Prognostic models for surgical-site infection in gastrointestinal surgery: systematic review

BACKGROUND: Identification of patients at high risk of surgical-site infection may allow clinicians to target interventions and monitoring to minimize associated morbidity. The aim of this systematic review was to identify and evaluate prognostic tools for the prediction of surgical-site infection in gastrointestinal surgery.METHODS: This systematic review sought to identify original studies describing the development and validation of prognostic models for 30-day SSI after gastrointestinal surgery (PROSPERO: CRD42022311019). MEDLINE, Embase, Global Health, and IEEE Xplore were searched from 1 January 2000 to 24 February 2022. Studies were excluded if prognostic models included postoperative parameters or were procedure specific. A narrative synthesis was performed, with sample-size sufficiency, discriminative ability (area under the receiver operating characteristic curve), and prognostic accuracy compared.RESULTS: Of 2249 records reviewed, 23 eligible prognostic models were identified. A total of 13 (57 per cent) reported no internal validation and only 4 (17 per cent) had undergone external validation. Most identified operative contamination (57 per cent, 13 of 23) and duration (52 per cent, 12 of 23) as important predictors; however, there remained substantial heterogeneity in other predictors identified (range 2-28). All models demonstrated a high risk of bias due to the analytic approach, with overall low applicability to an undifferentiated gastrointestinal surgical population. Model discrimination was reported in most studies (83 per cent, 19 of 23); however, calibration (22 per cent, 5 of 23) and prognostic accuracy (17 per cent, 4 of 23) were infrequently assessed. Of externally validated models (of which there were four), none displayed 'good' discrimination (area under the receiver operating characteristic curve greater than or equal to 0.7).CONCLUSION: The risk of surgical-site infection after gastrointestinal surgery is insufficiently described by existing risk-prediction tools, which are not suitable for routine use. Novel risk-stratification tools are required to target perioperative interventions and mitigate modifiable risk factors.</p

Characterisation of in-hospital complications associated with COVID-19 using the ISARIC WHO Clinical Characterisation Protocol UK: a prospective, multicentre cohort study

Background: COVID-19 is a multisystem disease and patients who survive might have in-hospital complications. These complications are likely to have important short-term and long-term consequences for patients, health-care utilisation, health-care system preparedness, and society amidst the ongoing COVID-19 pandemic. Our aim was to characterise the extent and effect of COVID-19 complications, particularly in those who survive, using the International Severe Acute Respiratory and Emerging Infections Consortium WHO Clinical Characterisation Protocol UK. Methods: We did a prospective, multicentre cohort study in 302 UK health-care facilities. Adult patients aged 19 years or older, with confirmed or highly suspected SARS-CoV-2 infection leading to COVID-19 were included in the study. The primary outcome of this study was the incidence of in-hospital complications, defined as organ-specific diagnoses occurring alone or in addition to any hallmarks of COVID-19 illness. We used multilevel logistic regression and survival models to explore associations between these outcomes and in-hospital complications, age, and pre-existing comorbidities. Findings: Between Jan 17 and Aug 4, 2020, 80 388 patients were included in the study. Of the patients admitted to hospital for management of COVID-19, 49·7% (36 367 of 73 197) had at least one complication. The mean age of our cohort was 71·1 years (SD 18·7), with 56·0% (41 025 of 73 197) being male and 81·0% (59 289 of 73 197) having at least one comorbidity. Males and those aged older than 60 years were most likely to have a complication (aged ≥60 years: 54·5% [16 579 of 30 416] in males and 48·2% [11 707 of 24 288] in females; aged &lt;60 years: 48·8% [5179 of 10 609] in males and 36·6% [2814 of 7689] in females). Renal (24·3%, 17 752 of 73 197), complex respiratory (18·4%, 13 486 of 73 197), and systemic (16·3%, 11 895 of 73 197) complications were the most frequent. Cardiovascular (12·3%, 8973 of 73 197), neurological (4·3%, 3115 of 73 197), and gastrointestinal or liver (0·8%, 7901 of 73 197) complications were also reported. Interpretation: Complications and worse functional outcomes in patients admitted to hospital with COVID-19 are high, even in young, previously healthy individuals. Acute complications are associated with reduced ability to self-care at discharge, with neurological complications being associated with the worst functional outcomes. COVID-19 complications are likely to cause a substantial strain on health and social care in the coming years. These data will help in the design and provision of services aimed at the post-hospitalisation care of patients with COVID-19. Funding: National Institute for Health Research and the UK Medical Research Council

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Eye muscle nerves and the ciliary ganglion of Malpolon monspessulana (Colubridae, Ophidia)

In Malpolon monspessulana, the nervus oculomotorius arises from the ventral side of the pars peduncularis mesencephali of the midbrain by a single root. It runs closely applied to both the nervus abducens and the ramus nasalis of the nervus trigeminus. These nerves together with the nervus trochlearis leave the cranial cavity through the foramen orbitale magnum. Within this foramen the nervus oculomotorius divides into two rami: superior and inferior. The two rami innervate the rectus superior, rectus inferior, rectus medialis and the obliquus inferior muscles. The nervus trochlearis arises from the lateral side of the mesencephalon by a single root and passes to innervate the obliquus superior muscle. The nervus abducens arises from the ventral side of the medulla oblongata by a single root and passes for a distance through the vidian canal excavated in the parachordal cartilage. It innervates the rectus lateralis muscle. The eye muscle nerves carry special somatic motor fibres. The ciliary ganglion receives the preganglionic parasympathetic fibres from the ramus inferior of the nervus oculomotorius via the radix ciliaris brevis. Both the radix ciliaris longa and sympathetic root are absent. The ciliary ganglion is a well defined mass located in the postorbital region, irregular in shape formed of one type of neuron and gives off only one ciliary nerve

Educational impact and recommendations from implementation of student-led clinical trial recruitment:a mixed-methods study

Medical students have an essential role in medical research, yet often lack opportunities for involvement within randomised trials. This study aimed to understand the educational impact of clinical trial recruitment for medical students. Tracking wound infection with smartphone technology (TWIST) was a randomised controlled trial that included adult patients undergoing emergency abdominal surgery across two university teaching hospitals. All recruiters underwent prerecruitment training based on 'Generating Student Recruiters for Randomised Trials' principles, and completed prerecruitment and postrecruitment surveys. Respondent agreement with statements were assessed using 5-point Likert scales (from 1 ('strongly disagree') to 5 ('strongly agree')). Quantitative data were analysed using paired t-tests to compare differences pre-involvement and post-involvement. Thematic content analysis was performed on free-text data to generate recommendations for future student research involvement. Of 492 patients recruited to TWIST between 26 July 2016 and 4 March 2020, 86.0% (n=423) were recruited by medical students. Following introduction of student co-investigators (n=31), the overall monthly recruitment rate tripled (4.8-15.7 patients). 96.8% of recruiters (n=30/31) completed both surveys, and all respondents reported significant improvement in clinical and academic competencies. Three higher-level thematic domains emerged from the qualitative analysis: (1) engagement, (2) preparation and (3) ongoing support. Student recruitment in clinical trials is feasible and accelerates recruitment to clinical trials. Students demonstrated novel clinical research competencies and increased their likelihood of future involvement. Adequate training, support and selection of suitable trials are essential for future student involvement in randomised trials.</p

Characterisation of in-hospital complications associated with COVID-19 using the ISARIC WHO Clinical Characterisation Protocol UK: a prospective, multicentre cohort study

BackgroundCOVID-19 is a multisystem disease and patients who survive might have in-hospital complications. These complications are likely to have important short-term and long-term consequences for patients, health-care utilisation, health-care system preparedness, and society amidst the ongoing COVID-19 pandemic. Our aim was to characterise the extent and effect of COVID-19 complications, particularly in those who survive, using the International Severe Acute Respiratory and Emerging Infections Consortium WHO Clinical Characterisation Protocol UK.MethodsWe did a prospective, multicentre cohort study in 302 UK health-care facilities. Adult patients aged 19 years or older, with confirmed or highly suspected SARS-CoV-2 infection leading to COVID-19 were included in the study. The primary outcome of this study was the incidence of in-hospital complications, defined as organ-specific diagnoses occurring alone or in addition to any hallmarks of COVID-19 illness. We used multilevel logistic regression and survival models to explore associations between these outcomes and in-hospital complications, age, and pre-existing comorbidities.FindingsBetween Jan 17 and Aug 4, 2020, 80 388 patients were included in the study. Of the patients admitted to hospital for management of COVID-19, 49·7% (36 367 of 73 197) had at least one complication. The mean age of our cohort was 71·1 years (SD 18·7), with 56·0% (41 025 of 73 197) being male and 81·0% (59 289 of 73 197) having at least one comorbidity. Males and those aged older than 60 years were most likely to have a complication (aged ≥60 years: 54·5% [16 579 of 30 416] in males and 48·2% [11 707 of 24 288] in females; age

Global variation in postoperative mortality and complications after cancer surgery: a multicentre, prospective cohort study in 82 countries

Background 80% of individuals with cancer will require a surgical procedure, yet little comparative data exist on early outcomes in low-income and middle-income countries (LMICs). We compared postoperative outcomes in breast, colorectal, and gastric cancer surgery in hospitals worldwide, focusing on the effect of disease stage and complications on postoperative mortality. Methods This was a multicentre, international prospective cohort study of consecutive adult patients undergoing surgery for primary breast, colorectal, or gastric cancer requiring a skin incision done under general or neuraxial anaesthesia. The primary outcome was death or major complication within 30 days of surgery. Multilevel logistic regression determined relationships within three-level nested models of patients within hospitals and countries. Hospital-level infrastructure effects were explored with three-way mediation analyses. This study was registered with ClinicalTrials.gov, NCT03471494. Findings Between April 1, 2018, and jan 31, 2019, we enrolled 15 958 patients from 428 hospitals in 82 countries (high income 9106 patients, 31 countries; upper-middle income 2721 patients, 23 countries; or lower-middle income 4131 patients, 28 countries). Patients in LMICs presented with more advanced disease compared with patients in high-income countries. 30-day mortality was higher for gastric cancer in low-income or lower-middle-income countries (adjusted odds ratio 3.72, 95% CI 1.70-8.16) and for colorectal cancer in low-income or lower-middle-income countries (4.59, 2.39-8.80) and upper-middle-income countries (2.06,1.11-3.83). No difference in 30-day mortality was seen in breast cancer. The proportion of patients who died after a major complication was greatest in low-income or lower-middle-income countries (6.15, 3.26-11.59) and upper-middle-income countries (3.89, 2- 08-7- 29). Postoperative death after complications was partly explained by patient factors (60%) and partly by hospital or country (40%). The absence of consistently available postoperative care facilities was associated with seven to 10 more deaths per 100 major complications in LMICs. Cancer stage alone explained little of the early variation in mortality or postoperative complications. Interpretation Higher levels of mortality after cancer surgery in LMICs was not fully explained by later presentation of disease. The capacity to rescue patients from surgical complications is a tangible opportunity for meaningful intervention. Early death after cancer surgery might be reduced by policies focusing on strengthening perioperative care systems to detect and intervene in common complications. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide. Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital. Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer. Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license

Impact of malnutrition on early outcomes after cancer surgery: an international, multicentre, prospective cohort study

Background: malnutrition represents a key priority for global health policy, yet the impact of nutritional state on cancer surgery worldwide remains poorly described. We aimed to analyse the effect of malnutrition on early postoperative outcomes following elective surgery for colorectal or gastric cancer. Methods: we did an international, multicentre, prospective cohort study of patients undergoing elective surgery for colorectal or gastric cancer between April 1, 2018, and Jan 31, 2019. Patients were excluded if the primary pathology was benign, they presented with cancer recurrence, or if they underwent emergency surgery (within 72 h of hospital admission). Malnutrition was defined with the Global Leadership Initiative on Malnutrition criteria. The primary outcome was death or a major complication within 30 days of surgery. Multilevel logistic regression and a three-way mediation analysis were done to establish the relationship between country income group, nutritional status, and 30-day postoperative outcomes. Findings: this study included 5709 patients (4593 with colorectal cancer and 1116 with gastric cancer) from 381 hospitals in 75 countries. The mean age was 64·8 years (SD 13·5) and 2432 (42·6%) patients were female. Severe malnutrition was present in 1899 (33·3%) of 5709 patients, with a disproportionate burden in upper-middle-income countries (504 [44·4%] of 1135) and low-income and lower-middle-income countries (601 [62·5%] of 962). After adjustment for patient and hospital risk factors, severe malnutrition was associated with an increased risk of 30-day mortality across all country income groups (high income: adjusted odds ratio [aOR] 1·96 [95% CI 1·14–3·37], p=0·015; upper-middle income: 3·05 [1·45–6·42], p=0·003; low income and lower-middle income: 11·57 [5·87–22·80], p&lt;0·0001). Severe malnutrition mediated an estimated 32% of early deaths in low-income and lower-middle-income countries (aOR 1·41 [95% CI 1·22–1·64]) and an estimated 40% of early deaths in upper-middle-income countries (1·18 [1·08–1·30]). Interpretation: Severe malnutrition is common in patients undergoing surgery for gastrointestinal cancers and is a risk factor for 30-day mortality following elective surgery for colorectal or gastric cancer. There is an urgent need to examine whether perioperative nutritional interventions can improve early outcomes following gastrointestinal cancer surgery worldwide. Funding: National Institute for Health Research Global Health Research Unit.</p