Nissenweiss8202

The accurate ranking of analogs of lead molecules with respect to their estimated binding free energies to drug targets remains highly challenging in molecular docking due to small relative differences in their free energy values. Free energy perturbation (FEP) method, which provides the most accurate relative binding free energy values was earlier used to calculate free energies of many ligands for several important drug targets including Fructose-1,6-BisphosPhatase (FBPase). The availability of abundant structural and experimental binding affinity data for FBPase inhibitors provided an ideal system to evaluate four widely used docking programs, AutoDock, Glide, GOLD and SurflexDock, distinct from earlier comparative evaluation studies. The analyses suggested that, considering various parameters such as docking pose, scoring and ranking accuracy, sensitivity analysis and newly introduced relative ranking score, Glide provided the most consistent results in all respects for the system studied in the present work. Whereas GOLD and AutoDock.also demonstrated better performance, AutoDock results were found to be significantly superior in terms of scoring accuracy compared to the rest. Present analysis serves as a useful guide for researchers working in the field of lead optimization and for developers in upgradation of the docking programs.This case report illustrates the difficulty associated with diagnosing acquired hemophilia A by reviewing the case of an 80-year-old man admitted to the hospital for anemia. A prolonged activated partial thromboplastin time (aPTT) was not noticed until the patient developed a severe hemorrhagic syndrome.Objective To investigate the association between sociodemographic characteristics and changes in dietary intake in patients with ischemic heart disease who were following a cardiac rehabilitation program.Methods Longitudinal study among patients with first-time admission to outpatient cardiac rehabilitation after ST-elevation myocardial infarction, non-ST-elevation myocardial infarction, unstable angina pectoris or stable angina pectoris. We used a validated self-administered food frequency questionnaire to assess the dietary intake before rehabilitation, post rehabilitation and 6 months after baseline. The intake was summarized into a fat and fish-fruit-vegetable score for both sexes. To assess the within-patient differences in dietary scores, a paired t-test was applied. Regression analyses were performed to assess the association between sociodemographic characteristics and changes in diet.Results 186 patients completed two measurements, 157 patients completed all three measurements. Fat and fish-fruit-vegetable scores increased statistically significantly and improvements remained statistically significant at follow-up. Fat scores increased less in employed men than in retired men (-11 (95% CI -17; -5)). Fish-fruit-vegetable scores increased less in men with a bachelor degree than in men with a vocational education (-8 (95% CI -13; -3)) as well as in retired women compared with employed women (-18 (95% CI -32; -4)).Conclusions Patients statistically significantly improved their dietary intake and improvements remained at follow-up. Dietary improvements were sensitive to marital status, living arrangements and employment status. Unemployed and retired women did not seem to improve their diet as much as employed women. Additional dietary intervention may become relevant in some patient groups defined by sociodemographic characteristics. (250).Introduction Ureteral access sheaths (UAS) are commonly utilized during ureteroscopy (URS) to facilitate stone removal, improve visibility and maintain low intrarenal pressures. However, the use of a UAS can cause ureteral wall ischemia and ureteral tears, potentially increasing the risk of postoperative ureteral stricture and obstruction. The primary objective of this study was to study the impact that UAS use has on postoperative imaging studies. Secondary objectives included studying the impact of other intraoperative parameters on postoperative imaging studies. Methods A retrospective chart review was conducted of cases that underwent URS for nephroureterolithiasis across two high volume institutions between January 2012 and September 2016. Patient demographics, cumulative stone size, operative time, use of UAS, laser lithotripsy, basket extraction, preoperative ureteral stent, and postoperative ureteral stent placement were extracted from the electronic medical record. Findings of follow-up renal ultrasor URS remains a valuable prognostic tool.Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterised by diverse organ damages resulting from various autoantibodies, such as antinuclear or anti-DNA antibodies. Neuropsychiatric lupus (NPSLE) refers to the neurological and psychiatric disorders complicated with SLE and can be challenging for physicians to manage. NPSLE has a broad spectrum and high heterogeneity of clinical phenotypes, including headaches, psychiatric symptoms and peripheral neuropathy. Additionally, various immune effectors have been reported to contribute to the pathogenesis, including cytokines, cell-mediated inflammation and brain-reactive autoantibodies. In some patients with SLE, neuropsychiatric symptoms develop for the first time after the initiation of the steroid treatment, hindering the differentiation from steroid psychosis. The administration of high doses of steroids in patients with SLE is believed to trigger psychiatric symptoms. No clear evidence has yet been found regarding the treatment of NPSLE. Therefore, NPSLE-specific markers need to be developed, and treatment guidelines should be established. This article provides an overview of NPSLE as well as its pathogenesis and treatment.Purpose Acalabrutinib, a highly selective, potent, Bruton tyrosine kinase inhibitor, was evaluated in this global, multicenter, randomized, open-label, phase III study in patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL). Methods Eligible patients, aged ≥ 18 years with R/R CLL, were randomly assigned 11 centrally and stratified by del(17p) status, Eastern Cooperative Oncology Group performance status score, and number of prior lines of therapy. Patients received acalabrutinib monotherapy or investigator's choice (idelalisib plus rituximab [I-R] or bendamustine plus rituximab [B-R]). The primary end point was progression-free survival (PFS) assessed by an independent review committee (IRC) in the intent-to-treat population. Key secondary end points included IRC-assessed overall response rate, overall survival, and safety. Results From February 21, 2017, to January 17, 2018, a total of 398 patients were assessed for eligibility; 310 patients were randomly assigned to acalabrutinib monotts with R/R CLL.Purpose To develop a clinical practice guideline for systemic antifungal prophylaxis in pediatric patients with cancer and hematopoietic stem-cell transplantation (HSCT) recipients. Methods Recommendations were developed by an international multidisciplinary panel that included a patient advocate. We conducted a systematic review of systemic antifungal prophylaxis in children and adults with cancer and HSCT recipients. The Grading of Recommendations Assessment, Development, and Evaluation approach was used to make strong or weak recommendations and to classify level of evidence as high, moderate, low, or very low. The panel considered directness of the data to pediatric patients. Results There were 68 randomized trials included in the systematic review, of which 6 (9%) were conducted in a solely pediatric population. Strong recommendations were made to administer systemic antifungal prophylaxis to children and adolescents receiving treatment of acute myeloid leukemia, to those undergoing allogeneic HSCT pre-engraftment, and to those receiving systemic immunosuppression for graft-versus-host disease treatment. A strong recommendation was made to administer a mold-active agent with an echinocandin or a mold-active azole when systemic antifungal prophylaxis is warranted. For children younger than 13 years of age, an echinocandin, voriconazole, or itraconazole is suggested. Posaconazole may also be used in those age 13 years or older. A strong recommendation against routine administration of amphotericin as systemic antifungal prophylaxis was made. Conclusion We developed a clinical practice guideline for systemic antifungal prophylaxis administration in pediatric patients with cancer and HSCT recipients. Implementation and assessment of guideline-concordant rates and impacts are important future steps.Purpose Atezolizumab, bevacizumab, carboplatin, and paclitaxel (ABCP) demonstrated survival benefit versus bevacizumab, carboplatin, and paclitaxel (BCP) in chemotherapy-naïve nonsquamous non-small-cell lung cancer (NSCLC). IRAK4-IN-4 inhibitor We present safety and patient-reported outcomes (PROs) to provide additional information on the relative impact of adding atezolizumab to chemotherapy with and without bevacizumab in nonsquamous NSCLC. Methods Patients were randomly assigned to receive atezolizumab, carboplatin, and paclitaxel (ACP), ABCP, or BCP. Coprimary end points were overall survival and investigator-assessed progression-free survival. The incidence, nature, and severity of adverse events (AEs) were assessed. PROs, a secondary end point, were evaluated using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-Core 30 and EORTC QLQ-Lung Cancer 13. Results Overall, 400 (ACP), 393 (ABCP), and 394 (BCP) patients were safety evaluable (ie, intention-to-treat population related quality of life, symptoms) with each regimen.Many patients with sickle cell disease (SCD) need surgical management during their lifetime. The best approach for preoperative transfusion in SCD is still to be determined. In this single-center retrospective study, we included HBSS/HBS-Beta0-thalassemia patients younger than 16 years of age who underwent surgery between January 2008 and July 2019. Preoperative transfusion assignment (PTA) was based on SCD severity and surgical risk. Patients were assigned to no transfusion, simple transfusion, or exchange transfusion. A total of 284 patients were identified and 66 (23%) underwent 78 procedures. Mean age at the time of procedure was 8 (5-11) years, mean baseline hemoglobin was 8.5 (7.8-9.3) g/dl, and mean hemoglobin F was 18.4 ± 8.2%. SCD severity was low-risk in 57 (73%) and high-risk in 21 (27%) patients. Surgical risk was low-risk in 20 (25.6%) and medium-risk in 58 (74.4%) procedures. PTA was no transfusion in 17 (22%), simple transfusion in 40 (51%), and exchange transfusion in 21 (27%) procedures. Postoperative complications occurred in five (6.4%) of procedures only in the simple transfusion group (three acute chest syndrome, one hemolytic anemia, one pain crisis) undergoing medium-risk surgery. Preoperative risk-based transfusion assignment is feasible. Despite a high baseline hemoglobin level in the no transfusion group, none of the patients developed postoperative complications. It is possible that the high baseline hemoglobin F phenotype was protective and indicates the need to study the risk/benefit of interventions used in this phenotype.