Flindtherbert9694

Objectives We retrospectively analysed patients with advanced non-small-cell lung cancer (NSCLC) harbouring high PD-L1 expression (>50%) and treated with front-line pembrolizumab, comparing outcomes of patients with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) 2 to those with PS 0-1.Methods Data were collected by 16 participating centres. All patients with NSCLC and high PD-L1, treated with first-line pembrolizumab were included. We collected medical data from patient files, pathology and laboratory reports. Patient characteristics, comorbidities, PS, and tumour characteristics were reported. Overall survival (OS), progression-free survival (PFS) and response rate (RR) were calculated.Results 302 patients were included, 246 with PS 0-1, 56 with PS 2. RR was 72% among patients with PS 0-1 compared to 45% with PS2 (odds ratio (OR) 0.31 (95% CI 0.17-0.57), p  less then  .001). Median PFS was 2.6 months (95% CI 1.9-5.1) among patients with PS2 and 11.3 months (95% CI 8.5-14.4) among those with PS 0-1. Median OS was 7.8 months (95% CI 2.5-10.7) in the PS2 group, not reached in the PS 0-1 group. see more PS 2 remained predictive of poor outcomes in multivariate analysis.Conclusion PS 2 is a strong independent predictor of poor response and survival in NSCLC patients with high PD-L1, treated with front-line pembrolizumab. Prospective randomised trials comparing immunotherapy to chemotherapy in this population would be welcome.The aim of this study is to develop a tool that is aligned with patients' and health professionals' needs to address sexual health in the context of anorectal malformations and Hirschsprung's disease. A multiphased participatory action-research was conducted. First, an inventory of needs was made through interviews (11 patients, 11 professionals), three online focus groups (4 patients, 20 professionals), and a questionnaire (38 patients). Subsequently, four cocreation sessions with in total four patients and nine professionals were organized to translate the needs into a tool (in the form of a website). The websites' functionality was assessed via a questionnaire (n = 34). The website, directed to patients, their parents, and professionals, stimulates awareness, fills knowledge gaps, and shows possibilities for support. The website is expected to change restrictive attitudes toward sexual health and improve the legitimization of the topic needed for the allocation of resources and sexologists' involvement in current care pathways.

Heart failure (HF) is a common and potentially fatal condition. In 2015, HF affected approximately 40 million people globally. Evidence showing that the use of nitrates can improve clinical outcomes in patients with HF is limited. This study aimed to assess the effect of nitrates on functional capacity and exercise time in patients with HF.

PubMed, Cochrane Library, and Embase databases were reviewed for articles on the use of nitrates and other treatments for patients with HF. The primary endpoints were the 6-minute walk test distance, exercise time, and quality of life. Secondary endpoints were all-cause mortality, arrhythmia, hospitalization, and worsening HF. The weighted mean difference, risk ratio, and 95% confidence interval were calculated.

A total of 14 related studies that comprised 26,321 patients were included. No significant differences were found in the 6-minute walk test distance, exercise time, and quality of life between the nitrate and control treatment groups. There were also no differences in all-cause mortality, the incidence of arrhythmia, hospitalization, and worsening HF between these two groups.

Patients with HF who receive nitrate treatment do not have better quality of life or exercise capacity compared with controls.

Patients with HF who receive nitrate treatment do not have better quality of life or exercise capacity compared with controls.The emergence of increased resistance to the available drugs has created a situation that demands to find out more specific molecular drug targets for Leishmaniasis. The enoyl acyl carrier protein reductase (ENR), a regulatory enzyme in type II fatty acid synthesis, was confirmed as a novel drug target and triclosan as its specific inhibitor in many microorganisms. In this study, the triclosan was tested for the leishmanicidal property against Leishmania donovani (L. donovani) and the results of in vitro and ex vivo drug assays on promastigotes and amastigotes showed that triclosan possessed antileishmanial activity with a half minimal inhibitory concentration (IC50) of 30 µM. Consequently, adopting in silico approach, we have tested the triclosan's ability to bind with the L. donovani enoyl acyl carrier protein reductase (LdENR). The 3D structure of LdENR was modelled, triclosan and cofactors were docked in LdENR model and molecular dynamic simulations were performed to observe the protein-ligands interactions, stability, compactness and binding energy calculation of the ligands-LdENR complexes. The observation showed that triclosan stably interacted with LdENR in presence of both the cofactors (NADPH and NADH), however, simulation results favor NADH as a preferred co-factor for LdENR. These results support that the reduction of L. donovani growth in the in vitro and ex vivo drug assays may be due to the interaction of triclosan with LdENR, which should be confirmed through enzymatic assays. The results of this study suggest that LdENR could be a potential drug target and triclosan as a lead for Leishmaniasis. Communicated by Ramaswamy H. Sarma.The current COVID-19 pandemic is caused by SARS CoV-2. To date, ∼463,000 people died worldwide due to this disease. Several attempts have been taken in search of effective drugs to control the spread of SARS CoV-2 infection. The main protease (Mpro) from SARS CoV-2 plays a vital role in viral replication and thus serves as an important drug target. This Mpro shares a high degree of sequence similarity (>96%) with the same protease from SARS CoV-1 and MERS. It was already reported that Broussonetia papyrifera polyphenols efficiently inhibit the catalytic activity of SARS CoV-1 and MERS Mpro. But whether these polyphenols exhibit any inhibitory effect on SARS CoV-2 Mpro is far from clear. To understand this fact, here we have adopted computational approaches. Polyphenols having proper drug-likeness properties and two repurposed drugs (lopinavir and darunavir; having binding affinity -7.3 to -7.4 kcal/mol) were docked against SARS CoV-2 Mpro to study their binding properties. Only six polyphenols (broussochalcone A, papyriflavonol A, 3'-(3-methylbut-2-enyl)-3',4',7-trihydroxyflavane, broussoflavan A, kazinol F and kazinol J) had interaction with both the catalytic residues (His41 and Cys145) of Mpro and exhibited good binding affinity (-7.