Colchester Hospital

INTRODUCTION: Case reports have been a long held tradition within the surgical literature. Reporting guidelines can improve transparency and reporting quality. However, recent consensus-based guidelines for case reports (CARE) are not surgically focused. Our objective was to develop surgical case report guidelines. METHODS: The CARE statement was used as the basis for a Delphi consensus. The Delphi questionnaire was administered via Google Forms and conducted using standard Delphi methodology. A multidisciplinary group of surgeons and others with expertise in the reporting of case reports were invited to participate. In round one, participants stated how each item of the CARE statement should be changed and what additional items were needed. Revised and additional items from round one were put forward into a further round, where participants voted on the extent of their agreement with each item, using a nine-point Likert scale, as proposed by the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) working group. RESULTS: In round one, there was a 64% (38/59) response rate. Following adjustment of the guideline with the incorporation of recommended changes, round two commenced and there was an 83% (49/59) response rate. All but one of the items were approved by the participants, with Likert scores 7-9 awarded by >70% of respondents. The final guideline consists of a 14-item checklist. CONCLUSION: We present the SCARE Guideline, consisting of a 14-item checklist that will improve the reporting quality of surgical case reports.

Abstract The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-19 1,2 , host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases 3–7 . They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease.

Given the tissue-specific nature of epigenetic processes, the assessment of disease-relevant tissue is an important consideration for epigenome-wide association studies (EWAS). Little is known about whether easily accessible tissues, such as whole blood, can be used to address questions about interindividual epigenomic variation in inaccessible tissues, such as the brain. We quantified DNA methylation in matched DNA samples isolated from whole blood and 4 brain regions (prefrontal cortex, entorhinal cortex, superior temporal gyrus, and cerebellum) from 122 individuals. We explored co-variation between tissues and the extent to which methylomic variation in blood is predictive of interindividual variation identified in the brain. For the majority of DNA methylation sites, interindividual variation in whole blood is not a strong predictor of interindividual variation in the brain, although the relationship with cortical regions is stronger than with the cerebellum. Variation at a subset of probes is strongly correlated across tissues, even in instances when the actual level of DNA methylation is significantly different between them. A substantial proportion of this co-variation, however, is likely to result from genetic influences. Our data suggest that for the majority of the genome, a blood-based EWAS for disorders where brain is presumed to be the primary tissue of interest will give limited information relating to underlying pathological processes. These results do not, however, discount the utility of using a blood-based EWAS to identify biomarkers of disease phenotypes manifest in the brain. We have generated a searchable database for the interpretation of data from blood-based EWAS analyses ( http://epigenetics.essex.ac.uk/bloodbrain/).

Breast cancer is the most common global malignancy and the leading cause of cancer deaths. Despite this, undergraduate and postgraduate exposure to breast cancer is limited, impacting on the ability of clinicians to accurately recognise, assess and refer appropriate patients. This article provides a comprehensive review of the pathology, epidemiology, clinical presentation, referral pathways and management of breast cancer in the UK. It also describes how to conduct a thorough clinical breast examination.

BACKGROUND: Complete tumor regression may develop after neoadjuvant chemoradiation therapy for distal rectal cancer. Studies have suggested that selected patients with complete clinical response may avoid radical surgery and close surveillance may provide good outcomes with no oncologic compromise. However, definition of complete clinical response is often imprecise and may vary between different studies. The aim of this study is to provide a clear definition for a complete clinical response after neoadjuvant chemoradiation therapy in patients with distal rectal cancer in addition to actual endoscopic videos from patients managed nonoperatively. METHODS: Patients with nonmetastatic distal rectal cancer treated by neoadjuvant chemoradiation therapy, including 50.4 Gy and concomitant 5-fluorouracil and leucovorin, were assessed for tumor response at least 8 weeks after chemoradiation therapy completion. Complete and incomplete clinical responses were defined based on clinical and endoscopic findings. Patients with complete clinical response were not immediately operated on and were closely followed. Early and late endoscopic findings were recorded. RESULTS: Definition of a complete clinical response should be based on very strict clinical and endoscopic criteria. The finding of any residual superficial ulceration, irregularity, or nodule should prompt surgical attention, including transanal full-thickness excision or even a radical resection with total mesorectal excision. Standard or incisional biopsies should be avoided in this setting. Complete clinical responders should harbor no more than whitening of the mucosa, teleangiectasia with mucosal integrity to be considered for a nonoperative approach. In the presence of these findings, regularly scheduled reassessments may provide a safe alternative to these patients with early detection of recurrent disease. CONCLUSION: Strict definition of the clinical and endoscopic findings of patients experiencing complete clinical response after neoadjuvant chemoradiation therapy may provide a useful tool for the understanding of outcomes of patients managed with no immediate surgery allowing standardization of classifications and comparison between the experiences of different institutions.

OBJECTIVE: This study aims to report short-term clinical and oncological outcomes from the international transanal Total Mesorectal Excision (taTME) registry for benign and malignant rectal pathology. BACKGROUND: TaTME is the latest minimally invasive transanal technique pioneered to facilitate difficult pelvic dissections. Outcomes have been published from small cohorts, but larger series can further assess the safety and efficacy of taTME in the wider surgical population. METHODS: Data were analyzed from 66 registered units in 23 countries. The primary endpoint was "good-quality TME surgery." Secondary endpoints were short-term adverse events. Univariate and multivariate regression analyses were used to identify independent predictors of poor specimen outcome. RESULTS: A total of 720 consecutively registered cases were analyzed comprising 634 patients with rectal cancer and 86 with benign pathology. Approximately, 67% were males with mean BMI 26.5 kg/m. Abdominal or perineal conversion was 6.3% and 2.8%, respectively. Intact TME specimens were achieved in 85%, with minor defects in 11% and major defects in 4%. R1 resection rate was 2.7%. Postoperative mortality and morbidity were 0.5% and 32.6% respectively. Risk factors for poor specimen outcome (suboptimal TME specimen, perforation, and/or R1 resection) on multivariate analysis were positive CRM on staging MRI, low rectal tumor <2 cm from anorectal junction, and laparoscopic transabdominal posterior dissection to <4 cm from anal verge. CONCLUSIONS: TaTME appears to be an oncologically safe and effective technique for distal mesorectal dissection with acceptable short-term patient outcomes and good specimen quality. Ongoing structured training and the upcoming randomized controlled trials are needed to assess the technique further.

OBJECTIVE: hip fracture is a common and serious condition associated with high mortality. This study aimed to identify pre-operative characteristics which are associated with an increased risk of mortality after hip fracture surgery. DESIGN: systematic search of published and unpublished literature databases, including EMBASE, MEDLINE, AMED, CINAHL, PubMed and the Cochrane Library, was undertaken to identify all clinical studies on pre-operative predictors of mortality after surgery in hip fracture with at least 3-month follow-up. Data pertaining to the study objectives was extracted by two reviewers independently. Where study homogeneity was evidence, a meta-analysis of pooled relative risk and 95% confidence intervals was performed for mortality against pre-admission characteristics. RESULTS: fifty-three studies including 544,733 participants were included. Thirteen characteristics were identified as possible pre-operative indicators for mortality. Following meta-analysis, the four key characteristics associated with the risk of mortality up to 12 months were abnormal ECG (RR: 2.00; 95% CI: 1.45, 2.76), cognitive impairment (RR: 1.91; 95% CI: 1.35, 2.70), age >85 years (RR: 0.42; 95% CI: 0.20, 0.90) and pre-fracture mobility (RR: 0.13; 95% CI: 0.05, 0.34). Other statistically significant pre-fracture predictors of increased mortality were male gender, being resident in a care institution, intra-capsular fracture type, high ASA grade and high Charlson comorbidity score on admission. CONCLUSIONS: this review has identified the characteristics of patients with a high risk of mortality after a hip fracture surgery beyond the peri-operative period who may benefit from comprehensive assessment and appropriate management. PROSPERO REGISTRATION NUMBER: CRD42012002107.

Thoracoscopy under local anaesthetic and intravenous sedation, also known as local anaesthetic thoracoscopy, medical thoracoscopy or pleuroscopy, is increasingly being performed by chest physicians in the UK. In 1999, 11 centres across the UK offered a local anaesthetic thoracoscopy service, increasing to 17 centres in May 20041 and 37 centres in 2009 (Dr N Downer, personal communication). This document, which will use the term ‘local anaesthetic thoracoscopy’, aims to consider the following issues and to make appropriate recommendations on the basis of evidence where available: Creation of this guideline followed the Appraisal of Guidelines Research and Evaluation/Scottish Intercollegiate Guidelines Network (AGREE/SIGN) methodology of evidence assessment and integration (see introduction to pleural disease guidelines). Is there a need for a physician-based local anaesthetic thoracoscopy service in the UK? The majority of local anaesthetic thoracoscopy is carried out in the context of an undiagnosed exudative pleural effusion, the commonest cause of which is malignancy.2 This section of the document will therefore focus mainly on local anaesthetic thoracoscopy in the context of malignant disease. ### The increasing burden of pleural disease Malignant pleural effusion is a common clinical problem. Although the incidence of lung cancer in the UK is falling, the incidence of other cancers is rising. With increasing life expectancy in an ageing population and at current cancer incidence rates, an additional 100 000 cases of cancer per year are expected by 2025.3 Up to 15% of patients who die with malignancy have a pleural effusion at autopsy.4 Studies suggest that exudative effusions are caused by malignancy …

INTRODUCTION: Case series have been a long held tradition within the surgical literature and are still frequently published. Reporting guidelines can improve transparency and reporting quality. No guideline exists for reporting case series, and our recent systematic review highlights the fact that key data are being missed from such reports. Our objective was to develop reporting guidelines for surgical case series. METHODS: A Delphi consensus exercise was conducted to determine items to include in the reporting guideline. Items included those identified from a previous systematic review on case series and those included in the SCARE Guidelines for case reports. The Delphi questionnaire was administered via Google Forms and conducted using standard Delphi methodology. Surgeons and others with expertise in the reporting of case series were invited to participate. In round one, participants voted to define case series and also what elements should be included in them. In round two, participants voted on what items to include in the PROCESS guideline using a nine-point Likert scale to assess agreement as proposed by the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) working group. RESULTS: In round one, there was a 49% (29/59) response rate. Following adjustment of the guideline with incorporation of recommended changes, round two commenced and there was an 81% (48/59) response rate. All but one of the items were approved by the participants and Likert scores 7-9 were awarded by >70% of respondents. The final guideline consists of an eight item checklist. CONCLUSION: We present the PROCESS Guideline, consisting of an eight item checklist that will improve the reporting quality of surgical case series. We encourage authors, reviewers, editors, journals, publishers and the wider surgical and scholarly community to adopt these.

INTRODUCTION: Laparoscopic surgery requires a different and sometimes more complex skill set than does open surgery. Shortened working hours, less training times, and patient safety issues necessitates that these skills need to be acquired outside the operating room. Virtual reality simulation in laparoscopic surgery is a growing field, and many studies have been published to determine its effectiveness. AIMS: This systematic review and meta-analysis aims to evaluate virtual reality simulation in laparoscopic abdominal surgery in comparison to other simulation models and to no training. METHODS: A systematic literature search was carried out until January 2014 in full adherence to PRISMA guidelines. All randomised controlled studies comparing virtual reality training to other models of training or to no training were included. Only studies utilizing objective and validated assessment tools were included. RESULTS: Thirty one randomised controlled trials that compare virtual reality training to other models of training or to no training were included. The results of the meta-analysis showed that virtual reality simulation is significantly more effective than video trainers, and at least as good as box trainers. CONCLUSION: The use of Proficiency-based VR training, under supervision with prompt instructions and feedback, and the use of haptic feedback, has proven to be the most effective way of delivering the virtual reality training. The incorporation of virtual reality training into surgical training curricula is now necessary. A unified platform of training needs to be established. Further studies to assess the impact on patient outcomes and on hospital costs are necessary. (PROSPERO Registration number: CRD42014010030).

OBJECTIVE: To determine the incidence of anastomotic-related morbidity following Transanal Total Mesorectal Excision (TaTME) and identify independent risk factors for failure. BACKGROUND: Anastomotic leak and its sequelae are dreaded complications following gastrointestinal surgery. TaTME is a recent technique for rectal resection, which includes novel anastomotic techniques. METHODS: Prospective study of consecutive reconstructed TaTME cases recorded over 30 months in 107 surgical centers across 29 countries. Primary endpoint was "anastomotic failure," defined as a composite endpoint of early or delayed leak, pelvic abscess, anastomotic fistula, chronic sinus, or anastomotic stricture. Multivariate regression analysis performed identifying independent risk factors of anastomotic failure and an observed risk score developed. RESULTS: One thousand five hundred ninety-four cases with anastomotic reconstruction were analyzed; 96.6% performed for cancer. Median anastomotic height from anal verge was 3.0 ± 2.0 cm with stapled techniques accounting for 66.0%. The overall anastomotic failure rate was 15.7%. This included early (7.8%) and delayed leak (2.0%), pelvic abscess (4.7%), anastomotic fistula (0.8%), chronic sinus (0.9%), and anastomotic stricture in 3.6% of cases. Independent risk factors of anastomotic failure were: male sex, obesity, smoking, diabetes mellitus, tumors >25 mm, excessive intraoperative blood loss, manual anastomosis, and prolonged perineal operative time. A scoring system for preoperative risk factors was associated with observed rates of anastomotic failure between 6.3% to 50% based on the cumulative score. CONCLUSIONS: Large tumors in obese, diabetic male patients who smoke have the highest risk of anastomotic failure. Acknowledging such risk factors can guide appropriate consent and clinical decision-making that may reduce anastomotic-related morbidity.

after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes-including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)-in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease.

Pulmonary hypertension is defined as a mean arterial pressure of ≥25 mmHg as confirmed on right heart catheterisation. Traditionally, the pulmonary arterial systolic pressure has been estimated on echo by utilising the simplified Bernoulli equation from the peak tricuspid regurgitant velocity and adding this to an estimate of right atrial pressure. Previous studies have demonstrated a correlation between this estimate of pulmonary arterial systolic pressure and that obtained from invasive measurement across a cohort of patients. However, for an individual patient significant overestimation and underestimation can occur and the levels of agreement between the two is poor. Recent guidance has suggested that echocardiographic assessment of pulmonary hypertension should be limited to determining the probability of pulmonary hypertension being present rather than estimating the pulmonary artery pressure. In those patients in whom the presence of pulmonary hypertension requires confirmation, this should be done with right heart catheterisation when indicated. This guideline protocol from the British Society of Echocardiography aims to outline a practical approach to assessing the probability of pulmonary hypertension using echocardiography and should be used in conjunction with the previously published minimum dataset for a standard transthoracic echocardiogram.

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist.

COVID-19, a disease caused by a novel coronavirus, is a major global human threat that has turned into a pandemic. This novel coronavirus has specifically high morbidity in the elderly and in comorbid populations. Uraemic patients on dialysis combine an intrinsic fragility and a very frequent burden of comorbidities with a specific setting in which many patients are repeatedly treated in the same area (haemodialysis centres). Moreover, if infected, the intensity of dialysis requiring specialized resources and staff is further complicated by requirements for isolation, control and prevention, putting healthcare systems under exceptional additional strain. Therefore, all measures to slow if not to eradicate the pandemic and to control unmanageably high incidence rates must be taken very seriously. The aim of the present review of the European Dialysis (EUDIAL) Working Group of ERA-EDTA is to provide recommendations for the prevention, mitigation and containment in haemodialysis centres of the emerging COVID-19 pandemic. The management of patients on dialysis affected by COVID-19 must be carried out according to strict protocols to minimize the risk for other patients and personnel taking care of these patients. Measures of prevention, protection, screening, isolation and distribution have been shown to be efficient in similar settings. They are essential in the management of the pandemic and should be taken in the early stages of the disease.

AIMS/HYPOTHESIS: To assess thiamine status by analysis of plasma, erythrocytes and urine in type 1 and type 2 diabetic patients and links to markers of vascular dysfunction. METHODS: Diabetic patients (26 type 1 and 48 type 2) with and without microalbuminuria and 20 normal healthy control volunteers were recruited. Erythrocyte activity of transketolase, the concentrations of thiamine and related phosphorylated metabolites in plasma, erythrocytes and urine, and markers of metabolic control and vascular dysfunction were determined. RESULTS: Plasma thiamine concentration was decreased 76% in type 1 diabetic patients and 75% in type 2 diabetic patients: normal volunteers 64.1 (95% CI 58.5-69.7) nmol/l, type 1 diabetes 15.3 (95% CI 11.5-19.1) nmol/l, p < 0.001, and type 2 diabetes 16.3 (95% CI 13.0-9.6) nmol/l, p < 0.001. Renal clearance of thiamine was increased 24-fold in type 1 diabetic patients and 16-fold in type 2 diabetic patients. Plasma thiamine concentration correlated negatively with renal clearance of thiamine (r = -0.531, p < 0.001) and fractional excretion of thiamine (r = -0.616, p < 0.001). Erythrocyte transketolase activity correlated negatively with urinary albumin excretion (r = -0.232, p < 0.05). Thiamine transporter protein contents of erythrocyte membranes of type 1 and type 2 diabetic patients were increased. Plasma thiamine concentration and urinary excretion of thiamine correlated negatively with soluble vascular adhesion molecule-1 (r = -0.246, p < 0.05, and -0.311, p < 0.01, respectively). CONCLUSIONS/INTERPRETATION: Low plasma thiamine concentration is prevalent in patients with type 1 and type 2 diabetes, associated with increased thiamine clearance. The conventional assessment of thiamine status was masked by increased thiamine transporter content of erythrocytes.

The disproportionate effect of covid-19 on ethnic minorities in some high income countries throws into sharp relief the effects of racism on health. On almost all health measures, ethnic minority groups, especially black and South Asian people, have the worst outcomes. 1 -6 The covid-19 pandemic is just another example. 7 This is a moral issue that has outraged civilised societies. As Alexandre Dumas wrote: "Moral wounds have this peculiarity-they may be hidden, but they never close; always painful, always ready to bleed when touched, they remain fresh and open in the heart."

To investigate blood-barrier leakage of plasma proteins in acute plaques of multiple sclerosis (MS) the authors used immunocytological methods to examine frozen tissue removed at autopsy from recently active cases. Annular patterns of protein-rich leakage were seen which may help to elucidate the patterns observed using gadolinium-enhanced nuclear magnetic resonance imaging. Vessel wall damage was found in all acute plaques examined and this was associated with the intramural deposition of complement on smooth muscle components and with an infiltration of HLA-DR +ve macrophages. In addition, all acute cases examined had small plaques which contained particulate material within macrophages and astrocytes, on which complement and immunoglobulins colocated. Attempts to find similar material in cases of chronic MS, subacute sclerosing panencephalitis and in perivenous encephalomyelitis were unsuccessful. These results suggest that the inflammatory changes in early MS plaques may have some specificity which could be related to the antigens whose presence is inferred by the colocation of complement and immunoglobulin on material within activated macrophages and astrocytes.

Commercial activity-promoting gaming systems provide a potentially attractive means to facilitate exercise and rehabilitation. The Nintendo Wii, Sony EyeToy, Dance Dance Revolution, and Xbox Kinect are examples of gaming systems that use the movement of the player to control gameplay. Activity-promoting gaming systems can be used as a tool to increase activity levels in otherwise sedentary gamers and also be an effective tool to aid rehabilitation in clinical settings. Therefore, the aim of this current work is to review the growing area of activity-promoting gaming in the context of exercise, injury, and rehabilitation.

BACKGROUND: Acute diverticulitis (AD) presents a unique diagnostic and therapeutic challenge for general surgeons. This collaborative project between EAES and SAGES aimed to summarize recent evidence and draw statements of recommendation to guide our members on comprehensive AD management. METHODS: Systematic reviews of the literature were conducted across six AD topics by an international steering group including experts from both societies. Topics encompassed the epidemiology, diagnosis, management of non-complicated and complicated AD as well as emergency and elective operative AD management. Consensus statements and recommendations were generated, and the quality of the evidence and recommendation strength rated with the GRADE system. Modified Delphi methodology was used to reach consensus among experts prior to surveying the EAES and SAGES membership on the recommendations and likelihood to impact their practice. Results were presented at both EAES and SAGES annual meetings with live re-voting carried out for recommendations with < 70% agreement. RESULTS: A total of 51 consensus statements and 41 recommendations across all six topics were agreed upon by the experts and submitted for members' online voting. Based on 1004 complete surveys and over 300 live votes at the SAGES and EAES Diverticulitis Consensus Conference (DCC), consensus was achieved for 97.6% (40/41) of recommendations with 92% (38/41) agreement on the likelihood that these recommendations would change practice if not already applied. Areas of persistent disagreement included the selective use of imaging to guide AD diagnosis, recommendations against antibiotics in non-complicated AD, and routine colonic evaluation after resolution of non-complicated diverticulitis. CONCLUSION: This joint EAES and SAGES consensus conference updates clinicians on the current evidence and provides a set of recommendations that can guide clinical AD management practice.