Journal articles: 'UCG 90-20'

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Choque-Conde, Esteban, Hans Franklin Mercado-Ríos, Alberto Gutierrez, and Jhonny Ojeda-Choque. "Efecto del abono verde y fertilización química en tres variedades de Caña de Azúcar en suelos franco arenosos del municipio Fernández Alonso, Santa Cruz, Bolivia." Revista de Investigación Agropecuaria y Forestal Boliviana - RIAFB 6, no. 11 (2019): 8–21. https://doi.org/10.5281/zenodo.8215540.

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La investigación fue realizada en los predios del Centro Nacional de la Caña de Azúcar (CENACA), localizado en el municipio Fernández Alonso, departamento Santa Cruz, país Bolivia, conducidos bajo el diseño estadístico de parcelas sub divididas de tres niveles (abonos verdes, variedades de caña de azúcar y, parcelas con y sin fertilización), en el marco del objetivo de Determinar la respuesta de tres variedades de caña de azúcar -RBB 77- 26, UCG 90-20 y UCG 96-10- sobre rastrojos de abonos verdes (crotalaria, sorgo y barbecho). Como variables de respuesta se evaluaron la número de tallos (NT), altura de tallo molible (ATM), diámetro de tallo (DT) y peso de tallo molible (PTM), colateralmente, el porcentaje de sacarosa (PS) y Rendimiento (Y). Los resultados estadísticos indican una diferencia significativa entre tratamientos, mediante una comparación de medias, según la prueba DMS (diferencia mínima significativa) al 5% de probabilidad. Según los resultados, el rastrojo de crotalaria tuvo mayor efecto en cuanto al NT, ATM y PTM en relación al rastrojo de sorgo. Los óptimos resultados se dieron sobre los rastrojo de crotalaria tanto en el rendimiento y niveles de caña de azúcar, destacando la variedad UCG 96-10, seguido de la variedad UCG 90-20 y RBB 77-26 respectivamente, además, de existir respuesta a la fertilización con N, P y K.

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Huynh, Quoc Dung, Hoang Nhat Huy Luong, Nhat Tan Ngo, et al. "Recycling used coffee grounds as fine aggregate in alkali-activated lightweight non-load-bearing composites." CTU Journal of Innovation and Sustainable Development 17, Special issue: ETMD (2025): 24–31. https://doi.org/10.22144/ctujoisd.2025.004.

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Coffee is one of the most consumed drinks, which releases large amounts of used coffee grounds (UCG), causing environmental problems. Thus, UCG was re-used in combination with bottom ash (BA) as fine aggregates in making alkali-activated non-load-bearing lightweight composites (ANLC) in this study. To evaluate the effect of UCG on the properties of ANLC, seven ANLC mixtures with UCG/BA ratios of 0/100, 5/95, 10/90, 15/85, 20/80, 25/75, and 30/70 were prepared. Results showed that the properties of ANLC were influenced significantly by UCG contents. Indeed, an increase in UCG content led to a decrease in dry density, strength, and drying shrinkage while increasing the ANLC’s water absorption, except for the specimen with 5% UCG incorporation. Correlations among properties of ANLC were established and the potential applications of ANLC in real practice were also suggested, proving that the ANLC could be applied to non-load-bearing elements. Among the mixtures, the 28-day ANLC specimen containing 5% UCG exhibited the highest flexural and compressive strengths of 7.12 MPa and 39.4 MPa, respectively, and the lowest water absorption of 10.29% with the relatively low dry density of 1671 kg/m3, indicating the feasibility of using UCG as fine aggregate in the production and application of ANLC.

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Yoshimi, Akihide, Yasuhito Nannya, Kumi Oshima, et al. "Reduced Cyclophosphamide Combined with Etoposide and Total Body Irradiation as a Conditioning Regimen for Patients with Impaired Cardiac Function Undergoing Allogeneic Stem Cell Transplantation." Blood 110, no. 11 (2007): 2000. http://dx.doi.org/10.1182/blood.v110.11.2000.2000.

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Abstract Cardiac toxicity due to conditioning regimens is a critical problem in the hematopoietic stem cell transplantation (HSCT). High-dose cyclophosphamide, which is a major component of conventional myeloablative regimens, is considered to be a main cause of cardiac toxicity. Although reduced intensity conditioning regimens have been developed in order to diminish regimen related toxicities for patients with pre-transplant co-morbidity, their anti-neoplastic effects have been revealed to be insufficient especially for patients with acute lymphoblastic leukemia. Therefore, it is imperative to establish an alternative preparative regimen with myeloablative intensity for patients with impaired pre-transplant cardiac function. From June 1995 at the University of Tokyo, we have adopted a heart protective regimen (VP/rCY/TBI) which is composed of continuous infusion of VP-16 20 mg/kg for 2 days, CY 40 mg/kg for 1 day, and 12 Gy of fractionated total body irradiation (TBI) for 17 patients because they had impaired cardiac function defined by ejection fraction (EF) less than 0.55 (n=15) or a history of congestive heart failure (n=1) or pulmonary hypertension (n=1). The clinical relevance of VP/rCY/TBI regimen was evaluated by retrospectively comparing the outcome of VP/rCY/TBI recipients with that of conventional CY/TBI (CY 60 mg/kg for 2 days + fractionated TBI 12 Gy, which was administered to 140 patients during the same period) recipients. The characteristics analysis revealed that VP/rCY/TBI recipients had higher cumulative doses of anthracyclines (354 mg/m2 vs 150 mg/m2 calculated as the equivalence of native doxorubicin, p&lt;0.0001), lower EF (0.51 vs 0.66, p=0.005), larger left ventricular end-systolic dimension (LVDs) (35 mm vs 30 mm, p&lt;0.0001), and worse Karnofsky performance scales (KPS) (90 vs 100, p=0.0037) than CY/TBI recipients. There was no difference in the other characteristics between the two groups, including age, disease status, ferritin level, and the other UCG findings. The median follow up period for surviving patients was 43.9 months after transplantation (range: 4–146 months). Survival analysis was conducted considering non-relapse mortality (NRM) and relapse rates as competing risk factors of each other. The relapse rate was not significantly different between the two groups (p=0.24), which indicates that VP/rCY/TBI regimen has a comparable anti-tumor effect to standard CY/TBI regimen. In addition, despite poorer KPS and more cardiac co-morbidity in the VP/rCY/TBI arm, no difference in the NRM rates was observed between the two groups. Especially, it is noteworthy that Bearman grade III-IV cardiac toxicity within 28 days after HSCT was not significantly increased in VP/rCY/TBI group (one in VP/rCY/TBI recipients (5.9%) and five in CY/TBI recipients (3.6%), p=0.64). There was no significant difference in the incidence of grade II-IV (p=0.35) or grade III-IV (p=0.10) acute GVHD. From these results, we conclude that VP/rCY/TBI regimen can be safely administered for patients with pre-transplant cardiac co-morbidity while preserving anti-neoplastic effects.

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Kekre, Natasha, Jennifer Philippe, Ranjeeta Mallick, Susan Smith, and David Allan. "Modelling Improvements in Cell Yield of Banked Umbilical Cord Blood and the Impact on Availability of Donor Units for Transplantation into Adults." Stem Cells International 2013 (2013): 1–6. http://dx.doi.org/10.1155/2013/124834.

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Umbilical cord blood (UCB) is used increasingly in allogeneic transplantation. The size of units remains limiting, especially for adult recipients. Whether modest improvements in the yield of cells surviving storage and thawing allow more patients to proceed to transplant was examined. The impact of improved cell yield on the number of available UCB units was simulated using 21 consecutive anonymous searches. The number of suitable UCB units was calculated based on hypothetical recipient weight of 50 kg, 70 kg, and 90 kg and was repeated for a 10%, 20%, and 30% increase in the fraction of cells surviving storage. Increasing the percentage of cells that survive storage by 30% lowered the threshold of cells needed to achieve similar engraftment rates and increased numbers of UCB units available for patients weighing 50 (P=0.011), 70 (P=0.014), and 90 kg (P=0.003), controlling for differences in HLA compatibility. Moreover, if recipients were 90 kg, 12 out of 21 patients had access to at least one UCB unit that met standard criteria, which increased to 19 out of 21 patients (P=0.035) when the fraction of cells surviving storage and thawing increased by 30%. Modest increases in the yield of cells in banked UCB units can significantly increase donor options for adult patients undergoing HSCT.

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Corradini, Paolo, Anna Raganato, Cristiana Carniti, et al. "CD8-Depleted Donor Lymphocyte Infusions Can Boost Immune Reconstitution after Haploidentical Stem Cell Transplantation Following Reduced-Intensity Conditioning Regimen." Blood 108, no. 11 (2006): 3138. http://dx.doi.org/10.1182/blood.v108.11.3138.3138.

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Abstract Haploidentical stem cell transplantation (SCT) can be used in relapsed haematological malignancies for patients lacking a matched sibling or unrelated donor. Major barriers of this strategy are the poor immune reconstitution and the high risk of relapse. Here, we report results of a phase I–II trial evaluating early add-backs of CD8-depleted donor lymphocytes (DLIs) (from 1x10^4 up to 1x10^5 cells/kg starting at day+45 up to day +105 at monthly intervals) after a reduced intensity conditioning (RIC) regimen [thiotepa (10 mg/kg), fludarabine (120 mg/sqm), cyclophosphamide (60 mg/kg) and TBI (2 Gy)]. Ex-vivo and in-vivo TCD were carried out by CD34+ cell selection using the CliniMACS device and alemtuzumab (15mg/m2, day-2), respectively. Twenty-one patients [n= 10 NHL (n=5 CLL, n=5 high-grade NHL), n=7 HL, n=1 MM, n=1 ALL, n=2 AML] were transplanted with advanced disease: 16 (76%) failed a previous autograft and 13 (62%) had refractory disease. A median of 10.4x10^6/Kg CD34+, 1x10^4/kg CD3+, 10x10^4/kg CD19+, 0.9 x10^4/kg NK+ were infused. All patients engrafted with full donor chimerism from day +90. At a median follow-up of 12 months (range, 4–41 months), 12 of 21 pts are alive (7 CR, 2 PR and 3 PD) and 9 died [n=3 infection with GVHD (+610, +187, +253), n=6 disease]. The estimated 2-year overall survival was 49%: pts transplanted in remission had better outcome (83% versus 31%, p=0.13). The estimated 2-year cumulative incidence of TRM and relapse were 27% and 58%, respectively. CMV reactivation and hospital readmissions for opportunistic infections occurred in 76% and 57% of patients, respectively. For CD8 depletion of donor leukaphereses, a new depletion protocol using clinical grade CD8 microbeads (Miltenyi) was applied. This procedure is efficient to reduce the content of CD8 T cells by 3 logs while the median cell recovery of CD3+, CD4+, CD56+/CD3+, CD 20+ was 60%, 86%, 54%, 72%, respectively. Before DLIs, only 2 of 21 patients (10%) developed acute GVHD (no grade III–IV). A total of 36 CD8-depleted DLIs were administered to 17 pts without any acute toxicity. Following DLIs, 6 pts (35%) developed acute GVHD (grade II) and 5 (30%) chronic GVHD (n=2 limited, n=3 extensive). Overall, the incidence of acute GVHD is higher (50% vs 22%, p=0.33) in pts receving larger numbers of donor cells (10–15x10^4/kg versus 3–5x10^4/kg CD8-depleted DLIs). The median values of CD4+/uL, CD8+/uL and NK+ were 100, 280 and 680 at 4 months and 220, 200, 500 at 6 months after SCT in patients receiving CD8-depleted DLIs. Measurable TREC/ucg DNA (mean value 316; mean value donors 3740) and polyclonal T cell repertoire, evaluated by spectratyping, were observed at 9 months in patients younger than 40 years and/or without GVHD. Our results suggest that: haploidentical SCT with RIC regimen provides high engraftment rate T-cell addback allows the achievement of more than 100/uL CD4+ at 4 months after SCT in the majority of patients Survival rate is promising in patients who had transplantation in remission suggesting that this strategy should be evaluated earlier in high risk haematological diseases.

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Waller, Anthony F., Fengrong Wang, and Ned Waller. "A Mathematical Model of Stochastic Engraftment by Non-Interacting Single Umbilical Cord Blood (UCB) Grafts Predicts Accelerated Engraftment Using Multiple UCB Grafts." Blood 110, no. 11 (2007): 2034. http://dx.doi.org/10.1182/blood.v110.11.2034.2034.

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Abstract Background: The use of UCB transplants is limited by the difficulty of finding units with sufficient cells to provide reliable engraftment, and the slower kinetics of hematopoietic engraftment compared to other hematopoietic progenitor cell grafts. Grafts consisting of two unrelated UCB result in accelerated engraftment compared to single unit UCB transplants, but the mechanism for enhanced engraftment is unknown. Methods: We extracted data from published studies on myeloid engraftment following transplantation of single (9 studies, 1542 engrafted patients) or double (4 studies, 94 engrafted patients) UCB units (Table). A weighted average of median days (and estimated SD) to engraft for single and double UCB transplants was calculated. The cumulative incidence of myeloid engraftment for single or double UCB transplants was modeled based the assumption that the time to engraft was described by a normal distribution. For double and triple UCB transplants, the probability of myeloid engraftment at any time post-transplant was calculated as 1 minus the probability of non-engraftment for a single UCB unit squared or cubed, respectively. Results: The weighted average percentage for myeloid engraftment following single UCB transplants was 89%, with a median day of engraftment of 26.4 days. The weighted average for the rate of myeloid engraftment following double UCB transplants was 96%, with a median day of engraftment of 22 days. The calculated median days to engraft from single or double UCB transplants, using the assumption of normal distributions, were 22 and 26 days, respectively. Applying the mathematical model, the predicted cumulative engraftment for a double UCB graft is 99%, with a the curve for cumulative engraftment kinetics quite similar to the observed engraftment in Barker 2005 and the calculated curve for double UCB transplants based upon analysis of extracted data (Figure). Conclusion: UCB units do not appear to facilitate engraftment in grafts containing multiple units. A stochastic statistical model, in which different UCB grafts engraft independently, appears to account for the observed 4-day decrease in the median time to achieve myeloid engraftment following a double versus single UCB transplant. The use of a triple UCB graft is predicted to shorten the median time to achieve neutrophil engraftment to a median of 20 days. Published experiences describing myeloid engraftment following single and double UCB transplants Single UCB Transplant N, % engrafted Median day to engraft Double UCB Transplants N, % engrafted Median day to engraft Laughlin NEJM 2001 N=61, 90% 27 Barker Blood 2005 N=50, 100% 23 Hamza BJH 2004 N=28, 86% 29 Yoo ASH 2005 N=12, 100% 23 Barker Blood 2001 N=31, 88% 26 Kai ASH 2004 N=11, 82% 21 Thomson Blood 2000 N=30, 81% 25 Ballen ASH 2005 N=21, 90% 20 Sanz Blood 2001 N=22, 100% 22 Terakura BBMT 2007 N=148, 81% 22 Wagner Blood 2002 N=102, 86% 22 Migliaccio Blood 2000 N=200, 91% 28 Stevens Blood 2002 N=1111, 90% 27 Figure Figure

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Chehrazi-Raffle, Alexander, Tanya B. Dorff, Sumanta K. Pal та Yung Lyou. "Wnt/β-Catenin Signaling and Immunotherapy Resistance: Lessons for the Treatment of Urothelial Carcinoma". Cancers 13, № 4 (2021): 889. http://dx.doi.org/10.3390/cancers13040889.

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Urothelial cell carcinoma (UCC) is a significant public health burden. It accounts for approximately 90 percent of all bladder cancers with an estimated 200,000 annual deaths globally. Platinum based cytotoxic chemotherapy combinations are the current standard of care in the frontline setting for metastatic UCC. Even with these treatments the median overall survival is estimated to be about 15 months. Recently, immune checkpoint inhibitors (ICIs) have demonstrated superior clinical benefits compared to second line chemotherapy in UCC treatment. However only a minority of patients (~20%) respond to ICIs, which highlights the need to better understand the mechanisms behind resistance. In this review, we (i) examine the pathophysiology of Wnt/β-catenin signaling, (ii) discuss pre-clinical evidence that supports the combination of Wnt/β-catenin inhibitors and ICI, and (iii) propose future combination treatments that could be investigated through clinical trials.

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Chow, Robert, David Gjertson, Joseph Rosenthal, et al. "Clinical Outcome of Hematopoietic Stem Cell Transplantation (HSCT) Using Plasma Depleted Umbilical Cord Blood Units (UCB) That Were Not Depleted of Red Blood Cells Prior to Cryopreservation." Blood 106, no. 11 (2005): 2045. http://dx.doi.org/10.1182/blood.v106.11.2045.2045.

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Abstract Background: UCB is an attractive source for HSCT because of less stringent HLA matching requirements, lower incidence and severity of GvHD, and ready availability of a physical inventory. However, unlike BMT or PSCT, the limiting cell dose associated with UCB units has hampered its widespread use. The red cell depletion (RCD) techniques that are widely used by UCB banks incur significant nucleated cell loss after processing. One method of minimizing cell loss during processing is to deplete plasma (PD) but not red blood cells. A large racially diverse inventory of 18,000 PD UCB is now available on stem cell registries; however, clinical outcome for HSCT using PD UCB products is unavailable. Hypothesis: Usage of PD UCB in unrelated HSCT will result in acceptable clinical outcome for myeloid (ANC 500) and platelet engraftment, overall survival (OS), event-free-survival (EFS), and transplant related mortality (TRM). Methods: A retrospective analysis limited to patients without prior transplants and transplanted during remission (“eligible”) was performed on 98 HSCT using PD UCB. An additional 20 “high risk” patients with prior transplants or transplanted during relapse were included in the engraftment and survival analysis. Results: Average loss of less than 0.1% nucleated cells was found in the discarded plasma fraction after PD UCB processing (n=27), though cell clumping limited the cellular fraction recovery to 90%. Outcome on engraftment and/or survival was available for 98 patients (median age 6.7 yo, range 0.3–54 yo, 24 >16 yo; median weight 23.5 kg, range 4.5–88 kg, 27 >50kg; male 60%; median # HLA ABDR matches 4.0; median pre-freeze TNC dose 5.7 x 107/kg; transplant center reported median post-thaw TNC dose 5.5 x 107/kg; median pre-freeze CD34 dose 2.0 x 105/kg; malignant indications 71%; transplants outside U.S. 37%; double unit transplant 14%; and non-myeloablative 7%). The median time to engraftment for ANC 500 (n=87), platelet 20K (n=72) and 50K (n=68) were 22.0 days (range 7–49 days), 49.5 days (range 13–94 days), and 58.0 days (range 21–132 days) respectively. The unadjusted cumulative incidence of ANC500 and platelet 20K and 50K engraftment were 94±3%, 81±5% and 80±5% respectively for 98 eligible patients, and 90±3%, 77±5% and 75±5% respectively for the eligible plus high risk patients. The incidence of grade III–IV acute GVHD and extensive chronic GVHD were 15% and 14% respectively. Relapse rate for malignancies (n=67) and TRM (n=98) were 20±6% and 20±4% respectively at 1 year. With a median follow-up of 297 days (range 50–1,263 days), the Kaplan-Meier estimates of 1-year survival (n=98) and disease-free survival (n=67) are 73±5% and 59±7% respectively for the eligible patients, and 65±5% (n=118) and 50±6% (n=85) respectively for the eligible plus high risk patients. Conclusion: These results demonstrate that HSCT using PD UCB can be performed safely and effectively.

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Lauritzen, Esben S., Thomas Voss, Ulla Kampmann, et al. "Circulating acylghrelin levels are suppressed by insulin and increase in response to hypoglycemia in healthy adult volunteers." European Journal of Endocrinology 172, no. 4 (2015): 357–62. http://dx.doi.org/10.1530/eje-14-0880.

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ObjectiveGhrelin has glucoregulatory and orexigenic actions, but its role in acute hypoglycemia remains uncertain. We aimed to investigate circulating levels of acylghrelin (AG) and unacylated ghrelin (UAG) in response to hyperinsulinemia and to hypoglycemia.DesignA randomized, single-blind, placebo-controlled crossover study including 3 study days was performed at a university hospital clinical research center.MethodsNine healthy men completed 3 study days: i) saline control (CTR), ii) hyperinsulinemic euglycemia (HE) (bolus insulin 0.1 IE/kg i.v. and glucose 20% i.v. for 105 min, plasma glucose ≈5 mmol/l), and iii) hyperinsulinemic hypoglycemia (HH) (bolus insulin 0.1 IE/kg i.v.).ResultsHH and HE suppressed AG concentrations at t=45–60 min as compared with CTR (P<0.05). At t=90 min, a rebound increase in AG was observed in response to HH as compared with both HE and CTR (P<0.05). UAG also decreased during HH and HE at t=45 min (P<0.05), whereas the AG-to-UAG ratio remained unaffected.ConclusionsThis study demonstrates that AG and UAG are directly suppressed by hyperinsulinemia and that AG concentrations increase after a latency of ≈1 h in response to hypoglycemia, suggesting a potential counterregulatory role of AG.

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Mcinnes, I., P. J. Mease, K. Eaton, et al. "AB0820 COMPARATIVE EFFICACY OF GUSELKUMAB IN PATIENTS WITH PSORIATIC ARTHRITIS: RESULTS FROM SYSTEMATIC LITERATURE REVIEW AND NETWORK META-ANALYSIS." Annals of the Rheumatic Diseases 79, Suppl 1 (2020): 1713–14. http://dx.doi.org/10.1136/annrheumdis-2020-eular.6013.

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Background:The efficacy of the interleukin (IL)-23 subunit p19 inhibitor guselkumab (GUS) for psoriatic arthritis (PsA) has recently been demonstrated in two Phase 3 trials (DISCOVER-1 & -2) but has not been evaluated versus existing targeted therapies for PsA.Objectives:To compare GUS to targeted therapies for PsA through network meta-analysis (NMA).Methods:A systematic literature review was performed to identify PsA randomized controlled trials from 2000 to 2018. Bayesian NMAs were performed to compare treatments on American College of Rheumatology (ACR) 20/50/70 response, Psoriasis Area Severity Index (PASI) 75/90/100 response, Health Assessment Questionnaire Disability Index (HAQ-DI) score, resolution of enthesitis (RoE), resolution of dactylitis (RoD), adverse events (AEs) and serious adverse events (SAEs). Analyses used random effects models that adjusted for placebo response via meta-regression on baseline risk when feasible. Results are summarized by ranking treatments according to median absolute probabilities of response derived from NMAs.Results:Twenty-six Phase 3 studies were included in the quantitative synthesis. Studies were placebo-controlled up to 24 weeks and evaluated 13 targeted therapies for PsA. Absolute probabilities are reported for PASI 90 & ACR 20 responses according toFigure 1,and a forest plot of relative risks versus placebo for AEs is reported according toFigure 2. For ACR 20 response, GUS 100 mg every 4 weeks (Q4W) and every 8 weeks (Q8W) ranked 5th and 8th out of 20 interventions and were comparable to IL-17A inhibitor (IL-17Ai) and most tumor necrosis factor inhibitor (TNFi) agents. Similar findings were observed for ACR 50 and 70 responses. For PASI 90 response, GUS Q4W and Q8W ranked 1st and 2nd out of 15 interventions and were highly likely to provide a greater benefit than most other agents. Similar findings were observed for PASI 75 and 100 responses. For HAQ-DI score, GUS Q4W and Q8W ranked 6th and 10th out of 20 interventions and were comparable to IL-17Ai and most TNFi agents. For RoE, GUS Q4W and Q8W ranked 8th and 6th out of 13 interventions and were comparable to IL-17Ai and TNFi agents. For RoD, GUS Q4W and Q8W ranked 8th and 9th out of 13 interventions and were comparable to most IL-17Ai and TNFi agents. For AEs, GUS Q4W and Q8W ranked 3rd and 2nd out of 19 interventions and were comparable to IL-17Ai and TNFi agents. Likewise, for SAEs, GUS Q4W and Q8W ranked 4th and 5th out of 20 interventions and were comparable to IL-17Ai and TNFi agents. Analyses that controlled for previous exposure to biologics or assessed outcomes at alternative timepoints were broadly consistent with primary analysis results.Conclusion:NMA results indicate that GUS is comparable to most targeted PsA treatments for improvement in arthritis, soft tissue damage, physical function, and safety outcomes. For PASI outcomes, GUS is highly likely to provide a greater benefit than other targeted PsA treatments.Disclosure of Interests:Iain McInnes Grant/research support from: Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Janssen, and UCB, Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Gilead, Janssen, Novartis, Pfizer, and UCB, Philip J Mease Grant/research support from: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – grant/research support, Consultant of: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – consultant, Speakers bureau: Abbott, Amgen, Biogen Idec, BMS, Eli Lilly, Genentech, Janssen, Pfizer, UCB – speakers bureau, Kiefer Eaton Shareholder of: Test Pharma, Consultant of: Janssen, Agata Schubert Employee of: Janssen-Cilag, Steve Peterson Employee of: Janssen Research & Development, LLC, Tim Disher Consultant of: Janssen, Wim Noel Employee of: Janssen Pharmaceuticals NV, Hassan Fareen Employee of: Janssen, Chetan Karyekar Shareholder of: Johnson & Johnson, Consultant of: Janssen, Employee of: Janssen Global Services, LLC. Previously, Novartis, Bristol-Myers Squibb, and Abbott Labs., Suzy Van Sanden Employee of: Janssen, Christopher T. Ritchlin Grant/research support from: UCB Pharma, AbbVie, Amgen, Consultant of: UCB Pharma, Amgen, AbbVie, Lilly, Pfizer, Novartis, Gilead, Janssen, Wolf-Henning Boehncke Grant/research support from: Janssen Research & Development, LLC, Consultant of: Janssen

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Perez, Sonia A., Panagiota A. Sotiropoulou, Dimitra G. Gkika, et al. "A novel myeloid-like NK cell progenitor in human umbilical cord blood." Blood 101, no. 9 (2003): 3444–50. http://dx.doi.org/10.1182/blood-2002-05-1501.

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Natural killer (NK) cell differentiation from pluripotent CD34+ human hematopoietic stem cells or oligopotent lymphoid progenitors has already been reported. In the present study, long-term cultures of the CD56−/CD34−myeloid-like adherent cell fraction (ACF) from umbilical cord blood (UCB), characterized by the expression of CD14+ as well as other myeloid markers, were set up with flt3 ligand (FL) and interleukin-15 (IL-15). The UCB/ACF gradually expressed the CD56 marker, which reached fairly high levels (approximately 90% of the cells were CD56+) by day 15. FL plus IL-15–driven ACF/CD56+ cells progressively expressed a mature NK functional program lysing both NK- and lymphokine-activate killer (LAK)–sensitive tumor targets and producing high levels of interferon-γ (IFN-γ), granulocyte-macrophage colony-stimulating factor, tumor necrosis factor α, and IL-10 upon stimulation with IL-12 and IL-18. Similar results were obtained when highly purified CD14+ cells from UCB were cultured with FL and IL-15. In contrast, UCB/CD34+ cells cultured under the same conditions showed a delayed expression of CD56 and behaved functionally differently in that they exhibited NK but not LAK cytotoxicity and produced significantly fewer cytokines. Kinetic studies on the phenotype of UCB/ACF or UCB/CD14+ cells cultured in the presence of FL and IL-15 showed a rapid decrease in CD14 expression after day 5, which reached levels of zero by day 20. Approximately 60% of the CD56+ derived from the UCB/ACF or the UCB/CD14+ cells coexpressed CD14 by day 5. Taken together, our data support the role of CD14+ myeloid-like cells within UCB as a novel progenitor for lymphoid NK cells.

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Yadav, Namita, Vita Leena D'Souza, and T. Geethamani. "Assessment of Knowledge and Attitude Among College Students Toward Umbilical Cord Blood and its Banking." Nepal Journal of Health Sciences 1, no. 1 (2021): 1–7. http://dx.doi.org/10.3126/njhs.v1i1.38493.

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Introduction: Umbilical cord blood (UCB) is a good source of haematopoietic stem cells and progenitor cells. UCB stem cells are used in treatment of a variety of blood and bone marrow diseases, blood cancers, metabolic disorders and immune deficiencies. Objective: This study aimed in investigating college students’ knowledge and attitude about UCB and UCB banking. Methods: It is a descriptive cross-sectional study. The study was conducted in East West College of Management, Bangalore, India from September 2018 to August 2019. A total 80 college students were selected by random sampling techniques. There were self-structured questionnaires used to assess the knowledge and attitude regarding UCB and UCB banking. The data analysis was done using descriptive and inferential statistics in SPSS version 21. Results: The maximum number of participants were from age group 19-21 years followed by age group 16-18 years. The overall knowledge score was 21.05±5.11 with mean percentage score of 60.14. The 71.25% (57) of subjects had moderately adequate knowledge; whereas, 25% (20) of subjects showed adequate knowledge. Similarly, the overall attitude score of subjects was 61.5±5.17 with a mean percentage score of 51.25%. Out of the total participants, 90% (72) had neutral attitude, 10% (8) exhibited positive attitude and none of the subjects exhibited negative attitude towards UCB banking. There was no association found between knowledge and sociodemographic variables and between attitude and sociodemographic variables. Conclusion: The majority of the respondents had moderate knowledge and maximum had neutral attitude on umbilical cord blood and umbilical cord blood banking.

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Pal, Sumanta K., Jean H. Hoffman-Censits, Julia Andrea Elvin, et al. "Comprehensive genomic profiling of relapsed and refractory small cell neuroendocrine carcinoma of the urinary bladder." Journal of Clinical Oncology 35, no. 6_suppl (2017): 350. http://dx.doi.org/10.1200/jco.2017.35.6_suppl.350.

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350 Background: Small cell neuroendocrine carcinoma of the bladder (SCCB) is rare but aggressive form of genitourinary cancer that can arise de novo or in conjunction with urothelial carcinoma (UCB). Methods: DNA was extracted from 40 microns of FFPE specimen from 29 cases of relapsed, refractory and metastatic SCCB and 1,113 UCB. Comprehensive genomic profiling (CGP) was performed using a hybrid-capture, adaptor ligation based next generation sequencing assay to a mean coverage depth of > 503X. Tumor mutational burden (TMB) was calculated from a minimum of 1.11 Mb of sequenced DNA as previously described and reported as mutations/Mb. The results were analyzed for all classes of genomic alterations (GA), including base substitutions, insertions and deletions (short variants; SV), fusions, and copy number changes including amplifications (amp) and homozygous deletions. Results: 29 SCCB cases were confirmed on routine histology and featured positive IHC staining for chromogranin, synaptophysin or both. Patients had a mean age of 68.1 years (range 49-90 years) and 25 (86%) were male. At the time of CGP, 3 (10%) SCCB were Stage III and 26 (90%) were stage IV. The primary SCCB was used for sequencing in 14 (48%) of cases and a metastasis sample in 15 (52%). The 29 SCCB featured 2.86 GA/case.The genomics of SCCB differed significantly from UCB (Table). The most frequent clinically relevant GA in SCCB were RICTOR amp (21%) and PIK3CA (10%), BRCA1, HGF, FBXW7 and CCND2 SV (7% each). The relatively high TMB in SCCB (7% TMB > 20 mut/Mb and 28% TMB > 10 mut/Mb) is similar to that seen in UCB. No SCCB cases were MSI-high. ERBB2 and FGFR1 GA frequencies (both 3%) in SCCB were lower than in similarly studied UCB. Conclusions: SCCB differs in genomic landscape from UCB in having higher frequencies of TP53 and RB1 GA and lower frequencies of FGFR3 and ERBB2 GA. However, like UCB, SCCB shares the presence of multiple GA associated with potential responses to targeted therapies and high TMB associated with response to immune checkpoint inhibitor therapy. [Table: see text]

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Crisinel, Pierre Alex, Michel Duval, Delphine Thuillard Crisinel, et al. "Risk of Cytomegalovirus Infection and Disease after Umbilical Cord Blood Transplantation in Children." Canadian Journal of Infectious Diseases and Medical Microbiology 24, no. 1 (2013): e11-e15. http://dx.doi.org/10.1155/2013/159691.

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BACKGROUND: Pediatric data regarding cytomegalovirus (CMV) infections in pediatric patients receiving umbilical cord blood (UCB) transplantation are sparse.OBJECTIVE: To determine whether UCB transplantation increases the risk of CMV infection and disease compared with other graft sources.METHODS: The medical files of patients who underwent allogeneic hematopoietic stem cell transplantation at CHU Ste-Justine (Montreal, Quebec) from April 2000 to December 2006 were retrospectively reviewed. A Cox proportional hazard model was used to assess the effect of potential predictors of outcomes.RESULTS: A total of 176 patients with a median age of nine years (range 0.1 to 18 years) underwent hematopoietic stem cell transplantation. The source of stem cells were UCB, bone marrow and peripheral blood stem cells in 86, 86 and four of the cases, respectively. CMV infection occurred in 29 patients (16%). At day 100 post-transplantation, the rate of CMV infection was 13% in UCB transplant recipients (11 of 86) versus 20% in those with other sources of graft (18 of 90) (P=0.19). Positive CMV serology of the recipient and leukocyte depletion were two independent variables associated with an increased risk of CMV infection. Among infected patients, six developed CMV disease (20.7%). The rate of CMV disease one year after infection was 49% in patients who received UCB (five of 11) and 6% in others (one of 18). This difference was significant by univariate (P=0.01) but not by multivariate analysis.CONCLUSION: In the setting of the current study, with a moderate CMV infection rate (16.5%), UCB transplantation did not appear to increase the risk of CMV infection and disease.

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Christakopoulos, Georgios E., Todd E. DeFor, Stefanie M. Hage, et al. "Romiplostim Improves Platelet Recovery after UCB Transplant." Blood 134, Supplement_1 (2019): 1979. http://dx.doi.org/10.1182/blood-2019-125424.

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Background: Prolonged thrombocytopenia after hematopoietic stem cell transplant is a relatively common complication associated with intricate mechanisms including impaired thrombopoiesis and increased platelet turnover. Platelet recovery is particularly delayed after umbilical cord blood transplant (UCBT). Romiplostim is a thrombopoietin receptor agonist that is FDA approved for the treatment of chronic ITP. Although an increasing number of studies recently show promising results on the use of romiplostim in chemotherapy induced thrombocytopenia, the effect of romiplostim on platelet recovery in patients with persistent thrombocytopenia after UCBT remains unknown. Objectives: The primary objective of the study was to determine the maximum tolerated dose (MTD) of romiplostim in patients who failed to achieve platelet recovery by day +28 after UCBT. Secondary objectives were to determine if romiplostim influences the speed of platelet recovery, decreases the risk of thrombocytopenia related complications or affects the incidence of bone marrow (BM) fibrosis or relapse. Methods: This was a single center dose escalation trial of weekly romiplostim in patients >18 years who failed to achieve an untransfused platelet count (PLT) of 20 x 109/L by day +28 after myeloablative (MA) or nonmyeloablative (NMA) UCBT. A total of 21 patients were enrolled from April 2015 to December 2018. One patient withdrew and was replaced so 20 patients are included in the analysis. Romiplostim was administered at the assigned dose as 6 weekly injections beginning by day +42 post UCBT with an end date by day +100. Four dose levels (4, 6, 8, and 10 mcg/kg/dose) were evaluated. There was no intra-patient dose escalation. The MTD of romiplostim was determined by the Continual Reassessment Method, with a goal to identify a dose level which corresponds to the desired toxicity rate of £ 20%. Toxicities of interest included thrombosis, PLT>400x109/L and any grade 4-5 adverse event (AE) attributed to romiplostim. The comparison group were historical controls selected from our prospectively collected database based on age, gender, underlying disease, conditioning intensity and transplant type (1:1 matching). Results: Median (range) age of the patients was 59.5 (18-68) years and 60% were female. Ten patients had AML, 5 ALL, 3 MDS, 1 NHL and 1 MM. Of those, 11 received NMA double UCBT, 7 MA single UCBT and 2 received NMA single UCBT. Two patients received 4 mcg/kg/dose, two 6 mcg/kg/dose, four 8 mcg/kg/dose and the remaining 12 received 10 mcg/kg/dose. Only 5 patients completed the full 6 doses of treatment. Of the 15 patients who received less than 6 doses, 12 were due to a PLT>100×109/L, 2 due to PLT>400×109/L, and 1 was due to physician choice after the subject developed right upper extremity edema (without thrombosis). As shown in figure 1, 100% of romiplostim treated patients achieved platelet engraftment to 20 x 10^9/L at a median of 45 days post UCBT compared to 85% of controls who achieved platelet engraftment at a median of 49 days (p=0.07). Similarly, 90% of romiplostim treated patients achieved platelet engraftment to 50 x 10^9/L at a median of 48 days compared to 70% of historical controls who achieved platelet engraftment at a median of 52 days (p=0.04). The most common AEs were insomnia (30%), arthralgia (25%), myalgia (20%), headache (20%), dizziness and abdominal pain (15%). Only three patients experienced serious AEs requiring discontinuation of the drug: two had a PLT>400x109 /L (without complications) and one developed right upper extremity edema. Bleeding episodes improved with the use of the drug as well as need of transfusions (patients vs controls, p<0.05). All dose levels appear to be effective with overall low toxicity. Therefore, the MTD of romiplostim was 10mcg/kg/dose. All study patients were evaluated for BM fibrosis and relapse at regular intervals. There were no BM findings suggestive of increased fibrosis or relapse by day +100, and peripheral blood morphology was normal (no significant dacryocytosis, normal platelet morphology). Conclusion: Our study showed that romiplostim was well tolerated and accelerates platelet engraftment in patients undergoing UCBT, with the MTD being 10mcg/kg/dose. These results indicate that romiplostim is safe and potentially effective therapy to improve platelet recovery after UCBT. Further studies in larger numbers of patients are needed to confirm these observations. Disclosures Wagner: BlueRock: Research Funding; Rocket Pharmaceuticals: Consultancy; Novartis: Research Funding; Magenta: Consultancy, Research Funding; Gadeta: Membership on an entity's Board of Directors or advisory committees. Brunstein:Gamida: Research Funding; Magenta: Research Funding; Astex: Research Funding. Bejanyan:Kiadis Pharma: Other: advisory board. Smith:Amgen: Research Funding; Jazz Pharmaceuticals: Research Funding. OffLabel Disclosure: Romiplostim (Nplate) is an FDA approved drug for chronic ITP. In this study (phase I trial) we aimed to evaluate the safety and effectiveness of romiplostim on platelet recovery following UCBT.

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Gottlieb, A. B., C. T. Ritchlin, R. C. Chou, A. M. Mendelsohn, S. Rozzo, and L. Espinoza. "SAT0417 TILDRAKIZUMAB EFFICACY ON PSORIASIS IN PATIENTS WITH PSORIATIC ARTHRITIS—A 52-WEEK ANALYSIS FROM A PHASE 2 STUDY." Annals of the Rheumatic Diseases 79, Suppl 1 (2020): 1161.2–1162. http://dx.doi.org/10.1136/annrheumdis-2020-eular.778.

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Background:Tildrakizumab (TIL)—a high-affinity anti–interleukin-23p19 monoclonal antibody—is approved in the US, EU, and Australia to treat moderate to severe plaque psoriasis.1A randomised, double-blind, multidose, placebo-controlled, phase 2b study (NCT02980692) evaluating the efficacy and safety of TIL for the treatment of psoriatic arthritis (PsA) was recently completed.Objectives:To evaluate the proportion with 75%/90%/100% improvement in Psoriasis Area and Severity Index (PASI 75/90/100) among patients (pts) with PsA and measurable psoriasis (≥3% of the body surface area [BSA] affected at baseline) over 52 weeks of treatment.Methods:Pts ≥18 years old with PsA2and ≥3 tender and ≥3 swollen joints, stratified by prior anti-TNF use and baseline body weight (≤90 kg and >90 kg), were randomised 1:1:1:1:1 to receive TIL 200 mg every 4 weeks (Q4W) to week 52 (W52), TIL 200 mg every 12 weeks (Q12W) to W52, TIL 100 mg Q12W to W52, TIL 20 mg Q12W to W24→TIL 200 mg Q12W to W52, or placebo (PBO) Q4W to W24→TIL 200 mg Q12W to W52. PASI 75/90/100 were prespecified endpoints and were assessed by an independent assessor. Pts who received ≥1 dose of study drug were analysed. Safety assessments included treatment-emergent adverse event (TEAE) monitoring.Results:Overall, 391/500 pts screened met inclusion criteria; 235 (60.1%) had ≥3% BSA involvement at baseline (41–55/treatment arm). Demographics and baseline disease characteristics were generally consistent across treatment arms. Mean (standard deviation [SD]) age was 48.8 (12.6) years, average body mass index was 29.7, 96.7% of pts were White, and 23.3% were anti–tumour necrosis factor (TNF)-experienced. At baseline, the mean (SD) PASI score was 6.8 (8.2) and mean (SD) BSA affected was 10.5% (14.3%) overall. Among pts with baseline BSA ≥3%, TIL treatment significantly increased the proportion of PASI 75/90/100 responders vs PBO at W24; the proportion of responders continued to increase thereafter and was sustained through W52 (Figure). Similarly, in pts switching from PBO→TIL 200 mg Q12W or escalating from TIL 20→200 mg Q12W after W24, PASI 75/90/100 response rates increased through W36 and remained stable through W52. From W0→W24/W25→W52, 50.4%/39.9% pts experienced a TEAE. The most frequent TEAEs were nasopharyngitis (pooled TIL arms 5.4%/4.2% vs PBO 6.3%/3.8%) and upper respiratory tract infection (pooled TIL arms 3.8%/4.2% vs PBO 1.3%/0.0%). One pt (0.3%) discontinued before 24 weeks due to hypertension. There were no deaths or major adverse cardiac events during W0→W24 or W25→W52.Conclusion:PASI75/90/100 response rates progressively improved with treatment; PASI 75 responses were significantly improved vs placebo as early as W4 (TIL 200 mg Q12W), and all response rates were significantly improved vs placebo at W24. Response rates continued to improve through W36 and were sustained through W52. These results demonstrate TIL significantly reduced psoriasis disease activity and was generally well tolerated in a mixed population of anti–TNF-naïve and -experienced patients with PsA and BSA ≥3% through W52.References:[1]Reich K, et al.Lancet.2017;390(10091):276−88.[2]Taylor W, et al.Arthritis Rheum. 2006; 54(8):2665–73.Disclosure of Interests:Alice B Gottlieb Grant/research support from:: Research grants, consultation fees, or speaker honoraria for lectures from: Pfizer, AbbVie, BMS, Lilly, MSD, Novartis, Roche, Sanofi, Sandoz, Nordic, Celltrion and UCB., Consultant of:: Research grants, consultation fees, or speaker honoraria for lectures from: Pfizer, AbbVie, BMS, Lilly, MSD, Novartis, Roche, Sanofi, Sandoz, Nordic, Celltrion and UCB., Speakers bureau:: Research grants, consultation fees, or speaker honoraria for lectures from: Pfizer, AbbVie, BMS, Lilly, MSD, Novartis, Roche, Sanofi, Sandoz, Nordic, Celltrion and UCB., Christopher T. Ritchlin Grant/research support from: UCB Pharma, AbbVie, Amgen, Consultant of: UCB Pharma, Amgen, AbbVie, Lilly, Pfizer, Novartis, Gilead, Janssen, Richard C Chou Consultant of: Sun Pharmaceutical Industries, Inc, Alan M Mendelsohn Shareholder of: Johnson and Johnson, Employee of: Sun Pharmaceutical Industries, Inc, Stephen Rozzo Employee of: Sun Pharmaceutical Industries, Inc, Luis Espinoza: None declared

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Punnapu, Deepika, and Sanakayala Priyanka. "Study of Common Congenital Renal Anomalies." International Journal of Pharmaceutical and Clinical Research 16, no. 10 (2024): 136–40. https://doi.org/10.5281/zenodo.14031364.

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Background: Congenital anomalies are not uncommon; some remain asymptomatic, while the same lead to considerable morbidity and early death. Method: 90 congenital renal anomalies were observed in pregnant women during an ultrasound study. A 2-5 MHz sector or linear transducer is used to scan the urinary tract. The kidneys are scanned in the transverse and coronal planes. Results: Out of 90 fetuses, 70 (77.7%) were male, 19 (21.1%) were female, and 1 (1.1%) was ambiguous. Age of mother was 30.2 (± 5.80) range between 20-42. The major anomalies were hydronephrosis: 22 (24%) bilateral, 17 (18%) right, and 15 (16%) left; 11 (12%) multi cystic dysplastic kidney disease; 6 (6.6%) renal agenesis; 6 (6.6%) congenital poly cystic kidney disease; 3 (3.3%) pelvic kidney; 2 (2.2%) echogenic kidney; and 2 (2.2%) renal dysplasia. Conclusion: Congenital renal anomalies are commonly encountered on ultrasound imaging studies. Despite dramatic improvements in MRI, CT, and nuclear studies, sonography continues to occupy a central role in the evaluation and detection of congenital renal diseases due to its advantages of rapid scanning time, lack of radiation exposure, cost-effectiveness, and easy feasibility.

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Gordon, K., J. F. Merola, P. Foley, et al. "AB1473 EFFICACY RESPONSES ACROSS DISEASE SEVERITY AND TREATMENT HISTORY SUBGROUPS OF PATIENTS WITH MODERATE TO SEVERE PLAQUE PSORIASIS TREATED WITH GUSELKUMAB: POOLED RESULTS FROM VOYAGE-1 AND VOYAGE-2 THROUGH 5 YEARS." Annals of the Rheumatic Diseases 81, Suppl 1 (2022): 1842.1–1842. http://dx.doi.org/10.1136/annrheumdis-2022-eular.1530.

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BackgroundThe VOYAGE-1 and VOYAGE-2 phase 3 studies evaluated efficacy and safety of guselkumab (GUS) in patients with moderate-to-severe plaque psoriasis.ObjectivesTo assess the five-year efficacy of GUS by baseline disease characteristics and treatment history.MethodsThis study evaluated 1829 patients randomized to GUS, placebo (PBO)→GUS, and adalimumab (ADA) →GUS from the VOYAGE-1 and VOYAGE-2 trials. All patients received open-label GUS 100 mg every 8 weeks (Q8W) during Week (W) 52 to W252 in VOYAGE-1 and during W76 to W252 in VOYAGE-2. The proportions of combined GUS patients (including PBO→GUS and ADA→GUS) achieving Investigator’s Global Assessment of cleared or minimal (IGA-0/1) and Psoriasis Area and Severity Index (PASI) 90 response were evaluated from W100 to W252 by baseline PASI (<20/≥20) and IGA (<4/=4) scores, body surface area (BSA; <20%/≥20%), and prior psoriasis treatments. Analysis was performed using observed data after applying treatment failure rules.ResultsAt W252, proportions of combined GUS patients achieving IGA 0/1 or PASI 90, respectively, were comparable or numerically greater for patients with baseline PASI < 20 (85.4%; 81.1%) vs PASI ≥ 20 (81.4%; 83.8%); IGA < 4 (85.1%; 82.7%) vs IGA = 4 (78.9%; 81.1%); BSA < 20% (85.1%; 82.7%) vs BSA ≥ 20% (82.6%; 82.0%); no prior phototherapy (83.3%; 84.0%) vs prior phototherapy (83.8%; 81.1%); no prior non-biologic systemic therapy (84.5%; 83.0%) vs prior non-biologic systemic therapy (83.2%; 82.0%); and no prior biologics (85.3%; 83.8%) vs prior biologics (76.7%; 76.3%). This trend was consistent at each timepoint evaluated from W100 to W252.ConclusionThis analysis demonstrated that the high degree of efficacy of GUS treatment is durable through 5 years among broad subpopulations of patients with varying disease severity characteristics and previous psoriasis treatments.ReferencesNoneDisclosure of InterestsKenneth Gordon Grant/research support from: AbbVie, Almirall, Amgen, BMS, Celgene, Dermira, Dermavant, Eli Lilly, Janssen, LEO Pharma, Novartis, Ortho Dermatologics, Pfizer, Sun Pharma, and UCB Pharma, Joseph F. Merola Consultant of: AbbVie, Arena, Avotres, Biogen, Bristol-Myers Squibb, Celgene, Dermavant, Eli Lilly, EMD Sorono, Janssen, Leo Pharma, Merck, Novartis, Pfizer, Regeneron, Sanofi, Sun Pharma, and UCB pharma, Peter Foley Speakers bureau: AbbVie, Celgene, Eli Lilly, Galderma, GSK, Janssen, Leo Pharma, Merck, Novartis, Pfizer, Roche, and Valeant, Consultant of: AbbVie, Amgen, Arcutis, Aslan, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Celtaxsys, CSL, Cutanea, Dermira, Eli Lilly, Galderma, Genentech, GSK, Hexima, Janssen, Leo Pharma, Merck, Novartis, Pfizer, Regeneron Pharmaceuticals Inc, Reistone, Roche, Sanofi, Sun Pharma, UCB Pharma, and Valeant, Grant/research support from: grant/research support from AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Leo Pharma, Merck, Novartis, Pfizer, Sanofi, and Sun Pharma; and travel grants from AbbVie, Eli Lilly, Galderma, Janssen, Leo Pharma, Merck, Novartis, Pfizer, Roche, Sanofi, and Sun Pharma, Olivia Choi Shareholder of: may own stock or stock options in Johnson & Johnson, Employee of: Janssen Scientific Affairs, LLC, Daphne Chan Shareholder of: may own stock or stock options in Johnson & Johnson, Employee of: Janssen Scientific Affairs, LLC, Megan Miller Shareholder of: may own stock or stock options in Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Yin You Shareholder of: may own stock or stock options in Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Yaung-Kaung Shen Shareholder of: may own stock or stock options in Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Ya-Wen Yang Shareholder of: may own stock or stock options in Johnson & Johnson, Employee of: Immunology Global Medical Affairs, Janssen Pharmaceutical Companies of Johnson & Johnson, Andrew Blauvelt Speakers bureau: AbbVie, Almirall, Arena, Athenex, Boehringer Ingelheim, Bristol-Myers Squibb, Dermavant, Eli Lilly, Evommune, Forte, Galderma, Incyte, Janssen, Leo Pharma, Novartis, Pfizer, Rapt, Regeneron, Sandoz, Sanofi Genzyme, Sun Pharma, and UCB Pharma, Consultant of: AbbVie, Almirall, Arena, Athenex, Boehringer Ingelheim, Bristol-Myers Squibb, Dermavant, Eli Lilly, Evommune, Forte, Galderma, Incyte, Janssen, Leo Pharma, Novartis, Pfizer, Rapt, Regeneron, Sandoz, Sanofi Genzyme, Sun Pharma, and UCB Pharma

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Ashikur Rahaman, H. N., and Shravana Kumar Chinnikatti. "Clinical and USG Findings of Patients Presented with Breast Pain." Clinical Oncology Research and Reports 2, no. 2 (2021): 01–04. http://dx.doi.org/10.31579/2693-4787/026.

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Introduction: Breast pain also known as mastalgia is the dull acne in the breast, cause is multifactorial. It can affect any age group. Breast cancer is the most common site-specific cancer in women and is the leading cause of death from cancer for women aged 20-59 years worldwide. In India, breast cancer has ranked number one cancer among females, with age adjusted incidence as high as 25.8 per 100,000 women and mortality 12.7 per 100,000 women. Objective: To find out the Clinical and USG Findings of Patients Presented with Breast Pain. Settings and Design: Prospective cross-sectional descriptive study. Materials and Methods: Patients with complaints of breast pain in the age group 15 to 60 years with clinically no palpable mass attending to the Dept. of Clinical Oncology, Enam Medical College & Hospital, Savar, Dhaka, Bangladesh between January 2020 to December 2020 were included in the study. Detailed history with particular reference to age, duration of symptoms, Size, menstruation, marital status, parity, lactation, Nipple discharge and tenderness are recorded. Pain intensity was evaluated as mild, moderate and severe. Ultrasound of the breast including the axilla was done for all cases and findings recorded to correlate with clinical features. Results: Out of 90 patients studied, majority was in the age group (21-30) years, (43%) followed by (31-40 years) (40%) respectively. 57(63%) were married and 33(43%) were single. 21 patients had 1 child, 18 had 2 children with 6 of them having no children. Out of 90 patients only 3 attained menopause, rest of them have their monthly cycles. 51 patients had cyclical breast pain and 39 had noncyclical breast pain, 39 had pain on right breast, 36 on left side and bilateral in 15 patients. Pain was mild in 15 patients, moderate in 27 patients and severe in 6 patients. Various USG findings of the affected breast were normal study in 48 patients followed by duct ectasia and hetrogenous ectogenicity fibroadenosis, small cystic lesion and enlarged axillary lymph nodes etc. Conclusion: The study results show that majority of patients with breast pain without clinically palpable lump had normal USG study. But it also detects other early changes in the breast tissue. It can be used as a baseline investigation for any breast pain without palpable lump.

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P. Mungwari, Chakanaka, Wilfred Chipangura, B.Ndlovu, et al. "Kinetic and Equilibrium Modelling of Lead, Zinc and Copper Ions Sorption from Aqueous Solution Using Charcoal Fines." Asian Journal of Applied Science and Technology 08, no. 01 (2024): 14–32. http://dx.doi.org/10.38177/ajast.2024.8102.

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The potential of chemically modified charcoal fines UCF (unmodified charcoal fine) and MCF (modified charcoal fines) as low cost adsorbents for the removal of Pb2+, Cu2+ and Zn2+ ions from aqueous solution was studied. MCF was prepared by chemical modification of UCF with HNO3 and KOH followed by pyrolysis. The factors influenced the effectiveness of biosorption process were pH, contact time, initial metal concentration, temperature and adsorbent dosage. FT–IR spectra confirmed the existence and interaction of the adsorbents with the effluent pollutants. MCF exhibited optimum pH, temperature, contact time, initial metal ion concentration and biosorbent dosage values of 5, 35 0C, 90 minutes, 15 mg/L and 2 g, respectively. UCF exhibited optimum pH, temperature, contact time, initial metal ion concentration and biosorbent dosage values of 6, 35 0C, 100 minutes, 20 mg/L and 2.5 g, respectively. The adsorption isotherm modelling using both adsorbents showed that the equilibrium data conformed more to Langmuir than the Freundlich model. Kinetic studies showed that the adsorption processes followed a pseudo-second order kinetic model. Thermodynamic studies confirmed the spontaneity and feasibility of the adsorption process. The results showed that both adsorbent have the potential to be applied as alternative low cost biosorbent.

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López García, A., J. M. Benítez, C. Maroto-Martín, et al. "P327 Characteristics of esophago-gastro-duodenal Crohn's disease in the biologic era: a nationwide study of the Young GETECCU Group." Journal of Crohn's and Colitis 17, Supplement_1 (2023): i465—i467. http://dx.doi.org/10.1093/ecco-jcc/jjac190.0457.

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Abstract Background There is scarce information about Crohn’s disease (CD) affecting oesophagus, stomach and duodenum. The aim of the study was to describe phenotypic features, disease course and treatment response in these patients. Methods Patients with CD and upper involvement (oesophagus, stomach and/or duodenum) were included (upper CD=UCD). Extensive CD (ECD) was defined as concomitant distal involvement (jejunal, ileal and/or colonic). A multicentric, longitudinal and retrospective study was designed to evaluate disease characteristics at diagnosis and behaviour of UCD in patients &gt;= 18 years between January 2000 and December 2019 with at least 1 year follow-up since diagnosis. All treatments for UCD diagnosis and reason to start them were recorded, as well as 14- and 52-week response. Incidence of malignancy was also evaluated. Descriptive statistics were applied for quantitative and qualitative variables. Exact Fisher test was used for comparison of proportions. Results 197 (0.9%) UCD among 21.670 patients with Crohn’s Disease (CD) from 28 Spanish centres were included with a median of 10.7 years follow-up (min 2.2– max 22.1). Nearly 55% were men: median age at CD diagnosis was 29 years whereas for UCD was 32 years, with a mean of 2 months between CD and UCD diagnosis (SD 0.4). Only 9 patients had isolated UCD, whereas the rest presented ECD. 97% were diagnosed by endoscopy, in 2/3 due to symptoms (epigastric pain and dyspepsia). Inflammatory phenotype was prevalent in UCD with aphthous ulcer as the main endoscopic lesion (42%). Isolated duodenal location was the most frequent, followed by the antrum. Systemic corticosteroids and thiopurines were the most used treatments after UCD diagnosis. Treatment response at 14- and 52-weeks is detailed in Figures 1 and 2. Treatment withdrawal due to UCD activity was seen in 2-11% of patients. Thiopurines was the most durable treatment (median 50 months, min 0–max 210) followed by infliximab and adalimumab. Ten patients presented phenotype change over time (90% from inflammatory to stricturing). 53% of patients underwent endoscopic control (44% due to symptoms). De novo metaplasia was detected in 3 patients, and low-grade visible dysplasia in one. Two patients developed neoplasia: 1 gastric MALT lymphoma and 1 oesophagus carcinoma 5.5 and 20 years after UCD diagnosis, respectively. Conclusion UCD in adult population is infrequent. Upper involvement does not have an impact on immunosuppressive treatment requirements, but extensive disease does, appreciating a similar response to treatments for proximal and distal disease, both in the short and medium term. Although rare, risk of malignancy in UCD exists.

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Korotaeva, T., I. Gaydukova, V. Mazurov, et al. "AB0791 NETAKIMAB REDUCES SKIN MANIFESTATIONS OF PSORIATIC ARTHRITIS: RESULTS OF SUBANALYSIS FROM A DOUBLE-BLIND RANDOMIZED PHASE 3 STUDY (PATERA)." Annals of the Rheumatic Diseases 79, Suppl 1 (2020): 1694.2–1695. http://dx.doi.org/10.1136/annrheumdis-2020-eular.3583.

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Background:Patients with psoriatic arthritis (PsA) have skin manifestations that negatively affect their quality of life. Netakimab (NTK) is a humanized anti-interleukin 17A antibody approved for the treatment of moderate-to-severe plaque psoriasis.Objectives:To evaluate the efficacy of NTK on PsA skin manifestations. This abstract presents 24-week data from the ongoing phase 3 PATERA study (NCT03598751).Methods:PATERA is an international, multicenter, double-blind, placebo (PBO)-controlled study. 194 eligible adult patients with psoriatic arthritis (CASPAR, 2006), with inadequate response to csDMARD or one TNFi, were randomly assigned (1:1) to receive NTK 120 mg or placebo (PBO) subcutaneously at Week (Wk) 0, 1, 2, 4, 6, 8, 10, 14, 18, 22. 84 patients from PBO arm, failed to achieve ACR20 (20% improvement in American College of Rheumatology criteria) at Wk 16, were switched to NTK. Endpoints for assessment of skin involvement included PASI the proportion of patients achieving 75%, 90%, and 100% improvement in Psoriasis Area and Severity Index score (PASI75, PASI90 and PASI100, respectively).Results:184 patients (NTK arm, N=94; PBO arm, N=90) had PASI>0 at baseline (BL). Demographics and BL characteristics were balanced between treatment arms (Table 1). Treatment response was assessed in patients with ≥3% body surface area involvement (BSA) at BL. PASI75/90/100 response rates for NTK arm were significantly greater than for PBO and increased throughout the whole analyzed period. At Wk 24 PASI75 was achieved by 82.89% vs 11.11% for NTK and PBO, respectively (p<0.0001). A significantly higher percentage of patients achieved complete skin clearance (PASI100) in NTK arm compared to PBO (48.68% vs 6.94%, p<0.0001). PASI90 response rate was also higher for NTK (Figure 1). Relative change (%) from baseline in PASI score correlated with PASI75/90/100 response rates throughout the entire analyzed period. PASI decreased by 87.5 % in NTK arm vs only 4.4% in PBO arm after 24 wks of treatment (Table 2).Table 1.BL characteristics (for patients with PASI>0 at BL)ArmNTK (N=94)PBO (N=90)Age (years)*44.0 (11.82)42.9 (12.14)Male, n (%)51 (54.26)48 (53.33)PsA duration, mo*63.3 (73.81)68.1 (79.79)PASI*12.27 (11.31)10.35 (9.80)* mean (standard deviation); mo=months, PASI=Psoriasis Area and Severity IndexTable 2.Percentage (%) change from baseline in PASI total score (mean (SD))NTK (N=76)PBO (N=72)Week 4*-61.1 (36.04)-8.6 (31.99)Week 8*-74.2 (35.36)-8.4 (37.57)Week 16*-80.8 (49.38)-2.3 (61.06)Week 24*-87.5 (32.83)-4.4 (63.48)Data are presented for patients with BL BSA ≥ 3%; *p<0.0001 vs placeboFigure 1.Percentage of patients with PASI75/90/100 at Wk 24 (in patients with BL BSA≥3)Conclusion:24-week treatment with NTK at the dose of 120 mg resulted in significant improvement in skin manifestations in PsA patients: more than half of the patients with BSA≥3 at BL achieved complete skin clearance.Acknowledgments:This study was sponsored by JSC BIOCAD.Disclosure of Interests:Tatiana Korotaeva Consultant of: Pfizer, MSD, Novartis, AbbVie, Celgene, JSC BIOCAD, Janssen, UCB, Lilly and Novartis-Sandoz, Speakers bureau: Pfizer, MSD, Novartis, AbbVie, Celgene, JSC BIOCAD, Janssen, UCB, Lilly and Novartis-Sandoz, Inna Gaydukova Grant/research support from: JSC BIOCAD, Speakers bureau: Pfizer, Novartis, AbbVie, JSC BIOCAD, Сelgene, MSD, Sanofi, V Mazurov: None declared, Aleksey Samtsov Grant/research support from: JSC BIOCAD, Novartis, Eli Lilly, Johnson&Johnson, Celgene, Glenmark, Galderma, Sanofi, Vladislav Khayrutdinov Grant/research support from: Akrikhin, Alkoy, Belupo, JSC BIOCAD, Bosnaliejk, Verteks, Glenmark, Elfa, Leo Pharma, MSD, Novartis, Pfizer, Sun Pharma, Sanofi, Celgene, Pharmtec, AbbVie, Eli Lilly, Jadran, Janssen, Andrey Bakulev Grant/research support from: AbbVie, Eli Lilly, Pfizer, UCB, MSD, Novartis, Galderma, Celgene, Leo Pharma and Johnson&Johnson, JSC BIOCAD, Consultant of: Novartis, Celgene and Johnson&Johnson, Speakers bureau: AbbVie, Eli Lilly, Galderma, UCB, Novartis, Celgene and Johnson&Johnson, Muza Kokhan Grant/research support from: AbbVie, Eli Lilly, Pfizer, UCB, MSD, Novartis, Galderma, Celgene, Leo Pharma and Johnson&Johnson, JSC BIOCAD, Consultant of: Novartis, Celgene and Johnson&Johnson, Speakers bureau: AbbVie, Eli Lilly, Galderma, UCB, Novartis, Celgene and Johnson&Johnson, Alena Kundzer: None declared, Nikolaj Soroka Grant/research support from: JSC BIOCAD, Ekaterina Dokukina Employee of: JSC BIOCAD, Anna Eremeeva Employee of: JSC BIOCAD

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Martínez-Feito, A., B. Hernández-Breijo, M. Novella-Navarro, et al. "POS0647 DOES TNF INHIBITOR MOLECULAR STRUCTURE MATTER? ANALYSIS OF IMPACT OF BASELINE RHEUMATOID FACTOR TITERS ON DRUG LEVELS IN PATIENTS WITH RHEUMATOID ARTHRITIS." Annals of the Rheumatic Diseases 81, Suppl 1 (2022): 594–95. http://dx.doi.org/10.1136/annrheumdis-2022-eular.2486.

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BackgroundElevated rheumatoid factor (RF) in patients with rheumatoid arthritis (RA) is associated with higher disease activity and increased risk for disease progression1.Recent publications indicate significantly lower efficacy of TNF inhibitors (TNFi) in RA patients with high RF levels compared with low/negative RF subgroup2,3. Fab therapy with Certolizumab pegol (CZP), a PEGylated, Fc-free monoclonal antibody (mAb), has shown comparable efficacy and consistent serum levels irrespective of baseline RF4.RF binds the Fc region of IgG1, the subtype used to engineer the majority of mAbs5. Formation of large immune complexes may likely explain the inceased clearance of mAbs in patients with high RF titers and reported reduced TNFi efficacy.ObjectivesWe aimed to evaluate in clinical practice whether RF levels in RA patients influence serum drug levels of 3 TNFi with different molecular structures.MethodsWe evaluated retrospectively a cohort of RA patients from La Paz University Hospital (RA-Paz Registry, 1999-2019) treated with Infliximab (IFX), Adalimumab (ADA) or CZP. Clinical and demographic data were collected at baseline (T0) and after 6 months (T6) of treatment. RF titers and serum drug levels were measured at T0 and T6 using nephelometry and ELISA respectively. Association between baseline RF titers and drug levels was assessed using non-parametric test (Mann-Whitney).Results168 patients were evaluated: 90 received IFX, 48 ADA and 32 CZP. Characteristics at T0 are shown in Table 1. All patients had active disease at baseline and 76% were RF positive: ADA subgroup had lower percentage of positive RF than IFX and CZP subgroups. Patients were stratified into quartiles based on baseline RF titers: low (20-57 IU/ml), medium (57-380 IU/ml), high (>380 IU/ml) and seronegative (<20 IU/ml).Table 1.Baseline characteristics.CharacteristicsTotal (n=168)IFX (n=90)ADL (n=48)CZP (n=32)p valueAge, years*55.5(45.3-66)57(46-65)50(42-64)61(47-70)0.08Body mass index, Kg/m2*24.5(21.7-29)24.2(21.8-27.7)24.7(21.5-30.3)24.6(22.2-30.3)0.3Male, n(%)28(17%)14(15%)9(19%)5(17%)0.2Disease duration, years*8.7(4.5-14.3)8.4 (4.4-14.3)8.8 (3.9-16)9.7(5-12)0.06Smoking status, n(%)0.03Currently/ex-smoker66(39%)29(32%)22(48%)16(57%)Non-smoker96(57%)61(68%)24(52%)12(43%)RF, n(%)128(76%)75(83%)28(58%)25(81%)0.002ACPA, n(%)134(80%)73(81%)35(73%)27(84%)0.3DAS28**5.1(1.3)5.4(1.3)4.5(1.3)4.9(1.3)0.002CRP levels*7.8(3-21.8)10.3(3.2-25.2)5.1(1.4-10.1)7.8(2.3-18.2)0.1Prior bDMARDs, n(%)26(15%)10 (11%)10 (21%)6(20%)0.2Monotherapy, n(%)16(10%)8(9%)8(17%)00.2csDMARDS, n(%)152(90%)82(91%)82(91%)32(100%)Methotrexate, n(%)112(67%)64(78%)33(83%)17(53%)0.2Other csDMARDs, n(%)24(24%)18(22%)7(18%)15(50%)0.0008Prednisone, n(%)85(51%)49(54%)21(44%)16(50%)0.6*Median and interquartile range;**mean and standard deviationDrug levels of IFX and ADA at T6 were significantly lower in those patients who had higher RF titers at T0 compared to seronegative. In contrast, CZP levels remained stable irrespectively of baseline RF titers, without significant differences among quartiles (Figure 1).ConclusionHigher baseline RF titers are associated with lower IFX and ADA levels at T6 in a cohort of RA patients. A concentration-response association has been clearly established for TNFi, and baseline RF levels appear to influence drug levels.Reduced immune complexes formation with CZP may result in a limited impact of baseline RF titers on drug levels.References[1]Aletaha D. Arthritis Res Ther2015;17(1):229.[2]Bobbio-Pallavicini F. Ann Rheum Dis 2007;66(3):302–7.[3]Potter C. Ann Rheum Dis 2009;68(1):69–74.[4]Tanaka Y. APLAR 2020. Oral Communication.[5]Levy RA. Immunotherapy 2016;8(12):1427-1436.AcknowledgementsThis study was funded by an anrestricted reserch grant from UCB pharma.Disclosure of InterestsANA MARTÍNEZ-FEITO: None declared, Borja Hernández-Breijo: None declared, Marta Novella-Navarro Grant/research support from: UCB, Alejandro Villalba: None declared, Diana Peiteado: None declared, Pilar Nozal: None declared, DORA PASCUAL-SALCEDO Speakers bureau: Abbvie, Pfizer, Novartis, Takeda, Menarini and MSD., Grant/research support from: Abbvie, Pfizer, Novartis, Takeda, Menarini and MSD., Alejandro Balsa Speakers bureau: Pfizer, AbbVie, Galapagos, Lilly, Gilead, UCB, Nordic, Sandoz, Consultant of: Galapagos, Pfizer, AbbVie, Lilly, UCB, Nordic, Grant/research support from: Pfizer, Abbvie, UCB, Chamaida Plasencia Speakers bureau: Abbvie, Pfizer, UCB, Sandoz, Sanofi, Biogen, Lilly, Roche and Novartis, Grant/research support from: Abbvie, Pfizer, UCB, Sandoz, Sanofi, Biogen, Lilly, Roche and Novartis

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Marcu, Radu Dragos, Arsenie Dan Spinu, Bogdan Socea, et al. "Castleman�s Disease - Clinical, Histological and Therapeutic Features." Revista de Chimie 69, no. 4 (2018): 823–30. http://dx.doi.org/10.37358/rc.18.4.6208.

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Castleman�s disease (CD) is a rare and benign lymphoproliferative pathology, characterized by lymphoid tissue hyperplasia, process that can occur at any site of the lymphoid chain. The purpose of this paper is to review the existing data regarding Castleman�s disease etiopathogenesis and treatment. Considering the extent of the lymphoid tissue involvement Castleman�s disease can be classified as unicentric (UCD) and multicentric (MCD). Another classification of this pathology is based on the histopathological features: hyaline vascular CD (90% of cases), plasma cell CD (less than 10%) and mixed cell type. Patients with UCD have good prognosis, the gold standard treatment being complete surgical excision. The multicentric type in contrast to UCD has a worse prognosis and associates the risk of evolving to lymphoma. Over the years different therapeutic strategies have been applied in the management of multicentric Castleman�s disease: glucocorticoids, chemotherapy, antiviral agents and monoclonal antibodies that target CD (cluster of differentiation) 20, interleukin -6 (IL-6) and IL-6 receptors. Castleman�s disease is a rare and complex pathology, whose etiopathogenesis is still incompletely elucidated. In the past few years the overall survival and progression free survival has significantly increased, due to different therapeutic options that have emerged, options that have constantly offered better and better results. Further investigation regarding the chemical interactions between different receptors and therapeutic molecules, understanding the mechanism of action and the potential benefits of each therapeutic agent may prove useful in clinical practice for treating CD.

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Maksymowych, W. P., L. Caplan, A. Deodhar, et al. "AB1358-HPR DIAGNOSIS OF AXIAL SPONDYLOARTHRITIS: A PRIMARY UNMET EDUCATIONAL NEED FOR RHEUMATOLOGISTS." Annals of the Rheumatic Diseases 79, Suppl 1 (2020): 1966.2–1966. http://dx.doi.org/10.1136/annrheumdis-2020-eular.6115.

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Background:Diagnosis of axial spondyloarthritis (axSpA) is challenging because of absent physical findings in early disease and the limited diagnostic performance of laboratory markers. Considerable reliance is placed on imaging of the sacroiliac joints (SIJ) but specialty training is primarily focused on interpretation of plain radiographic abnormalities.Objectives:We aimed to identify what might be the primary unmet educational needs of rheumatologists completing fellowship training by using clinical and imaging data from an inception cohort of patients presenting with undiagnosed back pain. We hypothesized that concordance would increase after imaging is reviewed after the clinical data.Methods:The diagnosis of axSpA was compared between local rheumatologists, axSpA experts and pF using clinical and imaging data from the multicenter Screening for Axial Spondyloarthritis in Psoriasis, Iritis, and Colitis (SASPIC) Study. In this inception cohort, patients ≤45 years of age with ≥3 months back pain undergo diagnostic evaluation by a local SASPIC rheumatologist, including imaging of the SIJ, who then records a global evaluation of presence/absence of axial SpA. This is done at 3 consecutive stages: 1.After the clinical evaluation. 2.After the results of labs (HLA B27, CRP) and radiography. 3.After review of the local MRI. In this exercise, 20 cases were selected from the SASPIC cohort and the rheumatologist global evaluations were removed from the eCRFs. Four experts in axSpA reviewed the clinical and imaging data in each eCRF and provided their global evaluations for stages 1, 2, and 3 of these 20 cases. Subsequently, 4 pF rheumatologists conducted the same exercise blinded to the assessments of the local rheumatologist and experts in axSpA. Concordance (% agreement) between the assessors was analyzed.Results:Diagnosis of axSpA by the local SASPIC rheumatologist was made in 90%, 65%, and 75% of cases after stages 1, 2, and 3, respectively. Majority diagnosis of axSpA by experts was made in 84.2% (16/19), 57.9% (11/19), and 63.2% (12/19), after stages 1,2, and 3, respectively. Majority diagnosis of axSpA by pF rheumatologists was made in 94.4% (17/18), 100% (16/16), and 93.8% (15/16). Concordance among experts and between experts and local SASPIC rheumatologists increased after review of imaging data. For pf-rheumatologists concordance with experts increased after review of imaging for 2 assessors and decreased for the other 2 assessors. For the latter, the primary reason for decrease in concordance with experts was false positive diagnosis of axSpA in 35% and 30% of the cases after review of the imaging.Conclusion:A structured case-based and sequential evaluation of clinical and imaging data suggests a gap in the training of recently graduated rheumatologists, with over-interpretation of imaging leading to false positive diagnosis of axSpA.AssessorsMean % Concordance (range) for diagnosis of axSpAStage 1Stage 2Stage 3Experts in axSpA64.2 (45-80)75.8 (65-85)84.2 (70-95)Local rheumatologist vs Experts in axSpA73.8 (70-80)83.8 (80-85)83.8 (80-90)pF rheumatologist 1 vs Experts consensus78.994.494.7pF rheumatologist 2 vs Experts consensus89.561.168.4pF rheumatologist 3 vs Experts consensus63.272.284.2pF rheumatologist 4 vs Experts consensus89.566.768.4Disclosure of Interests:Walter P. Maksymowych Grant/research support from: AbbVie, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Boehringer Ingelheim, Celgene, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, and UCB, Employee of: Chief Medical Officer of CARE Arthritis Limited, Speakers bureau: AbbVie, Janssen, Novartis, Pfizer, and UCB, Liron Caplan: None declared, Atul Deodhar Grant/research support from: AbbVie, Eli Lilly, GSK, Novartis, Pfizer, UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myer Squibb (BMS), Eli Lilly, GSK, Janssen, Novartis, Pfizer, UCB, Speakers bureau: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myer Squibb (BMS), Eli Lilly, GSK, Janssen, Novartis, Pfizer, UCB, Soha Dolatabadi: None declared, Mark Hwang: None declared, Adam Carlson: None declared, Kelly Steed: None declared, Amanda Carapellucci: None declared, Joel Paschke: None declared, Lianne S. Gensler Grant/research support from: Pfizer, Novartis, UCB, Consultant of: AbbVie, Eli Lilly, GSK, Novartis, UCB

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Kaur, Rupinderjit, Mridu Manjari, and Sanjay Piplani. "Clinicopathological correlation of p63 in Urothelial Carcinoma: Immunohistochemical Study." Annals of Pathology and Laboratory Medicine 7, no. 6 (2020): A269–274. http://dx.doi.org/10.21276/apalm.2738.

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Background: Urothelial cancer (UCa) poses a significant medical and public health concern in most parts of the world and is defined as a pan- urothelial disease in which entire urothelium of the renal pelvis to the urethra can undergo malignant transformation. Bladder tumors account for 90–95% of urothelial carcinomas and are the most common urinary tract malignancy. It is three times less common in females. Methods: The study was conducted on 40 cases of Urothelial Carcinoma received as biopsy specimens in a tertiary care hospital. There were 20 cases each of low grade and high grade and after grading these were subjected to p63 expression. Result: 78% of the patients were from 50-75 year age group with Male to Female ratio being 4:1. Painless hematuria was most common complaint. The size varied from 0.5 to 7.2 cm. For P63, 38 (95%) cases showed positive p63 expression. Of which 20 cases were low grade and 18 (90%) were high grade papillary urothelial carcinomas. Of P63 positive cases 36 cases showed moderate to strong staining intensity whereas two cases showed mild staining intensity. The p63 expression decreased with grade and invasion. Conclusion: P63 immunoexpression decreases with increasing grade of tumor as well as with invasion thus showing that its expression is related with good prognosis.

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Peters, Rowayda E., Roger Strair, Arnold D. Rubin, et al. "Successful Expansion of Umbilical Cord Blood Cells as a Source of Hematopoietic Progenitors for Adult Transplantation." Blood 104, no. 11 (2004): 2857. http://dx.doi.org/10.1182/blood.v104.11.2857.2857.

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Abstract The low yield of progenitor CD34+ cells recovered from umbilical cord blood (UCB) limits the utility of this source for transplantation in adults. This limitation has triggered investigations into how ex vivo expansion of hematopoietic stem cells (HSC) could be achieved to allow for transplantation in larger recipients. In the present study, the incubation of MNC and not selected CD34+cells in the presence of SCF 25ng/ml+MGDF 10ng/ml+FLt-3 25ng/ml+IL-6 20ng/ml, and 10% human serum in stroma-free liquid culture generated long-term expansion of transplantable UCB HSC. In vitro, HSC expansion from 13 UCB lasted &gt;7 months giving 39, 1.3x104, and 4.7 x109 fold increase in total cell count after 14, 70 and 217 d of expansion as compared to d0 (105/ml). Similarly, CD34+ and CD34+/CD38− cell populations increased reaching 229 and 2.2x105 and 91 and 2.2x104 fold after 14 and 70d of expansion. Examination of cell morphology and analysis by flow cytometry showed the presence of primitive and mature cells belonging to all hematopoietic cell lineages. Similarly, multilineage colonies with recloning capacity were generated in culture. Erythroid, myeloid and mixed colonies increased by 116 and 1.8x104 fold and megakaryocytic colonies by 8 and 527 fold after 14 and 70d. Expanded cells were karyotypically normal and lacked the most common chromosome translocations seen in AML and CML t (15,17) and t (9, 22). HSC expanded for 6 and 13 weeks and cropreserved for 6–11 months were able to re-expand in liquid culture and generate colonies capable of recloning and multi-lineage differentiation. We estimated the frequency of SCID repopulating cells (SRC) in UCB samples expanded for 2 and 12 w using 1000,500,250 and 125 unselected CD34+ cells injected intravenously into sublethally irradiated NOD/SCID mice. Mice were sacrificed 20 weeks after transplantation. Human cell engraftment measured as CD45+ (HuCD45+) was detected in all mice (x3mice/dilution) (0.1–9.8%). In addition, HuCD45+ cells with multilineage phenotype were present, (CD19 (lymphoid), CD33 (myeloid), CD71and Glycophorin-A (erythroid) as well as CD34+/CD38− cells). SRC increased by 90 fold after 2 weeks of expansion and by 187 fold after 12 weeks compared to unexpanded CD34+cells. Additional proof of human cell engraftment was documented using semisolid culture (MethoCultTM GF H4434 Stem Cell Technologies). Human myeloid and erythroid colonies were generated from all dilutions, and counts ranged between 63–271/500,000 MNC. Initial studies to test the relative magnitude of UCB HSC expansion from 24-well plates to culture bags (OptiCyte TM, Baxter) using one UCB, the total cell count increased by (6.3 and 20 (bags) Vs 2.3 and 3.3 fold (wells) after 7 and 14d) and CD34+ subpopulations including CD34+/CD38−. Based on these ongoing results, a phase II clinical trial using ex vivo expanded UCB for 14d in a setting of sub ablative Conditioning is planned.

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Okuku, Fred Machyo, Jackson Orem, George Holoya, Christopher J. De Boer, and Matthew M. Cooney. "Prostate cancer burden at the Uganda Cancer Institute (UCI)." Journal of Clinical Oncology 33, no. 7_suppl (2015): 246. http://dx.doi.org/10.1200/jco.2015.33.7_suppl.246.

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246 Background: In Uganda prostate cancer is the most common cancer and the incidence is increasing 5.2% annually. This burden is seen without screening programs in a country with limited access to cancer care. Data describing patient presentation and outcomes are lacking. Methods: Retrospective chart review for men with histologically-confirmed prostate cancer at the UCI from January 1 to December 17, 2012. Patient characteristics, treatments, and survival data were obtained. Results: There were 181 men with confirmed prostate cancer [C1] . Mean age was 69.5 (SD 9.0) with a median age of 70 (IQR: 64-75). Men presented with symptoms of lower urinary tract symptoms 73% (n=131), bone pain in 18% (n=32), elevated PSA 3% (n=5) and other causes 6% (n=11). Median baseline PSA was 91.3 ng/ml (IQR: 19.5-311.3 ng/ml) and upon presentation 51.1% (n=92) had a PSA value over 100 ng/ml. Gleason Score was 9 or 10 in 66.7% (n=120), Gleason Score 7 to 8 in 23.4% (n=44), and Gleason six or lower in 10% (n=18). Ninety percent (n=136) of patients had stage IV disease, 6.5% (n=11) were stage III, 11.9% were (n= 20) stage II, and 1 individual (0.6%) had stage I. Common sites of metastases included bone 73% (n=102), visceral metastases 21% (n=29), and lymph node involvement 4% (n=5). Spinal cord compression occurred in 30.9% (n=55) and 5.6% (n=10) experienced a fracture. A total of 14.9% (n=27) patients underwent radical prostatectomy and 17.7% (n=32) received radiotherapy. GNRH agonist was given to 45.3% (n=82) of patients, 29.2% (n=53) of men received diethylstilbestrol, and 26% (n=47) underwent bilateral orchiectomy. Chemotherapy was administered to 21.6% (n=39) and 52.5% (n=95) received bisphosphonates. During the 12 months of study 23.8% (n=43) of men experienced death and 54.4% (n=98) were lost to follow up. Conclusions: UCI patients present with significant symptoms, high PSA, and aggressive Gleason Scores. 90% present with stage IV disease and almost 33% develop spinal cord compression. Prostatectomy and radiotherapy are infrequently given and the primary treatments are hormonal manipulation and chemotherapy. Almost 25% of patients succumb within a year of presentation and there is a high rate of patients lost to follow up.

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Mease, P. J., A. Setty, K. Papp, et al. "POS1539 SAFETY AND EFFICACY OF UPADACITINIB IN PATIENTS WITH PSORIATIC ARTHRITIS AND INADEQUATE RESPONSE TO BIOLOGICS: 3-YEAR RESULTS FROM THE PHASE 3 SELECT-PSA 2 STUDY." Annals of the Rheumatic Diseases 82, Suppl 1 (2023): 1136–37. http://dx.doi.org/10.1136/annrheumdis-2023-eular.2513.

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BackgroundThe efficacy and safety of upadacitinib (UPA) in patients (pts) with psoriatic arthritis (PsA) and inadequate response to ≥1 biologic disease-modifying antirheumatic drug (bDMARD-IR) have been demonstrated up to 56 and 104 weeks of treatment[1,2].ObjectivesTo assess the long-term safety and efficacy of UPA in bDMARD-IR pts with PsA through 152 weeks of treatment in the SELECT-PsA 2 study.MethodsPts were randomized to receive UPA 15 or 30 mg once daily (QD), or placebo (PBO) for 24 weeks, followed by blinded switch to UPA 15 or 30 mg QD for pts initially randomized to PBO. After 56 weeks, pts continued their assigned dose up to 152 weeks in an open-label extension (OLE). Following approval of the 15 mg QD dose, the protocol was amended and all pts on UPA 30 mg QD were switched to the approved dose (earliest switch at week 116). Endpoints assessed at 152 weeks included: % of pts achieving 20/50/70% improvement in American College of Rheumatology (ACR) criteria, minimal disease activity (MDA), and 75/90/100% improvement in Psoriasis Area and Severity Index, as well as patient-reported outcomes. Efficacy data were evaluated using non-responder imputation (NRI) and as-observed (AO) data (binary endpoints), and mixed effect model for repeated measures (continuous endpoints). Treatment-emergent adverse events (TEAEs) through 3 years (cut-off date, 05 May 2022) are also reported.ResultsOf the 641 pts randomized to receive UPA 15 or 30 mg QD, or PBO followed by UPA 15 or 30 mg QD (n=211, 218, 106, and 106, respectively), 478 entered the OLE. Improvements in efficacy outcomes with UPA observed at 561and 1042weeks were maintained through the OLE, with ACR20 achieved by 43–51% (NRI) and 79–87% (AO) of pts across treatment arms at week 152. The highest % of MDA responders at week 152 (31% [NRI] and 44% [AO]) were in the continuous UPA 15 mg arm (Table 1). UPA was well tolerated through 152 weeks, with no new safety signals identified. The overall exposure-adjusted event rates for any TEAE were higher for UPA 30 vs 15 mg (295 vs 226 events/100 PY, respectively [Figure]).ConclusionObserved improvements in the signs and symptoms of PsA with UPA were maintained through 3 years of treatment in bDMARD-IR pts. The long-term safety profile of UPA in this treatment-refractory population was consistent with its known safety profile across indications.References[1]Mease PJ, et al.Rheumatol Ther2021;8:903–919[2]Mcinnes I, et al.Rheumatol Ther2022. doi.org/10.1007/s40744-022-00499-wTable 1.Efficacy endpoints at week 152EndpointUPA 15 mg QD (n=211)UPA 30 mg QDa(n=218)PBO/UPA 15 mg QD (n=106)PBO/UPA 30 mg QDa(n=106)Proportion of patients (%)NRIAONRIAONRIAONRIAOACR20/50/7051/39/2481/60/3649/35/2279/56/3443/29/2087/60/4043/28/1879/53/36MDA3144254116411937PASI75/90/10043/31/2066/46/3041/36/2972/61/4845/34/2379/61/4241/35/3075/63/55Resolution of enthesitis (LEI=0)b3869366824762562Resolution of dactylitis (LDI=0)c4994501003410028100Change from BLMixed effect model for repeated measuresmean (95% confidence interval)Health Assessment Questionnaire – Disability Index-0.4(-0.5, -0.3)-0.5(-0.5, -0.4)-0.5(-0.6, -0.3)-0.3(-0.4, -0.2)Bath Ankylosing Spondylitis Disease Activity Indexd-2.6(-3.1, -2.1)-2.0(-2.5, -1.5)-2.3(-3.1, -1.5)-2.5(-3.2, -1.7)Ankylosing Spondylitis Disease Activity Scored-1.4(-1.6, -1.1)-1.1(-1.4, -0.9)-1.0(-1.4, -0.7)-1.2(-1.5, -0.8)aFollowing a protocol amendment, all pts on UPA 30 mg QD switched to UPA 15 mg QD (earliest switch at week 116).bBL LEI >0.cBL LDI >0.dAmong pts with psoriatic spondylitis at BL, as determined by the investigator.ACR20/50/70, 20/50/70% improvement in American College of Rheumatology Criteria; AO, as observed; BL, baseline; LDI, Leeds Dactylitis Index; LEI, Leeds Enthesitis Index; MDA, minimal disease activity; NRI, non-responder imputation; PASI75/90/100, 75/90/100% improvement in Psoriasis Area and Severity Index; PBO, placebo; pt, patient; QD, once daily; UPA, upadacitinib.AcknowledgementsAbbVie funded this study; contributed to its design; participated in data collection, analysis, and interpretation; and participated in the writing, review, and approval of the abstract. AbbVie and the authors thank all study investigators for their contributions and the patients who participated in this study. No honoraria or payments were made for authorship. Medical writing support was provided by Katerina Betsista, MD, of 2 the Nth (Cheshire, UK), and was funded by AbbVie.Disclosure of InterestsPhilip J Mease Grant/research support from: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squib, Celgene, Galapagos, Genentech, Gilead, GlaxoSmithKline, Janssen, Lilly, Novartis, Pfizer, Sun Pharma, and UCB, Arathi Setty Employee of: AbbVie, and may own stock or options, Kim Papp Speakers bureau: AbbVie, Akros, Allergan, Almirall, Amgen, Bausch Health, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Dermavant, Dermira, Eli Lilly and Company, Galderma, Genentech/Roche, Janssen, Kyowa Kirin, LEO, Meiji, Merck Sharp & Dohme, Novartis, Pfizer, Regeneron, Sanofi Genzyme, Sienna Pharmaceuticals, Sun Pharma, Takeda, UCB, and Valeant, Consultant of: AbbVie, Akros, Allergan, Almirall, Amgen, Arcutis, Avillion, Bausch Health, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Dermavant, Dermira, Eli Lilly and Company, Galderma, Genentech/Roche, GlaxoSmithKline, Janssen, Kyowa Kirin, LEO, Meiji, Merck Sharp & Dohme, Novartis, Pfizer, Regeneron, Sanofi Genzyme, Sienna Pharmaceuticals, Sun Pharma, Takeda, UCB, and Valeant, Filip van den Bosch Speakers bureau: AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, Janssen, Merck, Novartis, Pfizer, Sanofi, and UCB, Consultant of: AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, Janssen, Merck, Novartis, Pfizer, Sanofi, and UCB, Shigeyoshi Tsuji Speakers bureau: AbbVie, Eli Lilly, Janssen, Novartis, and UCB, Consultant of: AbbVie, Eli Lilly, Janssen, Novartis, and UCB, Grant/research support from: AbbVie, Eli Lilly, Janssen, Novartis, and UCB, MAURO KEISERMAN Speakers bureau: AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly, Roche, Novartis, Pfizer, Janssen, and UCB, Grant/research support from: AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly, Roche, Novartis, Pfizer, Janssen, and UCB, Kyle Carter Employee of: AbbVie, and may own stock or options, Reva McCaskill Employee of: AbbVie, and may own stock or options, Erin McDearmon-Blondell Employee of: AbbVie, and may own stock or options, Peter Wung Employee of: AbbVie, and may own stock or options, William Tillett Speakers bureau: AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Celgene, Eli Lilly, MSD, Novartis, Ono Pharma, Pfizer, and UCB, Grant/research support from: AbbVie, Celgene, Janssen, Eli Lilly, Pfizer, and UCB.

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Brunstein, Claudio G., Sarah Larson, Tyson Rodgers, Ted Eastlund, Katherine Symons, and Daniel Weisdorf. "Red Blood Cell (RBC) and Platelet (PLT) Transfusion after Allogeneic Transplant for Leukemia: Similar Utilization after Sibling (SIB) Peripheral Blood Stem Cell (PBSC) and Umbilical Cord Blood (UCB) Graft." Blood 106, no. 11 (2005): 1755. http://dx.doi.org/10.1182/blood.v106.11.1755.1755.

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Abstract Transfusion independence is an important goal of hematopoietic stem cell transplantation (HSCT) for acute leukemia. We hypothesized that time to red blood cell (RBC) and platelet (PLT) transfusion independence would differ depending on the source of stem cells and the intensity of the preparative regimen. We retrospectively analyzed all transfusions administered to 146 acute leukemia patients who underwent a HSCT at our institution receiving a sibling (SIB) peripheral blood stem cell (PBSC) or an unrelated umbilical cord blood (UCB) graft, between 7/01 and 12/03. Median age was 35.6 yrs. (range 0.5–69.6) and 88 (60%) were male. Ninety-eight (67%) patients (pts) received an UCB and 48 (33%) a SIB graft. Thirty-four (71%) SIB and 56 (57%) UCB pts. received a myeloablative preparative regimen. Median time to RBC independence among all SIB PBSC recipients (n= 25) was 56 days [myeloablative conditioning (MA) (n= 18) 52.5 days; non-myeloablative conditioning (NMA) (n=7) 58 days], and the cumulative incidence of RBC independence at 6 months was 52% (95%CI: 39–69) [MA 53% (95%CI: 38–73); NMA 43% (95%CI: 28–89)]. For recipients of a UCB graft (n= 58) median time to RBC independence was 47 days [MA (n= 38) 56.5 days; NMA (n=20) 41.5 days], and the cumulative incidence of RBC independence at 6 months was 59% (95%CI: 50–70) [MA 68% (95%CI: 56–82); NMA 48% (95%CI: 34–66)]. Median time to platelet (PLT) independence among all SIB PBSC recipients (n= 27) was 25 days [MA (n= 19) 26 days; NMA (n=8) 12 days], and the cumulative incidence of PLT independence at 6 months was 56% (95%CI: 44–73) [MA 56% (95%CI: 41–76); NMA 57% (95%CI: 35–94)]. There was no statistically significant difference in the cumulative incidence of RBC independence between SIB PBSC vs. UCB (p=0.49), and MA vs. NMA (p=0.18). For recipients of an UCB graft (n= 68) median time to PLT independence was 43 days [MA (n= 44) 47.5 days; NMA (n=24) 39 days], and the cumulative incidence of PLT independence at 6 months was 69% (95%CI: 61–79) [MA 79% (95%CI: 68–90); NMA 57% (95%CI: 44–75)]. There was no statistically significant difference in the cumulative incidence of PLT independence between SIB PBSC vs. UCB (p=0.52), and MA vs. NMA (p=0.21). In multivariate analysis, the source of HSC and intensity of the preparative regimen were not predictors of RBC or PLT independence. This analysis shows similar RBC and PLT utilization in recipients of SIB PBSC and UCB following either MA or NMA conditioning. The substantial costs associated with transfusion support for allogeneic HSC transplant are similar in SIB PBSCT and UCB graft recipients.

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Bernardo, Maria Ester, Maria Antonietta Avanzini, Cesare Perotti, et al. "Phenotypical and Functional Characterization of Umbilical Cord Blood-Derived Mesenchymal Stromal Cells Expanded in the Presence of Platelet Lysate and Comparison with Their Bone Marrow-Derived Counterpart." Blood 112, no. 11 (2008): 3484. http://dx.doi.org/10.1182/blood.v112.11.3484.3484.

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Abstract The presence of mesenchymal progenitors in full-term umbilical cord blood (UCB) has been object of discussion in recent years, as attempts to obtain these cells have either failed or yielded low frequency of mesenchymal stromal cells (MSCs). MSCs have been so far mainly expanded in vitro in the presence of fetal calf serum (FCS), which potentially carries the risk of both transmitting zoonoses and causing immune reactions against animal proteins. For these reasons, alternative culture supplements, devoid of animal components, such as platelet lysate (PL), have been tested, allowing efficient MSC isolation and expansion from bone marrow (BM). In this study, we tested the ability of PL-additioned medium to isolate and expand ex vivo MSCs from full-term UCB (UCB-MSCs) and we characterized these cells in terms of clonogenic efficiency, proliferative capacity, morphology, immunophenotype, differentiation potential and biosafety profile, comparing these characteristics with those of PL-expanded BM-MSCs. Moreover, we focused our attention on immunoregulatory properties of UCB-MSCs on alloantigen-specific immune responses and on the mechanisms by which these cells exert their effect. Ten UCB units (median volume 45 ml, range 40–60), from full-term deliveries, were selected according to the following criteria: total nucleated cell (TNC) count ranging from 500 to 750 ×106; isolation performed within 24 hours after delivery; overall cell viability > 75%, investigated by 7-amino-actinomycin D (7-AAD) and Aldeflour (ALDH). Two of the 10 UCB units (20%, UCB3 and UCB6) gave rise to MSC-like clones, which were expanded ex vivo and characterized. UCB-MSCs displayed the typical morphology, immunephenotype and differentiation capacity into osteoblasts and adypocytes reported in the literature. Although displaying a rather low clonogenic efficiency, UCB-MSCs showed to have a higher proliferative potential compared to BM-MSCs, as demonstrated by the calculated cumulative cell counts from P0 to P5. Thereafter, UCB3- and UCB6-MSCs displayed a progressive decrease in proliferative capacity, until they reached senescence after 83 (P10) and 90 (P11) days of culture. The cells progressively died during the senescence period, without showing any alteration in morphology or proliferative rate. The lack of spontaneous transformation into tumor cells was demonstrated by both the absence of telomerase activity and hTERT transcripts and by molecular karyotyping through array-Comparative Genomic Hybridization (array-CGH) assay. The immune-regulatory effect of UCB-MSCs on alloantigen-specific immune response in mixed lymphocyte culture (MLC) was investigated, together with some of the mechanisms potentially responsible for this effect, including PGE2 production and IDO activity. We found that, similarly to BM-MSCs, UCB-MSCs expanded in PL are able to: strongly inhibit alloantigen-induced lymphocyte subset (CD3+, CD4+, CD8, CD3negCD56+ NK lymphocytes) proliferation; decrease alloantigen-induced cytotoxic activity; increase secretion of IL-6 and IL-10 in MLC supernatant. While the addition of BM-MSCs to MLC increased the percentage of CD4+CD25+FoxP3+T cells, the addition of UCB-MSCs did not result in any increase of this cell subset. Moreover, we found that the immune modulation of UCB-MSCs is apparently due to PGE2 production, while the addition of IDO-specific inhibitor was not able to reverse the suppressive effect exerted by MSCs. Altogether, these data indicate that relevant differences exist between UCB- and BM-MSCs, ex vivo cultured in the presence of PL, in terms of clonogenic efficiency, proliferative capacity and immunomodulatory properties. These aspects may be relevant for the clinical application of UCB-MSCs.

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Carubbi, F., P. Bosch, P. M. Machado, et al. "AB1083 CURRENT PRACTICE AND OPINIONS ON IMAGING-GUIDED INTERVENTIONAL PROCEDURES IN RHEUMATIC AND MUSCULOSKELETAL DISEASES: INTERIM RESULTS OF A MULTINATIONAL MULTIDISCIPLINARY SURVEY TO INFORM EULAR POINTS TO CONSIDER." Annals of the Rheumatic Diseases 79, Suppl 1 (2020): 1830.2–1831. http://dx.doi.org/10.1136/annrheumdis-2020-eular.6070.

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Background:maging is widely used for diagnostic purposes in patients with rheumatic and musculoskeletal diseases (RMDs). In recent years, it is increasingly used also to guide interventional procedures. However, the extent of imaging application for this purpose as well as the different technical standards employed across Europe are not known.Objectives:To learn how much imaging is used for interventional procedures in RMDs. To explore the technical standards employed in different settings and how important they are rated by users.Methods:As part of the work of a multidisciplinary EULAR Task Force to develop recommendations for the use of imaging to guide interventional procedures in patients with RMDs, a survey was developed. The survey explored aspects of different interventional procedures (e.g. joint aspiration/injection) such as the use of imaging guide and the technical standards. Respondents provided also a 0-10 rating of how important they considered the same conditions/items with regard to each procedure. The survey was distributed to: rheumatologists across Europe, USA, Central America, South America, Asia and Pacific Area, HPs across Europe, European and American associations of other specialities (e.g. radiology, anaesthesiology). The survey was launched in December 2019. Interim results after 4 weeks are presented.Results:200 responses from 36 countries were collected. The respondents were mainly rheumatologists (90%) (Figure 1). 90% of respondents performed interventional procedures related to RMDs and of these, 76% use imaging guide. Ultrasonography (US) is the most commonly used technique (96%) followed by X-ray/fluoroscopy (13%). Among respondents using imaging guide, 60% received training on both imaging and imaging-guided procedures, 20% only on imaging and 16% no training. 49% of respondents perform the whole procedure using direct image guidance, 21% use imaging to find the appropriate anatomical landmark and then perform the procedure blindly. Air and contrast agent to control needle placement are rarely used (≤20%). Respondents provided also a rating (0-10) of how important they considered different technical conditions/items for each procedure and an estimate on a Likert scale of how often they used them for each of the procedures (Figure 1 shows an example). In most cases respondents use always/most of the times the conditions/items that they considered important. Discrepancies were mainly due to barriers at their own center.Conclusion:Imaging, mainly US, is widely used to guide interventional procedures. However, training is not homogeneous and the use of imaging guide as well as technical conditions are based on the operator’s opinion/experience. This survey will inform the EULAR points to consider for the use of imaging to guide interventional procedures in patients with RMDs.Table 1.Characteristics of respondents (n=200) NN%Age≤ 30381931 –35562836 – 39502540 - 493316.5≥ 502311.5GenderFemale8944.5Male11155.5Specialty/PositionRheumatology18090Radiology115Physical medicine and rehabilitation31.5Pediatrics42Non-clinical researcher31.5Health professionals31.5Other31.5Disclosure of Interests:Francesco Carubbi Speakers bureau: Francesco Carubbi received speaker honoraria from Abbvie and Celgene outside this work., Philipp Bosch: None declared, Pedro M Machado Consultant of: PMM: Abbvie, Celgene, Janssen, Lilly, MSD, Novartis, Pfizer, Roche and UCB, Speakers bureau: PMM: Abbvie, BMS, Lilly, MSD, Novartis, Pfizer, Roche and UCB, Carlo Alberto Scirè: None declared, Alessia Alunno: None declared, Xenofon Baraliakos Grant/research support from: Grant/research support from: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Consultant of: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Speakers bureau: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Christian Dejaco: None declared

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Steuten, Lotte Maria Gertruda, Aasthaa Bansal, Li Li, et al. "Cost effectiveness of reduced intensity conditioning and transplantation of unrelated umbilical cord blood versus HLA haploidentical related bone marrow for adults with hematologic malignancies." Journal of Clinical Oncology 40, no. 16_suppl (2022): 6591. http://dx.doi.org/10.1200/jco.2022.40.16_suppl.6591.

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6591 Background: BMT CTN 1101 was a Phase III randomized controlled trial evaluating the comparative effectiveness of unrelated umbilical cord blood (UCB) versus HLA-haploidentical related donor bone marrow (haplo-BM) cell sources for hematopoietic cell transplantation (HCT) in patients with high-risk hematologic malignancies (leukemias, lymphomas). We report results of an economic evaluation conducted as part of the clinical trial. Methods: 368 patients (90% of planned accrual) enrolled from 33 centers in the U.S. were randomly assigned to unrelated UCB (n=186) or haplo-BM (n=182) transplant. Healthcare utilization and costs were estimated using propensity-score matched cohorts of BMT patients in the OptumLabs Data Warehouse for trial participants <65 years, and Medicare claims for trial participants ≥65 years. Cost-effectiveness was calculated from payer perspectives (commercial, Medicare) over a 20-year time horizon from time of transplant. Weibull models (best fit based on AIC/BIC) were used to extrapolate survival from 5-year trial follow-up data. Trial participant surveys (EQ-5D) were used to derive health state utilities for estimating Quality-Adjusted Life Years (QALYs). One-way and probabilistic sensitivity analyses were conducted to assess uncertainty in results. Outcomes were discounted at 3% annually. Results: At 5-year follow-up, overall survival was 42% for haplo-BM versus 36% for UCB (P=.06). Over a 20-year time horizon, haplo-BM is expected to be more effective and more costly for <65 year-olds and in ≥65 year-olds it is expected to be more effective and less costly. In one-way uncertainty analyses, for persons <65, the cost/QALY result was most sensitive to life years and health state utilities. For persons ≥65, life years were more influential than costs and health state utilities. Using probabilistic sensitivity analysis, for persons <65 there was a 43% chance that haplo-BM was cost-effective using a willingness to pay threshold of $150k/QALY and 52% at a $200K/QALY threshold. Conclusions: Results from a large national clinical trial indicate that compared to UCB, haplo-BM was moderately cost-effective for patients aged <65 years, and less costly and more effective for persons ≥65 years. Haplo-BM is a fair value choice for commercially insured patients with high-risk leukemia and lymphoma who require HCT. For Medicare enrollees, haplo-BM is a preferred choice when considering costs and outcomes. [Table: see text]

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Steuten, Lotte Maria Gertruda, Aasthaa Bansal, Li Li, et al. "Cost effectiveness of reduced intensity conditioning and transplantation of unrelated umbilical cord blood versus HLA haploidentical related bone marrow for adults with hematologic malignancies." Journal of Clinical Oncology 40, no. 16_suppl (2022): 6591. http://dx.doi.org/10.1200/jco.2022.40.16_suppl.6591.

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6591 Background: BMT CTN 1101 was a Phase III randomized controlled trial evaluating the comparative effectiveness of unrelated umbilical cord blood (UCB) versus HLA-haploidentical related donor bone marrow (haplo-BM) cell sources for hematopoietic cell transplantation (HCT) in patients with high-risk hematologic malignancies (leukemias, lymphomas). We report results of an economic evaluation conducted as part of the clinical trial. Methods: 368 patients (90% of planned accrual) enrolled from 33 centers in the U.S. were randomly assigned to unrelated UCB (n=186) or haplo-BM (n=182) transplant. Healthcare utilization and costs were estimated using propensity-score matched cohorts of BMT patients in the OptumLabs Data Warehouse for trial participants <65 years, and Medicare claims for trial participants ≥65 years. Cost-effectiveness was calculated from payer perspectives (commercial, Medicare) over a 20-year time horizon from time of transplant. Weibull models (best fit based on AIC/BIC) were used to extrapolate survival from 5-year trial follow-up data. Trial participant surveys (EQ-5D) were used to derive health state utilities for estimating Quality-Adjusted Life Years (QALYs). One-way and probabilistic sensitivity analyses were conducted to assess uncertainty in results. Outcomes were discounted at 3% annually. Results: At 5-year follow-up, overall survival was 42% for haplo-BM versus 36% for UCB (P=.06). Over a 20-year time horizon, haplo-BM is expected to be more effective and more costly for <65 year-olds and in ≥65 year-olds it is expected to be more effective and less costly. In one-way uncertainty analyses, for persons <65, the cost/QALY result was most sensitive to life years and health state utilities. For persons ≥65, life years were more influential than costs and health state utilities. Using probabilistic sensitivity analysis, for persons <65 there was a 43% chance that haplo-BM was cost-effective using a willingness to pay threshold of $150k/QALY and 52% at a $200K/QALY threshold. Conclusions: Results from a large national clinical trial indicate that compared to UCB, haplo-BM was moderately cost-effective for patients aged <65 years, and less costly and more effective for persons ≥65 years. Haplo-BM is a fair value choice for commercially insured patients with high-risk leukemia and lymphoma who require HCT. For Medicare enrollees, haplo-BM is a preferred choice when considering costs and outcomes. [Table: see text]

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Maksymowych, W. P., I. Eshed, P. M. Machado, et al. "FRI0317 CONSENSUS DEFINITIONS FOR MRI LESIONS IN THE SPINE OF PATIENTS WITH AXIAL SPONDYLOARTHRITIS: FIRST ANALYSIS FROM THE ASSESSMENTS IN SPONDYLOARTHRITIS INTERNATIONAL SOCIETY CLASSIFICATION COHORT." Annals of the Rheumatic Diseases 79, Suppl 1 (2020): 749.2–750. http://dx.doi.org/10.1136/annrheumdis-2020-eular.6304.

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Background:A recent consensus from the ASAS MRI group has culminated in updated spine lesion definitions for axial spondyloarthritis (ASAS_MRI_defn)1. There has been no central reader evaluation of MRI scans from the ASAS Classification Cohort (ASAS-CC)2to determine the spectrum of MRI lesions in the spine in this cohort.Objectives:To determine the spectrum of active and structural lesions on MRI images of the spine from the ASAS-CC according to the consensus ASAS_MRI_defnupdate.Methods:ASAS_MRI_defnwere recorded by 9 central readers in an eCRF for global assessment and detailed scoring of each discovertebral unit and postero-lateral structures. Vertebral corner bone marrow edema (VCBME) and corner fat (VCFAT) lesions were recorded if present on 2 slices; facet joint, lateral, and posterior inflammatory lesions were recorded if present on a single slice. Vertebral corner erosion, bone spurs, and ankylosis were each scored on a single slice. Comparison of active and structural lesion frequencies by local rheumatologist diagnosis of axSpA was assessed descriptively according to ≥2 and majority reader (≥5/9) concordant data.Results:MRI scans of the spine were available from 69 cases with axSpA diagnosed in 44/64 (68.8%). VCBME was most frequent with ≥1 lesion in 32(46.4%) and 19 (27.5%) by ≥2 and ≥5/9 readers, respectively. VCFAT was the most frequent structural lesion with ≥1 lesion in 24 (34.8%) and 14 (20.3%) by ≥2 and ≥5/9 readers, respectively. There were significantly more VCBME lesions in axSpA patients than non-axSpA (mean(SD):1.8(2.7) vs 0.3 (0.5)) (p<0.001) while differences in VCFAT were not significant (Table). The presence of ≥2 VCBME had 90-95% specificity for axSpA. Significantly more VCBME and VCFAT were observed in the setting of radiographic sacroiliitis (modified New York criteria (mNY)).Conclusion:Spine lesions on MRI are relatively frequent in patients with undiagnosed back pain presenting to the rheumatologist. The presence of ≥2 VCBME, but not VCFAT, may have some diagnostic utility.References:[1]Maksymowych WP, et al. Arthritis Rheumatol 70 (suppl 10): 654, 2018[2]Rudwaleit et al. Ann Rheum Dis 2009;68: 777-83Vertebral Corner MRI lesionsmajority of readers (>=5)≥2 readersaxSpA=Yes (n=44)axSpA=No (n=20)p-valueaxSpA=Yes (n=44)axSpA=No (n=20)p-valueCorner Fat ≥112 (27.3%)2 (10%)0.1917 (38.6%)7 (35%)0.78Corner Fat ≥210 (22.7%)2 (10%)0.3113 (29.5%)4 (20%)0.64Corner Fat ≥38 (18.2%)1 (5%)0.2510 (22.7%)3 (15%)0.74Corner Fat ≥47 (15.9%)1 (5%)0.429 (20.5%)2 (10%)0.48Corner BME ≥117 (38.6%)1 (5%)0.00625 (54.5%)6 (30%)0.047Corner BME ≥215 (34.1%)1 (5%)0.01319 (43.2%)2 (10%)0.009Corner BME ≥311 (25%)0 (0%)0.01316 (36.4%)1 (5%)0.008Corner BME ≥48 (18.2%)0 (0%)0.09412 (27.3%)1 (5%)0.048mNY=Yes (n=10)mNY=No (n=49)p-valuemNY=Yes (n=10)mNY=No (n=49)p-valueCorner Fat ≥15 (50%)9 (18.4%)0.0475 (50%)17 (34.7%)0.48Corner Fat ≥25 (50%)7 (14.3%)0.0225 (50%)11 (22.4%)0.12Corner Fat ≥34 (40%)5 (10.2%)0.0364 (40%)9 (18.4%)0.20Corner Fat ≥44 (40%)4 (8.2%)0.0224 (40%)7 (14.3%)0.079Corner BME ≥15 (50%)11 (22.4%)0.1167 (70%)22 (44.9%)0.18Corner BME ≥25 (50%)9 (18.4%)0.0475 (50%)14 (28.6%)0.27Corner BME ≥35 (50%)6 (12.2%)0.0145 (50%)11 (22.4%)0.12Corner BME ≥45 (50%)3 (6.1%)0.0025 (50%)7 (14.3%)0.022Disclosure of Interests:Walter P. Maksymowych Grant/research support from: AbbVie, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Boehringer Ingelheim, Celgene, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, and UCB, Employee of: Chief Medical Officer of CARE Arthritis Limited, Speakers bureau: AbbVie, Janssen, Novartis, Pfizer, and UCB, Iris Eshed: None declared, Pedro M Machado Consultant of: PMM: Abbvie, Celgene, Janssen, Lilly, MSD, Novartis, Pfizer, Roche and UCB, Speakers bureau: PMM: Abbvie, BMS, Lilly, MSD, Novartis, Pfizer, Roche and UCB, Susanne Juhl Pedersen Grant/research support from: Novartis, Ulrich Weber: None declared, Manouk de Hooge: None declared, Joachim Sieper Consultant of: AbbVie, Boehringer Ingelheim, Eli Lilly and Company, Janssen, Merck, Novartis, Pfizer, Roche, and UCB Pharma, Speakers bureau: AbbVie, Boehringer Ingelheim, Eli Lilly and Company, Janssen, Merck, Novartis, Pfizer, Roche, and UCB Pharma, Stephanie Wichuk: None declared, Denis Poddubnyy Grant/research support from: AbbVie, MSD, Novartis, and Pfizer, Consultant of: AbbVie, Bristol-Myers Squibb, Eli Lilly, MSD, Novartis, Pfizer, Roche, UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb, Eli Lilly, MSD, Novartis, Pfizer, Roche, UCB, Martin Rudwaleit Consultant of: AbbVie, BMS, Celgene, Janssen, Eli Lilly, MSD, Novartis, Pfizer, Roche, UCB Pharma, Désirée van der Heijde Consultant of: AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Cyxone, Daiichi, Eisai, Eli-Lilly, Galapagos, Gilead Sciences, Inc., Glaxo-Smith-Kline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCB Pharma; Director of Imaging Rheumatology BV, Robert B.M. Landewé Consultant of: AbbVie; AstraZeneca; Bristol-Myers Squibb; Eli Lilly & Co.; Galapagos NV; Novartis; Pfizer; UCB Pharma, Robert G Lambert: None declared, Mikkel Ǿstergaard Grant/research support from: AbbVie, Bristol-Myers Squibb, Celgene, Merck, and Novartis, Consultant of: AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Novo Nordisk, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, and UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Novo Nordisk, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, and UCB, Xenofon Baraliakos Grant/research support from: Grant/research support from: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Consultant of: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Speakers bureau: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen

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Fernandes, Juliana Folloni, Vanderson Rocha, Myriam Labopin, et al. "Comparison of Outcomes of Mismatched Related Stem Cell and Unrelated Cord Blood Transplants in Children with Severe T-Cell Deficiencies." Blood 114, no. 22 (2009): 664. http://dx.doi.org/10.1182/blood.v114.22.664.664.

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Abstract Abstract 664 Severe combined immune deficiency (SCID) diseases, as well as other severe T-cell deficiencies like Omenn syndrome, are considered pediatric emergencies. To date, hematopoietic stem cell transplantation (HSCT) is the only curative therapy for these children. Considering the urgency of these transplants, for patients lacking an identical sibling donor, the use of mismatched related donors (MMRD) and unrelated umbilical cord blood (UCB) are important alternatives. In a retrospective study, we compared the outcomes of 175 children with severe T-cell deficiencies (SCID=152, Omenn syndrome=23) receiving MMRD transplants and 74 (SCID=52, Omenn syndrome=15) receiving UCB transplants, reported to the SCETIDE and Eurocord databases, from 1995 to 2005. MMRD transplants were performed in 12 different centers and UCB transplants were distributed among 30 different centers. Only 5 centers performed the two techniques. The median age at transplant was 6.4 months for the UCB group and 6.5 months for the MMRD group (p=0,87). Median time elapsed between diagnosis and transplant was 47 days for MMRD (range 4-485) and 55 days (range 17-526) for UCB transplants (p=0.06). There were no statistically significant differences between the two groups regarding gender and incidence of failure to thrive, chronic diarrhea or respiratory impairment before transplant. Patients receiving UCB had more often B-negative phenotype (61% UCB vs. 41% MMRD; p=0.009), while patients receiving MMRD had a greater incidence of viral infections prior to transplant (59% MMRD vs. 36% UCB; p=0.004). The year of transplantation also differed between the two groups, as more patients receiving UCB were transplanted between 2000-2005 (65%) compared to MMRD (50%) (p=0.014). Regarding HLA (considering HLA-A,B-low resolution and DRB1-high resolution), in the UCB group, 67% of patients had 0 or 1 disparities while 33% had 2 or 3 disparities. In the MMRD group, 10% had 1 disparity and 90% had 2 or 3 disparities. Seven patients receiving UCB (16%) transplants and 30 patients receiving MMRD (17%) did not receive any preparative regimen prior to graft infusion. Conditioning regimen was non-myeloablative in 45% of MMRD transplants and 30% of UCB transplants. The remaining received myeloablative regimens. Graft-versus-host disease (GVHD) prophylaxis was cyclosporine A-based in the majority of the UCB transplants (n=71). T-cell depletion was used in all transplants with MMRD and 52 patients received immunosuppressants, mostly cyclosporine A. The median follow-up time was 84 months for patients given a MMRD and 59 months for UCB transplants recipients. Sixty-one patients receiving UCB transplants engrafted (82%), all with full donor chimerism in CD3+ cells. On the CD3- compartment 75% had full donor, 5% mixed and 20% had recipient chimerism. In MMRD group, 130 patients engrafted (74%), 98% with full donor chimerism in CD3+ cells. On CD3- cells, 33% had full donor chimerism, 48% were mixed and 19% recipient chimerism. Forty-six patients in the MMRD group and 7 patients in the UCB group needed to receive second transplants. The cumulative incidence of acute GVHD had no statistically significant difference between groups (33% UCB vs. 23% MMRD; p=0.13). However, patients receiving UCB transplants had more chronic GVHD (22% UCB vs. 11% MMRD; p=0.04). In a univariate analysis, 5-year overall survival was 62 ± 4% for MMRD and 58% ± 6% for UCB transplants (p=0.83). In a multivariate analysis adjusting for differences between the two groups, 5-year overall survival was not statistically different (p=0.54). Regarding T-cell reconstitution, we analyzed the total lymphocyte, CD3+ and CD4+ cell numbers and there were no statistically significant differences between the two groups comparing absolute numbers at 6, 12 and 24 months after transplantation. In conclusion, both unrelated cord blood and mismatched related donors are choices for transplants in severe T-cell deficiencies lacking an HLA-identical sibling donor. The choice of donor type will depend on centre's strategy regarding the possibility of efficiently deplete MMRD grafts of T-cells, or find a rapidly available UCB unit. Disclosures: No relevant conflicts of interest to declare.

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de Latour, Regis Peffault, Claudio G. Brunstein, Raphael Porcher, et al. "Similar Outcome Between Siblings, Unrelated Donors and Cord Blood After Reduced Intensity Allogeneic Hematopoietic Cell Transplantation for Patients Older Than 50 Years with Acute Myeloid Leukemia in Complete Remission." Blood 120, no. 21 (2012): 1985. http://dx.doi.org/10.1182/blood.v120.21.1985.1985.

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Abstract Abstract 1985 Introduction: For older patients with acute myeloid leukemia (AML), allogeneic hematopoietic cell transplantation (HCT) provides the best chance of long-term survival. Because older patients less often have available healthy sibling donors, alternative donors may be more important. We compared the outcomes of reduced intensity conditioning (RIC) HCT for AML patients over 50 years in complete remission (CR) using matched sibling (SIB), unrelated (URD) or umbilical cord blood (UCB) donors. Patients, methods and HCT characteristics: From January 2000 to December 2010, 197 consecutive patients (median age 59, range 50–74) received RIC and allogeneic HCT in 3 independent centers, either from SIB (n=82), HLA 8/8 allele-matched URD (n=35) or UCB (n=80; 10 single unit). One patient received an HLA 7/8 allele-mismatched URD. SIB and URD all received peripheral blood as source of stem cells. Conditioning was fludarabine-based in the majority (86%) and most received Graft versus Host Disease (GvHD) prophylaxis using cyclosporine plus MMF (79%). 68% were in CR1; 6% of patients had good risk cytogenetics and 29% had poor risk (MRC classification). Results: Patient characteristics were similar between the 3 groups for age, gender, CR# and the median time interval from diagnosis to HCT. UCB recipients had more frequent high risk features including: KPS<90% (19% versus 10% and 3% for SIB and URD, respectively, p=0.04); female donor: male recipient (44% versus 20% SIB and 17% URD, p=0.04); and somewhat more high risk cytogenetics (UCB 34%, SIB 22%, URD 17%, p=0.06). Conditioning regimens using Fludarabine and low dose TBI were more frequent in UCB: 100% vs. 24% for SIB and 11% for URD, p<0.0001); Fludarabine and Busulfan (more in URD: 71% vs. 43% for SIB and 0 for UCB, p<0.0001); and Cyclophosphamide plus low dose TBI (more in SIB: 28% vs. 3% for URD and 0 for UCB, p<0.0001) also differed between the 3 groups. Moreover, more ATG was used in URD (86% vs. 29% for SIB and 29% for UCB, p<0.0001). After a median follow-up of 39 months (range 2 to 104, 42 months for SIB, 25 months for URD and 51 months for UCB), 103 patients survive. The 3-year cumulative incidence function (CIf) of transplant related (non-relapse) mortality (TRM) was 18%, 14% and 24% with SIB, URD and UCB, respectively (p=0.22). The 3-year CIf of relapse was 33%, 29% and 43% with SIB, URD and UCB, respectively (p=0.04). Consequently, the 3-year CIf of leukemia free survival (LFS) was 48%, 57% and 33% with SIB, URD and UCB, respectively (p=0.009). In multivariate analysis, poor cytogenetic risk was associated with a higher rate of relapse (HR 1.7 [95% CI 1.0–3.0], p=0.04), worse LFS (HR 1.6 [1.0–2.5], p=0.03) and a trend for worse OS (HR 1.6 [1.0–2.4], p=0.06), but survival using each donor sources was similar (UCB HR 1.2 [0.7–2.1], p=0.45; URD 1.2 [0.5–2.7], p=0.73 as compared to SIB). Adjusted, 3-year OS was 55% with SIB, 45% with URD and 43% with UCB (p=0.26) (Figure 1). The use of TBI-containing regimen was associated with a non-significant, but worse OS in recipients of MRD and URD grafts (HR 1.8 [0.9–3.8], p=0.11). Outcome was similar between the 3 centers. Conclusion: These data suggest equivalence of outcome using SIB, URD or UCB in patients >50 years with AML in CR. Poor cytogenetic risk was the dominant prognostic factor, influencing relapse and LFS with a trend for worse OS. Until prospective studies are completed, this study supports the recommendation to consider SIB, URD or UCB for HCT for patients with older AML in CR. Disclosures: No relevant conflicts of interest to declare.

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Pio Proaño, Cristina Paulette, and Carlos Andrés Guim Martínez. "Prevalencia de biotipos gingivales según el somatotipo en estudiantes de la UCSG semestre A-2017." Medicina 23, no. 1 (2021): 29–35. http://dx.doi.org/10.23878/medicina.v23i1.1013.

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Introducción: el biotipo gingival tiene un impacto importante en la supervivencia de los diferentes tratamientos odontológicos. Varios autores aseguran que cada biotipo gingival tiene una respuesta diferente ante fuerzas externas. Por ello debemos tener una comprensión clara del comportamiento del mismo, para que en investigaciones posteriores se pueda conocer adecuadamente su manejo. Además, para tener un diagnóstico preciso se debe de analizar también el somatotipo del sujeto, este puede ser ectomorfo, mesomorfo y endomorfo, según sus características clínicas. Objetivo: observar la relación que existe entre el biotipo gingival y el somatotipo. Metodología: el estudio analítico es de tipo transversal se realizó en 107 estudiantes de odontología de la UCSG, seleccionados al azar según los criterios de inclusión y exclusión. Se determinó el biotipo gingival mediante el método de translucidez de la sonda en los dientes 11, 12, 13. El somatotipo se lo determino mediante el método fotográfico de sheldon, con una fotografía de cuerpo entero. Resultados: fueron analizados 107 sujetos, 72 mujeres y 35 hombres. El 57% del total de los sujetos tuvieron biotipo grueso, el 43% mostró biotipo delgado. Un 39% mostró somatotipo ectomorfo, el 38% somatotipo mesomorfo y el 22% somatotipo endomorfo. Al relacionar las dos variables, de somatotipo ectomorfo un 90% =biotipo delgado, 10%= biotipo grueso, de somatotipo endomorfo un 100%= biotipo grueso, de somatotipo mesomorfo un 80%= biotipo grueso y un 20% biotipo delgado. Conclusión: el somatotipo más prevalente fue ectomorfo, y el biotipo más encontrado fue el grueso. Concluyendo de esta manera que no hay una relación clara entre el somatotipo y el biotipo gingival.

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Zhu, Jizan, Kuangang Fan, Qing He, Jingzhen Ye, and Aigen Fan. "Two-Dimensional Real-Time Direction-Finding System for UAV RF Signals Based on Uniform Circular Array and MUSIC-WAA." Drones 9, no. 4 (2025): 278. https://doi.org/10.3390/drones9040278.

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To address the growing security risks posed by unauthorized unmanned aerial vehicle (UAV) activities, this paper proposes a real-time two-dimensional direction-finding (DF) system for UAVs based on radio frequency (RF) signals. This system employs a six-element uniform circular array (UCA), synchronized HackRF One receivers, and a hybrid algorithm integrating the multiple signal classification (MUSIC) method with a novel weighted average algorithm (WAA). By optimizing the MUSIC spectrum search process, the WAA reduces the computational complexity by over 99.9% at a resolution of 0.1° (from 3,240,000 to 1200 spectral function calculations), enabling real-time estimation of the azimuth and elevation angles. The experimental results demonstrate an average azimuth error of 7.0° and elevation error of 7.7° for UAV hovering distances of 30–200 m and heights of 20–90 m. Real-time flight tracking further validates the system’s dynamic monitoring capabilities. The hardware platform, featuring omnidirectional coverage (0–360° azimuth, 0–90° elevation) and dual-band operation (2.4 GHz/5.8 GHz), offers scalability and cost-effectiveness for low-altitude security applications. Despite limitations in the elevation sensitivity due to the UCA’s geometry, this work establishes a practical foundation for UAV monitoring, emphasizing computational efficiency, real-time performance, and adaptability to dynamic environments.

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Bachanova, Veronika, Claudio Brunstein, Linda J. Burns, et al. "Alternative Donor Transplantation For Adults With Lymphoma: Comparison Of Umbilical Cord Blood Versus 8/8 HLA-Matched Donor (URD) Versus 7/8 URD." Blood 122, no. 21 (2013): 161. http://dx.doi.org/10.1182/blood.v122.21.161.161.

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Abstract Allogeneic donor hematopoietic cell transplantation (HCT) is increasingly used to treat relapsed lymphoma with curative intent; however, many patients will not have a suitable matched sibling donor. Transplant centers are investigating the use of alternative stem cell sources although data comparing outcomes by stem cell source are limited. We compared outcomes of 1593 non-Hodgkin and Hodgkin lymphoma patients who underwent alternative donor HCT from 2000-2010 and were reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). Umbilical cord blood (UCB) (n=142), 8/8 (human leukocyte antigen [HLA] –A, B, C, and DRB1) matched adult unrelated donor (URD) (n=1176) and 7/8 HLA matched URD (n=275) HCT recipients were followed for a median of 25, 57 and 65 months, respectively. The median age in the 3 groups were UCB: 45 years (range 19-73 yrs), 8/8 URD: 50 (range 18-75 yrs) and 7/8 URD: 45 years (range 18-71yrs). Male gender and mantle cell lymphoma were more frequent in 8/8 URD recipients. 7/8 URD HCT recipients had lower Karnofsky performance scores, and UCB recipients were more likely to be non-Caucasian, have chemosensitive disease and to have undergone HCT in recent years. UCB recipients had inferior neutrophil and platelet engraftment rates at 100 days; however they were less likely to develop acute and chronic graft versus host disease (GVHD) compared to 7/8 URD and 8/8 URD (Table). The cumulative incidence of treatment related mortality (TRM) at 3 years was higher in 7/8 URD. There were no differences among the 3 groups in the 3-year relapse/progression, progression free survival (PFS) or overall survival (OS).Table.OutcomesUCBURD 8/8URD 7/8% (95%CI)% (95%CI)%( (95%CI)P-valueTime to ANC>0.5 x 109/L at 28 days66 (57-73)94 (92-95)94 (90-96)<0.001Platelet recovery ≥ 20 x 109/L at 100 days68 (59-76)86 (84-88)85 (80-89)<0.001Acute GVHD (II-IV) at 100 days26 (19-34)37 (35-40)49 (43-55)<0.0013 years Chronic GVHD at 3 years22 (15-30)51 (48-54)48 (42-54)<0.0013 years Treatment related mortality38 (29-46)35 (32-37)46 (41-52)0.0023 years Relapse/Progression29 (22-37)32 (29-34)25 (20-31)0.1073 years Progression free survival33 (25-42)33 (31-37)29 (23-34)0.1863 years Overall survival44 (35-53)43 (40-46)34 (29-40)0.017 In multivariate analysis stratified for performance status, lymphoma histology, GVHD prophylaxis, and disease status, no significant difference in OS was detected between UCB and 8/8 URD (HR 0.87 [95% CI 0.68-1.12]; p=0.29), UCB and 7/8 URD (HR 1.04 [95% CI 0.78-1.40]; p=0.77), and 8/8 and 7/8 URD (HR 1.19 [95%CI 0.97-1.45; p=0.08). Lower risk of treatment failure (death or relapse; inverse of PFS) was observed in transplants performed after 2007 (HR 0.79 [95% CI 0.66-0.96]; p=0.01) as compared to the time periods 2000-2003. Patients' age, time from diagnosis to HCT, race, history of prior HCT, and conditioning intensity did not influence OS or PFS. In conclusion, our results suggest that UCB and 7/8 URD grafts for patients with advanced lymphoma provide similar survival to 8/8 URD, extending allogeneic HCT to most patients with no suitable matched sibling donors. Graft source needs to be determined by availability, the clinical urgency of transplant, and transplant center experience. Disclosures: No relevant conflicts of interest to declare.

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Overgaard Donskov, A., S. Mackie, E. M. Hauge, et al. "AB0583 REFERRAL PATTERN AND TREATMENT OF POLYMYALGIA RHEUMATICA IN GENERAL PRACTICE: AN INTERNATIONAL QUESTIONNAIRE BASED STUDY." Annals of the Rheumatic Diseases 81, Suppl 1 (2022): 1416.2–1417. http://dx.doi.org/10.1136/annrheumdis-2022-eular.1380.

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BackgroundIn most countries polymyalgia rheumatica (PMR) is diagnosed and managed by both general practitioners (GP) and rheumatologists. However, the referral pattern from GP’s to specialist around the world has not been described. The initial prednisolone dose recommended by EULAR/ACR is between 12.5 and 25 mg1, but little is known about whether these guidelines are followed everywhere by GP’s in clinical practice2.ObjectivesThis study aims to describe the refererral pattern and treatment strategy for PMR in general practice in several countries worldwide.MethodsAn English language questionnaire was drafted by a working group of rheumatologists and GP’s from 6 different countries. The questionnaire contained questions on: 1: Respondent, 2: Referral pattern and 3: Prednisolone. Questionnaires were distributed to GP’s via members of the International PMR/GCA study group. Answers were collected via an online survey tool (Redcap), from 3rd of November 2021 to 27th of January 2022. Countries with more than 15 responders to the questionnaire were included in the analysis.ResultsData from 11 countries were analysed. Referral patterns differed widely among countries (Table 1). Almost all patients initially seen by rheumatologists were returned to GP’s for treatment. In all countries a proportion of the GP’s prescribed higher initial prednisolone doses than recommended, with a large variation between countries (Table 1).Table 1.Characteristics of responders, referral pattern, and treatment strategyAustriaCanadaColombiaDenmarkItalyNether-landsNew ZealandRomaniaRussiaSwitzer-landUnited KingdomRespondersResponders (n), Completed questionnaire (total)26 (29)15 (15)17 (23)53 (53)36 (41)22 (22)17 (17)37 (43)42 (49)26 (26)34 (35)Experience (years)20 (12-34)8 (4-10)6 (4-9)12 (10-17)15 (5-27)23 (17-30)14 (9-27)21 (16-30)6 (5-9)26 (15-32)16 (11-24)Available PMR/GCA guideline, n (%)26 (100)15(100)17 (100)53 (100)36 (100)22 (100)17 (100)37 (100)42 (100)26 (100)34 (100)Adherence to guideline, n (%)21 (82)15 (100)17 (100)51 (97)34 (94)21 (95)17 (100)37 (100)42 (100)26 (100)34 (100)ReferralsNew PMR patients referred for diagnose (%)58 (10-100)50 (2-100)100 (13-100)50-(20-100)60 (28-100)20 (10-50)10 (10-20)60 (10-88)1 (1-2)28 (10-50)10 (1-25)Patients returned to GP for treatment (%)100 (50-100)50 (2-100)8 (0-50)85 (40-100)50 (0-100)50 (10-90)100 (90-100)80 (50-98)1 (1-1)80 (10-100)100 (100-100)Patients referred during treatment (%)50 (25-90)50 (10-100)100 (50-100)20 (10-33)50 (15-80)15 (10-30)20 (10-25)30 (10-80)1(1-1)20 (10-30)10 (10-20)PrednisoloneInitial dose (mg)38 (25-50)20 (20-50)20 (10-30)25 (15-40)25 (25-25)15 (15-15)20 (15-40)15 (12-20)15 (15-15)50 (25-50)15 (15-20)Initial dose > 25 mg, n (%)12 (47)4 (25)7 (40)14 (26)9 (25)1 (5)6 (38)7 (20)3 (8)22 (83)3 (9)Duration of treatment (months)9 (6-12)6 (2-9)6 (4-24)12 (8-18)5 (3-12)11 (6-12)12 (10-18)2 (2-5)6 (6-6)12 (12-14)15 (12-24)Data are presented as weighted median (interquartile range) unless otherwise stated. GP: general practitioner, PMR: polymyalgia rheumatica, GCA: great cell arteritis.ConclusionAlthough many patients were referred to the hospital for initial PMR diagnosis or during the disease course, a large proportion of patients received treatment in general practice worldwide. GPs frequently use a higher starting dose of prednisolone and shorter treatment duration than recommended by EULAR/ACR.References[1]Dejaco C, Singh YP, Perel P, et al. 2015 Recommendations for the management of polymyalgia rheumatica: a European League Against Rheumatism/American College of Rheumatology collaborative initiative. Annals of the rheumatic diseases 2015; 74(10): 1799-807.[2]Helliwell T, Hider SL, Mallen CD. Polymyalgia rheumatica: diagnosis, prescribing, and monitoring in general practice. The British journal of general practice: the journal of the Royal College of General Practitioners 2013; 63(610): e361-6.AcknowledgementsThis study was endorsed by the international PMR/GCA study group.Disclosure of InterestsAgnete Overgaard Donskov: None declared, Sarah Mackie: None declared, Ellen-Margrethe Hauge Speakers bureau: AbbVie, Sanofi, Sobi, MSD, UCB, Consultant of: AbbVie, Sanofi, Sobi, MSD, UCB, Grant/research support from: Novo Nordic Foundation, Danish Rheumatism Association, Danish Regions Medicine Grants, Roche, Novartis,Celgene, MSD, Pfizer, Roche, Sobi, CARLOS TORO GUTIÉRREZ: None declared, Andrea Hemmig: None declared, Aatke van der Maas: None declared, Berit Dalsgaard NIelsen Paid instructor for: Roche, Ib Hansen: None declared, Max Yates: None declared, Line Frølund: None declared, Karen Douglas: None declared, Kornelis van der Geest Speakers bureau: Roche, Elena Rezus: None declared, Sara Monti: None declared, Margarita Gromova: None declared, Vanessa Ocampo Speakers bureau: Abvie, Simone Appenzeller Speakers bureau: Janssen, UCB, Lilly and Pfizer, Mariama Erraoui: None declared, Adeola Ajibade: None declared, Andre Marun Lyrio: None declared, Rebecca Grainger: None declared, Maria Sandovici: None declared, Toby Helliwell: None declared, Elisabeth Brouwer Speakers bureau: Roche, Consultant of: Roche, Christian Dejaco Speakers bureau: Abbvie, Eli Lilly, Janssen, Novartis, Pfizer, Roche, Galapagos and Sanofi, Consultant of: Abbvie, Eli Lilly, Janssen, Roche, Galapagos and Sanofi, Kresten Keller: None declared

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Mease, P. J., S. Chohan, F. J. García Fructuoso, et al. "OP0230 EFFICACY AND SAFETY OF TILDRAKIZUMAB, A HIGH-AFFINITY ANTI–INTERLEUKIN-23P19 MONOCLONAL ANTIBODY, IN PATIENTS WITH ACTIVE PSORIATIC ARTHRITIS IN A RANDOMISED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTIPLE-DOSE, PHASE 2B STUDY." Annals of the Rheumatic Diseases 79, Suppl 1 (2020): 145–46. http://dx.doi.org/10.1136/annrheumdis-2020-eular.3908.

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Background:Tildrakizumab (TIL), a high-affinity anti–interleukin-23p19 monoclonal antibody, is approved to treat moderate to severe plaque psoriasis and is under investigation for treatment of psoriatic arthritis (PsA).1Objectives:To evaluate efficacy and safety of TIL up to week (W)52 in a randomised, double-blind, placebo-controlled, multiple-dose, phase 2b study in PsA (NCT02980692).Methods:Patients (pts) ≥18 years with active PsA2were randomised 1:1:1:1:1 to TIL 200 mg every 4 weeks (Q4W) to W52, TIL 200 mg Q12W to W52, TIL 100 mg Q12W to W52, TIL 20 mg Q12W until W24 then TIL 200 mg Q12W to W52, or placebo (PBO) Q4W until W24 then TIL 200 mg Q12W to W52. Efficacy assessments included ACR20/50/70, 75%/90%/100% improvement in Psoriasis Area and Severity Index (PASI), proportion of pts with residual minimal disease activity (MDA) response; and mean change from baseline (BL) in HAQ-DI, Leeds Dactylitis Index (LDI, pts with BL LDI ≥1), and Leeds Enthesitis Index (LEI, pts with BL LEI ≥1) to W52. Treatment-emergent adverse events (TEAEs) were monitored.Results:Of 500 pts screened, 391 were randomised and received ≥1 dose of drug. Proportions of ACR20/50/70 responders were superior with TIL vs PBO through W24; after W24 rates of responses further increased for TIL 20→200 mg Q12W and PBO→200 mg Q12W through W52 (Figure 1, 2). Other efficacy results are shown in Table. Overall from BL→W24/W25→W52, 50.4%/39.9% and 2.3%/1.0% of pts experienced a TEAE and serious AE, respectively. From BL→W24, 1 case of pyelonephritis and urinary tract infection was reported in the TIL 100 mg Q12W arm and 1 case of chronic tonsillitis was reported in the TIL 20 mg→200 mg Q12W arm. During W25→W52, 1 malignancy (intraductal proliferative breast lesion) was reported with TIL 20 mg→200 mg Q12W. No deaths or major adverse cardiac events occurred.Table.W52 clinical efficacyTIL 200 mg Q4Wn=78TIL 200 mg Q12Wn=79TIL 100 mg Q12Wn=77TIL 20→200 mg Q12Wn=78PBO→TIL 200 mg Q12Wn=79HAQ-DI, BLa1.0 ± 0.61.0 ±0.61.0 ± 0.71.1 ± 0.61.2 ± 0.6 W52b−0.5 ± 0.5−0.5 ± 0.6−0.5 ± 0.6−0.5 ± 0.5−0.5 ± 0.5LEI, BLa,c1.9 ± 2.01.5 ± 1.92.2 ± 2.12.2 ± 2.01.5 ± 1.9 W52b−1.3 ± 1.9−1.0 ± 1.6−1.7 ± 2.1−1.2 ± 1.8−1.2 ± 1.8LDI, BLa,d32.8 ± 32.961.3 ± 73.593.8 ± 146.571.4 ± 118.599.6 ± 170.7 W52b,d−21.4 ± 37.1−42.1 ± 76.7−41.6 ± 89.3−56.5 ± 123.4−81.5 ± 173.0 BL, W52 mediand21.8, 7.428.3, 3.232.1, 20.028.6, 034.0, 5.6MDAe56.964.445.047.142.0PASI 100e54.044.443.947.535.0PASI 90e72.080.658.555.050.0PASI 75e82.094.482.975.067.5aBL mean ± SD.bMean change from BL ± SD.cPts with BL LEI ≥1 will be presented at EULAR.dPts with BL LDI ≥1 (n = 27, 21, 21, 19, 25) using nonresponder imputation.e% at W52Missing data not imputed.SD, standard deviation.Conclusion:TIL was well tolerated and improved joint and skin manifestations of PsA through W52.References:[1]Reich, et al.Lancet2017;390:276−88.[2]Taylor, et al.Arthritis Rheum2006;54:2665–73.Disclosure of Interests:Philip J Mease Grant/research support from: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – grant/research support, Consultant of: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – consultant, Speakers bureau: Abbott, Amgen, Biogen Idec, BMS, Eli Lilly, Genentech, Janssen, Pfizer, UCB – speakers bureau, Saima Chohan Employee of: Partner/physician at Arizona Arthritis and Rheumatology Associates, Ferran J García Fructuoso Grant/research support from: AbbVie, Eli Lilly, Gedeon Richter, MedImmune, Nichi-Iko, Pfizer, Sanofi-Aventis, Takeda, and UCB, Consultant of: AbbVie, Eli Lilly, Gedeon Richter, MedImmune, Nichi-Iko, Pfizer, Sanofi-Aventis, Takeda, and UCB, Speakers bureau: AbbVie, Eli Lilly, Gedeon Richter, MedImmune, Nichi-Iko, Pfizer, Sanofi-Aventis, Takeda, and UCB, Alice B Gottlieb Grant/research support from:: Research grants, consultation fees, or speaker honoraria for lectures from: Pfizer, AbbVie, BMS, Lilly, MSD, Novartis, Roche, Sanofi, Sandoz, Nordic, Celltrion and UCB., Consultant of:: Research grants, consultation fees, or speaker honoraria for lectures from: Pfizer, AbbVie, BMS, Lilly, MSD, Novartis, Roche, Sanofi, Sandoz, Nordic, Celltrion and UCB., Speakers bureau:: Research grants, consultation fees, or speaker honoraria for lectures from: Pfizer, AbbVie, BMS, Lilly, MSD, Novartis, Roche, Sanofi, Sandoz, Nordic, Celltrion and UCB., Michael E Luggen Grant/research support from: AbbVie; Amgen; Eli Lilly; Genentech; Nichi-Iko; Novartis; Pfizer; R-Pharm; and Sun Pharmaceutical Industries, Inc., Consultant of: AbbVie; Amgen; Eli Lilly; Genentech; Nichi-Iko; Novartis; Pfizer; R-Pharm; and Sun Pharmaceutical Industries, Inc., Speakers bureau: AbbVie; Amgen; Eli Lilly; Genentech; Nichi-Iko; Novartis; Pfizer; R-Pharm; and Sun Pharmaceutical Industries, Inc., Proton Rahman Grant/research support from: Janssen and Novartis, Consultant of: Abbott, AbbVie, Amgen, BMS, Celgene, Lilly, Janssen, Novartis, and Pfizer., Speakers bureau: Abbott, AbbVie, Amgen, BMS, Celgene, Lilly, Janssen, Novartis, Pfizer, Siba P Raychaudhuri Grant/research support from: AbbVie; Janssen; Novartis, Pfizer; Sun Pharmaceutical Industries, Inc, Consultant of: Amgen; Eli Lilly; Janssen; Novartis and Pfizer, Richard C Chou Consultant of: Sun Pharmaceutical Industries, Inc, Alan M Mendelsohn Shareholder of: Johnson and Johnson, Employee of: Sun Pharmaceutical Industries, Inc, Stephen Rozzo Employee of: Sun Pharmaceutical Industries, Inc, Ana-Maria Orbai Grant/research support from: Abbvie, Eli Lilly and Company, Celgene, Novartis, Janssen, Horizon, Consultant of: Eli Lilly; Janssen; Novartis; Pfizer; UCB. Ana-Maria Orbai was a private consultant or advisor for Sun Pharmaceutical Industries, Inc, not in her capacity as a Johns Hopkins faculty member and was not compensated for this service.

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Mitchell, W. Beau, Marketa Jirouskova, JiHong Li та Barry S. Coller. "Differences in αIIbβ3 Biogenesis Dynamics between Umbilical Cord Blood-Derived Human Megakaryocyte-Like Cells and Transfected HEK293 Cells as Revealed by a Mathematical Model." Blood 104, № 11 (2004): 1559. http://dx.doi.org/10.1182/blood.v104.11.1559.1559.

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Abstract Most studies of αIIbβ3 biogenesis have been conducted in transfected HEK293 and CHO cells or megakaryocyte-like cell lines, but the protein processing mechanisms in native megakaryocytes may differ. To address this issue we have studied αIIbβ3 biogenesis in human megakaryocyte-like cells derived from umbilical cord blood (UCB) and in 293 cells stably expressing αIIbβ3, and developed a mathematical model to express the kinetics. The leukocyte pool of whole UCB units was separated by Dextran and Ficoll sedimentation and enriched for CD34+ progenitor cells by negative selection using a commercial antibody panel. These cells were then cultured in the presence of 20 ng/ml thrombopoietin. By day 10 of culture approximately 90% of cells expressed αIIbβ3, 80% expressed GPIb, 45% expressed α2β1 and 55% expressed P-selectin. The cells adhered to fibrinogen and collagen, spread in a manner similar to platelets, and formed focal adhesions as judged by vinculin and phalloidin (F-actin) staining. While αIIbβ3 on the surface of 293 cells cannot undergo inside-out activation, 18% of the UCB-derived cells exhibited increased binding of PAC-1, an activation-specific monoclonal antibody, in response to TRAP, and the majority bound PAC-1 after adhesion to collagen. The ploidy of the UCB-derived cells ranged from 2 to 128. The dynamics of αIIbβ3 biosynthesis was analyzed by pulse-chase analysis with 35S-Cys/Met followed by immunoprecipitation, SDS-PAGE, and densitometry of exposed x-ray film. Using non-linear regression, curves were fitted to the observed data and a 3-compartment mathematical model (pro-αIIb, mature αIIb in complex with β3, and degraded αIIb) was used to describe the αIIb dynamics. There were important similarities and differences between the two types of cells. In both cell types, pro-αIIb decreased over time in a pattern best described by a simple exponential function, P = (a)exp(-bt), where P is the amount of pro-αIIb, a is the initial amount of pro-αIIb, and b is a rate constant. The half-lives (ln2/b) of pro-αIIb in the UCB-derived cells and the 293 cells were similar (120 and 140 min, respectively). In both cell types, mature αIIb increased over time with a pattern best described by a sigmoidal function, M = c/(1+exp(−(x−x0)/d), where M is the measured amount of mature αIIb, c is the asymptotic value of αIIb, d is the rate constant, and x0 is the time to half maximum mature αIIb. In the megakaryocyte-like cells, the time to half maximum (x0) was 120 min, while in the 293 cells it was only 55 min. The amount of pro-αIIb that has been degraded at any time point (D) can be calculated by subtracting the amounts of pro-αIIb and mature αIIb at that time point from the initial amount of pro-αIIb (D = a-P-M). In the UCB-derived cells ~ 25% of pro-αIIb is degraded without being processed to mature αIIb, while in 293 cells ~ 40% is degraded. In both cell types there is a ~90 minute lag time before the onset of net αIIb degradation. These findings suggest that while the ability to degrade αIIb may be similar between megakaryocytes and 293 cells, the folding, complex formation, and quality control mechanisms are quite different. These observations have implications for the study of integrin dynamics and may be useful in analysis of the molecular mechanisms of integrin biogenesis.

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Ochoa Yumbla, Cecibel. "Infección bacteriana asociada a ventilación mecánica en pacientes de UCI-COVID-19 del Hospital Homero Castanier Crespo." Revista Ecuatoriana de Ciencia, Tecnología e Innovación en Salud Pública 6, no. 2 (2022): 1–7. http://dx.doi.org/10.31790/inspilip.v6i2.295.

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Introduction: bacterial infections associated with health care, in the intensive care unit (ICU), represent a significant problem at the global and local levels, in the context of the health crisis caused by COVID-19. In fact, a significant number of hospitalized patients develop dangerous secondary bacterial infections. Objective: To determine the incidence of bacterial infection associated with mechanical ventilation, in patients with COVID-19, in the ICU of the Homero Castanier Crespo Hospital. Methodology: A retrospective, descriptive study with a quantitative approach was carried out. In the period May 2020 - April 2021, the results of microbiological cultures of 70 samples of endotracheal secretion were analyzed. The study population was characterized by descriptive statistics. Results: In 71,4 % of cultures, positivity for bacteria was reported. Regarding the study population, men represented 80 %, (n=40), the average age was 56 years. 66 %, (n=33) of patients came from the province of Cañar. 40 % of the studied sample did not present a history of any morbidity, arterial hypertension represented 22 % and diabetes mellitus with 20 %, they were the main associated comorbidities. The microorganism with the highest incidence was Klebsiella pneumoniae, producer of beta lactamases and resistant to carbapenems with 90 %. Conclusion: Bacterial infections associated with mechanical ventilation had a high incidence, predominantly in males, constituting a risk factor for a poor prognosis in patients with COVID-19 as they are multi-resistant strains, especially beta-lactamase-producing Klebsiella pneumoniae.

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Kristensen, L. E., M. Keiserman, K. Papp, et al. "POS1024 EFFICACY AND SAFETY OF RISANKIZUMAB (RZB) FOR ACTIVE PSORIATIC ARTHRITIS (PsA): 52-WEEK RESULTS FROM KEEPsAKE 1." Annals of the Rheumatic Diseases 81, Suppl 1 (2022): 823.2–824. http://dx.doi.org/10.1136/annrheumdis-2022-eular.1186.

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BackgroundRZB, a humanized immunoglobulin G1 monoclonal antibody that specifically inhibits the p19 subunit of the human cytokine IL-23, is being investigated as a treatment for PsA.ObjectivesTo compare efficacy and safety of RZB vs. placebo (PBO) in patients with PsA who had an inadequate response or intolerance to conventional synthetic disease modifying antirheumatic drug (csDMARD-IR).MethodsKEEPsAKE 1 (NCT03675308) is an ongoing, phase 3 study that includes a screening period; a 24-week double-blinded, placebo-controlled, parallel-group period (period 1); and an open-label extension period (period 2). Eligible patients aged ≥18 years with active PsA (symptom onset ≥6 months prior to screening, meeting the Classification Criteria for PsA [CASPAR], and ≥5 swollen and ≥5 tender joints) and who had an inadequate response or intolerance to ≥1 csDMARD-IR, were randomized 1:1 to receive RZB 150 mg or placebo (PBO) at weeks 0, 4, and 16. The primary endpoint was the proportion of patients achieving ≥20% improvement in American College of Rheumatology (ACR20) response at week 24. Period 2 started at week 24, and patients were switched to receive open-label RZB 150 mg every 12 weeks through week 208. Mixed-effect model repeated measures and nonresponder imputation methods were used to assess continuous and binary variables, respectively. Efficacy and safety were analyzed in all patients who received ≥1 dose of study drug through week 52. Treatment-emergent adverse events (TEAE) were summarized using exposure-adjusted event rates (EAERs, events/100 patient-years [PY]).ResultsAt week 24, a greater proportion of RZB-treated (N=483) vs PBO-treated (N=481) patients achieved ACR20 (55.3% and 32.8%, respectively). At week 52, 70% of patients who were randomized to receive RZB and 63% of patients who were randomized to receive PBO and switch to RZB at week 24 achieved ACR20. In patients with ≥3% of body surface area affected at baseline, 52.7% of RZB-treated patients (N=273) and 9.9% of PBO-treated patients (N=272) achieved ≥90% improvement in Psoriasis Area and Severity Index (PASI 90) at week 24; 67.8% who were randomized to receive RZB and 59.9% who were randomized to receive PBO and switch to RZB at week 24 achieved PASI 90 at week 52. Similar results were observed for other efficacy measures. RZB was well tolerated through 52 weeks of treatment. EAERs of adverse events were stable between weeks 24 and 52. At the week 52 data cut-off (19 April 2021), the total EAER of any TEAE in patients receiving RZB was 143.1/100 PY.ConclusionContinuous RZB treatment provided durable efficacy and a consistent safety profile through 52 weeks of treatment in patients with active PsA who were csDMARD-IR.AcknowledgementsAbbVie, Inc. participated in the study design; study research; collection, analysis, and interpretation of data. AbbVie funded the research for this study. Medical writing assistance, funded by AbbVie, was provided by Jay Parekh, PharmD, of JB Ashtin.Disclosure of InterestsLars Erik Kristensen Speakers bureau: AbbVie, Amgen, Biogen, Bristol Myers Squibb, Gilead, Janssen, Lilly, Merck, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Biogen, Bristol Myers Squibb, Gilead, Janssen, Lilly, Merck, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Biogen, Gilead, Janssen, Lilly, Novartis, Pfizer, and UCB, MAURO KEISERMAN Speakers bureau: AbbVie, Amgen, Bristol Myers Squibb, Celgene, GlaxoSmithKline, Janssen, Novartis, Pfizer, Roche, and UCB, Consultant of: AbbVie, Amgen, Bristol Myers Squibb, Celgene, GlaxoSmithKline, Janssen, Novartis, Pfizer, Roche, and UCB, Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Celgene, GlaxoSmithKline, Janssen, Novartis, Pfizer, Roche, and UCB, Kim Papp Speakers bureau: AbbVie, Amgen, Arcutis, Astellas, Bausch Health, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Dermavant, Dermira, Incyte, Janssen, LEO Pharma, Lilly, Novartis, Pfizer, Sandoz, Sanofi Genzyme, and UCB, Consultant of: AbbVie, Amgen, Arcutis, Astellas, Bausch Health, Baxalta, Baxter, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Coherus, Dermavant, Dermira, EMD Serono, Forward Pharma, Galderma, Genentech, Gilead, Incyte, Janssen, LEO Pharma, Lilly, Meiji Seika Pharma, Merck, Mitsubishi Tanabe Pharma, Novartis, Pfizer, Regeneron, Sandoz, Sanofi Genzyme, Stiefel, Sun Pharma, Takeda, and UCB, Grant/research support from: AbbVie, Amgen, Arcutis, Astellas, Bausch Health, Baxalta, Baxter, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Coherus, Dermavant, Dermira, EMD Serono, Forward Pharma, Galderma, Genentech, Gilead, Incyte, Janssen, LEO Pharma, Lilly, Merck, Novartis, Ortho Dermatologics, Pfizer, Regeneron, Sanofi Genzyme, Sun Pharma, and UCB, Leslie McCasland Consultant of: Lilly, Douglas White Speakers bureau: AbbVie and Novartis, Consultant of: AbbVie and Novartis, Wenjing Lu Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Ahmed M. Soliman Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Ann Eldred Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Lisa Barcomb Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Frank Behrens Speakers bureau: AbbVie, Amgen, Boehringer Ingelheim, Celgene, Chugai, Galapagos, Genzyme, Gilead, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, and Sanofi, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Celgene, Chugai, Galapagos, Genzyme, Gilead, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, and Sanofi, Grant/research support from: AbbVie, Amgen, Boehringer Ingelheim, Celgene, Chugai, Galapagos, Genzyme, Gilead, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, and Sanofi

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Mease, P. J., A. Setty, K. Papp, et al. "POS1041 LONG-TERM EFFICACY AND SAFETY OF UPADACITINIB IN PATIENTS WITH PSORIATIC ARTHRITIS REFRACTORY TO BIOLOGIC THERAPIES: 2-YEAR RESULTS FROM THE PHASE 3 SELECT-PsA 2 STUDY." Annals of the Rheumatic Diseases 81, Suppl 1 (2022): 836–37. http://dx.doi.org/10.1136/annrheumdis-2022-eular.1897.

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BackgroundUpadacitinib (UPA), an oral Janus kinase (JAK) inhibitor, demonstrated efficacy and safety in patients (pts) with psoriatic arthritis (PsA) and prior inadequate response or intolerance to ≥1 biologic disease-modifying antirheumatic drug (bDMARD) at week (wk) 56 in the phase 3 SELECT-PsA 2 study.1ObjectivesTo evaluate the efficacy and safety of UPA at wk 104 from the ongoing long-term extension of SELECT-PsA 2.MethodsPts were randomized to UPA 15 mg (UPA15), UPA 30 mg (UPA30), or placebo (PBO) for 24 wks; PBO pts were then switched to UPA15 or UPA30. For continuous UPA treatment groups, efficacy endpoints at wk 104 were analyzed using non-responder imputation (NRI) and as observed (AO) (binary endpoints) or mixed-effect model repeated measures (MMRM) and AO (continuous endpoints). Treatment-emergent adverse events (TEAEs) were summarized for pts who received ≥1 dose of study drug using visit-based cut-off at wk 104.ResultsA total of 641 pts received ≥1 dose of study drug. At wk 104, 38.4% of all patients had discontinued study drug, with the highest discontinuation observed in patients randomized to PBO at baseline (all PBO: 46.7%). The most common reasons for discontinuation were lack of efficacy (UPA15: 12.3%, UPA30: 8.7%, all PBO: 21.7%) and adverse event (UPA15: 10.9%, UPA30: 13.3%, all PBO: 12.7%). The proportion of UPA pts that achieved ACR20/50/70, MDA, PASI75/90/100, and resolution of dactylitis and enthesitis were generally similar, or further improved, with 104 wks of treatment vs 56 wks1 (Table 1). Similarly, mean change from baseline in HAQ-DI, patient’s assessment of pain, BASDAI, and ASDAS was improved with UPA treatment. At 104 wks of therapy, clinical responses were largely similar with UPA15 and UPA30. Generally, safety data at wk 104 (Figure 1) were consistent with that reported at wk 56.1 Rates of serious infection, herpes zoster, hepatic disorder, anemia, neutropenia, lymphopenia, and CPK elevation remained numerically higher with UPA30 vs UPA15, while rates of malignancies, MACE, and VTE were similar for both UPA groups. One death was reported with UPA15 (unexplained due to lack of information; however, the patient had recently been diagnosed with ovarian cancer) and 2 with UPA30 (pancytopenia and COVID-19 pneumonia).Table 1.Efficacy Endpoints at Week 104EndpointUPA15 (n=211)UPA30 (n=218)Proportion of Pts (%)aNRIAONRIAOACR2055.580.354.681.8ACR5044.562.939.959.4ACR7023.232.221.631.5Minimal Disease Activity (MDA)29.441.333.949.3PASI75b47.769.852.781.1PASI90b37.755.244.367.8PASI100b23.135.435.955.6Resolution of enthesitis by LEIc39.867.837.568.4Resolution of dactylitis by LDId54.597.452.096.9Change from BLeMMRMAOMMRMAOHealth Assessment Questionnaire - Disability Index (HAQ-DI)-0.36-0.39-0.50-0.53Patient’s assessment of pain (numeric rating scale)-2.7-3.0-2.9-3.1Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)f-2.6-3.0-2.6-2.9Ankylosing Spondylitis Disease Activity Score (ASDAS)f-1.4-1.7-1.3-1.5ACR20/50/70, ≥20%/50%/70% improvement in American College of Rheumatology criteria; AO, as observed; BL, baseline; LDI, Leeds Dactylitis Index; LEI, Leeds Enthesitis Index; MMRM, mixed effect model repeated measurement; NRI, non-responder imputation; PASI75/90/100, ≥75%/90%/100% improvement in Psoriasis Area and Severity Index; pts, patients; UPA, upadacitinib.aData shown as NRI and AO for binary endpoints.bFor pts with psoriasis affecting ≥3% of body surface area at BL.cFor pts with LEI >0 at BL; resolution LEI=0.dFor pts with LDI >0 at BL; resolution LDI=0.eData shown as MMRM (LS mean) and AO (mean) for continuous endpoints.fFor pts with psoriatic spondylitis at BL.ConclusionIn PsA pts with prior inadequate response or intolerance to ≥1 bDMARD, clinical responses were maintained with UPA15 and UPA30 up to 2 years of treatment. No new safety signals were identified in this long-term extension.References[1]Mease PJ, et al. Rheumatol Ther. 2021;8:903-19.AcknowledgementsAbbVie and the authors thank the patients, study sites, and investigators who participated in this clinical trial (NCT03104374). AbbVie funded this study and participated in the study design, research, analysis, data collection, interpretation of data, reviewing, and approval of the publication. All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship. Medical writing support was provided by Monica R.P. Elmore, PhD of AbbVie.Disclosure of InterestsPhilip J Mease Speakers bureau: AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squib, Celgene, Eli Lilly, Galapagos, Genentech, Gilead, GSK, Janssen, Novartis, Pfizer, Sun Pharma, and UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squib, Celgene, Eli Lilly, Galapagos, Genentech, Gilead, GSK, Janssen, Novartis, Pfizer, Sun Pharma, and UCB, Grant/research support from: AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squib, Celgene, Eli Lilly, Galapagos, Genentech, Gilead, GSK, Janssen, Novartis, Pfizer, Sun Pharma, and UCB, Arathi Setty Shareholder of: Employee of AbbVie and may hold stock options, Employee of: Employee of AbbVie, Kim Papp Speakers bureau: AbbVie, Akros, Allergan, Almirall, Amgen, Bausch Health, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Dermavant, Dermira, Eli Lilly, Galderma, Genentech/Roche, Janssen, Kyowa Kirin, LEO, Meiji, MSD, Novartis, Pfizer, Regeneron, Sanofi Genzyme, Sienna Pharmaceuticals, Sun Pharma, Takeda, UCB, and Valeant, Consultant of: AbbVie, Akros, Allergan, Almirall, Amgen, Arcutis, Avillion, Bausch Health, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Dermavant, Dermira, Eli Lilly, Galderma, Genentech/Roche, GSK, Janssen, Kyowa Kirin, LEO, Meiji, MSD, Novartis, Pfizer, Regeneron, Sanofi Genzyme, Sienna Pharmaceuticals, Sun Pharma, Takeda, UCB, and Valeant, Grant/research support from: AbbVie, Akros, Allergan, Almirall, Amgen, Arcutis, Avillion, Bausch Health, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Dermavant, Dermira, Eli Lilly, Galderma, Genentech/Roche, GSK, Janssen, Kyowa Kirin, LEO, Meiji, MSD, Novartis, Pfizer, Regeneron, Sanofi Genzyme, Sienna Pharmaceuticals, Sun Pharma, Takeda, UCB, and Valeant, Filip van den Bosch Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Merck, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Merck, Novartis, Pfizer, and UCB, Shigeyoshi Tsuji Speakers bureau: AbbVie, Eli Lilly, Janssen, Novartis, and UCB, Consultant of: AbbVie, Eli Lilly, Janssen, Novartis, and UCB, Grant/research support from: AbbVie, Eli Lilly, Janssen, Novartis, and UCB, MAURO KEISERMAN Speakers bureau: AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Roche, and UCB, Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Roche, and UCB, Grant/research support from: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Roche, and UCB, Xianwei Bu Shareholder of: Employee of AbbVie and may hold stock options, Employee of: Employee of AbbVie, Liang Chen Shareholder of: Employee of AbbVie and may hold stock options, Employee of: Employee of AbbVie, Reva McCaskill Shareholder of: Employee of AbbVie and may hold stock options, Employee of: Employee of AbbVie, Erin McDearmon-Blondell Shareholder of: Employee of AbbVie and may hold stock options, Employee of: Employee of AbbVie, Peter Wung Shareholder of: Employee of AbbVie and may hold stock options, Employee of: Employee of AbbVie, William Tillett Speakers bureau: AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Celgene, Eli Lilly, MSD, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Celgene, Eli Lilly, and Janssen

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Bartlett, S. J., O. Schieir, M. F. Valois, et al. "POS0584-HPR PROS AND DISEASE ACTIVITY IN YEAR PRIOR TO COVID PREDICT TRAJECTORIES OF DEPRESSION IN ADULTS WITH RA IN FIRST 2 YEARS OF PANDEMIC: DATA FROM THE CANADIAN EARLY ARTHRITIS COHORT." Annals of the Rheumatic Diseases 82, Suppl 1 (2023): 561.2–562. http://dx.doi.org/10.1136/annrheumdis-2023-eular.6315.

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BackgroundGrowing evidence points to considerable mental health impacts of the prolonged COVID-19 pandemic, though data from longitudinal studies in rheumatic diseases are sparse.ObjectivesWe explored distinct trajectories ofdepressive symptoms in the year prior to and throughout the first 2-years of the COVID-19 pandemic inadults with RA.MethodsCATCH is a prospective multi-center study of adults with early RA (symptoms <1 year; 81% met 2010 ACR/EULAR criteria at enrolment) who receive care from rheumatologists across Canada. Prior to the pandemic, participants completed PROs and rheumatologists conducted RA assessments during scheduled in-person study visits. After March 2020, ongoing collection of PROs continued at in-person and remote visits.We used group-based trajectory modeling to identify latent groups with at least mild depression (PROMIS 4a depression score ≥55) in participants with ≥1 visits in the year prior to the pandemic (3/19-2/20) and ≥1 visits during pandemic (3/20-1/22) and identified prepandemic individual and clinical characteristics and PROs associated with each trajectory.ResultsThe analytic sample included 989 participants with a mean (SD) age of 60 (14) and disease duration of 6 (4) years. 73% were women, 84% white, 60% had completed some post-secondary education, and 77% were in CDAI REM/LDA at visit closest to the start of pandemic.The best model included 4 groups (posterior probabilities ≥0.80 for each group): 1)Resilient(none-minimal depression throughout: N=594; 60%);Worsening(none/minimal to mild: N=222;22%);Improving(mild-resilient: N=80;8%); andPersistent(moderate-severe throughout: N=93;9%)(Figure 1).As compared with the Resilient group, those with Worsening Depression were more likely to be female, have a higher prepandemic CDAI, MD and patient global, and report worse pain, disability, anxiety, depression, fatigue, sleep disturbance, and lower participation (Table 1).Figure 1.Table 1.Mean(SD); N(%)Worsening N=222 (22%)Resilient N=594 (60%)Improving N=80 (8%)Persistent N=93 (9%)SIGAge60 (15)61 (13)59 (13)61 (13)0.538Female173 (78%)406 (68%)57 (71%)74 (80%)0.016White194 (87%)533 (90%)67 (84%)71 (76%)0.004Education > high school143 (64%)388(65%)56 (70%)42 (45%)0.001RDCI (excl depression)1.2 (1.2)1.0 (1.2)1.0 (1.1)1.0 (1.1)0.174CDAI6.7 (8.2)5.4 (8.5)11.3 (13.9)13.0 (13.1)<0.001csDMARDs ±MTX198 (89%)547 (92%)73 (91%)67 (94%)0.513MTX only153 (69%)436 (73%)62 (78%)67 (72%)0.443Biologic or JAK43 (19%)102 (17%)12 (15%)26 (28%)0.073Corticosteroids36 (16%)86 (14%)26 (33%)20 (22%)0.001Patient Global3.1 (2.4)1.2 (2.1)3.9 (2.9)5.3 (2.7)<0.001PROMIS Anxiety >5597 (44%)44 (7%)58 (73%)86 (92%)<0.001PROMIS Depression >5583 (37%)13 (2%)70 (88%)90 (97%)<0.001PROMIS Fatigue >5583 (37%)94 (16%)42 (53%)74 (80%)<0.001PROMIS Pain >55125 (56%)187 (31%)55 (69%)76 (82%)<0.001PROMIS Physical Function <45132 (59%)238 (40%)51 (64%)78 (84%)<0.001PROMIS Participation <45107 (48%)141 (24%)49 (61%)72 (77%)<0.001PROMIS Sleep Problems >5562 (28%)88 (15%)33 (41%)so (54%)<0.001ConclusionAlthough 60% of Canadian RA patients had consistently good mental health during the first 2 years of the COVID-19 pandemic, more than 1 in 5 reported deteriorating mood suggesting a cumulative impact over time; 9% had persistent depression and 8% improving mood. The proportion of adults with RA with at least mild symptoms of depression may be more than twice that reported for the general Canadian population. Participants with worsening depressive symptoms during the pandemic were more likely to be female, have higher prepandemic disease activity, symptoms, disability, and higher impairments in participation. Given the impact of depression on quality of life, inflammation, and disease management, vulnerable groups may benefit from more frequent evaluation and additional support from rheumatology providers.AcknowledgementsCATCH was designed and implemented by the investigators and financially supported through unrestricted research grants from: Amgen and Pfizer Canada since 2007; AbbVie Canada since 2011; Medexus since 2013; Sandoz Canada since 2019; Fresenius Kabi Canada since 2021; Organon Canada since 2021.Previous funding from Hoffman La Roche (2011-21); Sanofi Genzyme (2016-7); Eli Lilly Canada (2016-20); Merck Canada (2017-21) and; Gilead Sciences Canada (2020-21).Disclosure of InterestsSusan J. Bartlett Speakers bureau: Janssen, Merck, Organon, Pfizer, Sandoz, Consultant of: Janssen, Merck, Organon, Orit Schieir: None declared, Marie-France Valois: None declared, Janet Pope Speakers bureau: UCB. Sandoz, Consultant of: AbbVie, Actelion, Amgen, Bayer, BMS, Eicos Sciences, Eli Lilly & Company, Emerald, Gilead, Janssen, Merck, Novartis, Pfizer, Roche, Sandoz, Sanofi, UCB, Grant/research support from: Abbvie, BMS, Eli Lilly & Company, Merck, Roche, Seattle Genetics, UCB, Louis Bessette Speakers bureau: Amgen, BMS, Janssen, Roche, UCB, AbbVie, Pfizer, Merck, Celgene, Sanofi, Lilly, Novartis, Grant/research support from: Amgen, BMS, Janssen, Roche, UCB, AbbVie, Pfizer, Merck, Celgene, Sanofi, Lilly, Novartis, Gilles Boire Speakers bureau: Merck, BMS, Pfizer, Janssen, Consultant of: Amgen, BMS, Celgene, Eli Lilly, Pfizer, Grant/research support from: Amgen, Abbvie, BMS, Eli Lilly, Merck, Novartis, Pfizer, Sandoz, Carol Hitchon Grant/research support from: Pfizer, UCB, Edward Keystone Speakers bureau: Amgen, AbbVie, Bristol-Myers Squibb, F. Hoffmann-La Roche Inc., Janssen Inc., Merck, Pfizer Pharmaceuticals, Sanofi Genzyme, UCB, Consultant of: AbbVie, Amgen, AstraZeneca Pharma, Bristol-Myers Squibb Company, Celltrion, Myriad Autoimmune, F. Hoffmann-La Roche Inc, Genentech Inc, Gilead, Janssen Inc, Lilly Pharmaceuticals, Merck, Pfizer Pharmaceuticals, Sandoz, Sanofi-Genzyme, Samsung Bioepsis, Grant/research support from: AbbVie, Amgen, Gilead Sciences, Lilly Pharmaceuticals, Merck, Pfizer Pharmaceuticals, PuraPharm, Sanofi, Carter Thorne Speakers bureau: Medexus/Medac, Consultant of: Abbvie, Amgen, Celgene, Centocor, Janssen, Lilly, Mexexus/Medac, Merck, Novartis, Pfizer, Sanofi, Grant/research support from: Abbvie, Celgene, CaREBiodam, Diane Tin: None declared, Glen Hazlewood: None declared, Vivian Bykerk Grant/research support from: Amgen, BMS, Genzyme, Pfizer, Regeneron Sanofi Aventis, UCB.

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Mcinnes, I., K. Kato, M. Magrey, et al. "POS1541 LONG-TERM EFFICACY AND SAFETY OF UPADACITINIB IN PATIENTS WITH PSORIATIC ARTHRITIS: 3-YEAR RESULTS FROM THE PHASE 3 SELECT-PsA 1 STUDY." Annals of the Rheumatic Diseases 82, Suppl 1 (2023): 1137.2–1138. http://dx.doi.org/10.1136/annrheumdis-2023-eular.3116.

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BackgroundUpadacitinib (UPA) improved symptoms in patients (pts) with psoriatic arthritis (PsA) with prior inadequate response or intolerance to ≥1 non-biologic disease-modifying antirheumatic drug (nbDMARD-IR) through week (wk) 104 or 2 years of treatment in SELECT-PsA 1[1].ObjectivesTo evaluate efficacy and safety of UPA vs adalimumab (ADA) through wk 152 or 3 years from the ongoing long-term open-label extension of SELECT-PsA 1.MethodsPts were randomized to receive UPA 15 mg (UPA15) or UPA 30 mg (UPA30) once daily, ADA 40 mg (ADA) every other wk, or placebo (PBO). At wk 24, PBO pts switched to UPA15 or UPA30. Following approval of UPA15, the protocol was amended so pts on UPA30 switched to UPA15 (earliest at wk 104). Efficacy was assessed through wk 152, and safety through June 13, 2022.ResultsOf 1704 pts randomized, 911 completed 152 wks of treatment. The proportions of pts achieving.≥20%/50%/70% improvement in American College of Rheumatology criteria (ACR20/50/70), minimal disease activity (MDA), and ≥75%/90%/100% improvement in Psoriasis Area and Severity Index at wk 152 were generally consistent with those at wk 1041. UPA had greater ACR20/50/70 and MDA responses vs ADA, and a greater mean change from baseline (BL) in Health Assessment Questionnaire-Disability Index, pt’s assessment of pain, and Bath Ankylosing Spondylitis Disease Activity Index vs ADA. Change from BL in modified total Sharp/van der Heijde score were similar between UPA30 and ADA, and numerically higher with UPA15(Table 1). The overall UPA safety profile remained unchanged (Figure 1)[1,2]. UPA had numerically higher rates of serious infection (SI), herpes zoster (HZ), anemia, lymphopenia, creatine phosphokinase (CPK) elevation, and non-melanoma skin cancer (NMSC) vs ADA. Increases for SI, HZ, anemia, and CPK elevation with UPA were dose dependent. Rates of major adverse cardiovascular events, venous thromboembolism, and malignancy excluding NMSC were low and generally similar across groups. The most common cause of death was COVID-19.ConclusionEfficacy of UPA in nbDMARD-IR pts with PsA was maintained through 3 years of treatment. No new safety signals were identified.References[1]McInnes IB, et al. Rheumatol Ther 2022;1–18 [Epub ahead of print].[2]McInnes IB, et al. RMD Open 2021;7(3):e001838.Table 1.Efficacy endpoints at wk 152UPA15 (n=429)UPA30a(n=423)ADA (n=429)Proportion of pts (%)NRIAONRIAONRIAOACR20/50/7064.6/52.0/35.9*89.8/71.6/48.263.1/54.1*/35.787.9/74.4/47.861.1/46.6/28.786.2/65.2/39.8Minimal diseaseactivity37.555.143.5*60.335.950.2PASI75/90/100b50.5/42.5/32.269.2/58.5/43.458.1/46.7/37.678.6/63.5/50.954.0/40.8/30.379.6/59.9/44.6Resolution of enthesitis by Leeds EnthesitisIndexc50.475.248.973.846.077.0Resolution of dactylitis by Leeds DactylitisIndexd65.495.266.197.965.497.1Change from BLeMMRMAOMMRMAOMMRMAOHealth Assessment Questionnaire-Disability Index-0.51-0.55-0.53*-0.58-0.45-0.49Pt’s assessment of pain (numericrating scale)-3.3*-3.5-3.3*-3.6-2.8-3.0Bath Ankylosing Spondylitis Disease ActivityIndexf-3.09-3.27-3.16-3.54-2.81-2.71Modified totalSharp/van derHeijde score0.210.190.050.040.090.09aFollowing a protocol amendment, all pts on UPA30 switched to UPA15 (earliest switch at wk 104); data are presented by originally randomized group.bPts with psoriasis affecting ≥3% of body surface area at BL.cPts with LEI >0 at BL; resolution LEI=0.dPts with LDI >0 at BL; resolution LDI=0.eData shown as MMRM (least squares mean) and AO (mean).fPts with psoriatic spondylitis at BL. n value ranges: UPA15 (99–429), UPA30 (95–423), ADA (89–429). Nominal *p<0.05 UPA vs ADA.ACR20/50/70, ≥20%/50%/70% improvement in American College of Rheumatology criteria; ADA, adalimumab; AO, as observed; BL, baseline; MMRM, mixed effect model repeated measurement; NRI, non-responder imputation; PASI75/90/100, ≥75%/90%/100% improvement in Psoriasis Area and Severity Index; pt, patient; UPA15/30, upadacitinib 15/30 mg once daily; wk, weekAcknowledgementsAbbVie funded this study and participated in the study design, research, analysis, data collection, interpretation of data, and the review and approval of the publication. All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship. Medical writing support was provided by Carl Davies, MSc, of 2 the Nth (Cheshire, UK), and was funded by AbbVie.Disclosure of InterestsIain McInnes Grant/research support from: AbbVie, AstraZeneca, Bristol Myers Squibb, Celgene, Eli Lilly, Evelo, Causeway Therapeutics, Gilead, Janssen, Novartis, Pfizer, Sanofi Regeneron, and UCB Pharma, Koji Kato Employee of: AbbVie and may hold stock or options, Marina Magrey Consultant of: BMS, Eli Lilly, Janssen, Novartis, Pfizer, and UCB Pharma, Grant/research support from: AbbVie, Amgen, BMS, and UCB Pharma, Joseph F. Merola Consultant of: AbbVie, Arena, Avotres, Biogen, Bristol Myers Squibb, Celgene, Dermavant, Eli Lilly, EMD Sorono, Janssen, Leo Pharma, Merck, Novartis, Pfizer, Regeneron, Sanofi, Sun Pharma, and UCB Pharma, Mitsumasa Kishimoto Consultant of: AbbVie, Amgen, Asahi-Kasei Pharma, Astellas, Ayumi Pharma, BMS, Celgene, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Janssen, Kyowa Kirin, Novartis, Ono Pharma, Pfizer, Tanabe-Mitsubishi, and UCB Pharma, Derek Haaland Speakers bureau: AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, GlaxoSmithKline, Janssen, Novartis, Pfizer, Roche, Sanofi Genzyme, Takeda, Grant/research support from: AbbVie, Adiga Life Sciences, Amgen, Bristol Myers Squibb, Can-Fite Biopharma, Celgene, Eli Lilly, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, Regeneron, Sanofi-Genzyme, UCB; and has received honoraria or other fees from AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi Genzyme, Takeda, and UCB Pharma, Yihan Li Employee of: AbbVie and may hold stock or options, Yanxi Liu Employee of: AbbVie and may hold stock or options, Jianzhong Liu Employee of: AbbVie and may hold stock or options, Ralph Lippe Employee of: AbbVie and may hold stock or options, Peter Wung Employee of: AbbVie and may hold stock or options.

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Nouri, Sarah S., Patricia Avila-Garcia, Anupama Gunshekar Cemballi, Urmimala Sarkar, Adrian Aguilera, and Courtney Rees Lyles. "Assessing Mobile Phone Digital Literacy and Engagement in User-Centered Design in a Diverse, Safety-Net Population: Mixed Methods Study." JMIR mHealth and uHealth 7, no. 8 (2019): e14250. http://dx.doi.org/10.2196/14250.

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Background Health care systems are rapidly deploying digital tools for disease management; however, few studies have evaluated their usability by vulnerable populations. To understand the barriers to app usage among vulnerable populations, we employed user-centered design (UCD) methods in the development of a new text messaging app. Objective The study aimed to describe variations in patients’ engagement in the app design process, focusing on limited health literacy (LHL), limited English proficiency (LEP), and limited digital literacy (LDL). Methods We conducted 20 in-depth semistructured interviews with primary care patients at a public health care system, used open-ended discussions and card sorting tasks to seek input about mobile phones and text messaging, and used open coding to categorize the patterns of mobile phone usage and to evaluate engagement in the card sorting process. We examined qualitative differences in engagement by examining the extensiveness of participant feedback on existing and novel text messaging content and calculated the proportion of patients providing extensive feedback on existing and novel content, overall and by health literacy, English proficiency, and digital literacy. Results The average age of the 20 participants was 59 (SD 8) years; 13 (65%) were female, 18 (90%) were nonwhite, 16 (80%) had LHL, and 13 (65%) had LEP. All had depression, and 14 (70%) had diabetes. Most participants had smartphones (18/20, 90%) and regularly used text messaging (15/20, 75%), but 14 (70%) of them reported having difficulty texting because of inability to type, physical disability, and low literacy. We identified 10 participants as specifically having LDL; 7 of these participants had LEP, and all 10 had LHL. Half of the participants required a modification of the card sorting activity owing to not understanding it or not being able to read the cards in the allotted time. The proportion of participants who gave extensive feedback on existing content was lower in participants with limited versus adequate English proficiency (4/13, 30% vs 5/7, 71%), limited versus adequate health literacy (7/16, 44% vs 3/4, 75%), and limited versus adequate digital literacy (4/10, 40% vs 6/10, 60%); none of these differences were statistically significant. When examining the proportion of patients who gave extensive feedback for novel messaging content, those with LHL were less engaged than those with adequate health literacy (8/16, 50% vs 4/4, 100%); there were no statistical differences by any subgroup. Conclusions Despite widespread mobile phone use, digital literacy barriers are common among vulnerable populations. Engagement in the card sorting activity varied among participants and appeared to be lower among those with LHL, LEP, and LDL. Researchers employing traditional UCD methods should routinely measure these communication domains among their end-user samples. Future work is needed to replicate our findings in larger samples, but augmentation of card sorting with direct observation and audiovisual cues may be more productive in eliciting feedback for those with communication barriers.

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Zheng, Chao, Daniel Holden, Ming-Qiang Zheng, et al. "A metabolically stable PET tracer for imaging synaptic vesicle protein 2A: synthesis and preclinical characterization of [18F]SDM-16." European Journal of Nuclear Medicine and Molecular Imaging 49, no. 5 (2021): 1482–96. http://dx.doi.org/10.1007/s00259-021-05597-5.

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Abstract Purpose To quantify the synaptic vesicle glycoprotein 2A (SV2A) changes in the whole central nervous system (CNS) under pathophysiological conditions, a high affinity SV2A PET radiotracer with improved in vivo stability is desirable to minimize the potential confounding effect of radiometabolites. The aim of this study was to develop such a PET tracer based on the molecular scaffold of UCB-A, and evaluate its pharmacokinetics, in vivo stability, specific binding, and nonspecific binding signals in nonhuman primate brains, in comparison with [11C]UCB-A, [11C]UCB-J, and [18F]SynVesT-1. Methods The racemic SDM-16 (4-(3,5-difluorophenyl)-1-((2-methyl-1H-imidazol-1-yl)methyl)pyrrolidin-2-one) and its two enantiomers were synthesized and assayed for in vitro binding affinities to human SV2A. We synthesized the enantiopure [18F]SDM-16 using the corresponding enantiopure arylstannane precursor. Nonhuman primate brain PET scans were performed on FOCUS 220 scanners. Arterial blood was drawn for the measurement of plasma free fraction (fP), radiometabolite analysis, and construction of the plasma input function. Regional time-activity curves (TACs) were fitted with the one-tissue compartment (1TC) model to obtain the volume of distribution (VT). Nondisplaceable binding potential (BPND) was calculated using either the nondisplaceable volume of distribution (VND) or the centrum semiovale (CS) as the reference region. Results SDM-16 was synthesized in 3 steps with 44% overall yield and has the highest affinity (Ki = 0.9 nM) to human SV2A among all reported SV2A ligands. [18F]SDM-16 was prepared in about 20% decay-corrected radiochemical yield within 90 min, with greater than 99% radiochemical and enantiomeric purity. This radiotracer displayed high specific binding in monkey brains and was metabolically more stable than the other SV2A PET tracers. The fP of [18F]SDM-16 was 69%, which was higher than those of [11C]UCB-J (46%), [18F]SynVesT-1 (43%), [18F]SynVesT-2 (41%), and [18F]UCB-H (43%). The TACs were well described with the 1TC. The averaged test–retest variability (TRV) was 7 ± 3%, and averaged absolute TRV (aTRV) was 14 ± 7% for the analyzed brain regions. Conclusion We have successfully synthesized a novel SV2A PET tracer [18F]SDM-16, which has the highest SV2A binding affinity and metabolical stability among published SV2A PET tracers. The [18F]SDM-16 brain PET images showed superb contrast between gray matter and white matter. Moreover, [18F]SDM-16 showed high specific and reversible binding in the NHP brains, allowing for the reliable and sensitive quantification of SV2A, and has potential applications in the visualization and quantification of SV2A beyond the brain.

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Journal articles on the topic 'UCG 90-20'

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