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

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Assessing the potential for infections of Echinococcus multilocularis in dogs in a hotspot of human alveolar echinococcosis infections in North America

Echinococcus multilocularis is a zoonotic tapeworm, whose metacestode larval stage is the etiological agent for alveolar echinococcosis in humans and is a parasite of emerging concern according to the World Health Organization which is difficult to diagnose and has a case mortality rate of &gt;90% when left untreated. Echinococcus multilocularis requires two mammalian hosts to complete its lifecycle: wild and domestic canids as definitive hosts, and small mammals (mostly rodents) as intermediate ones. Because of their close relations with humans, domestic dogs have been indicated as a mean of infection to people. Alveolar echinococcosis has historically been rare in North America, however, since 2013, at least seventeen diagnoses have been confirmed in Alberta, Canada. Because of this unprecedented series of cases, assessing the frequency of infections in dogs in Alberta is key to estimate risk for dog owners and animal health professionals. This study was carried out in Edmonton to determine the frequency of E. multilocularis infection in domestic dogs and potential risk factors. Fecal samples and corresponding behavior risk surveys were collected from 775 dogs in seven urban off-leash parks within Edmonton city limits during the summer of 2020. A quantitative PCR fecal test was used to diagnose E. multilocularis infection. We found a single case of E. multilocularis infection (1/775) and determined that the overall true prevalence was 0.2% (95% CI: 0.0–0.8%) corrected for detection sensitivity and specificity. Overall, these findings confirm the presence of E. multilocularis infection in domestic dogs in Edmonton although further work is required to fully understand the risk factors that may contribute to infection and potential transmission to humans

Chapparvovirus DNA Found in 4% of Dogs with Diarrhea

Feces from dogs in an unexplained outbreak of diarrhea were analyzed by viral metagenomics revealing the genome of a novel parvovirus. The parvovirus was named cachavirus and was classified within the proposed Chapparvovirus genus. Using PCR, cachavirus DNA was detected in two of nine tested dogs from that outbreak. In order to begin to elucidate the clinical impact of this virus, 2,053 canine fecal samples were screened using real-time PCR. Stool samples from 203 healthy dogs were positive for cachavirus DNA at a rate of 1.47%, while 802 diarrhea samples collected in 2017 and 964 samples collected in 2018 were positive at rates of 4.0% and 4.66% frequencies, respectively (healthy versus 2017-2018 combined diarrhea p-value of 0.05). None of 83 bloody diarrhea samples tested positive. Viral loads were generally low with average real-time PCR Ct values of 36 in all three positive groups. The species tropism and pathogenicity of cachavirus, the first chapparvovirus reported in feces of a placental carnivore, remains to be fully determined

Genome Sequence of Canine Polyomavirus in Respiratory Secretions of Dogs with Pneumonia of Unknown Etiology

We report here the first canine polyomavirus genome, identified by metagenomics in respiratory secretions of two dogs with severe pneumonia, which tested negative for all canine respiratory pathogens except Mycoplasma cynos The isolate, Canis familiaris polyomavirus 1 (DogPyV-1), is a beta polyomavirus whose closest known LT antigen relatives are primate polyomaviruses

Lyon-IARC Polyomavirus DNA in Feces of Diarrheic Cats.

A viral metagenomic analysis of feces from an unexplained outbreak of feline diarrhea revealed the presence of Lyon-IARC polyomavirus (LIPyV) DNA. LIPyV, whose genome was originally sequenced from swabs of human skin, was fecally shed by three out of five diarrheic cats

DataSheet_1_Coyote scat in cities increases risk of human exposure to an emerging zoonotic disease in North America.docx

IntroductionZoonoses associated with urban wildlife are increasingly concerning for human health and include the recent emergence of alveolar echinococcosis (AE) in North America. AE develops following infection with the tapeworm Echinococcus multilocularis. In Alberta, up to 65% of urban coyotes (Canis latrans) are infected with E. multilocularis, and infected scats contain eggs that can be accidentally ingested by people. Our goal was to determine the predictors of infection prevalence and intensity in coyote scats in Edmonton, Canada, and to identify the predictors of coyote scat deposition and content, especially as related to anthropogenic food sources and infrastructure.MethodsTo study infection prevalence and intensity, volunteers collected 269 scats, which were tested for E. multilocularis using polymerase chain reaction. We compared infection prevalence and shedding intensity by habitat and scat content. To determine predictors of scat presence and content, we used snow tracking to identify 1263 scats. We compared landscape characteristics at scats and available points, and among scats with different contents. We used negative binomial regression to predict scat abundance in city-delineated green spaces.Results26.0% of tested scats were positive for E. multilocularis (n = 70), and infection was twice as common as expected near compost and 1.3x more common than expected when scats contained anthropogenic food. Scats were more common than expected near other scats (80% within 1 m of scats, 27% at 11.5 m), buildings (19% at buildings, 16% at 80 m), and the camps of people experiencing homelessness (24% at camps, 20% at 60 m). Scats frequently contained fruit (52.9%), anthropogenic material (36.7%), and birdseed (16.0%), and scats containing anthropogenic material often occurred near human infrastructure, supporting a relationship between anthropogenic attractants and scat accumulation.DiscussionThese results suggest that abundant food sources and anthropogenic food increase coyote aggregation, increasing both scat abundance and infection rates, which in turn increases risk of exposure to zoonotic parasites for humans. Risk to humans might be reduced by preventing coyote access to anthropogenic and aggregated food sources and educating people who are likely to encounter infected soil or vegetation, including gardeners, park users, and people experiencing homelessness.</p

Erymildbraedin A and B, two novel cytotoxic dimethylpyrano-isoflavones from the stem bark of Erythrina mildbraedii: Evaluation of their activity toward endocrine cancer cells

Two new dimethylpyrano-isoflavones, named erymildbraedin A (4) and B (5), were isolated from the stem bark of the Cameroonian medicinal plant Erythrina mildbraedii, along with four known ones, the linear congeners, scandenone (1), erysenegalinsein M (2), 5,4′-dihydroxy-2′-methoxy-8-(3,3- dimethylallyl)-2″,2″-dimethylpyrano[5,6:6,7]isoflavone (3), and the angular isoflavone eryvarin B (6), and two other compounds, fraxidin and scoparone. Their structures were elucidated by the usual spectroscopic methods and isoflavone effects on the growth of human breast, prostate, and endometrial adenocarcinoma cells were determined. Isoflavones 1, 3, and 6 strongly inhibited the growth of all three cell lines, supporting the notion that a non-oxidized isoprenyl group at C-8 is requisite for cytotoxic activity. © 2010 Informa UK Ltd