Статті в журналах: "547.704 53"

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Pletta, Karen H., Bradley R. Kerr, Jens C. Eickhoff, Gail S. Allen, Sanjeev R. Jain, and Megan A. Moreno. "Pediatric Asthma Action Plans: National Cross-Sectional Online Survey of Parents' Perceptions." JMIR Pediatrics and Parenting 3, no. 2 (November 9, 2020): e21863. http://dx.doi.org/10.2196/21863.

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Background Asthma Action Plans (AAPs) are recommended for pediatric patients to help improve asthma control. Studies have shown variable results for unscheduled doctor and emergency room visits. AAPs may have an impact on parental self-efficacy for asthma management as well as on other daily living factors that are valuable for patients and families, such as the number of missed school days and parental workdays, and on school and caregiver management. Objective The purpose of this study is to understand parent perceptions of AAPs. The goals of this analysis were threefold, including examining (1) the association between pediatric AAPs and parental self-efficacy, (2) parent perceptions of the helpfulness of an AAP for daily living factors, and (3) associations with the type of provider who gave the AAP (a primary care provider or an asthma specialist). Methods A national cross-sectional online survey was completed in October 2018 by parents of children with asthma aged 0-17 years. Survey questions included the presence or absence of a pediatric AAP, the Bursch Parental Self-efficacy for Asthma scale, parental perceptions of the AAP's helpfulness with regard to daily living factors ranked on a 5-point Likert scale, and the provider type who gave the AAP. Survey responses were summarized in terms of percentages or means and standard deviations. A 2-sample t test and analysis of covariance were used to compare self-efficacy for asthma and parental-perception-of-helpfulness scores between subjects with an AAP versus subjects without an AAP. All reported P values were 2-sided. Results A total of 704 parents with a child with asthma completed the survey. The parents had a mean age of 37.5 years (SD 10.9), and 82% (577/704) were women and 18% (127/704) were men. Most (564/704, 80%) parents had an AAP for their child; 65% (367/564) were written, 51% (286/564) were online, and 84% (474/564) were available at school. The Bursch Self-efficacy scale was significantly higher for parents with an AAP (mean 57.7, SD 8.6) versus no AAP (mean 55.1, SD 9.9; P<.001). Parents reported that they agreed/strongly agreed that an AAP was helpful for daily living factors, including managing asthma (446/544, 82%), decreased parental missed workdays (367/544, 68%), decreased child missed-school days (396/542, 73%), and for when a child is at school (422/541 78%), with other caregivers (434/543, 80%), doing normal activities (421/540 78%), and leading a normal life (437/540 81%). Parents agreed/strongly agreed that an AAP was helpful from all provider types: a pediatric provider (583/704, 82.8%), a family practice provider (556/704, 79%), and an asthma specialist (594/704, 84.4%). There was no significant difference (P=.53) between the type of provider who gave the AAP. Conclusions Parents who had pediatric AAPs for their children reported increased parental self-efficacy compared to those who did not have AAPs. Parents found AAPs helpful for decreasing missed time from work and school, and for asthma management when at home, school, and with other caregivers. Significant AAP helpfulness was seen regardless of the provider who gave the AAP, the parent's education, and income level. Findings support the usefulness of pediatric AAPs for families and the development of easily sharable electronic AAPs for children.

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LOEFFLER, A., D. U. PFEIFFER, J. A. LINDSAY, R. J. SOARES MAGALHÃES, and D. H. LLOYD. "Prevalence of and risk factors for MRSA carriage in companion animals: a survey of dogs, cats and horses." Epidemiology and Infection 139, no. 7 (October 14, 2010): 1019–28. http://dx.doi.org/10.1017/s095026881000227x.

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SUMMARYWe investigated the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) carriage in a convenience sample of purposely selected populations of dogs, cats and horses in the Greater London area. Swabs from carriage sites were pooled, enriched and processed by standard bacteriological methods. The presence of nuc and mecA was confirmed for MRSA. Risk factors were investigated among veterinary treatment group animals using exact logistic regression analysis. Twenty-six (1·53%) MRSA carriers were identified in the 1692 animals (15/704 dogs, 8/540 cats, 3/152 horses). Animals presenting for veterinary treatment more frequently carried MRSA than healthy animals (OR 7·27, 95% CI 2·18–24·31, P<0·001). Concurrent carriage of non-MRSA coagulase-positive staphylococci was associated with MRSA carriage (OR 0·088, 95% CI 0·016–0·31, P<0·001); none of the other 13 putative risk factors was significant. MRSA carriage was rare in the selected companion animal populations. The absence of typical risk factors indicates that companion animals act as contaminated vectors rather than as true reservoirs.

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Hiramatsu, Go, Yoshihiro Hirata, Soichiro Sameshima, and Naoki Matsunaga. "Electrochemical Properties of Perovskite Cathode for Solid Oxide Fuel Cell." Materials Science Forum 544-545 (May 2007): 985–88. http://dx.doi.org/10.4028/www.scientific.net/msf.544-545.985.

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Gd-doped ceria electrolyte (Ce0.8Gd0.2O1.9, GDC, 700 μm thick), 30 vol% Ni-GDC cermet anode and perovskite cathode La0.6Sr0.4CoO3 (LSC) or La0.6Sr0.4Co0.2Fe0.8O3 (LSCF) were used to evaluate the electric power of the cell using 3 vol%-H2O containing H2 fuel at 873 and 1073 K. Terminal voltage, ohmic resistance and overpotential were analyzed during the operation of the cell. The maximum power density with LSC and LSCF cathode was 53 and 113 mW/cm2 at 1073 K, respectively. The ohmic resistance and overpotential at the cathode was smaller for LSCF than for LSC.

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Wu, Haiting, Yubing Wen, Cai Yue, Xuemei Li та Ruitong Gao. "Serum TNF-α Level Is Associated with Disease Severity in Adult Patients with Immunoglobulin A Vasculitis Nephritis". Disease Markers 2020 (25 листопада 2020): 1–7. http://dx.doi.org/10.1155/2020/5514145.

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Background. Tumor necrosis factor-α (TNF-α) is a proinflammatory factor involved in the pathogenesis of immunoglobulin A vasculitis (IgAV). The association between serum TNF-α and disease severity in adult patients with IgAV nephritis (IgAV-N) has been inadequately evaluated. Methods. Serum TNF-α was measured by chemiluminescence immunoassay in 53 renal biopsy-proved IgAV-N patients, 53 healthy controls, and 53 IgA nephropathy (IgAN) patients. The correlations of clinicopathologic parameters of IgAV-N patients with serum TNF-α were analyzed. Results. In this cross-sectional study, the median age of IgAV-N patients was 29 (25-37) years, and 67.9% were female. Serum TNF-α was significantly higher in the IgAV-N group than in the healthy group [7.4 (5.7-9.4) pg/mL vs. 5.9 (5.0, 7.1) pg/mL, P = 0.001 ], but comparable with sex, age, and estimated glomerular filtration rate (eGFR) grade-matched IgAN patients. Serum creatinine ( P = 0.006 ) and serum cystatin C ( P = 0.001 ) were positively correlated with serum TNF-α level, while albumin ( P = 0.014 ) and eGFR ( P = 0.021 ) were negatively correlated with serum TNF-α level. Multivariate linear regression analysis revealed that eGFR ( P = 0.007 ) was an independent clinical predictor of serum TNF-α. Patients with higher pathological classification grade also had higher serum TNF-α. Conclusions. Serum TNF-α is associated with renal function and the pathological classification of adult patients with IgAV-N. TNF-α is a potential biomarker for the assessment of IgAV-N severity.

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Leung, Chris Poki, Minal A. Barve, Ming-Shiang Wu, Kathleen F. Pirollo, James F. Strauss, Wei-Chih Liao, Shih-Hung Yang, et al. "A phase II trial combining tumor-targeting TP53 gene therapy with gemcitabine/nab-paclitaxel as a second-line treatment for metastatic pancreatic cancer." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): 4139. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.4139.

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4139 Background: Nearly all stage IV pancreatic adenocarcinoma (PAC) patients progress after first-line treatment, and second-line options are limited. SGT-53 is an investigational product for tumor-targeted TP53 gene therapy that has completed phase Ia/Ib trials [Senser et al (2013), Mol Ther 21:1096; Pirollo et al (2016) Mol Ther 24:1697]. Methods: Here we provide an interim analysis of a Phase II trial (SGT53-02-1; NCT02340117) combining SGT-53 with gemcitabine/nab-paclitaxel (GEM/ABX). Eligible were first-line patients or those who had progressed after FOLFIRINOX (FFX) and/or gemcitabine-based therapy (second-line). In a 7-week treatment cycle, SGT-53 (3.6 mg DNA) was given once or twice weekly with GEM/ABX (1000 mg/m2/wk and 125 mg/m2/wk, respectively, for 3 of 4 weeks). Progression-free survival (PFS) and objective response rate (ORR) are primary endpoints.Overall survival (OS) and PFS are estimated by Kaplan-Meier analysis. Results: Of all evaluable patients (n=20), best response in 7 patients was determined to be partial response (PR) and 13 had stable disease (SD); none had progressive disease. In the second-line patients (n=11) there were 5 PR and 6 SD after 9 had failed FFX treatment, 3 had failed gemcitabine-based treatment and 1 had failed both. For patients with elevated CA19-9, SGT-53 + GEM/ABX resulted in marked reductions in the tumor marker. Published data for patients with PAC after therapy failure [Mita et al (2019) J Clin Med 8: 761; Portal et al (2015) Br J Cancer 113:989; Wang-Gillam et al (2016) Lancet 387:545] are shown for comparison. Notably, mPFS in our second-line patients was 7.4 months versus 3.1 months for the approved second-line therapy [Wang-Gillam et al (2016)]. This improvement in PFS exceeds the benchmark proposed to predict a clinically meaningful Phase III trial [Rahib et al (2016) Lancet Oncol 2:1209]. Conclusions: Our data suggest a clinically meaningful benefit of adding SGT-53 to GEM/ABX particularly for second-line PAC patients, most of whom had failed prior FFX treatment. Clinical trial information: NCT02340117. [Table: see text]

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Lu, Chang Wei, Szu Han Wu, Hung Hsiang Lin, Wen Hsiu Chung, Jing Kai Lin, Yung Neng Cheng, and Ruey Yi Lee. "Optimization of Operating Conditions for an SOFC Stack." Key Engineering Materials 656-657 (July 2015): 119–23. http://dx.doi.org/10.4028/www.scientific.net/kem.656-657.119.

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Performance testing for a single-cell solid oxide fuel cell (SOFC) stack is carried out to optimize its operating conditions. In this study, the Taguchi method is employed to effectively define the test matrix. The single-cell stack is composed of a 10x10 cm2 commercial anode-supported cell, metallic interconnects, current collectors, and glass-ceramic sealant. The major parameters for the experiments include: flow rates of fuel (hydrogen) and oxidant (air) gases, and temperatures. The target indices are the electrical power output, electrical efficiency, and fuel utilization. The fuel flow rates (400, 500, and 600 sccm), air flow rates (1000, 1500, and 2000 sccm) and temperatures (650, 675, and 700°C) are evaluated for different experimental combinations. The results reveal that, the operating temperature is the most crucial factor to the stack performance. The maximum power reaches to 46 W (570 mW/cm2) with a current of 58 A (715 mA/cm2) at test conditions of 700°C and fuel and oxidant flow rates of 600 sccm and 2000 sccm, respectively. As the fuel flow rate decreases to 400 sccm, the electrical efficiency can reach to 53% while the power at 34.6 W (427 mW/cm2) and current 42 A (518 mA/cm2). As the current increases to 44 A (543 mA/cm2), the fuel utilization reaches to 83%, nevertheless concentration polarization is observed in such operating condition.

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Voith, László, István Ferenc Édes, Fanni Nowotta, Réka Skoda, György Bárczi, Béla Merkely, and Dávid Becker. "Primer coronariaintervenció ST-elevációs infarktusban." Orvosi Hetilap 162, no. 13 (March 28, 2021): 497–503. http://dx.doi.org/10.1556/650.2021.31907.

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Összefoglaló. Bevezetés: Heveny myocardialis infarctusban a szívizommentés sikere, a beteg életkilátása nagymértékben függ a panasz kezdete és az elzáródott koszorúér rekanalizálása között eltelt ischaemiás időtől. Jelenleg az ér nyitása optimális esetben minden betegnél koszorúér-intervencióval történik. Célkitűzés: Annak vizsgálata, hogy öt év alatt mennyit változtak az ischaemiás idő összetevői, és miben változott az elzáródott ér nyitásának módszere ST-elevációs myocardialis infarctus (STEMI) miatt végzett primer coronariaintervencióban. Módszer: 2014. 01. 01. és 2018. 12. 31. között 1663, STEMI miatt koszorúér-intervencióval kezelt betegnél (1173 férfi és 490 nő) vizsgáltuk évenkénti bontásban a panasztól a koszorúér nyitásáig eltelt idő összetevőit és a 30 napos halálozást. Eredmények: Öt év alatt a panasztól az első egészségügyi kontaktusig medián 2:53 vs. 2:10 óra (p = 0,0132), ettől az intervenciós centrumba történt felvételig medián 1:17 vs. 1:03 óra (p = 0,009), a felvételtől a ballon nyitásáig medián 0:31 vs. 0:29 óra (p = ns) telt el. A panasztól a ballon nyitásáig eltelt idő (medián 5:29 vs. 4:07 óra, p = 0,0001) rövidült, döntően 2014 és 2015 között. A gyógyszerkibocsátó stent beültetése 15%-ról 96%-ra nőtt. A vizsgált években a légzés/keringés támogatás aránya 8,2–10,6–13,9–7,6–8,4, a 30 napos halálozásé 4,1–6,8–11,1–7,4–5,7% volt; a két érték korrelációt mutat (p = 0,827). Következtetés: Öt év alatt a panasztól az első egészségügyi kontaktusig és a kórházi beszállításig eltelt idő rövidült, de az Európai Kardiológiai Társaság ajánlásához képest hosszú; a kórházi felvételtől a ballon nyitásáig eltelt idő megfelelő. A négy órán belüli reperfúzió a betegek közel felében valósult meg. Az intervenciós centrumba való gyorsabb bekerülés javíthatna az eredményen. Orv Hetil. 2021; 162(13): 497–503. Summary. Introduction: In acute myocardial infarction, the heart muscle salvage, the patient’s life expectancy is highly dependent on the elapsed ischaemic time from the onset of complaint to target vessel recanalisation. Nowadays, target vessel recanalisation is performed with coronary intervention in all patients in optimal case. Objective: To examine how the components of ischemic time and the opening procedure of the occluded coronary have changed over five years in primary intervention done in acute ST-elevation myocardial infarction (STEMI). Method: Authors studied data of 1663 (1173 male and 480 female) STEMI patients in annual breakdowns treated with coronary intervention between 01. 01. 2014 and 31. 12. 2018, time from complaint to coronary artery opening, details of intervention and 30 days mortality rate. Results: During the five years, time intervals were as follows: from onset of complaint to first medical contact: median 2:53 vs. 2:10 hours (p = 0.0132), from this to admission in the interventional centre: median 1:17 vs. 1:03 hours (p = 0.009), from hospital admission to balloon opening: median 0:31 vs. 0:29 hours (p = ns). In total, the complaint to balloon opening time (median 5:29 vs. 4:07 hours, p = 0.0001) diminished, decisively from 2014 to 2015. Ratio of drug-eluting stent implantation increased from 15% to 96%. In the investigated years, the need of respiratory and/or circulatory device support ratio was 8.2–10.6–13.9–7.6–8.4, 30-day mortality rate between 4.1–6.8–11.1–7.4–5.7%; these two values showed a correlation (p = 0.827). Conclusion: The time from complaint to first medical contact and transfer to hospital against the significant decrease is still longer than the recommendation of the European Society of Cardiology. The time from hospital admission to balloon opening is adequate. Reperfusion within four hours was achieved in half of the patients in total. Faster hospitalization may improve results. Orv Hetil. 2021; 162(13): 497–503.

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Mouad, Assia, Fadoua Boughaleb, Loubna Aqqaoui, Toualouth Lafia, Aya Skiredj, Mounir Erraji, Fouad Ettayebi, and Houda Oubejja. "Unintentional Accidents among Children: Associated Factors with moderate /severe forms." E3S Web of Conferences 319 (2021): 01017. http://dx.doi.org/10.1051/e3sconf/202131901017.

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Unintentional accidents are very common in children and are the main reason for consultation and hospitalization in paediatric surgery. Aim: To determine the factors associated with unintentional accidents resulting in hospitalization. Material and methods: This is a cross sectional study carried out in the Paediatric Surgical Emergency Department of the Children's Hospital of Rabat over a period of 4 years. We processed 1205 children's files; the data was collected and analysed by Jamovi. Results: for the 545 files selected, the median was 8 years [4; 12] and boys were predominant (70.4%). Sociodemographic factors were represented by low health insurance. In 95.1% of cases, the family lived in a house (50.1%) or an apartment (45%) compared to 4.9% who had insanitary house. For parents' level of education, fathers had a high school education (43.6%) or never attended school (16.9%), compared to 32.9% of mothers who did not attend school. No adult was present during the accident (54.6%). The accident occurred on weekdays (73.2%), especially on winter and summer (41.6% and 33.8%). The main lesions were fractures (53%). The lesions involved the limbs (52.5%) and the head (30.2%) and were multiple in 6.5% of cases. The outcome was simple in 96.1%.

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Pootrakul, Pensri, Wanida Chua-anusorn, Adam Fleming, Paul Clark, Pornpan Sirankapracha, Udom Kachintorn, Somsak Chanyawattiwongse, Pichest Metarugcheep та Tim St. Pierre. "Non-Invasive Monitoring of Hepatic Iron Concentration during Oral Chelation in Patients with Non-Regularly Transfused β-Thalassemia/Hb E Disease." Blood 104, № 11 (16 листопада 2004): 3615. http://dx.doi.org/10.1182/blood.v104.11.3615.3615.

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Abstract Current non-invasive measurement techniques of hepatic iron concentration (HIC) include magnetic susceptometry (SQUID) and the magnetic resonance imaging (MRI) methods utilising T2 and T2*. HIC can be quantified through image measurement of the proton transverse relaxation rate (R2) (St. Pierre et al Blood 2004). The potential for using the St Pierre method to monitor changes in HIC of patients with β-thalassemia/Hb E undergoing iron chelation therapy was investigated. Seventeen non-tansfusion dependant β-thal/Hb E patients who had not previously undergone chelation were studied. Subjects were chelated with the oral iron chelator Deferiprone (DFP) and had their HIC measured using both the R2-MRI and biopsy non-heme iron techniques pre and post treatment. Ferritin levels were also assayed for comparison. The subjects ages ranged from of 13 to 53 years (mean 31.6, SD 11.5). DFP was administered at a low dose of 50 mg/kg/Day with divided doses 2 –3 times daily. The periods of drug exposure ranged between 53 and 77 weeks (mean 64.1, SD 8.4). HIC by R2-MRI and tissue iron chemical analysis, and serum ferritin Measurement R2-HIC (mg/g DW) Biopsy-HIC (mg/g DW) Serum Ferritin (ng/ml) Mean ± SD Range Mean ± SD Range G.Mean ± SE Range Initial 17.8 ± 6.6 5.7 – 29.7 18.3 ± 9.0 6.0 – 40.1 2526 ± 432 842 – 6072 Final 8.4 ± 7.9 1.0 – 23.9 7.4 ± 7.3 0.2 – 25.5 416 ± 236 113 – 4030 The results show a significant decrease of HIC after long term administration of DFP with MRI and biopsy (p= .0004 and p<0.0001 respectively). Spearman rank correlations of R2-HIC with the liver non-heme Fe and serum ferritin measures gave positive values of 0.866 (p < 0.0001) and 0.768 (p < 0.0001) respectively. The mean reduction of R2-HIC, biopsy-HIC and serum ferritin were 53%, 69%, and 74%, respectively. A decrease of 20.5% (SD ±14.9%) in the standard deviation of the R2 distribution was observed suggesting a decrease in iron heterogeneity accompanied the mean HIC decrease. The results suggest that R2 MRI has the potential to be used as a clinical monitoring tool in chelation therapy.

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Martinez-Trillos, Alejandra, Eva Gine, Jordina Rovira, Marcos González, Maria Jose Terol, Julio Delgado, Maria Rozman, et al. "Different Clinical Features but Not Outcome in SLL Patients Compared to CLL,." Blood 118, no. 21 (November 18, 2011): 3896. http://dx.doi.org/10.1182/blood.v118.21.3896.3896.

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Abstract Abstract 3896 Chronic lymphocitytic leukaemia/Small lymphocytic lymphoma (CLL/SLL) is a neoplasm composed of monomorphic small neoplastic B cells that usually co-express CD5 and CD23. The current WHO classification considers CLL/SLL as the same entity being SLL the non-leukemic lymphoma presentation of CLL. The criteria for SLL include the presence of lymphadenopathy with less than 5×109/L peripheral blood B cells. Patients with SLL usually develop PB involvement during the evolution of the disease. The aim of this study was to analyze the main clinico-biological features and outcome of a series of SLL patients and compare them with the CLL patients diagnosed in the same period of time.Patients and methods: we have included 588 patients (353M/ 233F; median age 61 years) diagnosed with CLL or SLL according to the WHO classification criteria in the same period of time.The main clinico-biological features and the outcome were recorded and analysed according to the CLL/SLL diagnosis. Results: five hundred forty-five patients (93%) fulfil the criteria for CLL and 43 patients (7%) for SLL. The main clinico-biological variables according to the CLL/SLL criteria are detailed in the table. No differences were observed in gender distribution, age at diagnosis or ECOG. Patients with SLL had more frequently Binet C stage, low haemoglobin levels and platelet counts. 320 patients eventually received therapy, including purine analogues containing regimens (159 patients), chlorambucil (113), CHOP-like regimens (31), and other therapies (17). Sixty-nine patients received rituximab in combination. SLL patients received more frequently CHOP-like regimens than CLL patients, but this difference did not reach statistical significance. During the follow-up, 58% of the SLL patients eventually developed leukemic presentation, after a median time from diagnosis of 4.6 years (0.2–15 years). Patients with SLL not receiving treatment progressed to PB involvement sooner than treated SLL (median time, 1 year vs 6 year, respectively; p=0.06).Twenty four of the 588 patients eventually developed Richter syndrome, with this proportion being higher in the SLL than in CLL patients (13.1% vs 3.5%; p=0.001). Moreover, the proportion of second neoplasm (excluding non melanoma skin cancer) was higher for SLL patients than for CLL patients. After a median follow-up for surviving patients of 7.4 years (range, 0.1 to 28), 207 patients eventually died with no differences in overall survival between the two groups of patients. In addition, the causes of death were also similar (50% in SLL and 43% in CLL due to disease progression). In conclusion, although the outcome is similar in SLL and CLL groups, SLL patients more frequently had cytopenias as well as higher risk to develop Richter syndrome and second neoplasias. Genetic and other biological studies are warranted to elucidate the particular presentation and features of SLL.Patients (n=588)CLL (=545)SLL (n=43)pMedian age (years)6161Gender (Male/female)324/21929/14Binet C27/536 (5%)8/43 (18%)<0.001Hemoglobin <110 g/L26/526 (5%)7/39 (18%)0.001Platelets <100x109/L22/525 (4%)4/39 (10%)0.08High serum LDH (%)57/496 (11%)7/37 (18%)n.s.High B2 microglobuline191/442 (43%)17/32 (53%)n.s.High CD 38 expression135/484 (27%)18/38 (47%)0.011High ZAP 70 expression138/527 (26%)14/41 (34%)n.s.Unmutated IGHV160/335 (48%)10/15 (66%)n.s.Presence of Monoclonal Paraprotein28/545 (5%)4/43 (9%)n.s.Second Neoplasia (excluding Skin)74/545 (14%)11/43 (25%)0.03110-year risk of Richter Syndrome5.3%32.8%0.00110-year OS59%53.1%n.s. Disclosures: No relevant conflicts of interest to declare.

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Born, C., and L. de la Fontaine. "Preliminary retrospective analysis of a refeeding program in a psychiatric intensive care unit for patients suffering from extreme severe anorexia nervosa." European Psychiatry 26, S2 (March 2011): 713. http://dx.doi.org/10.1016/s0924-9338(11)72418-x.

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IntroductionAnorexia nervosa (AN) is showing the highest mortality in psychiatric illness, especially because of its somatic consequences. A special program for refeeding patients with extreme severe underweight has been established in Munich.MethodsFrom 2000–2010 about 80 patients with any eating disorder were admitted. Data of 53 patients with AN were analysed. After admission most of the patients (n = 43) received a percutaneous gastric feeding tube. A high caloric solution (Fresubin energy) was administered adjusted to bodyweight aiming a weight gain of 700–1000 g per week. After reaching BMI 17 most patients were send for illness specific psychotherapy to a specialized clinic.ResultsThe sample consists of 50 (94.3%) females. Patients were diagnosed as having AN restrictive subtype in 25 cases (47.2%), AN binge/purge subtype in 24 cases (45,2%) and AN purging subtype in 4 cases (7.6%). Mean age at admission was 25.4 years (SD 7.0) and mean duration of illness until admission was 8.4 years (SD 5.7). Average length of stay in the intensive care unit was 135 days (SD 79.4). Mean BMI at admission was 12.3 (SD 1.6) and mean BMI at discharge 16.6 (SD 1.6). Thus, mean weight increase was 11.4 kg (SD 5.4).DiscussionThis intensive care program was established to enable patients with extreme severe AN to participate in psychotherapeutic programs afterwards as it was reported that cognitive function changed in regard to bodyweight. Further evaluation has to consider the occurrence of a refeeding syndrome.

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Vigil, Eugene L., and Tung K. Fang. "Comparative biochemical and morphological changes in imbibed cotton seed hypocotyls and radicles in situ and in vitro – Protein breakdown and elongation growth." Seed Science Research 5, no. 1 (March 1995): 41–51. http://dx.doi.org/10.1017/s0960258500002579.

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AbstractAxes, hypocotyls and radicles excised from dry cotton seeds (Gossypium hirsutum L. cv. M-8, a double haploid) were imbibed for 24 h and compared with axial segments (excised sections of embryos below the cotyledons) of imbibed, intact seeds. Radicles of excised axes had a 7.4-fold increase in length compared with only 5.2- and 5.7-fold increases, respectively, in radicles of intact seeds and in those isolated when dry. Change in hypocotyl length was not as extensive. EM data for hypocotyl and radicle cortical cells from dry and imbibed seeds revealed a major reduction in matrix protein in protein storage vacuoles along with significant organelle development at 24 h from the start of imbibition. This occurred in parallel with a reduction in salt-extracted proteins and an increase in 2% SDS-extractable proteins. SDS-PAGE of protein from low (0.2 M NaCI) and high (1.0 M NaCI) salt extracts showed a reduction in amount of the major storage proteins (53 and 48 kDa), these bands being almost totally absent in gels of protein extracts from imbibed radicles and significantly reduced in hypocotyls, within 24 h from the start of imbibition. These results indicate that initial elongation of hypocotyls and radicles in intact seeds or of excised axes, after 24 h imbibition, involves breakdown of storage proteins in these axial parts to supply nutrients for growth, with very limited contribution from the cotyledons.

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Ritschl, Valentin, Tanja A. Stamm, Daniel Aletaha, Johannes W. J. Bijlsma, Peter Böhm, Razvan Dragoi, Emma Dures, et al. "Prevention, screening, assessing and managing of non-adherent behaviour in people with rheumatic and musculoskeletal diseases: systematic reviews informing the 2020 EULAR points to consider." RMD Open 6, no. 3 (November 2020): e001432. http://dx.doi.org/10.1136/rmdopen-2020-001432.

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ObjectiveTo analyse how non-adherence to prescribed treatments might be prevented, screened, assessed and managed in people with rheumatic and musculoskeletal diseases (RMDs).MethodsAn overview of systematic reviews (SR) was performed in four bibliographic databases. Research questions focused on: (1) effective interventions or strategies, (2) associated factors, (3) impact of shared decision making and effective communication, (4) practical things to prevent non-adherence, (5) effect of non-adherence on outcome, (6) screening and assessment tools and (7) responsible healthcare providers. The methodological quality of the reviews was assessed using AMSTAR-2. The qualitative synthesis focused on results and on the level of evidence attained from the studies included in the reviews.ResultsAfter reviewing 9908 titles, the overview included 38 SR on medication, 29 on non-pharmacological interventions and 28 on assessment. Content and quality of the included SR was very heterogeneous. The number of factors that may influence adherence exceed 700. Among 53 intervention studies, 54.7% showed a small statistically significant effect on adherence, and all three multicomponent interventions, including different modes of patient education and delivered by a variety of healthcare providers, showed a positive result in adherence to medication. No single assessment provided a comprehensive measure of adherence to either medication or exercise.ConclusionsThe results underscore the complexity of non-adherence, its changing pattern and dependence on multi-level factors, the need to involve all stakeholders in all steps, the absence of a gold standard for screening and the requirement of multi-component interventions to manage it.

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González, A., J. L. Patier, M. López-Rodríguez, A. Guillén del Castillo, M. Rubio-Rivas, A. Argibay, B. Marí-Alfonso, et al. "SAT0322 PREVALENCE AND RISK FACTORS FOR LEFT VENTRICULAR DIASTOLIC DYSFUNCTION IN SYSTEMIC SCLEROSIS: RESULTS FROM RESCLE REGISTRY." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 1106.2–1107. http://dx.doi.org/10.1136/annrheumdis-2020-eular.963.

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Background:Left ventricular diastolic dysfunction (LVDD) is a very common finding in heart involvement in Systemic Sclerosis (SSc).Objectives:To determine the prevalence, risk factors and mortality associated with LVDD in a cohort of patients with SSc.Methods:A retrospective study was conducted with data from the multicentre Spanish Scleroderma Registry (RESCLE). A case-control study was performed to identify factors associated with LVDD.Results:Out of 1517 cases of SSc, 319 (21%) developed LVDD. Basal characteristics are shown in Table 1. In multivariate analysis, LVDD was associated to older age at diagnosis of SSc [54 vs 44 years, OR 1.05 (1,04-1.06)], presence of telangiectasia [67 vs 59%, OR 1.42 (1,88-1.08)], and treatment with calcium channel blockers [50 vs. 45%, OR 1.55 (1.16-1.96)], and inversely correlated to treatment with ACE inhibitors [74 vs. 83%, OR 0.59 (0.44-0.8)]. Mortality was increased in patients with LVDD (24 vs 17%, OR 1.4, p = 0.01). Kaplan–Meier cumulative survival for the SSc cohort, according to the presence or absence of LVDD showed significant differences in 30 years from the first SSc symptom (59 vs. 70%, p = 0.04).Table 1.Number of patients1517319 (21%)1198 (79%)PLimited SSc923 (61%)201 (63%)722 (60%)0.438Diffuse SSc304 (20%)51 (16%)253 (21%)0.041Sine Sclerodema SSc174 (11%)47 (15%)127 (11%)0.048Age at disease onset(years) med±SD46.4±16.554.1±15.944.5±16.1<0.001Arterial hypertensión491 (33%)148 (48%)343 (30%)<0.001Digital ulcers615 (41%)108 (34%)507 (42%)0.006Telangiectasia918 (61%)212 (67%)706 (59%)0.011Interstitial lung disease645 (43%)153 (48%)492 (41%)0.021Pulmonary hypertension139 (9.2%)34 (11%)105 (8.8%)0.325Capillaroscopy Slow pattern673 (51%)130 (46%)543 (53%)0.038Centromere Antibodies679 (49%)154 (55%)525 (48%)0.032Conclusion:In our cohort, LVDD is relative common in SSc patients, and it is associated with older age at diagnosis, treatment with calcium channel blockers and telangiectasia. ACE inhibitors could play a protective role against the development of LVDD. Mortality is higher in SSc patients with LVDD, and is more significative over time.References:[1]Tennøe AHet al. Left Ventricular Diastolic Dysfunction Predicts Mortality in Patients with Systemic Sclerosis. J Am Coll Cardiol. 2018;72:1804-13Disclosure of Interests:Andrés González: None declared, Jose Luis Patier: None declared, Mónica López-Rodríguez: None declared, Alfredo Guillén del Castillo: None declared, Manuel Rubio-Rivas: None declared, Ana Argibay: None declared, Begoña Marí-Alfonso: None declared, Antonio-J Chamorro: None declared, Ana Belén Madroñero-Vuelta: None declared, Eduardo L. Callejas-Moraga: None declared, Cristina González-Echávarri: None declared, Norberto Ortego: None declared, Vicent Fonollosa-Pla Consultant of: Actelion pharmaceuticals, GSK, MSD., Carmen Pilar Simeón-Aznar Consultant of: Actelion pharmaceuticals, GSK, MSD., on behalf of RESCLE Investigators, Autoimmune Diseases Study Group (GEAS): None declared

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Woelber, Linn Lena, Julia Kathrin Jueckstock, Felix Hilpert, Petra Neuser, Nikolaus De Gregorio, Severine Iborra, Frank Chen, et al. "Outcome parameters in node-negative vulvar cancer: A subset analysis of the AGO Care 1 study." Journal of Clinical Oncology 31, no. 15_suppl (May 20, 2013): 5531. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.5531.

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5531 Background: Prognosis of node-negative vulvar cancer is generally favorable compared to node positive disease. However, a small proportion of node-negative pts experience early recurrence with subsequent need for radical interventions. Aim of this analysis was to identify possible prognostic factors in this subset of pts. Methods: The AGO CaRE 1 study was designed as retrospective survey of treatment patterns and prognostic factors in vulvar cancer. Pts with primary squamous-cell vulvar cancer stage ≥1b treated at 29 gynecologic cancer centers in Germany 1998-2008 were included in a centralized database. Results: A total of 1618 pts were documented, 802 were node negative (pN0) after surgical staging and further analyzed. Median age was 66 yrs (21-94); 399 (49.8%) had pT1b, 365 (45.5%) pT2, 36 (4.5%) pT3 and 1 pT4 tumors; in 1 pt tumor stage was unknown. Median tumor size was 20 mm (1–345) and depth of invasion 4 mm (0.75–60). 703 (87.7%) pts had an R0 resection with a minimal margin of 5 mm (0.2–33); there were 46 R1 (5.7%) resections and 53 (6.6%) pts with unknown margin status. 692 pts (86.3%) received a full groin dissection (178 after sentinel node dissection) and in 85 pts (10.6%) only a sentinel node procedure was performed; surgery type was unknown in 25 pts (3.1%). 73 pts (9.1%) underwent adjuvant radiotherapy to the vulva. Median follow-up was 40 months. 169 pts (21.1 %) developed disease recurrence (thereof 111 (65.7%) at the vulva only and 53 (31.4%) at other locations, in 5 cases the localization was unknown) after a median of 17.7 months. 101 pts (12.6 %) died. To assess potential prognostic factors, multivariate analyses were performed including age, stage, tumor size, invasion depth, tumor grade, resection margin, adjuvant radiation, and mode of groin dissection [sentinel vs. full]) showing age as the only consistent prognostic factors for recurrence-free and overall survival. Conclusions: Even in the very large patient cohort of the AGO-CaRE database with more than 800 node-negative pts it was not possible to identify reliable clinicopathologic prognostic factors for node-negative disease. Identification of new biological markers will therefore be necessary to select high risk node negative pts for adjuvant treatment.

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Saeed, Omar B., Meredith Grogan Moore, H. Zawahrah, M. Tayem, Tazheh Kavoosi, and John A. van Aalst. "The Influence of Consanguinity on Familial Clefting Among Palestinians." Cleft Palate-Craniofacial Journal 56, no. 8 (April 17, 2019): 1072–79. http://dx.doi.org/10.1177/1055665619838381.

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Introduction: Orofacial clefts (OFC) are the most common congenital craniofacial anomaly. The relationship between intermarriage (consanguinity) and positive family history for OFC is not well described. Consanguinity rates in developed countries are <1% but are considerably higher in the Middle East (45%). Familial clefting rates in developed countries are under 20% but in the Middle East are reported at 30% or higher. Objective: To determine OFC demographics and to clarify the relationship between consanguinity and familial clefting among Palestinians. Design: The Palestinian Congenial Anomalies Database is based on a 700-question survey administered to mothers of children with congenital anomalies. Orofacial clefts were diagnosed in 540 children. All demographic data were analyzed using χ2 tests with a level of significance at α < .05. Results: Demographics for OFC among Palestinians were similar to other published reports. Overall consanguinity rate was 53% and familial clefting rate was 49%. Parental rates of consanguinity were significantly different for patients with cleft palate. Patients with consanguineous parents had a higher rate of positive family history of clefting (67%). Recurrence of clefts in siblings was significantly higher among those born to consanguineous parents (73%) when compared to nonconsanguineous parents. Conclusion: Consanguinity rates for Palestinians with OFC were higher than those reported in the Middle East. Familial clefting and sibling recurrence rates were also higher than expected. The risk of OFC may be mitigated with improved education about anticipated genetic consequences of consanguinity in high-risk populations such as the southern West Bank.

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Langella, Serena, Nadia Russolillo, Paolo Ossola, Andrea-Pierre Luzzi, Michele Casella, Roberto Lo Tesoriere, and Alessandro Ferrero. "Recurrence after Curative Resection for Intrahepatic Cholangiocarcinoma: How to Predict the Chance of Repeat Hepatectomy?" Journal of Clinical Medicine 10, no. 13 (June 26, 2021): 2820. http://dx.doi.org/10.3390/jcm10132820.

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(1) Background: Tumor recurrence after liver resection (LR) for intrahepatic cholangiocarcinoma (ICC) is common. Repeat liver resection (RLR) for recurrent ICC results in good survival outcomes in selected patients. The aim of this study was to investigate factors affecting the chance of resectability of recurrent ICC. (2) Methods: LR for ICC performed between January 2001 and December 2020 were retrospectively reviewed. Patients who had undergone first LR were considered for the study. Data on recurrences were analyzed. A logistic regression model was used for multivariable analysis of factors related to RLR rate. (3) Results: In total, 140 patients underwent LR for ICC. Major/extended hepatectomies were required in 105 (75%) cases. The 90-day mortality was 5.7%, Clavien–Dindo grade 3, 4 complications were 9.3%, N+ disease was observed in 32.5%, and the median OS was 38.3 months. Recurrence occurred in 91 patients (65%). The site of relapse was the liver in 53 patients (58.2%). RLR was performed in 21 (39.6%) patients. Factors that negatively affected RLR were time to recurrence ≤12 months (OR 7.4, 95% CI 1.68–33.16, p = 0.008) and major hepatectomy (OR 16.7, 95% CI 3.8–73.78, p < 0.001) at first treatment. Survival after recurrence was better in patients who underwent RLR as compared with not resected patients (31 vs. 13.2 months, p = 0.02). (4) Conclusions: Patients with ICC treated at first resection with major hepatectomy and those who recurred in ≤12 months had significantly lower probability to receive a second resection for recurrence.

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Argibay, A., I. Novo, M. Ávila, P. Diéguez González, M. Estévez Gil, B. Maure, B. Gimena, C. Vázquez Triñanes, and A. Rivera Gallego. "AB0545 GASTROINTESTINAL INVOLVEMENT IN SYSTEMIC SCLEROSIS." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 1569.2–1569. http://dx.doi.org/10.1136/annrheumdis-2020-eular.4868.

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Background:Systemic sclerosis (SSc) is a chronic, connective tissue disease with an autoimmune pattern characterized by inflammation, fibrosis and microcirculation changes leading to internal organs malfunctions. The gastrointestinal tract (GIT) is affected in up to 90% of patients with SSc. Any part of the GIT from the mouth to the anus can be affected. There are few descriptive studies about SSc-related GIT involvement.Objectives:We aimed to characterize the GIT involvement in patients with SSc.Methods:This retrospective study included all patients from SSc cohort of our autoimmune diseases unit in a tertiary referral centre. All patients fulfilled SSc criteria proposed by the American College of Rheumatology. All subjects’ histories were evaluated. Laboratory and imaging results were obtained from the hospital files. Patients with digestive manifestations were compared with patients without GIT involvement. Chi2 and t-student were used, using the statistical package SPSS25.0.Results:83 subjects with SSc were included, 68 (81,9%) of them were women. The mean age at the onset of SSc was 62,1 ± 15,3 years (range 26-89) with a mean follow-up of 9,6 ± 7,4 years. 80,7% of patients had limited SSc, 12% diffuse SSc, 4.8% SSc sine scleroderma and 2,4% early SSc. Considering the immunological profile 12 (14,5%) had Scl70 antibodies, 49 (59%) anticentromere and 21 (25,3%) had ANA antibodies without specificity for anti-Scl70 or anticentromere. 37,3% patients had lung involvement, 20,5% scleroderma and 30,1% digital ulcers. 79,5% of SSc patients were treated with proton pump inhibitors or H2 blockers. 53 (63,9%) patients with SSc had GIT involvement. In 11 patients (20,7%) digestive involvement was diagnosed before SSc (mean 26,2 months). Esophageal involvement occurred in 83%, gastric involvement in 28,3%, intestine involvement in 24,5% and liver and biliary tree involvement in 26,4%. See table 1. No significant differences in age, sex, SSc subtype, autoantibody profile, lung involvement, skin disease, mortality and therapy were observed between patients with or without GIT manifestations. There were no deaths associated with GIT involvement. The most common pharmacologic therapy used was proton pump inhibitors (86,8%), domperidone (20,8%) and antibiotic rotation (17%).EsophagealGastricIntestinalLiver and biliary tree44/53 (83%)15/53 (28,3%)12/53 (24,5%)14/53 (26,4%)Esophageal motility disorder 8 (15,1%)Gastroparesis 6 (11,3%)Small bacterial overgrowth 7 (13,2%)Primary biliary cholangitis 9 (17%)Gastroesophageal reflux 40 (75,5%)Abdominal pain /nausea 10 (18,9%)Colonic inertia 1 (1,9%)Autoimmune hepatitis 3 (5,7%)Dysphagia 11 (20,8%)Subacute gastritis 7 (13,2%)Diarrhea 6 (11,3%)Cholestatic liver enzymes 11 (20,8%)Flatulence / abdominal discomfort 6 (11,3%)Cirrhosis 2 (3,8%)Conclusion:Almost two thirds of our cohort of SSc have symptomatic gastrointestinal disease. GIT manifestations are heterogeneous. Symptoms are non-specific and overlapping for a particular anatomical site. Esophagus is the most commonly affected. More than seventy-five per cent of patients experience symptoms of gastroesophageal reflux. We did not find differences among patients with and without SSc GIT disease. 17% of patients had a Reynold’s syndrome.References:[1]Alastal Y et al. Gastrointestinal manifestations associated with systemic sclerosis: results from the nationwide inpatient simple. Ann Gastroenterol 2017; 30 (5): 1-6.[2]Savarino E et al. Gastrointestinal motility disorder assessment in systemic sclerosis. Rheumatology. 2013; 52(6):1095–100.[3]Steen VD et al. Severe organ involvement in systemic sclerosis with diffuse scleroderma. Arthritis and rheumatism. 2000; 43(11):2437–44.Disclosure of Interests:None declared

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Wermer, Marieke J. H., Maarten Donswijk, Paut Greebe, Bon H. Verweij, and Gabriël J. E. Rinkel. "ANOSMIA AFTER ANEURYSMAL SUBARACHNOID HEMORRHAGE." Neurosurgery 61, no. 5 (November 1, 2007): 918–23. http://dx.doi.org/10.1227/01.neu.0000303187.34308.7b.

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Abstract OBJECTIVE Anosmia has an important impact on well-being but is often neglected by physicians. In patients with subarachnoid hemorrhage (SAH), anosmia has mainly been reported after surgery for aneurysms of the anterior communicating artery. We studied the prevalence, predisposing factors (aneurysm site and type of treatment), impact, and prognosis of anosmia in patients with SAH. METHODS Of the patients with SAH who resumed independent living, we included all patients treated by coiling between 1997 and 2003 and a sample of patients treated by clipping between 1985 and 2001. Patients underwent structured interviews regarding the presence and duration of anosmia. The impact of anosmia was scored using a visual analog scale ranging from 0 (no influence) to 100 (the worst thing that ever happened to them). Risk factors for anosmia were assessed by logistic regression analysis. RESULTS Overall, 89 of the 315 interviewed patients (28%; 95% confidence interval [CI], 23–34%) reported anosmia after SAH (mean follow-up period, 7.4 yr), including 10 (15%) of the 67 coiled patients and 79 (32%) of the 248 clipped patients. The median visual analog scale impact score was 53 (range, 0–100). In 20 of the 89 patients (23%; 95% CI, 15–33), the symptoms had improved over time. Risk factors for anosmia were treatment by clipping (odds ratio [OR], 2.7; 95% CI, 1.3–5.7) and anterior communicating artery aneurysms (OR, 2.0; 95% CI, 1.2–3.3). CONCLUSION Anosmia after SAH has a high prevalence, considerable impact, and poor prognosis. Its occurrence after coiling suggests not only damage to the olfactory nerve by clipping but also that the SAH itself plays a role in its pathogenesis.

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Hamdani, Syed Usman, Zill-e. Huma, Atif Rahman, Duolao Wang, Tao Chen, Mark van Ommeren, Dan Chisholm, and Saeed Farooq. "Cost-effectiveness of WHO Problem Management Plus for adults with mood and anxiety disorders in a post-conflict area of Pakistan: randomised controlled trial." British Journal of Psychiatry 217, no. 5 (July 28, 2020): 623–29. http://dx.doi.org/10.1192/bjp.2020.138.

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BackgroundWith the development of evidence-based interventions for treatment of priority mental health conditions in humanitarian settings, it is important to establish the cost-effectiveness of such interventions to enable their scale-up.AimsTo evaluate the cost-effectiveness of the Problem Management Plus (PM+) intervention compared with enhanced usual care (EUC) for common mental disorders in primary healthcare in Peshawar, Pakistan. Trial registration ACTRN12614001235695 (anzctr.org.au).MethodWe randomly allocated 346 participants to either PM+ (n = 172) or EUC (n = 174). Effectiveness was measured using the Hospital Anxiety and Depression Scale (HADS) at 3 months post-intervention. Cost-effectiveness analysis was performed as incremental costs (measured in Pakistani rupees, PKR) per unit change in anxiety, depression and functioning scores.ResultsThe total cost of delivering PM+ per participant was estimated at PKR 16 967 (US$163.14) using an international trainer and supervisor, and PKR 3645 (US$35.04) employing a local trainer. The mean cost per unit score improvement in anxiety and depression symptoms on the HADS was PKR 2957 (95% CI 2262–4029) (US$28) with an international trainer/supervisor and PKR 588 (95% CI 434–820) (US$6) with a local trainer/supervisor. The mean incremental cost-effectiveness ratio (ICER) to successfully treat a case of depression (PHQ-9 ≥ 10) using an international supervisor was PKR 53 770 (95% CI 39 394–77 399) (US$517), compared with PKR 10 705 (95% CI 7731–15 627) (US$102.93) using a local supervisor.ConclusionsThe PM+ intervention was more effective but also more costly than EUC in reducing symptoms of anxiety, depression and improving functioning in adults impaired by psychological distress in a post-conflict setting of Pakistan.

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Mohammedi, Kamel, Yawa Abouleka, Charlyne Carpentier, Louis Potier, Severine Dubois, Ninon Foussard, Vincent Rigalleau, et al. "Association Between the ACE Insertion/Deletion Polymorphism and Risk of Lower-Limb Amputation in Patients With Long-Standing Type 1 Diabetes." Diabetes Care 45, no. 2 (December 1, 2021): 407–15. http://dx.doi.org/10.2337/dc21-0973.

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OBJECTIVE The ACE insertion/deletion (I/D) polymorphism has been widely studied in people with diabetes, albeit not with regard to lower-limb amputation (LLA). We examined associations among this polymorphism, plasma ACE concentration, and LLA in people with type 1 diabetes. RESEARCH DESIGN AND METHODS ACE I/D genotype and plasma ACE were assessed in three prospective cohorts of participants with type 1 diabetes. LLA was defined as minor (below-the-ankle amputation consisting of at least one ray metatarsal resection) or major (transtibial or transfemoral) amputation. Linear, logistic, and Cox regression models were computed to evaluate the likelihood of prevalent and incident LLA by ACE genotype (XD [ID or ID] vs. II) and plasma ACE, after adjusting for confounders. RESULTS Among 1,301 participants (male 54%, age 41 ± 13 years), 90 (6.9%) had a baseline history of LLA. Baseline LLA was more prevalent in XD (7.4%) than in II genotype (4.5%, odds ratio [OR] 2.17 [95 %CI 1.03–4.60]). Incident LLA occurred in 53 individuals during the 14-year follow-up and was higher in XD versus II carriers (hazard ratio 3.26 [95% CI 1.16–13.67]). This association was driven by excess risk of minor, but not major, LLA. The D allele was associated with increased prevalent LLA at the end of follow-up (OR 2.48 [1.33–4.65]). LLA was associated with higher mean (95% CI) ACE levels in II (449 [360, 539] vs. 354 [286, 423] ng/mL), but not XD (512 [454, 570] vs. 537 [488, 586]), carriers. CONCLUSIONS This report is the first of an independent association between ACE D allele and excess LLA risk, mainly minor amputations, in patients with type 1 diabetes.

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Windisch, Olivier, Ido Zamberg, Marie-Céline Zanella, Angèle Gayet-Ageron, Katherine Blondon, Eduardo Schiffer, and Thomas Agoritsas. "Using mHealth to Increase the Reach of Local Guidance to Health Professionals as Part of an Institutional Response Plan to the COVID-19 Outbreak: Usage Analysis Study." JMIR mHealth and uHealth 8, no. 8 (August 19, 2020): e20025. http://dx.doi.org/10.2196/20025.

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Background The ongoing coronavirus disease (COVID-19) pandemic forced health jurisdictions worldwide to significantly restructure and reorganize their medical activities. In response to the rapidly evolving body of evidence, a solid communication strategy is needed to increase the reach of and adherence to locally drafted and validated guidance to aide medical staff with COVID-19–related clinical decisions. Objective We present a usage analysis of a dedicated mobile health (mHealth) platform as part of an institutional knowledge dissemination strategy of COVID-19–related guidance to all health care workers (HCWs) in a large academic hospital. Methods A multidisciplinary team of experts drafted local guidance related to COVID-19. In total, 60 documents and 17 external links were made available through the platform. Documents were disseminated using a recently deployed mHealth platform for HCWs. Targeted dissemination of COVID-19–related content began on March 22, 2020. Using a third-party statistics tool, data concerning user activity and content use was anonymously collected. A quantitative analysis of user activity was performed over a 4-month period, separated into 3 periods: 2 months before (Period A), 2 weeks after (Period B), and 6 weeks following (Period C) targeted dissemination. Regional epidemiological data (daily new COVID-19 cases and total COVID-19–related hospitalizations) was extracted from an official registry. Results During the study period, the platform was downloaded by 1233 new users. Consequently, the total number of users increased from 1766 users before Period A to a total of 2999 users at the end of Period C. We observed 27,046 document views, of which 12,728 (47.1%) were COVID-19–related. The highest increase in activity occurred in Period B, rapidly following targeted dissemination, with 7740 COVID-19–related content views, representing 71.2% of total content views within the abovementioned period and 550 daily views of COVID-19–related documents. Total documents consulted per day increased from 117 (IQR 74-160) to 657 (IQR 481-1051), P<.001. This increase in activity followed the epidemiological curbing of newly diagnosed COVID-19 cases, which peaked during Period B. Total active devices doubled from 684 to 1400, daily user activity increased fourfold, and the number of active devices rose from 53 (IQR 40-70) to 210 (IQR 167-297), P<.001. In addition, the number of sessions per day rose from 166 (IQR 110-246) to 704 (IQR 517-1028), P<.001. A persistent but reduced increase in total documents consulted per day (172 [IQR 131-251] versus 117 [IQR 74-160], P<.001) and active devices (71 [IQR 64-89] versus 53 [IQR 40-70]) was observed in Period C compared to Period A, while only 29.8% of the content accessed was COVID-19–related. After targeted dissemination, an immediate increase in activity was observed after push notifications were sent to users. Conclusions The use of an mHealth solution to disseminate time-sensitive medical knowledge seemed to be an effective solution to increase the reach of validated content to a targeted audience.

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de Vos, Marit S., Jaap F. Hamming, Jolanda J. C. Chua-Hendriks, and Perla J. Marang-van de Mheen. "Connecting perspectives on quality and safety: patient-level linkage of incident, adverse event and complaint data." BMJ Quality & Safety 28, no. 3 (July 21, 2018): 180–89. http://dx.doi.org/10.1136/bmjqs-2017-007457.

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Background and objectiveIncident, adverse event (AE) and complaint data are typically used separately, but may be related at the patient level with one event triggering a cascade of events, ultimately resulting in a complaint. This study examined relations between incidents, AEs and complaints that co-occurred in admissions.MethodsIndependently and routinely collected incident, AE and complaint data were retrospectively linked for surgical admissions in an academic centre (2008–2014). Two investigators reviewed whether incidents/AEs in admissions were clinically related and in what sequence (incident preceding vs following AE). Likelihood of occurrence of AEs and AE cascades (ie, ≥3 AEs) was studied using logistic regression analyses.ResultsComplaints were filed for 33 (0.1%) of 26 383 admissions. Complaints filed by patients with incidents and/or AEs (n=13) mostly addressed quality/safety problems, whereas other complaints mostly addressed relationship problems. Incidents and AEs co-occurred in 730 (2.8%) admissions, which seemed clinically related in 34% of these cases. Incidents with related AEs preceded as well as followed AEs (56.6%/44.4%). Patients with incidents were at greater risk of AEs than patients without incidents, even for seemingly unrelated AEs (OR 1.4; 95% CI 1.3 to 1.6). Risk of AE cascades was greater when patients with AEs also had incidents, regardless of whether these seemed related (unrelated: OR 2.0; 95% CI 1.6 to 2.5; related: OR 5.7; 95% CI 4.3 to 7.4) or whether incidents preceded or followed AEs in these admissions (53% vs 52%, P>0.05).ConclusionsPatient-level linkage of incident, AE and complaint data can reveal relations between events that otherwise remain obscured, such as incidents that trigger as well as follow AEs, introducing event cascades, regardless of whether clinical relations seem present.

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Greenberg, P., G. Dine, A. Ganser, G. Verhoef, L. DeBusscher, G. Quarta, P. Zachée, et al. "Deferasirox (Exjade®, ICL670) Demonstrates Dose-Related Effects on Body Iron Levels Related to Transfusional Iron Intake in Transfusion-Dependent Anemia." Blood 106, no. 11 (November 16, 2005): 2694. http://dx.doi.org/10.1182/blood.v106.11.2694.2694.

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Abstract Iron overload, a potentially serious consequence of multiple blood transfusions, can be effectively managed with chelation therapy. Deferasirox, an investigational once-daily oral chelator, has been evaluated in a 1 year study of iron-overloaded adult and pediatric patients (n=184) with transfusion-dependent anemia including β-thalassemia, myelodysplastic syndromes (MDS) and Diamond-Blackfan anemia (DBA). Patients were stratified into four daily dose groups (5, 10, 20 and 30 mg/kg) according to baseline liver iron concentration (LIC; 2–3, >3–7, >7–14 and >14 mg Fe/g dw, respectively). Iron balance was determined for all patients, based on transfusional iron intake and chelator-induced iron excretion, derived from the change in LIC during the study (Table 1). Patient characteristics, LIC, serum ferritin and iron excretion/intake ratio during deferasirox treatment β-thalassemia (n=85) DBA (n=30) MDS (n=47) Other anemias (n=22) *Mean ± SD Age*, years 24.7 ± 10.0 16.1 ± 10.3 65.1 ± 12.5 35.8 ± 22.9 Body weight, kg 51.1 ± 14.1 39.1 ± 18.7 70.4 ± 12.5 56.1 ± 18.5 Deferasirox dose*, mg/kg 23.8 ± 7.2 23.6 ± 7.4 20.0 ± 8.3 21.9 ± 6.5 Iron intake*, mg/kg/day 0.35 ± 0.12 0.40 ± 0.11 0.28 ± 0.14 0.31 ± 0.19 <0.3, n (%) 28 (33) 6 (20) 25 (53) 10 (45) 0.3–0.5, n (%) 49 (58) 19 (63) 20 (43) 7 (32) >0.5, n (%) 8 (9) 5 (17) 2 (4) 5 (23) Serum ferritin*, ng/mL Baseline 4321 ± 2881 3245 ± 2439 3343 ± 1978 3144 ± 1850 Absolute change −386 ± 1626 −118 ± 1373 −268 ± 2053 −750 ± 1517 LIC*, mg Fe/g dw (n=76) (n=26) (n=28) (n=17) Baseline 19.3 ± 10.9 18.8 ± 10.7 15.6 ± 11.9 15.1 ± 6.2 Absolute change −4.7 ± 8.6 −1.6 ± 6.5 −5.7 ± 6.3 −3.7 ± 6.3 Iron excretion/intake ratio 1.5 ± 0.90 1.1 ± 0.46 1.7 ± 0.93 1.6 ± 1.48 Transfusion requirements and iron intake during the study varied widely between diseases. However, LIC and serum ferritin decreases were consistently achieved in all patient groups. More than one-third (38%) of patients, most of whom had MDS or other anemias, had an iron intake rate <0.3 mg/kg/day (average: 0.2 mg/kg/day; corresponding to 5.6 ml RBC/kg/month). In these patients, deferasirox at 10 and 20 mg/kg reduced LIC. Overall, an iron intake- and dose-related response pattern was observed for both LIC and serum ferritin (Figure 1). Effect of deferasirox dose and iron intake on changes in serum ferritin and LIC over 1 year Effect of deferasirox dose and iron intake on changes in serum ferritin and LIC over 1 year According to these results, deferasirox demonstrates the ability to stabilize and effectively decrease body iron levels at doses of 10, 20 and 30 mg/kg/day, depending on the degree of iron intake. In conclusion, dosing of chelation therapy should be guided by a patient’s transfusion requirements and the treatment goal, which is either to maintain or reduce body iron.

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Salam, Md Abdus, Md Robed Amin, and Quazi Tarikul Islam. "Clinical Presentation and Bacterial Etiology of Adult Community Acquired Pneumonia." Journal of Bangladesh College of Physicians and Surgeons 34, no. 3 (April 26, 2017): 128–34. http://dx.doi.org/10.3329/jbcps.v34i3.32343.

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Introduction: Pneumonia is a worldwide, serious threat to health and an enormous socio-economic burden for health care system. According to recent WHO data, each year 3-4 million patients die from pneumonia. The clinical presentations and bacterial agents responsible for community acquired pneumonia (CAP) varies according to geography and culture.Methods: A cross sectional observational study conducted among the 53 consecutive patients with a clinical diagnosis of CAP in admitted patient in the department of Medicine, DMCH, during January 2010 to December 2010. Hematological measurements (TC of WBC, Hb%, ESR, platelet count), blood culture, chest X-ray P/A view, sputum for Gram staining and culture sensitivity, sputum for AFB, blood urea and random blood sugar were done in all cases. ELISA for IgM antibody of Mycoplasma pneumoniae and Chlamydia pneumoniae were done in sputum culture negative cases.Results: The mean (±SD) age was 38.9±17.3 years and Male female ratio was 3:1. Fever, chest pain and productive cough were the most common clinical features. The mean (±SD) respiratory rate was 23.0±2.8 /minute . COPD and DM were found in 17.0% and 5.7% of patients respectively . Blood culture was found positive in only 1.9% of the study patients. Gram positive Cocci 62.26%, Gram negative Bacilli 9.43%, mixed Gram positive cocci and Gram negative bacilli 11.32% and Gram negative Cocco Bacilli 1.9% were observed and in 15.03 % cases, no bacteria could be seen. Sputum culture revealed 53.8% streptococcus pneumoniae, 26.9% Klebsiella pneumonia as predominant organism. Mycoplasma pneumoniae and Chlamydia pneumoniae were found in 7.4% and 3.7% respectively by serological test. For Streptococcus pneumoniae, sensitive antibiotics were Amoxyclav and Levofloxacin. For Gram negative bacilli and coccobacilli, more sensitive antibiotics were Meropenem, Ceftriaxone, and Clarithromycin. The best sensitive drug were found meropenem. The mean (±SD) duration of hospital stay was 5.0±1.7 days with ranging from 3 to 10 days.Conclusion: Region based bacteroiological diagnosis of Cap is important for selecting the best and sensitive drugs for complete cure.J Bangladesh Coll Phys Surg 2016; 34(3): 128-134

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Shoonaeva, N. D. "Features during labor in women with chronic hepatitis B." Kazan medical journal 96, no. 1 (February 15, 2015): 10–12. http://dx.doi.org/10.17750/kmj2015-010.

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Aim. To examine the course of labor in women with chronic hepatitis B.Methods. The course of labor was studied in 391 female patients with chronic viral hepatitis B, included in the study group (mean age 22.7±2.5 years), who delivered off in the National Maternity Hospital (Bishkek). The control group included 59 healthy women in labor (mean age 22.5±1.3 years).Results. The vast majority of patients - 53 (89.8%) of the control group and 328 (83.9%) of the study group - had delivered off at term. Post-term births were registered in both groups. Operative delivery by cesarean section was performed in 13.0% of chronic viral hepatitis B cases - by 4.5% higher compared to control group. In the study group, planned cesarean section was performed in 21 (5.4%) patients, the main indication was burdened obstetric history - in 8 (2.0%) patients; 5 (1.3%) patients had multiple indications. Emergency operations were conducted in 30 (7.7%) patients. Indications were premature rupture of membranes - 15 (3.8%) of cases, fetal hypoxia during labor and multiple indications - 10 (2.6%) cases each. The average blood loss at cesarean section in the group of patients with chronic viral hepatitis B was 870±15.2 ml, compared to 700±10.2 ml in the control group, which can be associated with low coagulation seen in hepatitis. Comparative analysis of the complications rate in the control group revealed that delayed rupture of membranes was the most frequent - 11 (18.6%) cases, followed by intrauterine fetal hypoxia - 5 (8.5%) cases, early postpartum bleeding - 4 (6.8%) cases, hypertensive disorders at labor and retained placenta - 3 (5.1%) cases each. In the group with chronic viral hepatitis B, premature rupture of membranes occurred in 51.5% of cases, (relative risk 2.8). Early postpartum bleedings were seen in 38.9% of the cases at the main group (relative risk 5.7).Conclusion. The above data gives us every reason to include women with chronic viral hepatitis B at high-risk group for possible bad pregnancy and childbirth outcomes both for the mother and the fetus.

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Kurkure, Purna Arun, Saroj Prasad Panda, Maya Prasad, and Savita Goswami. "Adolescent and young adult (AYA) survivors of childhood cancers: A challenge in after completion of therapy (ACT) clinic in resource-constrained country." Journal of Clinical Oncology 34, no. 3_suppl (January 20, 2016): 19. http://dx.doi.org/10.1200/jco.2016.34.3_suppl.19.

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19 Background: To assess the evaluation of late effects in childhood cancer survivors who have transitioned to AYA age group on longitudinal follow up in After Completion of Therapy (ACT) clinic at Tata Memorial Hospital, Mumbai. Methods: ACT clinic database was analyzed for childhood cancer survivors who have attained age 15-30 yrs at last follow up in the clinic for demographics, grade of late effects &pattern of follow up. Results: Of 1720 childhood cancer Survivors ( > , 2 yrs off therapy & disease free) registered in ACT clinic from Feb 91-Feb15, 976(56.7%) are in AYA group, M.F = 707/269 (2.6:1), Hematolymphoid : Solid tumours = 543/433 (1.3:1), Mumbai based: Non Mumbai = 306/670 (1:2.2).Median age at diagnosis 8 yrs, current median age 20 yrs, median duration of ACT clinic follow up is 6 yrs. At registration 448 (47%) had no late effects. 230(24%) had grade I, 81(8.4%) grade II 195 (20%) had grade III. Only 9(1%) had grade IV late effects which increased to 53 (6%) at last follow up due to recurrence & second neoplasia. Only 29(3%) were at low risk of developing potential late effects. 466(48.5%) were in intermediate risk & 48.5% (466) fell in high risk category requiring at least annual follow up. 72% of survivors registered in ACT clinic from 1991-2001 had stopped follow up as compared to 36% registered in subsequent decade (p < 0.01). Conclusions: AYA survivors of childhood cancers form major (56.7%) group in Long Term Follow up clinic. The increasing incidence of life threatening late effects on longitudinal follow up combined with statistically significant increasing trend of stopping follow up over period of time since ACT registration is alarming & calls for innovative approaches for maintaining good follow up through survivor centric approaches such as use of IT based communication technologies & formation of childhood cancer survivors support groups like Ugam.

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Akhtar, Zubair, Md Ariful Islam, Mohammad Abdul Aleem, Syeda Mah-E-Muneer, M. Kaousar Ahmmed, Probir K. Ghosh, Mustafizur Rahman, et al. "SARS-CoV-2 and influenza virus coinfection among patients with severe acute respiratory infection during the first wave of COVID-19 pandemic in Bangladesh: a hospital-based descriptive study." BMJ Open 11, no. 11 (November 2021): e053768. http://dx.doi.org/10.1136/bmjopen-2021-053768.

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ObjectiveTo estimate the proportion of SARS-CoV-2 and influenza virus coinfection among severe acute respiratory infection (SARI) cases-patients during the first wave of COVID-19 pandemic in Bangladesh.DesignDescriptive study.SettingNine tertiary level hospitals across Bangladesh.ParticipantsPatients admitted as SARI (defined as cases with subjective or measured fever of ≥38 C° and cough with onset within the last 10 days and requiring hospital admission) case-patients.Primary and secondary outcomesProportion of SARS-CoV-2 and influenza virus coinfection and proportion of mortality among SARI case-patients.ResultsWe enrolled 1986 SARI case-patients with a median age: 28 years (IQR: 1.2–53 years), and 67.6% were male. Among them, 285 (14.3%) were infected with SARS-CoV-2; 175 (8.8%) were infected with the influenza virus, and five (0.3%) were coinfected with both viruses. There was a non-appearance of influenza during the usual peak season (May to July) in Bangladesh. SARS-CoV-2 infection was significantly more associated with diabetes (14.0% vs 5.9%, p<0.001) and hypertension (26.7% vs 11.5%, p<0.001). But influenza among SARI case-patients was significantly less associated with diabetes (4.0% vs 7.4%, p=0.047) and hypertension (5.7% vs 14.4%, p=0.001). The proportion of in-hospital deaths among SARS-CoV-2 infected SARI case-patients were higher (10.9% (n=31) vs 4.4% (n=75), p<0.001) than those without SARS-CoV-2 infection; the proportion of postdischarge deaths within 30 days was also higher (9.1% (n=25) vs 4.6% (n=74), p=0.001) among SARS-CoV-2 infected SARI case-patients than those without infection. No in-hospital mortality or postdischarge mortality was registered among the five coinfected SARI case-patients.ConclusionsOur findings suggest that coinfection with SARS-CoV-2 and influenza virus was not very common and had less disease severity considering mortality in Bangladesh. There was no circulating influenza virus during the influenza peak season during the COVID-19 pandemic in 2020. Future studies are warranted for further exploration.

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Mol, Daniel, Anchee M. Boersma, Wouter R. Berger, Muchtiar Khan, Gijsbert S. de Ruiter, Geert-Jan P. Kimman, Joris R. de Groot, and Jonas S. S. G. de Jong. "Intermediate-term outcome of cryoballoon ablation of persistent atrial fibrillation and improvements in quality of life of patients." PLOS ONE 17, no. 1 (January 21, 2022): e0261841. http://dx.doi.org/10.1371/journal.pone.0261841.

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Background Clinical outcome of pulmonary vein isolation (PVI) has been predominantly focused on the reoccurrence of atrial fibrillation (AF) and the maintenance of sinus rhythm. However, there has been a limited intermediate follow-up on health-related quality-of-life (HRQoL) of patients. Given the relatively high recurrence rate of persistent AF after PVI treatment, it is important to follow up with clinical outcomes on symptom improvement as well as health-related quality-of-life. This study was designed to investigate the recurrence rate of atrial tachyarrhythmia (ATa), AF-related symptoms and HRQoL after PVI in patients with persistent AF who were treated with the second generation cryoballoon. Methods Total 148 patients participated in the study who were treated by PVI between 2013 and 2017 for persistent AF. All patients visited the out-patient clinic 2–5 years after PVI. During this visit all patients filled-out an AF Effect on Quality-of-life (AFEQT) questionnaire and a seven-day Holter was applied. All rhythm recordings acquired post ablation were collected and analysed, and the modified European Heart Rhythm Association score (mEHRA) scores were calculated before and after the ablation. Results The average age of patients was 63±9 year old and 44 (27.9%) were female. Mean CHA2DS2 VASc score was 1.9±1.4, and moderate and severe left atrial (LA) dilation was present in 53 (36.1%) and 15 (10.2%) patients, respectively. After a follow-up of 3.7±1.0 years, 81 (54.7%) patients had an ATa recurrence and 35 (23.6%) patients underwent a repeat LA ablation. However, the mEHRA score significantly improved in 80.4% of the patients (p <0.001), with the median overall AFEQT score of 88.9 [70.4–97.2]. Conclusions There is a considerable ATa recurrence rate after PVI of persistent AF at intermediate-term follow-up. However, our data indicate that PVI significantly improved AF-related symptoms and resulted in a high HRQoL for 2–5 years in patients with persistent AF.

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Почукалін, Антон Євгенійович, Сергій Володимирович Прийма та Олег Володимирович Різун. "ПЛЕМІННА ЦІННІСТЬ БУГАЇВ-ПЛІДНИКІВ ГОЛШТИНСЬКОЇ ПОРОДИ ЗА ЛІНІЯМИ". Bulletin of Sumy National Agrarian University. The series: Livestock, № 2 (29 вересня 2022): 49–53. http://dx.doi.org/10.32845/bsnau.lvst.2022.2.7.

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Використання плідників з високою племінною цінністю є важливим елементом удосконалення стад та й порід в цілому. Особливо це відчутно у молочному скотарстві, де організація елементів відбору та оцінки бугаїв-плідників має жорсткі критерії, а відібрані тварини передають через свій генотип високий потенціал молочної продуктивності. Щорічний каталог публікує результати оцінки бугаїв-плідників за різними методами, де основними є оцінка за потомством та геномна. Голштинська порода має широку генеалогічну структуру, де використовуються 26 ліній з наявним поголів’ям у 1206 бугаїв чорно- та червоно-рябої масті. Середнє значення селекційного індексу досліджуваних бугаїв становить 1075 ± 18,2, Cv=59%. Розподіл тварин за мастями має наступний характер: за червоно-рябою n=174, СІ+706 ± 52,3, Cv=98% та чорно-рябою відповідно n=1427, СІ+1138 ± 18,7, Cv=53%. Найбільш перспективними, з огляду на чисельність бугаїв, а відповідно для підбору батьківських пар є лінії Елевейшна 1491007, та Чіфа 1427381. Не чисельними (представлений один продовжувач) є лінії Ельбруса 897 (СІ-259), Магнета 156036 (СІ-79), Меджоріті 1599069 (СІ+576), Монтфреча 91779 (СІ+655), Судіна 917225 (СІ+216). Бугаї ліній Астронавта 1458744 та Імпрувера 333471 мають від’ємні значення селекційного індексу бугаїв. Аналіз різних оцінок засвідчив перевагу бугаїв, які оцінені геномно. Так, селекційний індекс 555 бугаїв становить 1483 ± 17,9, у тому числі червоно-рябої n=61, СІ+1244 ± 55,0 з амплітудою від 197 до 2326 та чорно-рябою n=494, СІ+1513 ± 18,6 lim 451 … 2602. Слід відмітити, що генеалогія геномних бугаїв звужена, внаслідок бугаї відносяться лише до ліній Елевейшна 1491007, Чіфа 1427381 та Маршала 2290977. Оцінка бугаїв за типом і продуктивністю потомства надає фактичні дані за комплексом основних ознак, але у порівнянні з геномними поступається останнім. Селекційний індекс 517 бугаїв становить 844 ± 23,0. Також спостерігається перевага племінної цінності тварин чорно-рябої масті над червоно-рябою з відповідними значеннями СІ+895 ± 22,5 проти СІ+524 ± 81,1. Лінії Маршала 2290977, Бесна 5694028588 мають бугаїв лише чорно-рябої масті, а Кадділака 2046246 та Рігела 352803 червоно-рябої.

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Williams, Benjamin, Michael Chau, Dylan McCreary, Brian Cunningham, Fernando Peña, and Marc Swiontkowski. "Does Hardware Removal Improve Function Following Ankle Open Reduction and Internal Fixation?" Foot & Ankle Orthopaedics 2, no. 3 (September 1, 2017): 2473011417S0004. http://dx.doi.org/10.1177/2473011417s000409.

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Category: Ankle, Trauma Introduction/Purpose: Orthopaedic hardware removal (HWR) is one of the most common orthopaedic procedures performed, with rates reported between 5% and 16%. Despite the high rates of HWR, there is still no consensus or guideline for removal after osseous healing without infection. Outcome studies for HWR are scarce, particularly in the lower extremity. The purpose of this study is to evaluate the effect of removal of symptomatic ankle hardware using the Short Musculoskeletal Function Assessment (SMFA) dysfunction index as the primary outcome. We hypothesize that HWR after ankle fracture will result in improved functional outcomes. Methods: Utilizing a prospectively collected ankle fracture registry, all patients that underwent HWR between 2013 and 2016 were retrospectively reviewed. Inclusion criteria were skeletal maturity, closed intra-articular ankle fracture, symptomatic ankle hardware and completion of the SMFA questionnaire prior to and 5-months after hardware removal. Exclusion criteria were development of a nonunion, infection or complex regional pain syndrome from initial surgery. The primary outcome was change in SMFA score from baseline. Paired t-test was used to compare baseline and follow-up SMFA scores. A multiple linear regression model evaluated the effects of age, sex, body mass index (BMI), smoking status, number of comorbidities, and Lauge-Hansen fracture classification on outcomes. Results: The study included 43 patients (31 females, 12 males), mean age 49.9 (range, 19 to 83). Mean time from initial surgery to HWR was 37±46 months (range, 2.2 to 209). Follow-up SMFA questionnaires were completed 5.7±0.5 months (range, 5.1 to 7.4) after HWR. The fractures were classified as 23 (53%) supination-external rotation, 6 (14%) pronation-external rotation, 2 (4.7%) pronation-abduction and 1 (2.3%) supination-adduction. Eleven fractures (26%) were classified as pilons. The SMFA dysfunction index improved significantly from baseline to follow-up (3.71±7.4, p=0.002). Significant improvement was seen in the secondary outcomes of SMFA bother index (4.40±8.9, p=0.003) and SMFA daily activities domain (4.12±9.1, p=0.006). Regression analysis revealed a significant improvement in the bother index correlating with female gender (p=0.01) and decreasing number of comorbidities (p=0.03). Conclusion: Our study demonstrates that patients with ankle fractures have a significant improvement in function following the removal of symptomatic ankle hardware. Patients also showed a significant improvement in the bother index and daily activities domain of the SMFA. Further investigation into the specific indications for HWR and the impact of injury and fracture pattern on outcomes is warranted.

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Derenzini, Enrico, Manuela Lemoine, Elisa Brighenti, Richard Eric Davis, Pier Luigi Zinzani, and Anas Younes. "The Small Molecule JAK1/JAK2 Inhibitor INCB16562 Shows Single Agent Activity and Strongly Synergizes with Bcl-2 Inhibitors in Lymphoma." Blood 118, no. 21 (November 18, 2011): 2731. http://dx.doi.org/10.1182/blood.v118.21.2731.2731.

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Abstract Abstract 2731 Constitutive activation of Janus Kinases has been shown to be an important mechanism supporting human lymphomagenesis. Aberrantly activated JAK/STAT signaling has been described in Hodgkin lymphoma (HL), Anaplastic Large T-cell lymphoma and Diffuse large B cell lymphoma (DLBCL) of the activated B-cell (ABC) subtype, making it an attractive target for therapy. In this study we report the activity profile of the JAK2 inhibitor INCB16562 in a panel of lymphoma cell lines (n=17) including Hodgkin (HL), Mantle Cell (MCL), Anaplastic Large T-cell (ALCL), and DLBCL. JAK-STAT pathway was found to be constitutively active (baseline p-STAT3 Tyr 705 detected by western immunoblotting) in the HL (HDLM-2, L.-428 and L-540), ALCL (SUP-M2, KARPAS-299, SUDHL-1) and the ABC derived DLBCL cell lines (HBL-1, U2932, TMD8, OCI-LY-3). In contrast, no activation of JAK-STAT was observed in the HL cell line KM-H2, in the MCL cell lines (Mino, Jeko-1, SP-53) and in the GCB-derived cell lines (SUDHL-4, SUDHL-6, BJAB). To assess the effect of INCB16562 on cell proliferation, cells were first incubated with increasing concentrations of INC16562 (from 0.1 to 10 μM) for 24, 48 and 72 hours (hrs) and cell viability was evaluated by MTS assay. The IC50 values at 48 hrs ranged from 1 to 9 μM. The ABC derived DLBCL cell line TMD8 showed the highest sensitivity, with a decrease in cell viability close to 50% following incubation with INCB16562 1μM for 24 hours. Of note, INCB16562 demostrated activity also in primary DLBCL cells. pSTAT3 negative cell lines were resistant to treatment (IC50 from 4.8 to 6.5 μM). However pretreatment level of pJAKs and pSTATs did not predict sensitivity to INCB16562. In fact inhibition of STAT3 phosphorylation alone was not sufficient to predict sensitivity to the drug in pSTAT3 expressing cells. Simultaneous inhibition of STAT3 and ERK phosphorylation was observed by western immunoblotting in the sensitive cell lines (TMD8, HBL-1, SUP-M2, KARPAS 299, SUDHL-1) (IC50 from 1 to 3 μM), whereas in the resistant cell lines (U2932, OCI-LY3, HD-LM2, L-540, L-428) a paradoxical hyperactivation of pERK was observed after incubation with INCB16562 (IC50 from 5–9 μM). Since it has been reported that sensitivity to JAK inhibition is associated to downregulation of bcl-2 family genes such as Bcl-xL and MCL-1, we investigated the baseline expression of these bcl-2 family members in our cell lines by western blot. Bcl-xL and MCL-1 were expressed at various levels, but there was no correlation between levels of baseline expression and outcome. Both Bcl-xL and MCL-1 were dowregulated in the sensitive cell lines following treatment with INCB16562. Furthermore The bcl-2 inhibitor ABT-737 synergistically enhanced the effect of INCB16562 particularly in HL cell lines (HDLM-2 and L-540) and DLBCL cells lines (HBL-1, TMD8, SUDHL-4). These data demonstrate that INCB16562 has a promising therapeutic value in lymphoma, and provide a rationale for combining INCB16562 with bcl-2 family inhibitors. Disclosures: No relevant conflicts of interest to declare.

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Shafqat, Madeeha, Faiza Jamil, Zunairah Shah, Ali Younas Khan, Seren Durer, Ceren Durer, Shehroz Aslam, et al. "A Systematic Review and Meta-Analysis: Efficacy and Toxicity Profile of Ixazomib for Treatment of Multiple Myeloma." Blood 132, Supplement 1 (November 29, 2018): 5639. http://dx.doi.org/10.1182/blood-2018-99-117159.

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Abstract Background: Ixazomib (Ixa) is the first FDA approved oral proteasome inhibitor to be used for relapsed and refractory multiple myeloma (MM). We conducted a comprehensive systematic review and meta-analysis of all published prospective clinical trials to analyze the efficacy and safety of ixazomib in newly diagnosed multiple myeloma (NDMM) and relapsed/refractory multiple myeloma (RRMM). Method: After review of literature (last updated June 30, 2018) using database searches (Pubmed, Embase, Cochrane Library, Web of Science and Clinical Trials.gov), from a total of 1290 studies, only fifteen clinical trials (n=1387) met the inclusion criteria for RRMM and eight clinical trials (n=537) met criteria for NDMM. CMA software v.3 was used for meta-analysis. Heterogeneity among studies was assessed using the I2 test. A random-effect model was applied. Result: Based on pooled analysis, an overall response rate (ORR) of 40.6% (95% CI:19.4-66.0) with a very good partial response or better (≥VGPR) of 15.7% (95% CI: 6.8-32.1) in RRMM and ORR (CR+VGPR+PR) of 77.5% (95% CI: 73.1-81.4, I2=48.05) in NDMM was observed. Most common grade (G) ≥ 3 adverse events (AE) based on regimen were calculated using pooled analysis in MM patients. Ixazomib Based Regimen in RRMM: Ixazomib as monotherapy: Four studies (n=192) evaluated the efficacy of ixazomib as a single agent. On subgroup pooled analysis on Ixa as monotherapy, an ORR of 22.7% (95% CI: 13.3-35.9, I2=45%) was observed with ≥VGPR of 7.8% (95% CI: 2.7-20.3). Pooled analysis for safety profile on most common G ≥ 3 adverse events (AEs) were thrombocytopenia 32.3% (95% CI: 22.4-44.2), neutropenia 21.5% (95% CI: 12.6-34.1), diarrhea 13.1% (95% CI: 6.8-23.9), fatigue 11.6% (95% CI: 7.4-17.7) and peripheral neuropathy 2.2% (95% CI: 0.7-6.6). Ixazomib in two drug regimen: In RRMM, two clinical trials (n=92) evaluated the efficacy of Ixa weekly with dexamethasone (D). In this subgroup pooled analysis, ORR of 40.7% (95% CI: 22.8-61.5, I2=41.76%) with ≥VGPR of 19.5% (95% CI: 4.6-52) was calculated. One study reported event-free survival (EFS) of 8.4 months(4.5-12.8) with a 1-year overall survival rate of 96% (95% CI: 91-100). In our analysis for safety (n=102), common G≥ 3 AEs calculated was thrombocytopenia in 20% (95% CI: 7.5-43.7), neutropenia in 14.3% (95% CI: 3.7-41.6), fatigue in 9.1% (95% CI: 5.0-16.2), diarrhea in 5.7% (1.1-25.5), nausea in 5.7% (95% CI: 1.4-20.2) and peripheral neuropathy in 5.7% (95% CI: 1.4-20.2). Ixazomib in three drug regimen: In RRMM, the efficacy of Ixa was evaluated inten clinical trials (n=646), an ORR of 56.3% (95% CI: 41.8-65.5, I2=82%) with ≥VGPR of 22.8% (95% CI: 13.2-36.4) was noted. Best response was seen when Ixa was used in combination with lenalidomide (R) and dexamethasone, with reported ORR of 78.3%. Common AEs were neutropenia 23.5% (95% CI: 16-33.1), thrombocytopenia 18.8% (95% CI: 13.4-25.6) anemia 10.5% (95% CI: 8.2-13.2), diarrhea 6.3% (95% CI: 3.4 -11.3), fatigue 4.2% (95% CI:2.7-6.4), nausea 1.8% (95% CI: 0.9-3.5) and peripheral neuropathy 2.3% (95% CI: 1.3-3.9). Ixazomib Based Regimen In NDMM: Pooled analysis of subgroup study for combination regimen of Ixa as IRD, Ixa-Thalidomide (T)-D, Ixa-Cyclophosphamide (C)-D, and with Ixa -melphalan-prednisone (IMP), their estimated ORR was 83.7% (95% CI: 75.6-89.5), 80.8% (95% CI: 72.8-86.9), 75% (95% CI: 66.6-82) and 66% (95% CI: 52.4-77.4) respectively. We also measured the efficacy of Ixa as a maintenance therapy, estimated ORR was 81.5% (95% CI: 36.6-97.1, I2=90.5%). In one phase II maintenance study (n=64), a combination of IR receiving patients (n=34), an ORR of 90.4% with VGPR of 53% was reported. Median progression-free survival (PFS) was not reached after a median follow up of 37.8 months and estimated 2-year PFS was 81%. Common G≥3 AEs in NDMM patients were neutropenia 21.6% (95% CI: 11.2-37.6), thrombocytopenia 15.9% (95% CI: 4.7- 42), infections 15.2% (95% CI: 10.3-21.9) and peripheral neuropathy 7.9% (95% CI: 4.7-13). Conclusion: In our pooled analysis (95%CI), Ixazomib has shown promising efficacy both in NDMM as well as RRMM. Especially in three drug regimen it showed an estimated ORR of 84.8% in NDMM and 56.3% RRMM.Cytopenia was a common side effect.Peripheral neuropathy was noted to be a rare side-effect (2.6%) in RRMM. Further studies are required to evaluate efficacy and safety of ixazomib in combination therapies in NDMM. Disclosures No relevant conflicts of interest to declare.

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Longo, Filomena, Fabio Marletto, Elisa Rivetti, Laura Sacchetti, and Antonio Piga. "Liver Fibrosis Assessment by Ultrasound Elastometry in Thalassemic Patients on Long-Term Iron Chelation." Blood 108, no. 11 (November 16, 2006): 1780. http://dx.doi.org/10.1182/blood.v108.11.1780.1780.

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Abstract BACKGROUND In thalassemic major patients liver fibrosis may be influenced by independent factors as hepatitis, degree of iron loading and iron chelation, and the specific effect of drugs. Due to its invasive nature, the histological evaluation of liver fibrosis on biopsy samples is difficult to be done and repeated. We analysed the relationship of these factors with the degree of liver fibrosis assessed non-invasively by ultrasound elastometry expressed as liver stiffness. We also compared the liver stiffness in patients on long term therapy with different iron chelators. METHODS We applied the ultrasound elastometry (Fibroscan®, Fibrosens, Paris) to a consecutive series of patients with ß thalassemia major on regular transfusion and chelation. Liver Iron Concentration (LIC) has been assessed by SQUID magnetic susceptometry (Tristan Technologies, Inc., San Diego, USA). We considered, as control, a group of healthy persons. All the subjects signed a written informed consent. RESULTS We studied 115 patients (64 males, 51 females) with beta thalassemia major, with mean age of 27.7 ± 7.6 years (range: 6.7–48.3). Eighty-six (75%) patients were HCV-Ab positive, and 52 (45%) HCV-RNA positive. Mean stiffness was 9.0 ± 6.6 KPa (range 3.3–43.5), significantly higher than in controls (4.0 ± 1.0, CI 3.3–4.8). Seven (6%) patients had a stiffness value above the cirrhosis threshold, and 18 (16%) were above the severe fibrosis threshold. Mean serum ferritin was 2064 ± 2011 μg/L, and mean LIC was 1845 ± 1199 microg/g ww. Considering the chelator, 34 patients have been on deferoxamine (DFO) therapy for 19.2 ± 9 years, 53 patients on deferiprone (L1) for 5.7 ± 3.7 years, and 28 on deferasirox (ICL670) for 3.3 ± 1.1 years. Mean stiffness was 9.5 ± 7.4 kPa, 9.9 ± 7.3 and 6.6 ± 2.8, respectively. On multivariate analysis, HCV Ab, HCV RNA and LIC were independent factors determining the degree of stiffness, while the chelator used was not significant. CONCLUSIONS Thalassemia major patients on regular transfusion and chelation have significantly abnormal degree of liver fibrosis. HCV positivity and the amount of iron overload seem to be the main related factors. The type of chelator used does not seem important.

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Cho, Kyoung Min, Tae Yong Kim, Do-Youn Oh, Kyung-Hun Lee, Sae-Won Han, Seock-Ah Im, Tae-You Kim, and Yung-Jue Bang. "Metabolic landscape using 18F-FDG PET and its clinical significances in advanced biliary tract cancer." Journal of Clinical Oncology 32, no. 3_suppl (January 20, 2014): 252. http://dx.doi.org/10.1200/jco.2014.32.3_suppl.252.

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252 Background: Metabolic landscape evaluated by 18F-FDG positron emission tomography (PET) in advanced biliary tract cancer (BTC) has not been studied. Furthermore, the clinical meanings of metabolic features have rarely been reported. We evaluated the metabolic features using 18F-FDG PET and its clinical significances in advanced BTC. Methods: We consecutively enrolled advanced BTC patientswho underwent PET prior to palliative chemotherapy between 2003 and 2013. We retrospectively evaluated the findings of PET such as SUVmax, lesion numbers, involved organ and pathologic findings and other clinical factors including response to chemotherapy, progression-free survival (PFS) and overall survival (OS). Results: A total of 106 patients were enrolled (intrahepatic cholangiocarcinoma (ICC):53, extrahepatic BTC :7, gallbladder cancer (GB Ca) :30, and ampulla of vater cancer (AoV Ca): 16 patients) ECOG PS 0-1 in 89 and PS 2 in11 patients. 52.8 % of patients received gemcitabine-based chemotherapy and 47.1% of patients received 5-FU-based chemotherapy. The SUVmax was median 7.8 (range 0-44). Fifty-four percent of patients showed higher SUVmax in metastatic lesion than primary site. The SUVmax was different according to primary origin (ICC: 9.10, extrahepatic BTC: 5.90, GB Ca : 9.10, AoV Ca :6.37, p=0.008) and histologic differentiation (well-differentiated: 4.95, moderately-differentiated :6.60, poorly-differentiated :14.50, p=0.004) Patients with a SUVmax of >7.5 had more poorly differentiated histology and more PET uptake-lesions (p < 0.05) than those with a SUVmax of <7.5. The OS and PFS of all patients were 8.3 (95% CI: 5.7 – 10.8 ) and 4.9 months (95% CI: 3.4 – 6.3), respectively. Patients with a SUVmax of <7.5 had a significantly longer OS (11.4 vs. 7.4 months, p = 0.007) and PFS (6.6 vs. 4.3 months, p = 0.024) than those with a SUVmax of >7.5. In multivariate analysis, SUVmax was also a significant prognostic factor for OS (p=0.012) and PFS (p=0.039). Conclusions: Metabolic landscapes of advanced BTC are different according to primary origin and histology. This metabolic feature such as SUVmax could be a potential prognostic factor for OS and PFS in advanced BTC.

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Guan, M., R. Pan, X. Gao, D. Xu, Q. Deng, and M. Deng. "First Report of Red Crown Rot Caused by Cylindrocladium parasiticum on Soybean in Guangdong, Southern China." Plant Disease 94, no. 4 (April 2010): 485. http://dx.doi.org/10.1094/pdis-94-4-0485b.

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In October 2006, occurrence of a disease on soybean (Glycine max) was observed in Guangdong Province of southern China with symptoms resembling red crown rot (3,4). Reddish brown lesions girdled the basal stems with numerous reddish orange perithecia on the lesion surface. Roots became black and rotted and whole plants wilted and died. More recently, outbreaks of this disease were observed in several counties in Guangdong. Disease incidence reached as much as 80% on cv. Huaxia 3 in some fields, causing severe yield losses. Isolation was made from the edge of lesions on potato dextrose agar at 25°C. The fungus produced white, aerial mycelia and a burnt orange-to-dark brown submerged growth. Conidiophores were borne laterally on a stipe, terminating in a hyaline, globose vesicle measuring 4.0 to 13.0 μm in diameter. After branching from the stipe, the conidiophore continued to develop by forming two to three single-celled branches. These cells might give rise to two or three shorter branches (14.8 to 36.9 μm long) and phialides. The phialides were doliform, nonseptate, and measured 7.4 to 19.7 × 3.7 to 4.9 μm. Conidia were hyaline, cylindrical with one to three septa (mostly three septa), and measured 54.1 to 76.3 × 4.9 to 7.4 μm. Perithecia were orange to red, subglobose to oval or globose, 212.1 to 454.5 μm high, and 111.1 to 333.3 μm wide. Asci were hyaline, clavate, thin walled, long stalked, measured 121.0 to 200.8 × 11.5 to 25.6 μm, and each contained eight ascospores that became aggregated in the upper half of the ascus at maturity. The ascospores were hyaline, fusoid to falcate with one to three septa (mostly with one septum), constricted slightly at the septum, and measured 29.5 to 73.8 × 4.9 to 9.8 μm. The fungus was identified as Cylindrocladium parasiticum (teleomorph Calonectria ilicicola) (1,2). The beta-tubulin gene fragment sequences of three isolates were obtained (one sequence being GenBank Accession No. GU073284) and comparisons with GenBank showed 99 to 100% similarity with Calonectria ilicicola (EF159730 and AY725643). Pathogenicity was confirmed by inoculation of 2-week-old seedlings of cv. Huaxia 3 in plastic pots (10 × 9 cm) by drenching with a conidia suspension (105 conidia per ml). All inoculated plants showed similar red crown rot symptoms on stem bases and roots 1 week after inoculation. C. parasiticum was reisolated from the diseased plants, and many orange-to-red perithecia of Calonectria ilicicola were formed on the lesions 3 weeks after inoculation. This pathogen may pose a serious threat to >300,000 ha of soybean production as well as >300,000 ha of peanut production in Guangdong Province. It has been previously reported in Jiangsu Province in eastern China (3) and Yunnan Province in western China (4). References: (1) D. K. Bell, and E. K. Sobers. Phytopathology 56:1361, 1966. (2) P. W. Crous et al. Mycol. Res. 97:889, 1993. (3) J. Y. Gai et al. Soybean Sci. (in Chinese) 11:113, 1992. (4) Z. H. Ma et al. Plant Pathol. 53:537, 2004.

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An, Ran, Yan Wang, Fuchenchu Wang, Akshara Singareeka Raghavendra, Chao Gao, Diana Amaya, Nuhad K. Ibrahim, and Jing Li. "Upfront stereotactic radiosurgery for brain metastases from triple-negative breast cancer." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): e14014-e14014. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.e14014.

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e14014 Background: Triple-negative breast cancer (TNBC) is an aggressive subtype with high propensity of brain metastases (BM). Outcomes after upfront stereotactic radiosurgery (SRS) for BM from TNBC patients are not well defined. We evaluated outcomes and identified prognostic factors for such patients. Methods: We reviewed 57 consecutive patients treated with upfront SRS for BM from TNBC in May 2008–April 2018 at a large-volume cancer center. Endpoints were overall survival (OS) from BM diagnosis and freedom from BM progression (FFBMP) after initial SRS. BM progression was defined as local and/or distant brain failure (LBF or DBF) after initial SRS; LBF was radiographic progression of treated lesions, assessed by a neuroradiologist or treating physician excluding post-radiation changes or radiation necrosis. Kaplan-Meier and Cox proportional hazard regression analyses were used to estimate survival outcomes and identify prognostic factors. Results: In this cohort of 57 patients with a median age of 53 y (range 26–82) at BM diagnosis and follow-up time of 12.2 months (mo, range 0.8–97.5), median time to BM development from TNBC diagnosis was 23.7 mo (range 0.7‒271.1). Estimated median OS time from initial BM diagnosis was 13.1 mo (95% CI 8.0‒19.5). In univariate analysis, Karnofsky performance score (KPS) > 70 (p = 0.03), having < 3 BMs (p = 0.016) at BM diagnosis, and BM as first site of metastasis (p = 0.041) were associated with longer OS. On multivariate analysis, KPS ≤70 was associated with higher risk of death (HR 3.0, p = 0.03). Of 46 patients with imaging follow-up for FFBMP assessment, 29 (63%) developed BM progression after initial SRS with an estimated median FFBMP of 7.4 mo (95% CI 5.7–12.7). Median times to LBF and DBF were 10 mo (range 0.3–97) and 5.9 mo (range 0.3–90.8). Estimated cumulative LBF rate was 17.8% (95% CI 2%–31.1%) and DBF 61.1% (95% CI 40.8%–74.4%) at 12 mo. Number of BMs at BM diagnosis (≥3 vs < 3) was not associated with FFBMP (p = 0.7). Of the 29 patients with BM progression, 5 did not receive salvage radiation therapy (RT) and 24 received salvage RT (SRS, whole-brain radiation [WBRT], or both SRS+WBRT). Receipt of salvage RT was associated with longer survival (median 21.7 mo vs. 7.0 mo for no salvage RT, p < 0.0001) and did not differ by type of salvage RT (median OS 18.6 mo for WBRT; 26.2 mo for SRS+WBRT; 35.9 mo for SRS, p = 0.08). Conclusions: We reported a median OS of 13.1 mo and FFBMP of 7.4 mo in TNBC patients with good local control. Good KPS was independent prognostic factor for better OS. FFBMP did not differ by number of SRS-treated brain lesions ( < 3 vs ≥3). Further prospective studies of larger numbers of patients needed for more accurate comparisons of treatment types.

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Preedeekanit, K., and A. Koolvisoot. "AB0228 LONG-TERM EFFECTIVENESS, DRUG SURVIVAL OF BIOLOGIC THERAPIES IN PATIENTS WITH ACTIVE RHEUMATOID ARTHRITIS AND SPONDYLOARTHRITIS AND PREDICTIVE FACTORS OF DRUG DISCONTINUATION DUE TO DISEASE REMISSION." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 1139.3–1140. http://dx.doi.org/10.1136/annrheumdis-2021-eular.2776.

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Background:Rheumatoid arthritis (RA) and spondyloarthropathies (SpA) are chronic rheumatic diseases that can progress to disability if left uncontrolled. Biologic therapies can induce remission in patients with inadequate response or intolerance to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). Due to the safety and economic concern, updated treatment recommendations now consider biologics discontinuation in patients with persistent remission. However, available data are still limited.Objectives:To evaluate the biologics effectivenss, drug survival, rate of discontinuation in real-life practice and to identify predictors of biologics discontinuation due to remission in RA and SpA.Methods:A total of 87 patients with RA and 49 patients with SpA, starting biologics between January 2005 and October 2020, were recruited from the Rheumatic Disease Prior Authorization (RDPA) registry of Siriraj hospital. Baseline data were recorded. Time-dependent rates in achieving remission were calculated. Cumulative probability of biologics discontinuation and predictive factors of drug discontinuation due to remission were analyzed.Results:The biologics used in RA patients were Etanercept (49.4%), Rituximab (44.8%), and Infliximab (5.7%). The 1- and 5- year remission rates were 8.5% and 23.9%, respectively. Drug survival rates were 33.6% for Etanercept, 40.7% for Rituximab, and 36% for Infliximab at five years. The main reasons for drug discontinuation were disease remission (32.1%), inadequate response (32.1%), and side effects (15.1%). Rituximab had the highest discontinuation rate due to remission (56.4%). There was no predictive factor for biologics discontinuation due to remission.SpA patients were treated with Etanercept (83.6%) and Infliximab (16.4%). The 1- and 5- year remission rates were 67.4% and 66.7%, respectively. Drug survival rates were 50.3% for Etanercept and 0% for Infliximab at five years. Biologics withdrawal due to side effects occurred in 16%, inadequate response in 10%, and disease remission in 10% of patients. The predictive factor for biologics discontinuation due to remission was disease duration < 5 years (Hazard ratio 6.92, 95%CI 1.10, 43.29)Conclusion:Biologic therapies are effective in patients with active RA and SpA despite csDMARDs treatment. The highest drug survival rates are Rituximab in RA and Etanercept in SpA. Infliximab has the shortest drug retention rate in SpA. Drug discontinuation due to remission is more successful in RA patients, particularly in the Rituximab group. The best predictor for biologics discontinuation due to remission in SpA is the disease duration of fewer than five years.Table 1.Effectiveness, Drug Survival and Causes of Biologic Discontinuation in RA and SpARA % (87 cases)BiologicsTotal % (N)5-year Remission rate %5-year Drug survival rate %Discontinuation % (N 53 cases)Total %(53)RemissionInadequate responseSide effectNon-adherence/ ReferDeathEtanercept49.4 (43)23.933.650.9(27)14.8(4)44.4(12)22.2(6)11.1(3)7.4(2)*Infliximab5.7 (5)365.7 (3)0(0)33.3(1)33.3(1)33.3(1)(0)Rituximab44.8 (39)40.743.4 (23)56.5(13)17.4(4)4.3(1)13.0(3)8.7(2)SpA %(49 cases)BiologicsTotal % (N)5-year Remission rate %Drug survival rate%Discontinuation % (N 23 cases)Total % (23)RemissionInadequate responseSide effectNon-adherence/ ReferDeathEtanercept83.6 (41)66.750.378.3(18)22.2(4)22.2(4)33.3(6)22.2(4)0(0)Infliximab16.4 (8)021.7 (5)20(1)20(1)40(2)20(1)0(0)*Cause of death: sudden cardiac death (1), intraabdominal infection (1)Cause of death: pneumonia (1), Lung cancer (1)Disclosure of Interests:None declared

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Hassan, Raffit, Anish Thomas, John J. Nemunaitis, Manish R. Patel, Jaafar Bennouna, Franklin Chen, Jean-Pierre Delord, et al. "Avelumab in patients with previously treated mesothelioma: Updated phase 1b results from the JAVELIN Solid Tumor trial." Journal of Clinical Oncology 36, no. 5_suppl (February 10, 2018): 166. http://dx.doi.org/10.1200/jco.2018.36.5_suppl.166.

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166 Background: Avelumab, a human anti-PD-L1 IgG1 monoclonal antibody, is approved for treatment of metastatic Merkel cell carcinoma (US and EU) and advanced urothelial carcinoma progressed on platinum therapy (US). Here, we report updated phase 1b data for avelumab in patients (pts) with previously treated mesothelioma. Methods: Pts with unresectable pleural or peritoneal mesothelioma whose disease had progressed after platinum and pemetrexed therapy received avelumab 10 mg/kg IV Q2W until progression, unacceptable toxicity, or withdrawal. Tumors were assessed every 6 wks (RECIST 1.1). Endpoints included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs; NCI CTCAE v4.0). Results: As of Dec 31, 2016, 53 pts were treated and followed for a median of 24.8 mos (range 16.8–27.8). Median age was 67 y (range 32–84). Pts had received a median of 2 prior lines of therapy (range 1–8). Confirmed ORR was 9.4% (95% CI 3.1–20.7; complete response in 1.9%, partial response in 7.5%). In pts with 1 (n = 18), 2 (n = 15) or ≥3 (n = 20) prior lines of therapy, ORR was 5.6%, 13.3% and 10.0% respectively. Median duration of response was 15.2 mos (95% CI 11.1–not estimable). 26 pts (49.1%) had stable disease as best response and the disease control rate was 58.5%. Median PFS was 4.1 mos (95% CI 1.4–6.2) and the 6-mo PFS rate was 38.0% (95% CI 24.2–51.7). Median OS was 10.9 mos (95% CI 7.5–21.0) and the 12-mo OS rate was 45.9% (95% CI 31.9–58.8). In evaluable pts with PD-L1+ (n = 16) and PD-L1− (n = 27) tumors (≥5% tumor cell cutoff), ORR was 18.8% (95% CI 4.0–45.6) and 7.4% (95% CI 0.9–24.3), and the 6-mo PFS rate was 37.5% (95% CI 14.1–61.2) and 42.0% (95% CI 23.1–59.8). 43 pts (81.1%) had a treatment-related (TR)AE, most commonly ( > 10%) infusion-related reaction (35.8%; all grade 1/2), chills (15.1%), fatigue (15.1%) and pyrexia (11.3%). 5 pts (9.4%) had a grade ≥3 TRAE. 14 pts (26.4%) had an immune-related AE, which was grade ≥3 in 3 pts (5.7%; pneumonitis, colitis, and type 1 diabetes mellitus). No treatment-related deaths occurred. Conclusions: Avelumab showed clinical activity and acceptable safety in pts with previously treated mesothelioma. Clinical trial information: NCT01772004.

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Elimimian, Elizabeth Blessing, Thomas A. Samuel, Hong Liang, Nadeem Bilani, Leah Elson, and Zeina A. Nahleh. "Rare triple-negative breast cancers (TNBC): An NCDB analysis." Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020): e19253-e19253. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.e19253.

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e19253 Background: The literature on rare triple negative breast cancer (TNBC) histology types is sparse; herein we present the clinical demographic and treatment patterns as well as overall survival (OS) for rare (< 10%) types of breast cancers that typically present as TNBCs: Medullary carcinoma (MedC), Adenoid cystic carcinoma (ACC), and Metaplastic breast cancer (MetC). Methods: Records of patients with a confirmed diagnosis of MedC, ACC, and MetC between 2010 and 2016 in the National Cancer Database (NCDB) were analyzed. Patients with an unknown stage were excluded. Univariate analyses and multivariable Cox-regression models were performed in SAS v. 9.4. Results: A total of 8,479 records were analyzed. MetC was the most commonly diagnosed histologic type in our cohort with 6,867 (81%) patients versus 255 (3.0%) MedC patients and 1,357 (16%) ACC patients. MedC presented earlier in life, with a median age of 53 years versus 62 years for ACC patients, and 63 years for MetC patients. The proportion of TNBC varied by histology type for MedC (70.4%), ACC (77.0%), and MetC (79.0 %). Patients with ACC were less likely to receive radiotherapy (52.4%) and chemotherapy (12.9%) compared to MedC (61.2%, 74.5%) and MetC (49.7%, 68.6%) respectively. On Cox multivariate regression, age ≥60 (HR 4.7), stage ≥3 [compared to patients with stage 0&1] (HR 5.7), and not receiving radiotherapy (HR 2.0) or chemotherapy (HR 1.25) conferred worse overall survival for MedC. Similarly, among patients with ACC, age ≥60 (HR 3.5), stage ≥3 (HR 5.3), and lymph node involvement (HR 4.8) were adverse prognostic indicators as well as not receiving radiation therapy (HR 1.47). Among MetC, lung metastasis (HR 2.6), stage ≥3 (HR 4.5), but also not receiving chemotherapy (HR 1.8) or radiation therapy (HR 1.47) was associated with worse survival outcomes. All p-values for cox regression is <0.0001. The 5-year OS was 92.6% for patients with MedC, 92.0% for ACC patients, 69.3% for MetC patients; all p-values <0.0001. Conclusions: This analysis describes rare types of TNBCs: MedC (most common), ACC, and MetC. We noted heterogeneity among these 3 rare types of TNBC, with the worst 5-year OS noted for MetC. Poor prognostic factors for MetC include advanced stage, lung metastasis, older age, and not receiving chemotherapy or radiation therapy. Future research focusing on rare subtypes of breast cancer is desirable and would potentially inform the optimal management of these breast carcinomas.

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Osipova, O. A., E. V. Gosteva, T. P. Golivets, O. N. Belousova, O. A. Zemlyansky, M. V. Pokrovsky, A. I. Golovin, N. V. Grigorenko, and A. A. Merezhko. "Changes of myocardial fibrosis markers with the use of beta-blockers and mineralocorticoid receptor antagonists in patients with heart failure with mid-range ejection fraction of ischemic origin." Cardiovascular Therapy and Prevention 20, no. 7 (November 28, 2021): 3068. http://dx.doi.org/10.15829/1728-8800-2021-3068.

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Aim. To compare the effect of 12-month pharmacotherapy with a betablocker (BB) (bisoprolol and nebivolol) and a combination of BB with a mineralocorticoid receptor antagonist (bisoprolol+eplerenone, nebivolol+eplerenone) on following fibrosis markers: matrix metalloproteinases 1 and 9 (MMP-1, MMP-9) and tissue inhibitor of MMP-1 (TIMP-1) in patients with heart failure with mid-range ejection fraction (HFmrEF) of ischemic origin.Material and methods. The study included 135 patients, including 40 (29,6%) women and 95 (70,4%) men aged 45-60 years (mean age, 53,1±5,7 years). Patients were randomized into subgroups based on pharmacotherapy with BB (bisoprolol or nebivolol) and their combination with eplerenone. The enzyme-linked immunosorbent assay was used to determine the level of MMP-1, MMP-9, TIMP-1 (ng/ml) using the commercial test system “MMP-1 ELISA”, “MMP-9 ELISA”, “Human TIMP-1 ELISA” (“Bender Medsystems “, Austria).Results. In patients with HFmrEF of ischemic origin, there were following downward changes in serum level of myocardial fibrosis markers, depending on the therapy: bisoprolol — MMP-1 decreased by 35% (p<0,01), MMP-9 — by 56,3% (p<0,001), TIMP-1 — by 17,9% (p<0,01); nebivolol — MMP-1 decreased by 45% (p<0,001), MMP-9 — by 57,1% (p<0,001), TIMP-1 — by 30,1% (p<0,01); combination of bisoprolol with eplerenone — MMP-1 decreased by 43% (p<0,001), MMP-9 — by 51,2% (p<0,001), TIMP-1 — by 25,1% (p<0,01); combination of nebivolol with eplerenone — MMP-1 decreased by 53% (p<0,001), MMP-9 — by 64,3% (p<0,001), TIMP-1 — by 39% (p<0,01). In patients with NYHA class I HFmrEF after 12-month therapy, the decrease in MMP-1 level was 39,9% (p<0,01), MMP-9 — 57,5% (p<0,001). In class II, the decrease in MMP-1 level was 47% (p<0,001), MMP-9 — 49,7% (p<0,001). A significant decrease in TIMP-1 level was revealed in patients with class I by 29% (p<0,01), in patients with class II by 27,1% (p<0,01) compared with the initial data.Conclusion. A significant decrease in the levels of myocardial fibrosis markers (MMP-1, MMP-9, TIMP-1) was demonstrated in patients with HFmrEF of ischemic origin receiving long-term pharmacotherapy. The most pronounced effect was determined in patients with NYHA class I HF.

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Torikai, E., Y. Hirano, D. Suzuki, and Y. Kanayama. "SAT0156 EFFECTIVE OF BARICITINIB ON RADIOGRAPHIC PROGRESSION OF STRUCTURAL JOINT DAMAGE AT 48 WEEKS IN PATIENTS WITH RHEUMATOID ARTHRITIS IN REAL-WORLD MULTICENTER CLINICAL DATA." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 1018–19. http://dx.doi.org/10.1136/annrheumdis-2020-eular.3019.

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Background:Baricitinib (bari) is an oral Janus kinase 1 (JAK1)/JAK2 selective inhibitor that has demonstrated good efficacy in patients with rheumatoid arthritis (RA) and adequate response to conventional synthetic (cs) DMARDs in some clinical trials [1,2]. We report the efficacy and safety of bari within 24 weeks in real-world clinical data at EULAR2019.Objectives:To evaluate the radiographic progression of structural joint damage at 48 weeks in Japanese patients with RA in real-world multicenter clinical data.Methods:We included 53 Japanese patients with RA who showed an inadequate response to csDMARDs or biologic (b) DMARDs. Patients were scheduled to receive a once-daily dose of 4 or 2 mg/day bari as monotherapy or in combination with other csDMARDs. We divided the patients into two groups: those treated with 2 mg/day of bari (2mg-group; n = 27) and those treated with 4 mg/day of bari (4-mg group; n = 26) throughout the observation period. Patients were allowed to decrease their predonisolone and csDMARDs combined with bari treatment if their disease activity improved. First, we evaluated changes in CDAI and HAQ-DI after 48 weeks. Second, we evaluated the change in the van der Heijdge modified total sharp score (ΔmTSS), erosion score (ΔERN), and joint space narrowing score (ΔJSN). In addition, we assessed predictors for suppression of joint destruction at 48 weeks after bari treatment.Results:The baseline characteristics of the patients were as summarized in Table 1. There were no significant differences in any items. CDAI scores significantly improved 4 weeks after the treatment. This tendency continued until the final evaluation (Table 2). At 48 weeks, remission and low disease activity rates were 37.0% and 74.1% in the 2-mg group and 38.4% and 76.9% in the 4-mg group, respectively. Structural remission (mTSS ≤ 0.5) was noted in 21 patients (80.8%) and 21 patients (77.8%) in 4-mg group and 2-mg group, respectively (Figure). Mean scores (ΔmTSS, ΔERN, and ΔJSN) of all patients in the 2-mg group and 4-mg groups were (0.26, 0.15, and 0.11), (0.30, 0.17, and 0.13) and (0.23, 0.13, and 0.10), respectively (Figure). There were no significant differences in ΔmTSS scores between the two groups. A matrix metalloproteinase-3 score within the standard value at 12 weeks after the treatment was associated with a predictor for suppression of joint destruction at 48 weeks (logistic regression analysis; odds ratio = 11.6, 95% confidence interval: 1.5–112.4,P= 0.020).Table 1.Characteristics of patients at baricitinib initiation2mg-group (n=27)4mg-group (n=26)p-valueAge (years)69.1 (12.0)65.6 (10.3)0.20Gender, female, n (%)19 (73.1)23 (85.2)0.28Disease duration (years),9.7 (10.4)5.7 (7.4)0.23Prior use of biologics, (0/1/2/3)(18/6/2/1)(18/2/5/1)------MTX (mg/week),4.5 (3.7)6.5 (4.29)0.08PSL (mg/day)1.0 (1.9)1.2 (1.8)0.49RF, U/ml254 (372)134 (222)0.21ACPA, U/m152 (176)133 (301)0.45MMP-3196 (220)215 (221)0.43Table 2.Serial change of clinical assessment2mg-groupBaseline4 week12 week24 week48 weekCDAI22.5 (9.2)7.4 (7.7)6.7 (6.9)6.9 (6.8)6.9 (6.8)HAQ-DI0.88 (0.51)0.45 (0.47)0.53 (0.58)0.56 (0.56)0.56 (0.56)MMP-3196 (221)98.9 (62.2)115 (164)106 (78)106 (78)4mg-groupBaseline4 week12 week24 week48 weekCDAI24.4 (9.7)9.4 (5.7)8.6 (6.3)6.7 (8.6)6.8 (8.6)HAQ-DI1.01 (0.51)0.58 (0.48)0.54 (0.60)0.45 (0.49)0.44 (0.45)MMP-3216 (222)99 (62)101 (123)89 (72)95 (81)Conclusion:The data showed that bari has a favorable effect on the radiographic progression of structural joint damage regardless of its dose in a real-world clinical setting. In consideration of the risk/benefit balance, we suggest that the dose of bari could be reduced in patients with favorable disease activity.References:[1]Tanaka Y et al. Mod Rheumatol. 2018;28:583-91[2]Tanaka Y et al. Mod Rheumatol. 2018;28:20-9Disclosure of Interests:Eiji Torikai: None declared, Yuji Hirano Speakers bureau: Tanabe-Mitsubishi, Pfizer, Eisai, Abbie, Chugai, Bristol-Meyers, Jansen, Astellas, UCB, Eli-Lilly, Asahikasei, Daiichi-Sankyo, Amgen, Daisuke Suzuki: None declared, Yasuhide Kanayama: None declared

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Shirin, Mahbuba, Mofazzal Sharif, Ayeshna Gurung, and Anindita Datta. "Resistive Index of Intrarenal Artery in Evaluation of Diabetic Nephropathy." Bangladesh Medical Research Council Bulletin 41, no. 3 (October 6, 2016): 125–30. http://dx.doi.org/10.3329/bmrcb.v41i3.29888.

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Diabetes mellitus is one of the systemic diseases affecting the kidneys. Diabetic nephropathy is a serious microvascular complication of diabetes mellitus. It is the most important cause of death in type I diabetic patients, of whom 30%-40% eventually develop end-stage renal failure and 40% of type II diabetics are at risk of developing diabetic nephropathy. So, diagnosis of diabetic nephropathy is paramount for the survivability of the diabetic patients not only because of the consequences of renal progression but also because of the strong association with the risk of developing cardiovascular disease. A total number of 53 subjects were enrolled in this present cross sectional study in the department of Radiology and Imaging, Bangabandhu Sheikh Mujib Medical University (BSMMU) in collaboration of Nephrology and Medicine of the same institution during two years (2011-13) aim to evaluate the diagnostic usefulness of renal resistive index (RI) by duplex Doppler ultrasonography for detection of renal dysfunction in diabetic patients. Clinically diagnosed diabetic patients having diabetic nephropathy referred to the department of Radiology and Imaging in BSMMU for ultrasonography of Kidneys, Ureters and Bladder (KUB) region or whole abdomen were selected as sample. Biochemical reports (Serum creatinine and Urinary albumin) and the RI value of intrarenal artery were correlated and analyzed. Only those patients biochemically were diagnosed as having diabetic nephropathy was included. Those with incomplete data, hydro nephrosis and renal calculus were excluded. Both the kidneys were visualized by commercially available real time scanner (GE Voluson) equipped with a curvilinear transducer operating at 3.5 MHz First Gray scale ultrasonography was done followed by Color Doppler of intra renal artery and then RI was measured. Majority (45.3%) patients were in 6th decade with the mean age was of 52.66±7.4 years and ranging from 38 to 65 years in patients. Male was found to be 54.7% of diabetic patients with male to female ratio 1.2:1. Resistive index of (? 0.7) was found in 73.6% patients with diabetes with the mean resistive index of 0.71±0.04. Positive correction between resistive index with serum creatinine (r=0.581, p<0.01) and albuminuria (r=0.725, p<0.01) were observed. It can be concluded that Resistive Index measured by duplex Doppler ultrasonography is useful diagnostic modality for detection of renal dysfunction in diabetic nephropathy patients. Resistive Index has value in identifying diabetic patients who are developing nephropathy and can be used as an additional diagnostic tool. Also it is well correlated with Serum Creatinine and Albuminuria which are the biochemical parameters to diagnose diabetic nephropathy.

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Goloeva, R., Z. Alekberova, T. Popkova, S. Glukhova, and D. Novikova. "POS0116 HEART RATE VARIABILITY IN PATIENTS WITH BEHCETS DISEASE." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 269.2–269. http://dx.doi.org/10.1136/annrheumdis-2021-eular.3682.

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Background:Behcet’s disease (BD) is a systemic vasculitis affecting all types and sizes of blood vessels. Heart rate variability (HRV) reflects sympathetic -parasympathetic imbalance in the autonomic NS regulation. Low HRV values are known as independent risk factor of death and non-fatal cardiovascular events in both - survivors of a myocardial infarction and in asymptomatic population.Objectives:The aim of this study is to evaluate HRV in BD pts vs healthy controls.Methods:The study group included 74 BD pts (53males/21females) with disease duration of 9,0 (5,0;15,0)/9,0 (7;20) years, and the control group - 32/15 age-matched healthy m/f. The following HRV parameters from 24h ECG ambulatory recording were assessed: MeanNN and time-domain variables, adjusted by MeanNN (SDNNn%, SDNNin%, RMSSDn%). Additionally, all traditional cardiovascular risk factors such as systolic blood pressure (SPB), smoking status, BMI values, dyslipidemia profile, ultrasonographic values of carotid intima-media thickness (IMT), and levels high sensitive CRP (hsCRP) as a marker of inflammation were evaluated.Results:In BD patients HRV values (RMSSDn%) were significantly lower compared to healthy controls (table 1).Table 1.HRV parameters in BD patients and control groupParametersMalesFemalesBD (n=53)Control (n=32)BD (n=21)Control (n=15)Age, years30 (24; 36)30 (26; 35)32 (26; 37)28 (24; 31)MeanNN, ms810 (732; 849)782 (732; 835)776 (708; 830)764 (694; 832)SDNN n (%)16,9 (13,6; 19,4)17,2 (16,3; 21,1)13,1 (11,3; 5,3)12,2 (10,7; 14,6)SDNNi n (%)6,8 (5,1; 8,1)6,8 (5,0; 8,3)7,1 (6,1; 7,7)5,2 (4,9; 5,7)RMSSD n (%)2,1 (1,5; 2,3)**4,1 (2,7; 5,2)**1,7 (1,4; 3,7)*2,8 (2,2; 3,9)*Data are presented in median values and interquartile range, *p<0,05, **p<0,005 vs controls.There was a significant negative correlation in BD patients between HRV (SDNNin%) and age (r= -0,4; p=0,00), disease duration (r= -0,3; p=0,00), BMI (r= -0,2; p<0,01), cholesterol levels (r= -0,3; p=0,00), LDLP (r= -0,3; p=0,00) and increased IMT (r= -0,2; p=0,04), and also between HRV (RMSSD%) and age (r= -0,2; p=0,04), disease duration (r= -0,2; p=0,01), cholesterol levels (r= -0,3; p=0,00), HDLP (r= -0,2; p=0,04); a positive correlation was established between HRV (SNNN%) and smoking (r= -0,2; p=0,04). The control group showed positive correlation between HRV (SNNN%) and increased IMT (r= 0,4; p=0,01).Conclusion:HRV reduction reflects impaired sympathetic -parasympathetic regulation in BD pts, associated with pts’ age, disease duration and presence of traditional cardiovascular risk factors: BMI, increased cholesterol levels, LDLP, and such asymptomatic manifestation of atherosclerosis as increased IMT.Disclosure of Interests:None declared

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Adwetewa-Badu, Abena A., Ryan M. O'Keefe, Joseph X. Callahan, Catherine A. Taylor, Chris P. Gjino, and Christine E. Hill-Kayser. "An analysis of content of lay-press articles focused on cancer from leading U.S. newspapers from 2010 to 2019." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): e24032-e24032. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.e24032.

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e24032 Background: Newspaper coverage of cancer-related topics has historically focused on research, treatment, survival, and impact of tobacco and diet on risk, with less coverage of prevention, death, and palliation/hospice. Coverage tends to be driven by celebrity and other seminal events, and highest during awareness-months, with over and under representation of breast and lung cancers, respectively, based on incidence. We sought to understand evolving trends in coverage over the last decade at 3 major U.S newspapers to identify areas for improvement for education, inclusion, and public health messaging. Methods: On 10/13/20, Factiva was queried with the keyword “cancer” for articles > 150 words published by NYTimes, Washington Post, and Wall Street Journal between 2010-2019. The top 100 articles by “relevance” were selected for each, representing 14.9% of all the 2016 hits. A coding scheme was created using articles from the same query for 2020; inter-rater reliability analysis between coders was conducted with a sample of 30 articles (10% of final set), and kappa-fleiss scores were calculated. Articles were excluded if they did not focus on cancer, or were an obituary, financial report, or editorial. Results: 230 articles were included. Kappa-fleiss scores were 0.74 - 1, suggesting excellent agreement between coders. 102 (44.3%) focused on research, 50 (21.7%) individual disease narratives, 22 (9.6%) drug development, 15 (6.5%) policy or regulation. 136 articles focused on one sub-type; breast (53, 39.0%) was most common, followed by colorectal (13, 9.6%), leukemia/ lymphoma (12, 8.8%), prostate (11, 8.1%), pancreatic (9, 6.6%), and lung (8, 5.9%). 154 articles discussed research; 22 (14.3%) non-human research. Commonly covered topics included pharmaceuticals (128, 55.7%), risk factors (71, 30.9%), cost of care (66, 28.7%) and adverse effects (58, 25.2%). Risk factors discussed included smoking (22, 31.0%), diet (21, 29.5%), and alcohol (7, 9.9%). Less common topics were radiation (18.7%), insurance coverage (13.9%), celebrities (12.6%), death (8.7%), race (4.3%), and disparities (3.9%). 156 (67.8%) provided quotes from HCPs/researchers, 59 (25.7%) patients, 17 (7.4%) families or other supports. 22 (9.6%) titles had “war” terminology; 13 (5.7%) had the word “may”. Conclusions: Most articles focused on research or personal narratives, most commonly in context of breast, colorectal, and leukemia/lymphoma. Pharmaceutical treatments were the most discussed content topic. Compared with previous analyses, risk factors, adverse effects, and cost of care were discussed more often. However, race, disparities, death, and end-of-life topics remain uncommon. There was good representation from the healthcare and scientific community; opportunities exist to include more educational information on risk and adverse events, as well as patient and family perspectives.

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Singh, N., J. Chow, M. Ebadi, M. Ma, A. J. Montano-Loza, and R. Bhanji. "A226 SEX-BASED DISPARITY COMPLICATIONS FOLLOWING LIVER TRANSPLANTATION." Journal of the Canadian Association of Gastroenterology 5, Supplement_1 (February 21, 2022): 116–18. http://dx.doi.org/10.1093/jcag/gwab049.225.

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Abstract Background Sex-based disparity exists in liver transplantation (LT) with women being disadvantaged at every stage of the process starting from assessment to post transplantation (Bryce et al., 2009). The reasons for this are multifactorial and include biological disparities, psychosocial, and allocation inequalities (Burra et al., 2013). Aims The purpose of this study was to identify differences in immediate or long-term complications post-LT by sex. Methods We analyzed 702 patients who underwent LT at the University of Alberta from 2002 to 2015. Patients aged < 18 years or requiring a repeat or multivisceral transplant were excluded. Renal dysfunction was defined according to the KDIGO criteria. Cardiovascular disease (CVD) was defined as hospitalization for or death from coronary artery disease, cardiac arrest or cerebrovascular disease. Results Male patients comprised 69% of the population. Time on the waitlist was similar for men (9.3 ± 11.7 months) and women (9.9 ± 12.3 months; p=0.57). Both sexes were comparable in age (males: 53 ± 10 years; females: 52 ± 11 years; p=0.19), MELD (males: 18 ± 9; females: 19 ± 10; p=0.16) and BMI (males: 27.7 ± 5.7 kg/m2; females: 27.3 ± 6.6 kg/m2; p=0.58). Women had lower creatinine pre-LT (males: 1.1 ± 0.60 mg/dL; females 0.96 ± 0.51 mg/dL; p<0.01). There were no differences in donor age, sex or BMI. Women had significantly longer hospital length of stay (males: 18 days [IQR: 11, 32]; females: 25 days [IQR: 14, 43]; p <0.001). There was no difference in risk of acute kidney injury (OR 1.4 [95% CI: 0.98, 2.1]; p=0.06), infection (OR 1.1 [95% CI: 0.8, 1.5]; p=0.52) or rejection episodes (OR 1.1 [95% CI: 0.8, 1.5]; p=0.74) following LT. Women had a higher risk of CKD post-LT (OR 2.3 [95% CI: 1.6, 3.2]; p<0.0001). There was no difference in de-novo diabetes (males: 22%; females: 16%; p=0.10), hypertension (males: 45%; females: 48%; p=0.41), dyslipidemia (males: 37%; females: 39%; p=0.67) and CVD (males: 20%; females: 19%; p=0.84) post-LT. Graft (males: 11.4 ± 0.4 years; females: 11.8 ± 0.5 years; p=0.32) and patient survival (males: 11.8 ± 0.4 years; females: 12.4 ± 0.5 years; p=0.18) were similar over a median follow up of 6.3 years [IQR: 3.5, 9.9]. Conclusions Women spend a longer time in hospital and are at an increased risk of CKD following LT. Despite these differences, overall graft and patient survival are comparable. Our data suggest the disparity between sexes likely exists pre-LT and females that undergo LT have similar outcomes to their male counterparts. Funding Agencies None

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Takahashi, Koichi, Naveen Pemmaraju, Miloslav Beran, Alfonso Quintás-Cardama, Jorge E. Cortes, Farhad Ravandi, Stefan Faderl, et al. "Refined MD Anderson Prognostic Scoring System (MDAPS-R) for Chronic Myelomonocytic Leukemia (CMML)." Blood 120, no. 21 (November 16, 2012): 3797. http://dx.doi.org/10.1182/blood.v120.21.3797.3797.

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Abstract Abstract 3797 Background: Since the time of initial proposal of the MD Anderson Prognostic Score (MDAPS) in 2000, there has been substantial development in diagnosis and treatment for patients (pts) with CMML. MDAPS did not incorporate cytogenetic abnormalities, which is one of the most important factors of prognostication in other myeloid malignancies. Therefore, we analyzed a large cohort of patients with CMML and developed new prognostic scoring system that also incorporates cytogenetic abnormalities (named MDAPS-R). Methods: From 2003 and 2012, we identified 358 pts with diagnosis of CMML, using standards strictly defined by World Health Organization (WHO) criteria. Potential prognostic factors were identified by log-rank test. Of those, independent prognostic factors were extracted after Cox proportional hazard regression. Based on the relative strength of hazard ratio (HR), MDAPS-R was developed and was verified by log-rank test. Result: Median age of the analyzed group was 68 years (range:23–89);113 (32%) pts were female. Two hundred twenty one (62%) pts were classified as CMML-1 and 104 (29%) were CMML-2 (unknown in 33 pts). Thirty nine (11%) pts had prior exposure to chemotherapy and/or radiation therapy. Mean (± SE) white blood cell count (WBC) was 24.5 ± 1.5 (x103/μL), hemoglobin (Hb) was 10.8 ± 0.1(g/dL), platelet count (Plt) was 132 ± 7.0 (x103/μL) and bone marrow blast count (BMBL) was 6.9 ± 0.3 (%), respectively. Cytogenetics was diploid in 224 (63%) pts. Trisomy 8 was detected in 14 (4%) pts, del 20q in 12 (3.4%), -Y in 13 (3.6%), del 7q/-7 in 25 (7%), and del 5q/-5 in 10 (2.8%) pts, respectively. Complex cytogenetic abnormality was detected in 16 (4.5%) pts. Two hundred eighty (78%) pts had RAS mutation analysis and 49 (18%) had NRAS mutation while 16 (5.7%) had KRAS mutation. FLT3 alteration was tested in 297 pts (83%):3 (1%) had D835 mutation while 10 (3.4%) had ITD. JAK2 mutation was tested in 161 (45%) pts of which 19 (12%) had V617F mutation. Less commonly occurring mutations included: NPM1 (5/88 tested), c-kit (3/156), CEBPA (6/83), IDH1 (1/59), IDH2 (3/58), and DNMT3a (1/4). During the median follow up duration of 15 months (range; 1–145), 53 (15%) pts transformed to acute leukemia and 182 (51%) pts died. Median transformation free survival (TFS) and overall survival (OS) of the analyzed group was 24.9 months (range; 1–145) and 26.8 months (range; 1–145), respectively. Log-rank test identified significant covariates in association with OS that include: BMBL (<10 vs. ≥10; P = 0.024), WBC (≤10 vs. >10; P = 0.01), Hb (<12 vs. ≥12; P < 0.001), CMML subtype (CMML-1 vs. 2; P = 0.007), prior exposure to chemo and/or radiation (Yes vs. No; P < 0.001), cytogenetics (diploid vs. complex or del7q/-7 vs. others; P < 0.001), serum β2 microglobulin (β2MG) (≤4.0 vs >4.0; P < 0.001), serum LDH (≤700 vs. >700; P < 0.001), peripheral absolute lymphocyte count (ALC) (≤2.5 vs. >2.5; P < 0.001), and peripheral absolute monocyte count (≤4.0 vs. >4.0; P = 0.012). None of the molecular mutations had impact on OS. After being fitted into Cox proportional hazard regression, following covariates remained independently significant: BMBL ≥10 % (vs. <10; HR = 1.6), Hb < 12 g/dL (vs. ≥12; HR = 1.9), LDH > 700 IU/L (vs. ≤700; HR = 1.5), ALC > 2.5 × 103/μL (vs. <2.5; HR = 1.7), β2MG > 4.0 mg/L (vs. ≤ 4.0; HR = 1.6), and complex cytogenetics or del 7q/-7 (vs. diploid; HR = 2.3 and others vs. diploid; HR = 1.5). We developed MDAPS-R based on relative strength of HR in each of these above factors (1 point assigned to each of the following: BM BL '10 %, Hb<12 g/dL, LDH 700 IU/L, ALC .2.5 × 103/μL, and β2MG > 4.0 mg/L; 0 points for diploid cytogenetics, 2 points for −7/del 7q or complex cytogenetics, and 1 point for all other abnormal karyotype). Among 358 pts, 282 (79%) were evaluable for analysis via MDAPS-R. MDAPS-R stratified pts into 4 distinct prognostic groups: score 0–1 = low risk (N = 70, median OS 56 months), 2–3 = intermediate-1 risk (N = 133, median OS 28 months), 4–5 = intermediate-2 risk (N = 68, median OS 18 months), and 6–7 = high risk (N = 11, median OS 7.5 months) (P < 0.001, Figure 1A). MDAPS-R also predicted TFS in the same cohort (median TFS: low = 54, int-1 = 26, int-2 = 15, and high = 7 months, P < 0.001, Figure 1B). Conclusion: We propose a refined version of MDAPS (MDAPS-R) specifically for pts with CMML that incorporates cytogenetic abnormalities. This model may help risk-stratified decision making in CMML pts. Disclosures: No relevant conflicts of interest to declare.

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Trneny, Marek, Pavel Klener, David Belada, Heidi Mocikova, Vit Prochazka, Samuel Vokurka, Jan Pirnos, et al. "The Outcome of Mantle Cell Lymphoma patients after Treatment Failure and Prognostic value of Secondary Mantle Cell International Prognostic Index (sec MIPI)." Blood 124, no. 21 (December 6, 2014): 4425. http://dx.doi.org/10.1182/blood.v124.21.4425.4425.

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Abstract Background: MCL is a distinct lymphoma entity with improved outcome achieved by the introduction of rituximab, high dose Ara-C and autologous stem cell transplantation (ASCT) into the first line therapy. The outcome of the relapsed patients (pts) remain however poor and there is little data on the outcome after subsequent relapses and there is no information on secondary MIPI prognostic value. Aim: To analyze the outcome of the MCL patients after first line treatment failure and to evaluate the prognostic role of the sec MIPI which is MIPI calculated at the time of relapse/progression. Methods: This analysis is a part of the Lymphoma project in which consecutive lymphoma patients are registered since the year 1999. Altogether 519 newly diagnosed MCL patients were registered in 5 university centers and 9 regional departments between 1999 and 2011. Patients who were treated with rituximab as part of the first line treatment (n=388) were included into the analysis. The diagnoses were confirmed according to WHO classification in the reference pathology centers. The median follow up is 4.5 years. Results: The whole cohort consists of 261 males and 127 females (2.1:1) with median age 65 y (28-87), the majority of pts had advanced disease (CS IV in 81.6% pts), PS ECOG ≥ 2 in 23.6% pts, elevated LDH in 52.5% of pts. The MIPI risk profile was as follows: low risk 21.7%, intermediate risk 27.2% and high risk in 51.1%. All pts received rituximab as part of the induction, 48.7% pts received CHOP, 5.7% alternation of CHOP and HD Ara-C, 26.2% intensive induction with HD Ara-C, 10.3% CVP, 6.4% FC. High dose therapy with ASCT was performed in 23.9% of pts. The ORR was 89.0% with 63.8 CR/CRu, 6.3% had stable disease and 4.9% were primary progressive. The PFS and OS were 2.9 y and 5.5 y with significant impact of MIPI risk (p<0.0001) for both PFS and OS. There were observed 179 relapses/progressions (R/P) and 70 deaths not related to subsequent progression. The cohort of patients with 1st R/P consisted out of 125 males and 54 females (2.3:1) with median age 68 years (38-89). The sed MIPI at the time of 1st R/P was low in 12.7% pts, intermediate in 32.1% and high 59.8% pts. Rituximab was used in 69.5% of patients, DHAP or ESHAP was used in 25.1% cases, FC in 22.8% of cases, CHOP like regimen in 9.4%, HD Ara-C in 11.8%, only 4.7% were treated with targeted therapy temsirolimus or lenalidomide. Altogether 77.2% pts were treated with the polychemotherapy and 22.8 with monotherapy. ASCT and AlloSCT were performed in 5.5% and 8.7% pts resp. During follow up there were observed 74 deaths not related to subsequent progression and 53 2nd R/Ps. The median of 2nd PFS and 2nd OS from the date of 1st R/P was 1.0 and 1.3 years resp. The sec MIPI low vs. intermediate vs. high risk had significant prognostic impact on 2nd PFS: 5.8 vs 1.7 vs 0.9 years (p<0.0001) (fig 1) as well as on OS : 5.8 vs 3.4 vs 1.1 years (p<0.0001) (fig 2). The cohort of 53 pts with 2nd R/P had median age 68 (38-85) yers, male/female ratio was 1.4. Rituximab was used in 45.9% of treated patients and 48.3% of pts were treated with single drug. During follow up 11 pts developed 3rd R/P and other 30 pts died due to current progression, toxicity or in remission. The median of 3rd PFS from the time of 2nd R/P was 6.8 m and OS 7.4 months. Pts who were treated for 3rd R/P recieved rituximab in 50% of cases and the majority (81.2%) were treated with other single drug. The median of 4th PFS from 3rdR/P was 4.9 m and OS 5.5 months . Conclusions: Our analysis of relapsed MCL patients shows that 1: Median PFS from the Dg was 2.9 y but each subsequent relapse resulted in significantly shorter PFS median 12.1, 6.8 and 4.9 months resp. 2: The median OS from Dg was 5.5y but after each relapse it became shorter - 15.7 m, 7.4 m and 5.5 months resp. 3: The sec MIPI at the time of relapse discriminates the groups with significantly different prognosis. Disclosures No relevant conflicts of interest to declare.

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Kastrati, K., N. Nakhost Lotfi, M. Tawfik, E. Gelpi, R. Hoeftberger, H. Kiener, D. Aletaha, M. Bonelli, and H. Radner. "POS0911 DIAGNOSTIC VALUE AND CLINICAL RELEVANCE OF MUSCLE BIOPSY IN PATIENTS WITH SUSPECTED MYOSITIS." Annals of the Rheumatic Diseases 81, Suppl 1 (May 23, 2022): 755.1–755. http://dx.doi.org/10.1136/annrheumdis-2022-eular.4161.

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BackgroundDiagnosis of idiopathic inflammatory myopathies (IIM) represents a clinical challenge and muscle biopsy itself is regarded as the cornerstone for confirming diagnosis of IIM. However, the significance of muscle biopsy as diagnostical tool remains inconclusiveObjectivesTo determine the diagnostic accuracy and clinical relevance of muscle biopsy in patients with suspected myositis.MethodsIn this retrospective cohort study, histopathological findings of muscle biopsy specimens of adult (≥ 18 years of age) patients with clinically suspected or differential diagnosis of myositis referred from all over Austria to the Medical University of Vienna through the period of 01.01.2007-31.10.2021 were analyzed. Following information were extracted from handwritten assignment sheets: referral department, suspected diagnosis (inflammatory and/or non-inflammatory myopathy), sampling location, demographic, clinical, laboratory and serologic data, and imaging results.Histological findings were grouped in: 1) inflammatory, 2) non-inflammatory (neurogenic, metabolic etc.), 3) inflammatory and non-inflammatory mixed, and 4) normal. Clinical information on start of immunosuppressive treatment after muscle biopsy could be partly retrieved form electronical medical records (EMR). Sensitivity, specificity, positive (PPV) and negative predictive values (NPV) of histological results were calculated using clinical diagnosis (defined as initiation of immunosuppressive therapy) as gold standard.Results778 muscle biopsy specimens of 762 patients with suspected myositis (49.6% female, mean age of 56 years) were analyzed. Cohort descriptives are displayed in Table 1.Overall, 373/778 (47.9%) muscle biopsies revealed inflammatory features only or had mixed results with non-inflammatory characteristics. Out of 541 samples with suspected diagnosis of myositis, diagnosis was confirmed histologically in 300 (55.5%) cases; 46 (8.5%) specimens additionally showed co-features of non-inflammatory myopathy, whereas 221 (40.3%) were non-inflammatory at all and 15 (2.8%) were normal. Proportion of myositis was more pronounced, when CK was elevated at time of biopsy (Figure 1).Figure 1.From suspicion to histological verification depending on CK-levelsOut of 237 samples with differential diagnosis of non-inflammatory myopathy in addition to myositis, 53 (22.4%) were histology. confirmed as inflammatory only and 20 (8.4%) showed mixed features. 153 (64.6%) biopsies were non-inflammatory only and 8 (3.4%) normal. Samples with no pathological features were observed in 24/778 (2.3%) of the cases, with 0.8% sampling error (no muscle tissue).Of 421/778 (54.1%) patients, clinical data could be extracted from EMR of which 209/421 (49.6%) had histological features of inflammation. In 287/421 (68%) cases, information regarding initiation of immunosuppressive treatment were available on EMR. 224/287 (78%) patients received immunosuppression (steroids and/or disease-modifying anti-rheumatic drug [DMARD]), thus fulfilled clinical diagnosis of myositis. In 155/224 (69.2%) cases, muscle biopsy confirmed histology. features of inflammation. Tests on diagnostic accuracy of muscle biopsy using initiation of any immunosuppressive treatment as gold standard were performed. The sensitivity of the test (biopsy) for diagnosing IIM was 71.4% with a specificity of 79.6%. PPV was high (92.8%), whereas NPV low (43.1%).ConclusionLess than 50% of biopsy samples with suspected diagnosis of myositis histologically revealed an inflammatory myopathy. The percentage increased when CK levels were elevated. Sensitivity and specificity of muscle biopsy was moderate, when using start of immunosuppressive therapy as gold standard for IIM diagnosis.References[1]Tanboon, J. & Nishino, I. Classification of idiopathic inflammatory myopathies: pathology perspectives. Curr. Opin. Neurol. 32, 704–714 (2019)Disclosure of InterestsNone declared

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Casucci, Monica, Serena Kimi Perna, Attilio Bondanza, Zulma Magnani, Massimo Bernardi, Alessandro Crotta, Cristina Tresoldi, et al. "Leukemic Dendritic Cells Expand Central Memory T Lymphocytes From HCT Donors Able to React against the Original Leukemia in Vitro and In Vivo." Blood 114, no. 22 (November 20, 2009): 4090. http://dx.doi.org/10.1182/blood.v114.22.4090.4090.

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Abstract Abstract 4090 Poster Board III-1025 Allogeneic hematopoietic transplantation (allo-HCT) is the only curative option for patients affected by high-risk acute myeloid leukemia (AML). This is largely due to the ability of allogeneic immune system to eradicate leukemic stem cells (LSC). However, the fact that some patients still relapse after allo-HCT, suggests that strategies to increase LSC targeting by donor T cells are needed. For this purpose, we exploited the unique ability of myeloid blasts to differentiate into leukemic dendritic cells (LDC). We observed that a short (48h) exposure to calcium ionophore A23187 and IL-4 is able to induce LDC differentiation in 14/16 (86%) of AML that we studied, both de novo and secondary. Importantly, despite phenotypic and functional changes indicative of differentiation into DC-like cells, the process was accompanied by the maintenance of disease markers such as CD34 and CD117. Moreover, LDC maintained the expression of the oncogenic protein WT1, which is a putative LSC antigen. Thanks to these favourable characteristics, LDC proved to be superior to the original blasts in expanding leukemia-reactive T lymphocytes both in the autologous and allogeneic HCT setting (on average, 5-fold expansion of blasts-stimulated T cells vs 95-fold expansion of LDC-stimulated T cells, SEM=2,7 and 67,7 respectively, p=0,01). We observed that the level of T-cell expansion directly correlate with the percentage of LDC obtained upon treatment with A23187 and IL-4. Most importantly, LDC proved to be more potent than blasts in expanding central memory T lymphocytes (TCM), which are known to confer superior anti-tumor immunity (on average, 29% of TCM upon stimulation with blasts vs 53% TCM upon stimulation with LDC, SEM=7,2 and 5,7 respectively, p=0,01). LDC-expanded T lymphocytes were able to efficiently recognize and kill leukemic blasts in vitro (on average, 953 specific spots of IFN-g/50'000 effectors at E:T ratio of 10:1 -SEM=120- and 29% of specific killing at E:T ratio of 50:1 -SEM=7,4-). Importantly, analysis of different HLA-settings and different targets of patient origin, suggests that LDC can expand T lymphocytes with specificities against multiple antigens expressed by the original leukemia. In particular, we observed the expansion of WT-1 specific T cells upon LDC stimulation. Finally, when infused in NOD/Scid mice transplanted with the original leukaemia, LDC-stimulated T lymphocytes were able to induce long-term complete remissions (>16 weeks) in all mice analyzed, suggesting that this approach may be active against leukemic stem cells. These results show for the first time that LDC-stimulated human T cells could exert a strong GvL activity in vivo. Disclosures: Bordignon: Molmed Spa: Employment.

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