Neutrophil extracellular traps (NETs), a unique DNA framework decorated with antimicrobial peptides, have been in the scientific limelight for their role in a variety of pathologies ranging from cystic fibrosis to cancer. The formation of NETs, as well as relevant regulatory mechanisms, physiological factors, and pharmacological agents have not been systematically discussed in the context of their beneficial and pathological aspects. Novel forms of NET formation including vital NET formation continue to be uncovered, however, there remain fundamental questions around established mechanisms such as NADPH-oxidase (Nox)-dependent and Nox-independent NET formation. Whether NET formation takes place in the tissue versus the bloodstream, internal factors (e.g. reactive oxygen species (ROS) production and transcription factor activation), and external factors (e.g. alkaline pH and hypertonic conditions), have all been demonstrated to influence specific NET pathways. Elements of neutrophil biology such as transcription and mitochondria, which were previously of unknown significance, have been identified as critical mediators of NET formation through facilitating chromatin decondensation and generating ROS, respectively. While promising therapeutics inhibiting ROS, transcription, and gasdermin D are being investigated, neutrophil phagocytosis plays a critical role in host defense and any therapies targeting NET formation must avoid impairing the physiological functions of these cells. This review summarizes what is known in the many domains of NET research, highlights the most relevant challenges in the field, and inspires new questions that can bring us closer to a unified model of NET formation.

Background COVID-19 causes significant morbidity and mortality. Despite the high prevalence of delirium and delirium-related symptoms in COVID-19 patients, data and evidence-based recommendations on the pathophysiology and management of delirium are limited. Objective We conducted a rapid review of COVID-19-related delirium literature to provide a synthesis of literature on the prevalence, pathoetiology, and management of delirium in these patients. Methods Systematic searches of Medline, Embase, PsycInfo, LitCovid, WHO-COVID-19, and Web of Science electronic databases were conducted. Grey literature was also reviewed, including preprint servers, archives, and websites of relevant organizations. Search results were limited to the English language. We included literature focused on adults with COVID-19 and delirium. Papers were excluded if they did not mention signs or symptoms of delirium. Results 229 studies described prevalence, pathoetiology, and/or management of delirium in adults with COVID-19. Delirium was rarely assessed with validated tools. Delirium affected >50% of all patients with COVID-19 admitted to the ICU. The etiology of COVID-19 delirium is likely multifactorial, with some evidence of direct brain effect. Prevention remains the cornerstone of management in these patients. To date, there is no evidence to suggest specific pharmacological strategies. Discussion Delirium is common in COVID-19 and may manifest from both indirect and direct effects on the central nervous system. Further research is required to investigate contributing mechanisms. As there is limited empirical literature on delirium management in COVID-19, management with non-pharmacological measures and judicious use of pharmacotherapy is suggested.

Suprascapular entrapment neuropathy is well known in certain athletes, especially volleyball players. A brother and sister presented with right shoulder pain and wasting of the scapular muscles, particularly the infraspinatus. They had played volleyball for over six years and were forced to retire because of disability. Investigations showed involvement of the rhomboid muscles also, suggesting a probable extension of this syndrome to other nerves in the region such as the dorsal scapular nerve.

BackgroundThere has been rapid growth in the demand for transcatheter aortic valve replacement (TAVR), which has the potential to overwhelm current capacity. This imbalance between demand and capacity may lead to prolonged wait times, and subsequent adverse outcomes while patients are on the waitlist. We sought to understand the relationship between regional differences in capacity, TAVR wait times and morbidity/mortality on the waitlist.Methods and resultsWe modelled the effect of TAVR capacity, defined as the number of TAVR procedures per million residents/region, on the hazard of having a TAVR in Ontario from April 2012 to March 2017. Our primary outcome was the time from referral to a TAVR procedure or other off-list reasons on the waitlist/end of the observation period as measured in days. Clinical outcomes of interest were all-cause mortality, all-cause hospitalisations or heart failure-related hospitalisations while on the waitlist for TAVR. There was an almost fourfold difference in TAVR capacity across the 14 regions in Ontario, ranging from 31.5 to 119.5 TAVR procedures per million residents. The relationship between TAVR capacity and wait times was complex and non-linear. In general, increased capacity was associated with shorter wait times (p<0.001), reduced mortality (HR 0.94; p=0.08) and all-cause hospitalisations (p=0.009).ConclusionsThe results of the present study have important policy implications, suggesting that there is a need to improve TAVR capacity, as well as develop wait-time strategies to triage patients, in order to decrease wait times and mitigate the hazard of adverse patient outcomes while on the waitlist.