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

Understanding the relationship between the perineuronal net and glia within the auditory pathway in a mouse model of age-related hearing loss

Age-related hearing loss (ARHL) affects over 11 million people in the UK and ~50% of over 75yr olds. Although hearing loss is often perceived as an inconsequential part of aging, there is evidence it is important in general brain health. Adults with ARHL develop significant impairments in their cognitive abilities 3 years sooner and 30-40% more severely than those with normal hearing. The severity of ARHL is associated with a greater risk (2-5 fold) of developing dementia. Hearing aids and cochlear implants improve quality of life for many individuals however there are no approved therapies to prevent or slow ARHL. This is likely due to inadequate understanding of the neurobiological changes underling the progression of this chronic debilitating condition. In a murine model of ARHL, we have observed changes within the auditory pathway in both the perineuronal net (PNN) and glia.We hypothesise that the loss of sensory input to the auditory nerve in ARHL may induce compensatory changes to the PNN to alter neuronal activity and synaptic plasticity. Such changes may contribute to a pathological glial response making the auditory pathway more vulnerable to inflammation and progression of hearing loss.The auditory circuit is modulated by synaptic inhibition to maintain temporal precision and process sound localization cues. The majority of fast-spiking interneurons associated with this inhibition are surrounded by a specialized extracellular matrix, the PNN. The PNN is important for synaptic stabilization, protects against glial activation and pathological insults and has restrictive effects on plasticity in the mature CNS.Here we exploit the well-characterized C57BL/6J mouse model of ARHL, to assess changes in expression and localization of the PNN and glial cells across the life-course and in disease progression. We have found changes in expression of the PNN during progression of hearing loss. We also observe changes in the organization and phenotype of microglia and astrocytes in the auditory pathway.Gaining a better understanding of the pathological processes involved in progression of ARHL may identify cellular or molecular compartments amenable to modulation. For example tempering the glial response and associated changes in the PNN may slow disease progression and help retain auditory function for longer. ARHL is associated with increased risk of developing dementia and exacerbating cognitive decline. Therapies that modulate ARHL could therefore be significant in the treatment of dementia and related neurodegenerative conditions

SARS-CoV-2 vaccination modelling for safe surgery to save lives: Data from an international prospective cohort study

Background: Preoperative SARS-CoV-2 vaccination could support safer elective surgery. Vaccine numbers are limited so this study aimed to inform their prioritization by modelling. Methods: The primary outcome was the number needed to vaccinate (NNV) to prevent one COVID-19-related death in 1 year. NNVs were based on postoperative SARS-CoV-2 rates and mortality in an international cohort study (surgical patients), and community SARS-CoV-2 incidence and case fatality data (general population). NNV estimates were stratified by age (18-49, 50-69, 70 or more years) and type of surgery. Best- and worst-case scenarios were used to describe uncertainty. Results: NNVs were more favourable in surgical patients than the general population. The most favourable NNVs were in patients aged 70 years or more needing cancer surgery (351; best case 196, worst case 816) or non-cancer surgery (733; best case 407, worst case 1664). Both exceeded the NNV in the general population (1840; best case 1196, worst case 3066). NNVs for surgical patients remained favourable at a range of SARS-CoV-2 incidence rates in sensitivity analysis modelling. Globally, prioritizing preoperative vaccination of patients needing elective surgery ahead of the general population could prevent an additional 58 687 (best case 115 007, worst case 20 177) COVID-19-related deaths in 1 year. Conclusion: As global roll out of SARS-CoV-2 vaccination proceeds, patients needing elective surgery should be prioritized ahead of the general population