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

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Therapeutic Applications of Ethanol: A Review

International audiencePurpose To review knowledge on therapeutic uses of ethanol and the latter's effectiveness and safety profiles in a range of indications. Method MEDLINE and PubMed databases were searched for relevant peer-reviewed papers published in English between 1888 and 2018 using the following search terms ethanol, therapeutic, alcohol withdrawal syndrome, antiseptic, antidote, methanol, ethylene glycol, neurolysis, embolization, cyst, sclerosing agent, sclerotherapy, arteriovenous malformations, ablating agent. Studies providing information about association between alcohol and therapeutic indications, or mechanic explanation for the association were included for review. Results According to the World Health Organization, approximately three millions deaths worldwide are attributable to alcohol consumption each year. However, the low-to-moderate consumption of ethanol has a number of beneficial effects (mainly on cardiovascular mortality and diabetes). Hence, ethanol has an unusual spectrum of effects that seems interesting for therapeutic purposes. Ethanol's risk-benefit ratio appears to be positive in some therapeutic indications such as antidote to methanol or ethylene glycol poisoning, neurolysis, alcohol withdrawal syndrome, or antiseptic. Conclusion With the development of interventional radio technologies, and thus extremely precise access to anatomical structures, alcohol has been given new indications - particularly as an embolization. sclerosing or ablation agent. Moreover, constant progress in our knowledge of ethanol's pharmacodynamics might highlight other therapeutic indications for this compound in the future. Ethanol's low cost and wide availability make it a valuable therapeutic agent, compared with other reference treatments. Furthermore, ethanol has a long track record of safety and effectiveness in the indications mentioned above

Ethanol and its metabolites: update on toxicity, benefits, and focus on immunomodulatory effects

International audienceThis article summarizes recent experimental and epidemiological data on the toxic and beneficial effects of ethanol and its metabolites (acetaldehyde), and focuses on their immunomodulatory effects. The section dealing with the toxic effects of alcohol focuses on its chronic toxicity (liver disorders, carcinogenic effects, cardiovascular disorders, neuropsychic disorders, addiction and withdrawal syndrome, hematologic disorders, reprotoxicity, osteoporosis) although acute toxicity is considered. The role of oxidative metabolism of ethanol by alcohol dehydrogenase, cytochrome P450 2E1, and aldehyde dehydrogenase, as well as the impact of genetic polymorphism in its physiopathology are also highlighted. The section dealing with the beneficial effects of low to moderate alcohol consumption (on cardiovascular system, diabetes, the nervous system and sensory organs, autoimmune diseases, and rheumatology) highlights the importance of anti-inflammatory and immunomodulatory effects in these observations. This knowledge, enriched by a focus on the immunomodulatory effects of ethanol and its metabolites, in particular on the NLRP3 inflammasome pathway, might facilitate the development of treatments that can reduce ethanol’s harmful effects or accentuate its beneficial effects

Toxic Effects of Amanitins: Repurposing Toxicities toward New Therapeutics

International audienceThe consumption of mushrooms has become increasingly popular, partly due to their nutritional and medicinal properties. This has increased the risk of confusion during picking, and thus of intoxication. In France, about 1300 cases of intoxication are observed each year, with deaths being mostly attributed to Amanita phalloides poisoning. Among amatoxins, alpha- and beta-amanitins are the most widely studied toxins. Hepatotoxicity is the hallmark of these compounds, leading to hepatocellular failure within three days of ingestion. The toxic mechanisms of action mainly include RNA polymerase II inhibition and oxidative stress generation, leading to hepatic cell apoptosis or necrosis depending on the doses ingested. Currently, there is no international consensus concerning Amanita phalloides poisoning management. However, antidotes with antioxidant properties remain the most effective therapeutics to date suggesting the predominant role of oxidative stress in the pathophysiology. The partially elucidated mechanisms of action may reveal a suitable target for the development of an antidote. The aim of this review is to present an overview of the knowledge on amanitins, including the latest advances that could allow the proposal of new innovative and effective therapeutics

Suitability of high-resolution mass spectrometry in analytical toxicology: Focus on drugs of abuse

International audienceHigh-resolution mass spectrometry (HRMS) is now the method of choice in several toxicology contexts. This paper reviews HRMS approaches for research and application in various toxicology fields, focusing on drugs of abuse in clinical and forensic toxicology. Papers concerning HRMS applications in screening, quantification and metabolism of drugs of abuse in biological and non-biological samples were included. Specific applications for new psychoactive substances in contexts such as online libraries, bioinformatic tools (molecular networking) and methods combinations were also included. (C) 2021 Societe Francaise de Toxicologie Analytique. Published by Elsevier Masson SAS. All rights reserved

Self-inflicted neck wounds under influence of lysergic acid diethylamide: A case report and literature review

International audienceRationale - Lysergic acid diethylamide (LSD) is a highly potent psychedelic drug derived from ergot alkaloids. The available literature data derived from controlled studies or usage in a medical setting seem reassuring; however the literature contains very rare cases of fatal self-inflicted injuries associated with LSD exposure. The behavioral disorder that created the conditions conducive to death is a maladaptive or irrational response to the psychiatric manifestations induced by the substance. Patient concern - Here, we report the case of a 26-year-old man found dead with large neck wounds in a locked house. No medical history other than recreational use of alcohol and narcotics was reported as well as any history of psychotic disease. The entirety of the other investigations carried out did not demonstrate the presence of a third party at the place of death and a dropper bottle containing LSD was found near the body. Diagnosis - We report the first case of fatal self-inflicted neck wounds with a cutting instrument in the context of acute exposure to LSD in a patient with no psychiatric history and without suicidal symptoms at the time of the self-aggressive act. Intervention and outcomes - In the present work, we used a validated method using liquid chromatography coupled with mass spectrometry for simultaneous quantification of LSD and its metabolites (O-H-LSD and Nor-LSD) in whole blood and urine samples. LSD and O-H-LSD were respectively found at 1460 and 182 pg/mL in blood. In the urine, the concentrations of LSD, nor-LSD, O-H-LSD were, respectively, 3670, 201, and 4890 ng/L. Lessons - This observation is particularly relevant in view of the resurgence of interest in the therapeutic use of LSD, notwithstanding the fact that the literature has not demonstrated a link between suicidal risk and acute or chronic exposure to LSD

Maximizing number of doses drawn from multi-dose COVID-19 vaccines by minimizing dead volume

International audienceThe COVID-19 pandemic constitutes an unprecedented challenge to health care systems and societies worldwide. On 21 December 2020, the highly effective Pfizer–BioNTech COVID-19 vaccine was authorized in Europe, bringing big hopes for overcoming the pandemic.1 However, there are concerns about delayed availability of sufficient vaccine doses, forcing to prioritize target populations.2 Vaccination with the Pfizer–BioNTech COVID-19 vaccine consists of two doses (0.3 ml each) administered intramuscularly, 3 weeks apart. Each vial (2.25 ml theorical and 2.27 ml actual volume after dilution) meet the requirements of the European Pharmacopoeia allowing to obtain five doses using a syringe of a capacity not exceeding three times the volume to be measured and fitted with a 21-G needle not less than 2.5 cm in length.3 On 8 January 2021, European Medicines Agency announced that six doses could be extracted from a single vial using low dead-volume syringes and/or needles; i.e. no more than 35 μl for the syringe–needle combination.4 To date, no study has been carried out to propose recommendations on the use of adapted equipment. Here, we report the dead-volume of different syringe–needle combinations in order to inform such debate by relevant medical devices data

Comparative molecular networking analysis of a Rauwolfia plant powder and biological matrices in a fatal ingestion case

International audiencePurpose Identifying xenobiotics involved in deaths remains a challenge in toxicology, especially when they are missing from the usual suspect databases. The tool development for the rapid processing of untargeted screening data is a valuable asset. In recent years, the molecular networking has been developed in various fields, including toxicology, because of its ability to graphically display and compare complex data acquired from tandem mass spectrometry. Here, we report a case of fatal poisoning by ingestion of an unknown powder (labelled as Tabernanthe iboga) and apply molecular networking to tentatively identify the plant involved in a woman's death. Methods The supposedly ingested powder, an authentic Tabernanthe iboga root powder and postmortemed biological samples (peripheral blood and bile) were extracted and analyzed according to a screening method using high resolution liquid chromatography hyphenated to tandem mass spectrometry (Q-Exactive(R)). Results Analysis of these four matrices by molecular networking revealed a cluster of nodes composed of indolomonoterpenic alkaloids, a characteristic of the Apocynaceae family (ibogaine, ibogamine, ajmaline, reserpiline, yohimbine). Analysis of the spectral annotations of the supposedly ingested powder also shows a majority of occurrences related to the genus Rauwolfia, which differed from the authentic Tabernanthe iboga root powder. Conclusions Molecular networking allowed us to discard the Tabernanthe iboga identification hypothesis and suggest an alternate Apocynaceae species, most likely belonging to the Rauwolfia genus. In addition, eleven putative compounds could be detected by the molecular networking, many of which seemed to be metabolites of the major components in the Rauwolfia genus