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The core pathology of coronavirus disease 2019 (COVID-19) is infection of airway cells by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that results in excessive inflammation and respiratory disease, with cytokine storm and acute respiratory distress syndrome implicated in the most severe cases. Thrombotic complications are a major cause of morbidity and mortality in patients with COVID-19. Patients with pre-existing cardiovascular disease and/or traditional cardiovascular risk factors, including obesity, diabetes mellitus, hypertension and advanced age, are at the highest risk of death from COVID-19. In this Review, we summarize new lines of evidence that point to both platelet and endothelial dysfunction as essential components of COVID-19 pathology and describe the mechanisms that might account for the contribution of cardiovascular risk factors to the most severe outcomes in COVID-19. We highlight the distinct contributions of coagulopathy, thrombocytopathy and endotheliopathy to the pathogenesis of COVID-19 and discuss potential therapeutic strategies in the management of patients with COVD-19. Harnessing the expertise of the biomedical and clinical communities is imperative to expand the available therapeutics beyond anticoagulants and to target both thrombocytopathy and endotheliopathy. Only with such collaborative efforts can we better prepare for further waves and for future coronavirus-related pandemics.

ObjectiveUse next-generation sequencing (NGS) technology to improve our diagnostic yield in patients with suspected genetic disorders in the Asian setting.DesignA diagnostic study conducted between 2014 and 2019 (and ongoing) under the Singapore Undiagnosed Disease Program. Date of last analysis was 1 July 2019.SettingInpatient and outpatient genetics service at two large academic centres in Singapore.PatientsInclusion criteria: patients suspected of genetic disorders, based on abnormal antenatal ultrasound, multiple congenital anomalies and developmental delay. Exclusion criteria: patients with known genetic disorders, either after clinical assessment or investigations (such as karyotype or chromosomal microarray).InterventionsUse of NGS technology—whole exome sequencing (WES) or whole genome sequencing (WGS).Main outcome measures(1) Diagnostic yield by sequencing type, (2) diagnostic yield by phenotypical categories, (3) reduction in time to diagnosis and (4) change in clinical outcomes and management.ResultsWe demonstrate a 37.8% diagnostic yield for WES (n=172) and a 33.3% yield for WGS (n=24). The yield was higher when sequencing was conducted on trios (40.2%), as well as for certain phenotypes (neuromuscular, 54%, and skeletal dysplasia, 50%). In addition to aiding genetic counselling in 100% of the families, a positive result led to a change in treatment in 27% of patients.ConclusionGenomic sequencing is an effective method for diagnosing rare disease or previous ‘undiagnosed’ disease. The clinical utility of WES/WGS is seen in the shortened time to diagnosis and the discovery of novel variants. Additionally, reaching a diagnosis significantly impacts families and leads to alteration in management of these patients.

Background and Aim: Preferences of service users is an important consideration for developing health-care services. This study aimed to assess the experiences of the patients with substance use disorders who were admitted to a tertiary health-care facility in India.Method: This cross-sectional sectional study recruited adult inpatients who stayed for a period of 7 days or more. The Picker Patient Experience questionnaire (PPE-15) was used to gather information about the views of the patients about the care received at the center.Results: Responses were available from 113 inpatients. Majority of the participants were males and were dependent on opioids. The experience was generally positive about being treated with respect and dignity and access to information. The participants were most satisfied with opportunity being given to discuss anxiety and fear about the condition or treatment (91.2% positive response) and least satisfied with differences in responses from doctors and nurses (43.4% positive response). Further attention seemed desired about communication with the staff and patients’ involvement in their own treatment-related decision-making.Conclusion: Efforts need to be made to involve patients in their own treatment-related decision-making and to improve communication with the treatment team. This might lead to better involvement in treatment process, which could enhance the treatment outcomes in this vulnerable population.

Background:The rising trend of obesity and morbid obesity around the world emphasizes the need for designing healthcare facilities that fit the needs of these patients. Keeping in view the safety of morbidly obese patients and also the staff handling them, it was thought pertinent to study and analyze the structural, manpower, and financial aspects that need consideration while planning a bariatric facility.Materials and Methods:This study was carried out in an apex tertiary care hospital in India through review of literature and in-depth interviews of stakeholders providing care and facilities as well as from the market to determine the spacing needs and cost of retrofitting a 10-bedded bariatric facility in an existing hospital. Traditional method of cost analysis was used to arrive at the cost estimates for the financial year 2016–2017.Results:An estimated cost of U.S. $39,139 (INR 2,616,500) per bed has been projected in retrofitting the setting of this study with a 10-bedded bariatric facility with an existing manpower pool for the same. For a retrofitting facility requiring additional manpower, an estimated cost of U.S. $90,496 (INR 6,049,700) per bed has been projected in this study setting.Conclusion:Given the growth of bariatric population both worldwide and in India, it is need of the hour to consider retrofitting existing healthcare facilities for bariatric patients. Although hospitals would incur an initial cost in such retro-fittings, in the long run, they would overrun their value in terms of patient needs and satisfaction, which indeed is the ultimate goal in healthcare.

Monotherapy of HIV-1 infection with single antiretroviral agents is ineffective because error-prone HIV-1 replication leads to the production of drug-resistant viral variants1,2. Combinations of drugs can establish long-term control, however, antiretroviral therapy (ART) requires daily dosing, can cause side effects and does not eradicate the infection3,4. Although anti-HIV-1 antibodies constitute a potential alternative to ART5,6, treatment of viremic individuals with a single antibody also results in emergence of resistant viral variants7–9. Moreover, combinations of first-generation anti-HIV-1 broadly neutralizing antibodies (bNAbs) had little measurable effect on the infection10–12. Here we report on a phase 1b clinical trial (NCT02825797) in which two potent bNAbs, 3BNC11713and 10-107414, were administered in combination to seven HIV-1 viremic individuals. Infusions of 30?mg?kg-1of each of the antibodies were well-tolerated. In the four individuals with dual antibody-sensitive viruses, immunotherapy resulted in an average reduction in HIV-1 viral load of 2.05 log10copies per ml that remained significantly reduced for three months following the first of up to three infusions. In addition, none of these individuals developed resistance to both antibodies. Larger studies will be necessary to confirm the efficacy of antibody combinations in reducing HIV-1 viremia and limiting the emergence of resistant viral variants.

Ectodermal dysplasia (ED) is a disorder that occurs due to abnormalities of ectodermal structures such as skin, teeth, hair, nails, and eccrine glands. Approximately 200 different conditions have been identified as ED, the most common being hypohidrotic ED. It is characterized by hypotrichosis (sparse scalp or body hair), hypodontia (absent or malformed teeth), and hypohidrosis (reduced ability to sweat). It is also associated with distinctive facial features, such as the prominent forehead, thick lips, flattened nasal bridge, and thin wrinkled skin. Ocular anomalies are less frequently observed, the most common ones being dysplasia of the lacrimal gland or meibomian gland that leads to dry eye and variable corneal involvement. We report a case of a 9-year-old child of hypohidrotic ED presenting with bilateral infantile glaucoma managed by the implantation of glaucoma drainage devices (GDDs) after a failed trabeculotomy and trabeculectomy in both eyes.

Current understanding of tumor immunosuppressive mechanisms forms the basis for modern day immunotherapies. Immunoregulatory role of platelets in cancer remains largely elusive. Platelets from non-small cell lung cancer (NSCLC) patients revealed a distinct activation phenotype. TREM-like transcript 1 (TLT-1), a platelet protein, was increased along with enhanced extracellular release from NSCLC platelets. The increased platelet TLT-1 was also evident in humanized mice with patient-derived tumors. In immunocompetent mice with syngeneic tumors, TLT-1 binding to T cells, in vivo, led to suppression of CD8 T cells, promoting tumor growth. We identified direct interaction between TLT-1 and CD3ε on T cells, implicating the NF-κB pathway in CD8 T cell suppression. Anti–TLT-1 antibody rescued patients’ T cells from platelet-induced suppression ex vivo and reduced tumors in mice in vivo. Clinically, higher TLT-1 correlated with reduced survival of NSCLC patients. Our findings thus identify TLT-1 as a platelet-derived immunosuppressor that suppresses CD8 T cells and demonstrate its therapeutic and prognostic significance in cancer.

Psychological distress associated with surgery is an emerging issue. The study was conducted to assess the impact of structured patient education viz-a-viz routine patient education on anxiety and depression levels in patients undergoing elective chest surgery. It is a prospective, double-blind randomized study, conducted from February 2019 to February 2020 at a tertiary care center in India, on patients who underwent elective chest surgeries. A total of 300 patients were randomized using a computer-generated randomization sequence, into 2 equal groups (150 subjects each). Study group included patients who underwent structured patient education (Group A), whereas control group included patients who underwent routine patient education (Group B). The 2 groups were compared for anxiety and depression levels at admission as well as discharge using Hospital Anxiety and Depression Scale. Also, at the time of discharge, the groups were compared for the effectiveness of patient education using a validated Questionnaire B. In comparison to routine education, patients receiving structured education showed significantly lesser scores for anxiety and depression at discharge (P< .001). Also, structured patient education proved to be effective in comparison to the routine education in educating the patients in all parameters as determined by the Questionnaire B (P< .05). It can be concluded that structured educational intervention is strongly recommended in patients undergoing chest surgery which can help alleviate perioperative anxiety and depression. Such intervention helps patient get an understanding of the surgical procedure and assist them in facing the condition in a better way.

Benzothiazole (BTZ)–boron dipyrromethene (BODIPY)-based dyads, Dyad 1and Dyad 2, containing BTZ as light energy absorbing and transferring antenna while BODIPY as an energy acceptor, linked together with ethoxy and ester spacers, respectively, have been synthesized, and photoinduced energy transfer (PEnT) events occurring within these systems were studied. Both of the dyads were characterized by 1H NMR, MALDI-MS, UV–visible, steady-state fluorescence, and femtosecond transient absorption spectroscopic as well as electrochemical methods. A comparison of the absorption spectra of the dyads with their reference compounds (i.e., BTZ-OMeand BODIPY-OMe) revealed minimal ground-state interactions between chromophores in Dyad 1while a more pronounced effect in case of Dyad 2. Electrochemical and computational studies revealed that the LUMO of both of the dyads is located on BODIPY, indicating that the reduction of BODIPY moiety is easier as compared to that of BTZ moiety. Selective excitation on BTZ in the dyads at ∼300 nm resulted in quenching of the BTZ emission followed by the appearance of BODIPY emission showing efficient energy transfer from singlet excited BTZ (1BTZ*) to BODIPY. The photoinduced energy transfer phenomenon was observed in four different solvents of varying polarity. The driving forces of energy transfer (ΔGEN) in both of the dyads were found to be exothermic, and, in case of Dyad 1, they followed the trend toluene > DCB ≈ DMF > acetonitrile. Transient absorption studies performed in polar solvents such as acetonitrile revealed an efficient photoinduced energy transfer (∼95%) from 1BTZ* to BODIPY (kEN= 6.17 × 1012s–1for Dyad 1and 2.5 × 1012s–1for Dyad 2in acetonitrile) creating singlet excited BODIPY (1BTZ*-BODIPY → BTZ-1BODIPY*), indicating the quenched pathway is exclusively a PEnT process.

Rhabdomyosarcoma (RMS) of the cervix in women older than 40 years of age is extremely rare. Embryonal RMS can appear deceptively benign both clinically and histopathologically. Diagnosis is made on the basis of histomorphologic and immunohistochemical findings. A high index of suspicion is, however, needed to make the diagnosis, as they can masquerade as benign polyps. A 41-year-old female with cervical RMS is described here. The initial biopsy diagnosis of embryonal RMS was confirmed on subsequent hysterectomy. The present case report is described with emphasis on histopathologic features and diagnostic difficulties along with a brief review of the literature.