Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Myofibroblastoma of the Breast: A Rare Cause of Breast Lump in a Postmenopausal Woman

A breast mass in a postmenopausal age woman is treated with a high index of clinical suspicion for malignancy. Myofibroblastoma (MFB) of the breast is a very rare benign stromal tumor, predominantly occurring in menopausal women and older men. Owing to its rarity, nonspecific radiology, cytomorphology, and many variants, it can be confused with other malignant and benign breast lesions and hence can be a source of diagnostic pitfall. We present a case of an MFB of the breast in a 55-year-old female, which was detected on a routine screening mammography. Fine-needle aspiration cytology was inconclusive. Final diagnosis was made by histopathology and immunohistochemistry examination. We report this case as the likelihood of encountering MFB has increased in recent years due to routine mammographic screening, and this lesion should be kept in the differential diagnosis of spindle-cell lesions of the breast

Squamous Cell Carcinoma Arising in Mature Teratoma of the Ovary Masquerading as Abdominal Tuberculosis

Pure squamous cell carcinoma (SCC) of the ovary is rare. SCC can arise in a mature teratoma (MT), ovarian endometriosis or in a Brenner tumor. SCC is the most common malignant transformation arising in MT and comprises 80% of all cases. Such neoplastic transformations are extremely difficult either to predict or detect early. The mechanism of malignant transformation has not been completely understood. Due to the rarity and the aggressive course, diagnosis and treatment constitute a big challenge. We report a case of SCC arising in MT presenting with a huge abdominopelvic mass and abundant peritoneal collections clinically masquerading as abdominal tuberculosis. A review of literature with special emphasis on prognosis and treatment modalities is also presented

Single Donor Plasmapheresis for COVID-19: An Experience from a Tertiary Care Hospital Based Blood Centre

Introduction: Corona Virus Disease-2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) became a global health problem since December 2019. No single treatment was found to be effective against COVID-19. Transfusion of COVID Convalescent Plasma (CCP) was found to be a useful and logistically feasible therapeutic strategy in COVID-19. Aim: To study the feasibility of single donor plasmapheresis for COVID-19, to analyse statistical significance of clinicodemographical data and biochemical parameters of convalescent plasmapheresis donors and to further study the adverse reactions and technical problems that occurred during the procedure of single donor plasmapheresis. Materials and Methods: A prospective observational study was carried out over a period of 10 months from June 2020 to March 2021. The study included 235 screened donors and 50 procedures for single donor plasmapheresis (SDPs). Donors were selected as per the standard criteria given by Indian Council of Medical Research (ICMR). All plasmapheresis procedures were performed on an automated blood cell separator. The results were tabulated and statistical analysis was performed using Statistical Package for the Social Sciences (SPSS) software. Results: Out of 235 prospective CCP donors, 164 (69.78%) were found eligible. The causes of non eligibility donors were unwillingness to donate, absence of SARS-CoV-2 antibody, Transfusion Transmitted Disease (TTD) positivity, and improper haematological parameters. Actual plasma donations were carried out in 50 (21.27%) eligible donors. Therapeutically needed amount of CCP (400 mL) could be collected from most of the donors. Adverse reactions were seen in 4 (8%) donors. Conclusion: Adequate amount of CCP could be collected by single donor plasmapheresis with satisfactory technical support. The procedure was well accepted by the prescreened donors with minimum adverse reactions

Whole-genome sequencing reveals host factors underlying critical COVID-19

Altres ajuts: Department of Health and Social Care (DHSC); Illumina; LifeArc; Medical Research Council (MRC); UKRI; Sepsis Research (the Fiona Elizabeth Agnew Trust); the Intensive Care Society, Wellcome Trust Senior Research Fellowship (223164/Z/21/Z); BBSRC Institute Program Support Grant to the Roslin Institute (BBS/E/D/20002172, BBS/E/D/10002070, BBS/E/D/30002275); UKRI grants (MC_PC_20004, MC_PC_19025, MC_PC_1905, MRNO2995X/1); UK Research and Innovation (MC_PC_20029); the Wellcome PhD training fellowship for clinicians (204979/Z/16/Z); the Edinburgh Clinical Academic Track (ECAT) programme; the National Institute for Health Research, the Wellcome Trust; the MRC; Cancer Research UK; the DHSC; NHS England; the Smilow family; the National Center for Advancing Translational Sciences of the National Institutes of Health (CTSA award number UL1TR001878); the Perelman School of Medicine at the University of Pennsylvania; National Institute on Aging (NIA U01AG009740); the National Institute on Aging (RC2 AG036495, RC4 AG039029); the Common Fund of the Office of the Director of the National Institutes of Health; NCI; NHGRI; NHLBI; NIDA; NIMH; NINDS.Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care or hospitalization after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes-including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)-in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease