Therapeutic Drug Monitoring Increase the Rates of Molecular Responses in Patients with Chronic Myeloid Leukemia. Final Results of the Randomized OPTIM Imatinib Study." Blood 126, no. 23 (December 3, 2015): 133. http://dx.doi.org/10.1182/blood.v126.23.133.133.

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Abstract Background Imatinib mesylate (IM) at 400 mg/d remains a standard for first line therapy in patients (pts) with newly diagnosed chronic phase CML (CP-CML). A sub analysis of the IRIS study (Larson et al. Blood, 2008) demonstrated that pts with high IM trough levels achieved higher rates of major molecular response (MMR). The level of 1000 ng/ml was established as the [C]min value threshold to predict molecular response (Picard et al. Blood, 2007). We conducted a randomized trial to evaluate the value of IM dose optimization based on the monitoring of [C]min levels in newly diagnosed CP-CML pts (OPTIM-imatinib trial, EudraCT number 2008-006854-17). Patients and Methods Pts diagnosed with CP- CML for less than 3 months, not previously treated or treated with IM for less than 3 months were eligible and treated with IM 400 mg/d. IM [C]min was determined by chromatography-tandem mass-mass spectrometry 15 days after enrollment. Pts with a [C]min < 1000 ng/ml were randomized between a dose-increase strategy aiming to reach the threshold of 1000 ng/ml (arm A1) versus standard IM management (arm A2). Pts with [C]min levels ≥1000 ng/ml were observed (arm A3). All pts were managed according to the ELN 2009 recommendations (amended with ELN 2013 recommendations). IM [C]min levels were assessed monthly in A1 and A2 and every 3 months in A3. BCR-ABLIS was assessed every 3 months. The primary end-point was MMR rates at 12 months. Results One hundred thirty nine pts were enrolled. Median follow-up was 31 months. Median age was 64y (25 to 88y), sex ratio (M/F) was 1.4 and Sokal score distribution was 21%, 41% and 38% for high, intermediate and low categories respectively, equally distributed in the 3 arms. In 6 pts the initial [C]min was not assessed (3 were intolerant and 3 declined the dosage). Thus 133 pts were studied. In 86 pts (65%), initial [C]min value was < 1000 ng/ml. These pts were randomized between A1 (43 pts) and A2 (43 pts). [C]min was ≥1000 ng/ml in the 47 remaining pts followed in A3. Table 1 shows the significant improvement of the median IM [C]min after dose adjustment in A1 (p<0.0001) as compared to standard management in A2. Correspondingly, IM daily dose increased in A1 (p<0.0001) to reach a mean value of 600 mg/d. In the experimental A1 arm, the distribution of IM doses at 12 months was 13% for 500 mg/d, 30% for 600 mg/d, 34% for 800 mg/d whereas 16% of the pts remained at 400 mg/d and 7% were dose decreased at 300 mg/d. During follow-up, a similar proportion of pts with AE was observed in A1 (58%) and A2 (51%). Eight SAE related to IM were equally distributed in A1, A2 and A3. Cumulative incidences of treatment discontinuation were comparable in the 3 arms (overall, 18.8% by 12 months and 34.1% by 24 months). Reasons for discontinuation were not similar in A1 and A2 with a trend for more treatment failures in A2 as compared to A1 (60% versus 18%, p=0.08). At 12 months, MMR was achieved in 27 out of 43 pts (63%; 95%CI 49-77) in A1 as compared to 16 out 43 pts (37%; 95%CI 23-51) in A2 (p=0,031). The rates of MMR were not statistically different between A1 and A3 (p=0.12). Conclusions Only 1/3 of pts on IM400 were correctly dosed and may not require systematic high dose IM. Two-thirds of the pts were not exposed enough to IM at standard dose and may benefit from individualized strategies. A tailored dose adjustment based on pharmacology resulted in higher MMR rate at 12 months (63% vs 37%), a magnitude in line with the results previously reported with second generation tyrosine kinase inhibitors or high dose IM front line. Our results may provide a strong rational to early personalize the use of IM and IM generic formulations in order to optimize the outcome for each patient. This study was supported by a grant from the French Department of Health (Programme Hospitalier de Recherche Clinique). Table 1. Median [C]min (ng/ml; (95% CI)) Initial Assessment M3 M6 M9 M12 A1 591; (508-654) 838; (746-922) 1001; (748-1261) 1062; (918-1221) 1013; (830-1277) A2 651; (558-797) 605; (487-786) 591; (517-722) 605; (460-720) 646; (576-894) A3 1314; (1199-1514) 1032; (899-1143) 1002; (784-1205) 935; (737-1073) 1000; (846-1098) Mean IM daily dose (mg/d; (95% CI)) Inclusion M3 M6 M9 M12 A1 400 538; (508-568) 611; (563-658) 607; (545-668) 600; (535-665) A2 400 395; (387-402) 392; (383-401) 391; (381-401) 391; (381-401) A3 400 400; (400-400) 398; (385-410) 389; (376-402) 382; (370-395) Disclosures Rousselot: BMS: Consultancy, Speakers Bureau; Novartis: Speakers Bureau; Pfizer: Consultancy. Johnson-Ansah:BMS: Speakers Bureau; Hybrigenics SA: Consultancy, Research Funding; Novartis: Consultancy, Speakers Bureau. Huguet:PFIZER: Consultancy, Speakers Bureau; ARIAD: Consultancy, Speakers Bureau; BMS: Consultancy, Speakers Bureau; Novartis: Consultancy, Research Funding. Legros:Novartis: Research Funding, Speakers Bureau; ARIAD: Speakers Bureau; BMS: Speakers Bureau. Gardembas:Novartis: Speakers Bureau. Coiteux:ARIAD: Speakers Bureau; BMS: Speakers Bureau; Novartis: Speakers Bureau. Deau:BMS: Honoraria. Mahon:ARIAD: Consultancy; Pfizer: Consultancy; Bristol-Myers Squibb: Consultancy, Honoraria; Novartis: Consultancy, Honoraria.

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Moorman, Anthony V., Christine J. Harrison, Sue M. Richards, Adele Fielding, Martin S. Tallman, Mark R. Litzow, Jacob M. Rowe, Anthony H. Goldstone, and Gordon W. Dewald. "Karyotype Is an Independent Prognostic Factor in Adult Acute Lymphoblastic Leukaemia (ALL): Analysis of Cytogenetic Data from 1,235 Patients on the Medical Research Council (MRC) UKALLXII /Eastern Cooperative Oncology Group (ECOG) 2993 Trial." Blood 106, no. 11 (November 16, 2005): 331. http://dx.doi.org/10.1182/blood.v106.11.331.331.

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Abstract Background: Pre-treatment cytogenetics is a known predictor of outcome in haematological malignancies. However, its value in adult ALL is generally limited to the presence of the Philadelphia (Ph) translocation; mostly due to the low incidence of other recurrent chromosomal abnormalities. Methods: Since 1993, cytogenetic data from patients enrolled on a joint MRC/ECOG trial have been collated and reviewed centrally in the UK and US. Karyotype data from patients registered before the Imatinib amendment were pooled using standard cytogenetic definitions and classification criteria. Results: A successful cytogenetic result was achieved in 938/1235 (76%) cases; while 297 (24%) failed with <20 normal metaphases analyzed. Patients were classified into the following mutually exclusive groups: t(9;22)(q34;q11) n=193(21%); t(4;11)(q21;q23) n=50(5%); other MLL translocations n=11(1%), t(8;14)(q24;q32) and variants n=14(1%); t(1;19)(q23;p13) n=23(2%); T cell receptor translocations n=35(4%); low hypodiploidy (30–39 chromosomes) /near triploidy n=23(2%); high hyperdiploidy n=83(9%); tetraploidy n=12(1%); complex karyotype (>=5 aberrations) n=48(5%); other abnormal n=255(27%); normal n=191(20%). MRC and ECOG patients showed similar cytogenetic distributions, except for t(9;22), which was significantly more prevalent in the ECOG cohort (27% v 18%, p<0.001). However, the incidence of t(9;22) increased with age and ECOG patients were significantly older. Overall, the 5 year event free survival (EFS) was 32% (95% CI 30%–35%) with a median follow-up time of 5.1 years and did not differ between the two cohorts. The EFS of t(9;22) patients [15% (11%–21%)] was significantly inferior compared with all other cases [36% (32%–39%)] (p<0.001) and was independent of age and white cell count (WCC). Univariate logrank analyses identified t(4;11) and high hyperdiploidy as indicators of poor and good prognosis, respectively, compared with other Ph negative cases, but neither was independent of age and WCC. Three subgroups were shown to have a significantly worse EFS compared to other Ph negative cases by logrank analyses after adjusting for age and WCC: t(8;14) 14% (2%–37%) v 36% (32%–40%) (p=0.01); low hypodiploidy 22% (8%–40%) v 36% (32%–40%) (p=0.02); complex karyotype 21% (10%–33%) v 32% (29%–35%) (p=0.005). Neither of the latter two subgroups were associated with other poor risk features such as age, WCC or failure to achieve a remission within 4 weeks. Conclusions: This is the largest cytogenetic dataset of adult ALL reported to date and demonstrates the importance of combining cohorts to increase the number of cases available for analysis. The observation that low hypodiploidy and, for the first time, karyotype complexity confer a poor risk, demonstrates that cytogenetic subgroups other than the Ph translocation can and should be used to risk stratify adults with ALL to alternative treatments.

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Pascal, Laurent, Odile Beyne Rauzy, Sabine Brechignac, Dominique Vassilieff, Olivier Ernst, Céline Berthon, Emmanuel Gyan, Francois Dreyfus, Pierre Fenaux, and Christian Rose. "Highly Transfused MDS Patients Often Have Cardiac Iron Overload, as Shown by MRI Assessment." Blood 116, no. 21 (November 19, 2010): 2906. http://dx.doi.org/10.1182/blood.v116.21.2906.2906.

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Abstract Abstract 2906 Background: Cardiac complications of transfusional iron overload are well documented in various inherited anemias. In regularly transfused MDS, the deleterious role of iron overload on cardiac disease is more disputed, due in particular to frequent concomitant causes of cardiac failure. Cardiac MRI T2* allows accurate and specific measurement of iron content. Methods: We prospectively evaluated in 4 centers of the GFM by standardized and transferable MRI methods both cardiac T2* according to Anderson (Eur Heart J. 2001Dec;22(23):2171-9) and liver iron content (LIC) according to Gandon (Lancet. 2004 Jan 31;363(9406):357-62), as well as cardiac function by routine echocardiography or MRI in regularly transfused MDS patients. Results: From Dec 2005 to March 2010, 73 patients (pts) were included (14 of them had more than one MRI evaluation over time): 38 M/35F, Median age 68 (24-86); WHO : RA=5, RARS=33, RMCD-RS=3, RMCD=1, RAEB1=9, RAEB2=5, RAEB-T/AML=1, 5q- syndrome=8 and unclassified=8; Karyotype: fav n=50, Int n=9, unfav n=4, failure n=10; IPSS: low n=29, Int-1 n=28, Int-2 n=5 and High n=1, unknown n=10. Median interval from MDS diagnosis and MRI T2* assessment was 49 months (range 0–324). Median serum ferritin at MRI assessment was 1750 ng/ml (range 282–7339) and 54/73 pts were on chelation therapy (CT) (median duration of CT prior to first MRI: 18 months, range 1–125). 37/73 pts had cardiac symptoms and 28 were on cardiac therapy. At first MRI T2* analysis, the median number of RBC units transfused was 68 (range 5–574). Median LIC was 330 micromoles/g/dw (range 40–908). Median Cardiac T2* was 27 ms (range 6–74). 14/73 pts had cardiac iron overload defined by MRI T2* ≤20 ms (19%) and among them 3/73 (4%) had severe cardiac iron overload (T2*≤ 10 ms). LVEF was below normal (55%) in 13/59 cases evaluated. A correlation was found between cardiac T2*and the number of RBC units transfused (Pearson correlation =-0.342, p=0.004) but not with LIC (p= 0.65) and serum ferritin (p=0.21). Cardiac overload was seen in 1/19 (5.5%) pts transfused <50 RBC units, 4/37(12.1%) pts transfused 50–150 units, 9/17 (52.9%) pts transfused >150 units (p= 0.0005). Those 3 pt subgroups also differed in median LIC (μmoles/g/dw) (<50 units= 250, 50–150 units=340, > 150 units=414) (p=0.044 Kruskall-Wallis' test), but not significantly in serum ferritin (p= 0.085). No significant correlation was found between decreased LVEF (< 55%) and cardiac T2* <20 ms (p=0.5), or T2*≤10 ms (p=0.23). In particular, 5/13 pts (38%) with LVEF <55% had T2*<20ms, vs versus 8/46 pts (17%) with LVEF >55% (p= 0.13). However, 1/14, 0/30 and 3/12 pts having received <50, 50–150 and > 150 RBC units had severe cardiac failure (ie LVEF≤35%)(p=0.012). 3/4 pts with severe cardiac failure had T2*< 20ms,compared to 8/54 pts without severe cardiac failure (p=0.023). 14 pts had another cardiac MRI 6 to 34 months (median 18) after the first. All were on CT and had received a median of 60 and 214 PRBC units at first and last MRI, resp. Median Cardiac T2* was 21.6 ms (range 8.5–35.3) and. 28 ms (range 6.4–41) at last and at first assessment, respectively (p=0.3) Conclusions: Moderate and severe post transfusional cardiac iron overload was seen in 19% and 4% of regularly transfused MDS, respectively. The level of cardiac iron overload was well correlated to the number of RBC transfused. The impact of cardiac overload on LVEF was unclear except in pts with severe cardiac impairment (LVEF <35%), possibly suggesting that iron overload is only one of the factors responsible for cardiac disease in many of those elderly patients. Disclosures: No relevant conflicts of interest to declare.

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Park, J. W., M. J. Kim, H. A. Kim, J. Kim, E. B. Lee, and K. Shin. "POS0628 FAILURE TO SUSTAIN TREATMENT TARGET AFTER TAPERING TOCILIZUMAB IN PATIENTS WITH RHEUMATOID ARTHRITIS: 4-YEAR LONGITUDINAL DATA FROM A NATIONWIDE COHORT." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 552.1–552. http://dx.doi.org/10.1136/annrheumdis-2021-eular.2818.

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Background:Tapering biologic therapy after achieving clinical remission or low disease activity (LDA) has become a viable option in daily clinical practice of treating patients with rheumatoid arthritis (RA). There are yet few studies investigating its effectiveness and safety compared with those of standard biologic treatment, especially with non-tumor necrosis factor inhibitors.Objectives:To investigate the effectiveness and safety of tapering tocilizumab (TCZ) in patients with RA who attained LDA after TCZ therapy.Methods:Data were collected from a nationwide cohort of patients with RA receiving biologic therapy in South Korea (KOBIO-RA). This study included 350 patients who were treated with TCZ and achieved Clinical Disease Activity Index (CDAI)-LDA or remission (CDAI ≤ 10) after one year of treatment. We performed a longitudinal analysis utilizing clinical data measured in all 1-year intervals using generalized estimating equations (GEE). A total of 575 one-year intervals were divided into two groups according to the dose quotient (DQ, 0-100%) of TCZ within the interval (tapering group vs. standard treatment group). The main outcome of this study was loss of CDAI-LDA in the following 1-year interval.Results:Tapering TCZ was conducted in 282 (49.0%) intervals with a mean (SD) DQ of 66.0 (15.5). Loss of CDAI-LDA occurred in 91 (15.1%) intervals. Multivariable GEE showed significantly increased loss of CDAI-LDA (adjusted OR (95% CI): 1.76 [1.01 to 3.07]) in the tapering group after adjusting for previous biologics use, route of TCZ administration, concomitant glucocorticoid use, and CDAI measured in the previous follow-up. In addition, the likelihood to achieve DAS28-deep remission (DAS28-ESR < 1.98) was also significantly lower in the tapering group (adjusted OR 0.68 [0.46 to 0.99]). In contrast, there was no significant difference in the proportion of fulfilling other remission criteria between the two groups (Table 1). Development any adverse drug event or event of special interest was comparable in both groups except for hypercholesterolemia, which was lower in the tapering group.Table 1.Demographic characteristics and csDMARDs before first bDMARDLoss of CDAI-LDADAS28-remissionDAS28-deep remissionCDAI-remissionSDAI-remissionACR/EULAR remissionUnadjusted OR (95% CI)(vs. standard-dose group)1.02 (0.67 to 1.55)1.03 (0.71 to 1.49)0.76 (0.54 to 1.06)1.23 (0.75 to 2.00)0.92 (0.59 to 1.44)0.98 (0.65 to 1.48)Adjusted OR(95% CI)(vs. standard-dose group)1.76 (1.01 to 3.07)0.87 (0.54 to 1.38)0.68 (0.46 to 0.99)0.94 (0.57 to 1.55)0.87 (0.54 to 1.38)0.76 (0.50 to 1.18)CDAI, clinical disease activity index; CI, confidence interval; DAS, disease activity score; LDA, low disease activity; OR, odds ratio; SDAI, simplified disease activity index.Conclusion:Tapering TCZ after achieving LDA in patients with RA increases the risk of losing the benefit of LDA without a significant merit in safety.References:[1]Smolen JS et al. Maintenance, reduction or withdrawal of etanercept after treatment with etanercept and methotrexate in patients with moderate rheumatoid arthritis (PRESERVE): a randomised controlled trial. Lancet. 2013;381:918-29.[2]Schett G et al. Tapering biologic and conventional DMARD therapy in rheumatoid arthritis: current evidence and future directions. Ann Rheum Dis. 2016;75:1428-37.Disclosure of Interests:None declared

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Ito, Hirotaka, Keisuke Takai, and Makoto Taniguchi. "Cervical duraplasty with tenting sutures via laminoplasty for cervical flexion myelopathy in patients with Hirayama disease: successful decompression of a “tight dural canal in flexion” without spinal fusion." Journal of Neurosurgery: Spine 21, no. 5 (November 2014): 743–52. http://dx.doi.org/10.3171/2014.7.spine13955.

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Object Hirayama disease, juvenile muscular atrophy of the distal upper extremity, is a rare type of cervical flexion segmental myelopathy and its etiology is still being debated. Two theories have been proposed: a “contact pressure” theory and “tight dural canal in flexion” theory. Previously reported treatments, including conservative neck collar therapy and surgical spinal fusion, used fixation of the cervical spine with the aim of avoiding contact pressure between the cord and anterior structures. On the other hand, treatment by duraplasty without spinal fusion has also been used, which aims at decompressing a tight dural canal in flexion by preventing abnormal forward displacement of the posterior dura mater without restricting cervical motion in young patients. The authors developed a new surgical approach for treating a tight dural canal in flexion in patients with Hirayama disease: cervical duraplasty with tenting sutures via laminoplasty without spinal fusion. With this treatment they aimed to both decompress the spinal cord and preserve as much cervical motion as possible. The purpose of this study was to assess the clinical outcomes of patients who underwent this new surgical procedure and to investigate the etiology of Hirayama disease. Methods Six male patients (age range 17–23 years) with Hirayama disease underwent surgery between 2006 and 2012. The pre- and postoperative anteroposterior diameters of the dural canal in the flexed neck position, grip strength of the bilateral upper extremities, cervical alignment (C2–7), and cervical local flexion range of motion were compared. The presence or absence of surgical complications was assessed. To investigate the comparison group of Hirayama disease treated with spinal decompression, the PubMed database was searched for all relevant Englishlanguage case reports and series published between 1990 and 2013. Results The postoperative anteroposterior diameters of the dural canal were significantly expanded in the flexed neck position (7.2 ± 2.2 mm preoperatively vs 9.8 ± 1.7 mm postoperatively, p = 0.001). Grip strength of the upper extremities significantly improved bilaterally (20 ± 14 kg preoperatively vs 26 ± 15 kg postoperatively, p = 0.001). No significant difference was observed between pre- and postoperative cervical alignment in the neutral neck position (7.7° ± 8.1° preoperatively vs 9.0° ± 7.7° postoperatively, p = 0.74) or the cervical local flexion angle in the flexed neck position at the corresponding level of laminoplasty (16.6° ± 5.1° preoperatively vs 15.0° ± 9.4° postoperatively, p = 0.8). No surgical complications were noted, except for transient CSF leakage, which was resolved after lumbar drainage. The systematic review identified 37 cases from 7 reports: 26 with spinal fusion only, 5 with duraplasty without fusion, and 6 with combined duraplasty and fusion. In the largest series, in which 12 cases were treated with anterior fusion, cervical alignment was maintained, but local flexion motion was significantly decreased as a result of fixation. Although significant improvements in or stabilization of grip strength occurred in all 7 reported studies regardless of decompression procedures, one major delayed surgical complication was noted in a patient treated with anterior fusion. The patient developed severe kyphotic changes, which required reconstruction surgeries. Conclusions Cervical duraplasty with tenting sutures via laminoplasty prevented abnormal forward displacement of the posterior dura mater while preserving normal anterior structures and flexion motion of the cervical spine without major surgical complications. The clinical improvements achieved by the authors' method support evidence that a tight dural canal in flexion largely contributes to segmental myelopathy in patients with Hirayama disease.

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Zhang, Muchen, Ying Fang, Pengpeng Xu, Shu Cheng, Li Wang, and Wei-li Zhao. "Chidamide Plus R-CHOP21 in Elderly Patients with Newly Diagnosed Diffuse Large B-Cell Lymphoma: Results of a Phase II Study." Blood 132, Supplement 1 (November 29, 2018): 2968. http://dx.doi.org/10.1182/blood-2018-99-113942.

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Abstract Background: Diffuse large B-cell lymphoma (DLBCL) represents the most common subtype of non-Hodgkin's lymphoma and is heterogeneous in clinical, immunophenotypic and genetic features. More than 50% of patients with DLBCL are older than 60 years at diagnosis. Among them, up to 40% of patients relapse or develop refractory disease upon R-CHOP treatment. Dose-dense R-CHOP14 failed to show superior efficacy or survival compared with standard R-CHOP21 in elderly patients and intensive chemotherapy followed by autologous stem cell transplantation was difficult due to toxicity. Therefore, development of new first-line therapy remains great interests to improve disease outcome in elderly patients with DLBCL. Perturbation of the epigenome plays a crucial role in lymphoma progression. Several histone deacetylase inhibitors (HDACIs) have been investigated in relapsed or refractory DLBCL as mono- or combination treatment, showing promising activities to suppress lymphoma growth and overcome resistance to immune-chemotherapies. This prospective phase II study was to evaluate the efficacy and safety of chidamide in combination with R-CHOP21 in elderly patients with newly diagnosed DLBCL (NCT02753647). Methods: Patients with newly diagnosed DLBCL, aged 61 to 75 years, Eastern Cooperative Oncology Group performance status of 0 to 2, IPI>1 were enrolled. The dose and administration schedule were as follows: rituximab 375 mg/m2 on day 0, cyclophosphamide 750mg/m2 on day 1, doxorubicin 50mg/m2 on day 1, vincristine 1.4 mg/m2 on day 1, prednisone 60 mg/m2 from day 1 to day 5, chidamide 20mg/d on days 1, 4, 8 and 11, every 21 days for 6 cycles. The primary endpoint was complete response (CR) rate assessed by PET-CT, and secondary endpoints included progression-free survival (PFS), overall survival (OS), overall response rate (ORR) and main adverse events (AEs). Results: From March 2016 to April 2018, 49 patients were enrolled; 41 patients completed all treatment and 8 patients were still in the treatment cycles. Median age was 67 years (range, 61-75) and 28 patients (57.1%) were male. Thirty-eight patients (77.6%) presented advanced Ann Arbor stage, and 41 patients (83.7%) showed elevated serum LDH level. Thirty-one patients (63.3%) had multiple extra-nodal sites, mainly involving bone, gastrointestinal, liver, and bone marrow. Forty-one patients (83.7%) had IPI scores ≥3 at diagnosis. By immunohistochemistry, 12 (24.5%) patients were categorized as germinal center B-cell (GCB) subtype based on Hans algorithm, and 12 (25.5%) patients were defined as BCL-2 and MYC double expression. Among 41 patients available for evaluation, the CR rate was 85.4% (35/41), and the ORR was 90.3% (37/41). After a median follow-up of 18 months (range, 3-30), the 1-year PFS was 92.1% and 1-year OS was 94.7%. There were 2 deaths due to disease progression, of which 1 had triple-hit lymphoma. Regarding toxicity, grade 3-4 neutropenia was observed in 167 cycles (60.5%), grade 3-4 thrombocytopenia in 27 cycles (9.8%), and grade 3 anemia in 11 cycles (4.0%). However, febrile neutropenia was reported in significantly fewer cycles (6.1%) and was a maximum of grade 3. Grade 3 liver dysfunction was observed in 7 cycles (2.5%). No grade 4 non-hematological events were reported. Of note, 2 patients positive for EBER-ISH at diagnosis remained in EBV-DNA negative during treatment and follow-up. Conclusion: Chidamide with R-CHOP21 is effective and safe in elderly patients with newly diagnosed DLBCL. Disclosures No relevant conflicts of interest to declare.

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