A Practical Synthetic Route to Cinnolines: Application to the Design and Synthesis of RSV NNI Inhibitor JNJ-8003 Analogues.

The manuscript describes the development of an efficient synthetic route to cinnolines, facilitating faster access to JNJ-8003 related Respiratory Syncytial Virus (RSV) non-nucleoside (NNI) inhibitors. Starting from correctly functionalized aryl halides, a Sonogashira reaction followed by SNAr reaction with hydrazine 1,2-dicabroxylate reagents provided dihydrocinnolines directly via in situ 6-endo-dig cyclization. The dihydrocinnolines were conveniently transformed to corresponding cinnolines in one step.

Empirical antibiotic therapy improves outcomes in mechanically ventilated patients with COVID-19: An emulated targeted trial within a prospective, multicentre cohort study.

Background: Bacterial pulmonary superinfections develop in a substantial proportion of mechanically ventilated COVID-19 patients and are associated with prolonged mechanical ventilation requirements and an increased mortality. Albeit recommended, evidence supporting the use of empirical antibiotics at intubation is weak and of low quality. The aim of this study was to elucidate the effect of empirical antibiotics, administered within 24hours of endotracheal intubation, on superinfections, duration of mechanical ventilation, and mortality in mechanically ventilated patients with COVID-19.

Understanding patients' emotional well-being, perceptions and concerns during an unprecedented deferment of arthroplasty: an Italian qualitative study.

Objectives: Nearly 40 000 Italian patients had their arthroplasty postponed between March and May 2020 (lockdown period) and experienced a period of several months without knowing when surgeries would resume. The hypothesis was that such conditions caused changes in perceived well-being and quality of life. The study aimed to explore the feelings, perceptions and concerns of orthopaedic patients in Italy during COVID-related arthroplasty rescheduling.

Hybrid Setting for Minimally Invasive Mitral Surgery in Patients With Inferior Vena Caval Filters.

Current cardiac surgery has evolved to include hybrid and minimally invasive settings. In parallel, less invasive techniques have been extended to complex clinical scenarios and may prove even more beneficial in higher-risk patients. However, comorbidities and challenging anatomy still represent limitations to widespread application of this philosophy.

Impact of Surreptitious Glucocorticoids in Over-the-Counter Arthritis Supplements.

Adrenal dysfunction due to over-the-counter (OTC) health supplements containing unlabeled glucocorticoids has been previously reported. Here, we present a case series of 12 patients at an urban safety net medical center evaluated by endocrinology for iatrogenic adrenal dysfunction, Cushing syndrome (CS) and/or adrenal insufficiency (AI), associated with use of OTC arthritis supplements surreptitiously containing glucocorticoids. There were 12 patients using OTC arthritis supplements (Artri King [n = 8], Ardosons [n = 3], Ajo Rey [n = 1]) included.