Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Molecular Basis of Cannabis-Induced Schizophrenia-Relevant Behaviours: Insights from Animal Models

Introduction: Cannabis use is a well-established component risk factor for schizophrenia; however, the mechanisms by which cannabis use increases schizophrenia risk are unclear. Animal models can elucidate mechanisms by which chronic cannabinoid treatment can induce schizophrenia-relevant neural changes, in a standardised manner often not possible using patient-based data. Methods: We review recent literature (within the past 10 years) using animal models of chronic and subchronic treatment with cannabinoids which target the cannabinoid 1 receptor [i.e. ∆9-tetrahydrocannabinol, CP55,940 and WIN55,212-2]. Schizophrenia-relevant behavioural consequences of chronic cannabinoid treatment are first briefly summarised, followed by a detailed account of changes to several receptor systems [e.g. cannabinoid, dopaminergic, glutamatergic, γ-aminobutyric acid (GABAe)rgic, serotonergic, noradrenergic], dendritic spine morphology and inflammatory markers following chronic cannabinoids. We distinguish between adolescent and adult cannabinoid treatments, to determine if adolescence is a period of susceptibility to schizophrenia-relevant molecular changes. Results: Chronic cannabinoid treatment induces behaviours relevant to positive, negative and cognitive symptoms of schizophrenia. Chronic cannabinoids also cause region- and subtype-specific changes to receptor systems (e.g. cannabinoid, dopaminergic, glutamatergic, GABAergic), as well as changes in dendritic spine morphology and upregulation of inflammatory markers. These changes often align with molecular changes observed in post-mortem tissue from schizophrenia patients and correspond with schizophrenia-relevant behavioural change in rodents. There is some indication that adolescence is a period of susceptibility to cannabinoid-induced schizophrenia-relevant neural change, but more research in this field is required to confirm this hypothesis. Conclusions: Animal models indicate several molecular mechanisms by which chronic cannabinoids contribute to schizophrenia-relevant neural and behavioural change. It is likely that a number of these mechanisms are simultaneously impacted by chronic cannabinoids, thereby increasing schizophrenia risk in individuals who use cannabis. Understanding how cannabinoids can affect several molecular targets provides critical insight into the complex relationship between cannabis use and schizophrenia risk