Notes

Autoantibodies towards ACE2 and angiotensin type-1 receptors improve harshness of COVID-19.
To compare the efficacy and safety between pyrotinib (Pyr) and trastuzumab emtansine (T-DM1) in pre-treated human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC) patients.

A comprehensive literature search of the PubMed, EMBASE, and Web of Science was performed in August 2020. Randomized clinical trials comparing the efficacy and safety between different anti-HER2 regimens in patients pre-treated with trastuzumab (Tra) and a taxane in metastatic settings (≤second-line treatment) were included. A fixed effects network meta-analysis based on the Bayesian inferential framework was conducted for progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and grade ≥3 adverse events (AEs). Values of surface under cumulative ranking probability curve (SUCRA) were calculated to offer a ranking of all regimens.

Twelve studies with 4,353 subjects were identified. Nine regimens were included into the network T-DM1, lapatinib-capecitabine (Lap-Cap), Tra-Ct Pyr may be more effective than T-DM1 in HER2+ MBC patients pre-treated with Tra and a taxane. However, it may be associated with more grade ≥3 AEs.Renal cell carcinoma (RCC) is the most lethal neoplasm of common urologic cancers with poor prognoses. SMAD4 has a principal role in TGF-β (Transformis growth factorβ)-induced epithelial to mesenchymal transition (EMT) as a key factor in gaining cancer stem cell (CSC) features and tumor aggressiveness. This study aimed to evaluate the expression patterns and clinical significance of SMAD4 in RCC and the impact of its targeting on stem cell/mesenchymal cells and EMT characteristics in renal spheroid derived cells (SDCs) compared to parental cells (PCs) in RCC. The expression pattern and clinical significance of SMAD4 was evaluated in RCC. SDCs were enriched using a sphere culture system. Then SDCs and their PCs were compared with respect to their sphere and colony formation, expression of putative CSC markers, invasiveness as well as expression of genes, including stemness/mesenchymal, SMAD4 and TGFβ1genes. Finally, the effect of SMAD4 knockdown on SDCs was analyzed. We demonstrated that SMAD4 is positively correlated with decreased disease specific survival (DSS) in RCC patients and clear cell RCC (ccRCC) subtype and associates with poor DSS in patients with RCC, especially in ccRCC as the most metastatic RCC subtype. SDCs exhibited higher stem cell/mesenchymal properties. Inhibition of SMAD4 in PCs accelerated the dissociation of SDCs and decreased their clonogenicity, invasiveness, expression of mesenchymal markers and expression of SMAD4 and TGFβ1 genes compared to SDCs before transfection. We suggest that targeting SMAD4 may be useful against renal CSCs and may improve RCC prognosis.Randomized controlled trials are the gold standard for determining the efficacy of a new intervention. Trials conducted for regulatory approval of an intervention compare the effect of the intervention with the standard of care or placebo to demonstrate efficacy. Randomization attempts to ensure that all known and unknown confounding factors are evenly distributed between the groups, and that the groups will be comparable at the end of the study, so that any inter-group differences in outcomes can be attributed to the intervention. However, in reality, intercurrent events may impact the assessment and subsequent interpretation of the outcome of interest. To address this, International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) in 2017, released an addendum to the E9 guideline (ICH E9 R1) putting forth the concept of Estimands and Sensitivity Analysis in Clinical Trials. This addendum addresses how these intercurrent events are to be handled using the Estimand concept, which is now expected to be detailed in a separate section of the study protocol. In this paper, we discuss what estimands are, and their likely impact on how regulatory trial protocols and their statistical analyses plans are written and implemented. We also look at the application of the concept of estimands to routine clinical practice.
Critical appraisal of published research papers is routinely conducted as a journal club (JC) activity in pharmacology departments of various medical colleges across Maharashtra, and it forms an important part of their postgraduate curriculum. The objective of this study was to evaluate the perception of pharmacology postgraduate students and teachers toward use of critical appraisal as a reinforcing tool for research methodology. Evaluation of performance of the in-house pharmacology postgraduate students in the critical appraisal activity constituted secondary objective of the study.

The study was conducted in two parts. Entinostat inhibitor In Part I, a cross-sectional questionnaire-based evaluation on perception toward critical appraisal activity was carried out among pharmacology postgraduate students and teachers. In Part II of the study, JC score sheets of 2
- and 3
-year pharmacology students over the past 4 years were evaluated.

One hundred and twenty-seven postgraduate students and 32 teachers participated in Part I of the study. About 118 (92.9%) students and 28 (87.5%) faculties considered the critical appraisal activity to be beneficial for the students. JC score sheet assessments suggested that there was a statistically significant improvement in overall scores obtained by postgraduate students (
= 25) in their last JC as compared to the first JC.

Journal article criticism is a crucial tool to develop a research attitude among postgraduate students. Participation in the JC activity led to the improvement in the skill of critical appraisal of published research articles, but this improvement was not educationally relevant.
Journal article criticism is a crucial tool to develop a research attitude among postgraduate students. Participation in the JC activity led to the improvement in the skill of critical appraisal of published research articles, but this improvement was not educationally relevant.
Clinical research in India has been besieged by controversies. While studies have addressed other stakeholders, few have addressed the patient. The present study was conducted to assess the extent of awareness and understanding about the nature and conduct of CR among people of Mumbai.

Institutional Ethics Committee approval was taken (EC/OA-12/15) and written informed consent was obtained. Adults who were residents of Mumbai were enrolled. A prevalidated and published 48-item questionnaire based on six themes, namely awareness and participation, voluntariness and autonomy, compensation, confidentiality, safety, and involvement in CR were administered. Perception based on themes and association of variables such as age, gender, socioeconomic class, and education on this perception was assessed. Descriptive statistics along with Chi-square test/Chi-square test for trend and crude odds ratio (cOR) were assessed.

Of the 453 participants approached, 400 (age 32 [18-96]) consented. Only 210/400 (52.5%) were aware of CR and 194/400 (48.
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