Iron Is Critical for Mucosal-Associated Invariant T Cell Metabolism and Effector Functions.

Mucosal-Associated Invariant T (MAIT) cells are a population of innate T cells that play a critical role in host protection against bacterial and viral pathogens. Upon activation, MAIT cells can rapidly respond via both TCR-dependent and -independent mechanisms, resulting in robust cytokine production. The metabolic and nutritional requirements for optimal MAIT cell effector responses are still emerging. Iron is an important micronutrient and is essential for cellular fitness, in particular cellular metabolism. Iron is also critical for many pathogenic microbes, including those that activate MAIT cells. However, iron has not been investigated with respect to MAIT cell metabolic or functional responses. In this study, we show that human MAIT cells require exogenous iron, transported via CD71 for optimal metabolic activity in MAIT cells, including their production of ATP. We demonstrate that restricting iron availability by either chelating environmental iron or blocking CD71 on MAIT cells results in impaired cytokine production and proliferation. These data collectively highlight the importance of a CD71-iron axis for human MAIT cell metabolism and functionality, an axis that may have implications in conditions where iron availability is limited.

Circulating microRNAs can predict chemotherapy-induced toxicities in patients being treated for primary breast cancer.

PURPOSE: Prescribing NAC for breast cancer is a pragmatic treatment strategy for several reasons; however, certain patients suffer chemotherapy-induced toxicities. Unfortunately, identifying patients at risk of toxicity often proves challenging. MiRNAs are small non-coding RNA molecules which modulate genetic expression. The aim of this study was to determine whether circulating miRNAs are sensitive biomarkers that can identify the patients likely to suffer treatment-related toxicities to neoadjuvant chemotherapy (NAC) for primary breast cancer. METHODS: This secondary exploratory from the prospective, multicentre translational research trial (CTRIAL ICORG10/11-NCT01722851) recruited 101 patients treated with NAC for breast cancer, from eight treatment sites across Ireland. A predetermined five miRNAs panel was quantified using RQ-PCR from patient bloods at diagnosis. MiRNA expression was correlated with chemotherapy-induced toxicities. Regression analyses was performed using SPSS v26.0. RESULTS: One hundred and one patients with median age of 55 years were recruited (range: 25-76). The mean tumour size was 36 mm and 60.4% had nodal involvement (n = 61) Overall, 33.7% of patients developed peripheral neuropathies (n = 34), 28.7% developed neutropenia (n = 29), and 5.9% developed anaemia (n = 6). Reduced miR-195 predicted patients likely to develop neutropenia (P = 0.048), while increased miR-10b predicted those likely to develop anaemia (P = 0.049). Increased miR-145 predicted those experiencing nausea and vomiting (P = 0.019), while decreased miR-21 predicted the development of mucositis (P = 0.008). CONCLUSION: This is the first study which illustrates the value of measuring circulatory miRNA to predict patient-specific toxicities to NAC. These results support the ideology that circulatory miRNAs are biomarkers with utility in predicting chemotherapy toxicity as well as treatment response.

Evaluating the Role of Circulating MicroRNAs to Aid Therapeutic Decision Making for Neoadjuvant Chemotherapy in Breast Cancer: A Prospective, Multicenter Clinical Trial.

OBJECTIVE: To evaluate whether circulating micro ribonucleic acids (miRNAs) predict response to neoadjuvant chemotherapy (NAC) and inform decision-making in breast cancer patients. INTRODUCTION: Deciphering response to NAC remains a challenge. Those unlikely to respond may benefit from NAC de-escalation before completion, while "responders" should complete treatment. Establishing biomarkers which identify response to NAC is imperative to personalize treatment strategies. miRNAs are small noncoding RNA molecules which modulate genetic expression. miRNAs are believed to inform response to NAC. METHODS: This prospective, multicenter trial (NCT01722851) recruited 120 patients treated with NAC across 8 Irish treatment sites. Predetermined miRNAs were quantified from patient whole bloods using relative quantification polymerase chain reactiond. Venous sampling was performed at diagnosis and midway during NAC. Trends in miRNA expression between timepoints were correlated with treatment response. Data analysis was performed using R 3.2.3. RESULTS: A total of 120 patients were included (median age: 55 years). Overall, 49.2% had luminal breast cancers (59/120), 17.5% luminal B (L/HER2) (21/120), 12.5% human epidermal growth factor receptor-2 positive (HER2+) (15/120), and 20.8% triple negative disease (25/120). In total, 46.7% of patients responded to NAC (56/125) and 26.7% achieved a pathological complete response (pCR) (32/120). For patients with L/HER2, increased Let-7a predicted response to NAC ( P =0.049), while decreased miR-145 predicted response to NAC in HER2+ ( P =0.033). For patients with luminal breast cancers, reduced Let-7a predicted achieving a pCR ( P =0.037) and reduced miR-145 predicted achieving a pCR to NAC in HER2+ ( P =0.027). CONCLUSIONS: This study illustrates the potential value of circulatory miRNA measurement in predicting response to NAC. Further interrogation of these findings may see miRNAs personalize therapeutic decision-making for patients undergoing NAC for early breast cancer.

Segmental versus extended colectomy for tumours of the transverse colon: a systematic review and meta-analysis.

AIM: There is no consensus on the appropriate extent of oncological resection for tumours of the transverse colon. Concerns regarding tumour factors such as pattern of lymph node spread and technical factors such as anastomotic perfusion lead to a variety of procedures being performed. METHODS: A comprehensive search for published studies examining outcomes following segmental versus extended colectomy for transverse colon tumours was performed adhering to PRISMA (Preferred Reporting Items in Systematic Reviews and Meta-analyses) guidelines. Random effects methods were used to combine data. RESULTS: Seven comparative series examining outcomes in 3395 patients were identified. Segmental colectomy results in shorter operating times (mean difference 15.80 min, 95% CI -20.98 to -10.62, P < 0.001) and less ileus (OR 0.52, 95% CI 0.33-0.81, P = 0.004). There was no difference in length of hospital stay (mean difference 1.53 days, 95% CI -3.79 to 0.73, P = 0.18). Extended colectomy results in a lower rate of anastomotic leak (OR 0.62, 95% CI 0.40-0.97, P = 0.04). There are fewer nodes retrieved in segmental colectomy (mean difference 7.60 nodes, 95% CI -9.60 to -5.61, P < 0.001) but no difference in disease recurrence (OR 0.88, 95% CI 0.59-1.34, P = 0.56) or overall survival (OR 0.98, 95% CI 0.68-1.4, P = 0.9). CONCLUSIONS: Available data are limited due to a lack of randomized controlled trials. However, based on current evidence, segmental resection for transverse colon tumours is associated with less ileus but lower lymph node yields and higher anastomotic leak rates. Length of stay is similar. Oncological outcomes are equivalent.

Prospective study of surgical site infections post-open esophageal cancer surgery, and the impact of care bundles.

SSIs represent common infection-related morbidity following major surgery. Modern care bundles have been established as prophylactic measures aimed at preventing SSI occurring postoperatively. SSI incidence and data on common culprit pathogens post-esophagectomy for cancer have not been previously reported. Patients (2013-2018) treated with curative intent were studied. SSI was defined as per the Center for Disease Control (CDC) definition. A care bundle pathway following the National Institute for Clinical Excellence (NICE) guidelines for prevention of SSIs was introduced in 2013 and was audited quarterly. Risk factors and associations of SSIs were analyzed, as was the prevalence of isolated pathogens. Multivariable logistic regression examined independently predictive factors of SSIs and oncologic outcomes. Of 343 patients, 34 (9.9%) developed a postoperative SSI, with a median (range) of 8 (6-17). Quarterly audit carried out over 6 years showed no significant annual variance or trend. The most prevalent pathogen cultured was Methicillin-sensitive Staphylococcus aureus (MSSA) in nine patients (32%) followed by Candida albicans (29%), Escherichia coli (14%), and Enterococcus faecium (11%). SSI was significantly associated with pneumonia (P = 0.001), respiratory failure (P = 0.014), atrial fibrillation (P = 0.004), anastomotic leak (P < 0.001), and in-hospital blood transfusions (P = 0.031). SSI did not impact the overall survival (P = 0.951). SSI rates can be maintained at less than 10% using strict care bundles and regular audit. The most common culprit pathogen is gram-positive MSSA representing 32% of cases. These data are novel and may represent a modern benchmark for SSI post-open esophagectomy for cancer. This study highlights the incidence and associations of SSI post-esophageal cancer surgery.

False-negative rate of ultrasound-guided fine-needle aspiration cytology for identifying axillary lymph node metastasis in breast cancer patients.

Axillary nodal status remains an important determinant of prognosis and of the therapeutic strategy in patients with a newly diagnosed breast cancer. The aim of this study was to assess the false-negative rate of ultrasound (US)-guided fine-needle aspiration cytology (FNAC) in axillary node staging at breast cancer diagnosis. All patients with a newly diagnosed breast cancer who had an indeterminate or suspicious axillary node sampled with an FNAC between 2007 and 2014 were included in the study. FNAC results were compared to the final histopathological results of surgically removed axillary lymph nodes. Patient demographics, tumor, and nodal characteristics were analyzed. Diagnostic accuracy tests were performed using IBM SPSS, version 22. A total of 3515 patients with breast cancer were identified, 675 of whom had ultrasound-guided FNAC of ipsilateral axillary lymph nodes (mean age: 55 years; Range: 26-84). A benign (C2) result was observed in 52% (n = 351) and a malignant (C5) result in 35% (n = 238). C1 was obtained in 11% (n = 76), C3 in 0.6% (n = 4), and C4 in 0.9% (n = 6). Of the 238 patients with a malignant (C5) FNAC, 99.6% had confirmed axillary lymph node metastatic disease on histopathology. Of the 351 patients with benign FNAC (C2), 31% (n = 108) of patients had a positive lymph node on histology. The false-negative rate of preoperative FNAC remains too high (31%) to omit definitive surgical staging of the axilla. The high diagnostic accuracy when a positive FNAC is obtained allows appropriate tailored decisions regarding definitive therapy.

Can CT-PET and Endoscopic Assessment Post-Neoadjuvant Chemoradiotherapy Predict Residual Disease in Esophageal Cancer?

OBJECTIVE: The aim of this study is to assess CT-PET and endoscopic assessment postneoadjuvant chemoradiotherapy (nCRT) in predicting complete pathologic response (pCR) in locally advanced esophageal cancer (LAEC). DESIGN: A prospective cohort study. BACKGROUND: nCRT is increasingly standard of care in LAEC, with pCR a surrogate for excellent outcome. Predicting pCR before surgery, with metabolic imaging and endoscopy, may spare patients' operative intervention. METHODS: One hundred thirty-eight consecutive patients [mean age 61 ±â€Š8, 99 male (72%), 103 (75%) adenocarcinoma] underwent nCRT with CT-PET and endoscopy 4 to 6 weeks later, and surgery subsequently. A complete metabolic response (cMR) was defined as SUVmax of <4. A complete endoscopic response (cER) was no residual mucosal abnormality. The association of pCR with cMR and cER was analyzed. RESULTS: pCR was achieved in 30 patients (22%); 37% SCC and 17% adenocarcinoma. A cMR was evident in 63 (46%), of whom 17 (27%) had a pCR and 17(27%) were ypN+. A cER was observed in 45 (33%). The Spearman correlation for cER and cMR was 0.066 (P = 0.479), for cER and pCR was 0.004 (P = 0.969), and cMR and pCR -0.120 (P = 0.160). The sensitivity, specificity, positive predictive value, and negative predictive value of cMR was 57%, 57%, 27%, and 82%, respectively, and for combined cMR and cER was 24%, 83%, 28%, and 79%, respectively. CONCLUSIONS: The prediction of pCR through CT-PET and endoscopy independently or combined is limited by low sensitivity and poor positive predictive value. Protocols to avoid surgery in patients with apparent complete clinical complete based on these criteria should be adopted with considerable caution.

Prospective Study of Malabsorption and Malnutrition After Esophageal and Gastric Cancer Surgery.

OBJECTIVE: To study malabsorption and malnutrition after curative resection of esophageal and gastric cancer. DESIGN: Prospective cohort study. BACKGROUND: Improved cure rates for esophageal and gastric cancer have increased focus on health-related quality of life (HR-QL) in survivorship. Although malnutrition is well described in long-term follow-up, and gastrointestinal symptoms are common, data on gut and pancreatic-related malabsorption are scant. METHODS: Disease-free patients at least 18 months after esophageal or gastric oncologic resections represented the study cohort. A modified Gastrointestinal Symptom Rating Scale questionnaire was completed, and weight, fecal elastase (FE), albumin, vitamins, and micronutrients measured preoperatively and at 1, 6, and 18 to 24 months postoperatively. Small intestinal bacterial overgrowth (SIBO) and changes in body composition were also evaluated postoperatively. RESULTS: At a median follow-up of 23 months, 45 of 66 patients in a consecutive series were disease-free. Mean weight (78 ±â€Š19 vs 67 ±â€Š16 kg), body mass index (27 ±â€Š5 vs 24 ±â€Š5 kg/m), Vitamin A (1.7 ±â€Š0.6 vs 1.2 ±â€Š0.4 umol/L), and Vitamin E (28 ±â€Š7 vs 20 ±â€Š7 umol/L) were significantly decreased (P < 0.01) at last follow-up compared with preoperatively. Malabsorption was evident in 73% of patients, of whom 44% had FE < 200 µg/g and 38% had evidence of SIBO. Total body fat-free mass (175 ±â€Š96 vs 84 ±â€Š71, P < 0.001) and skeletal muscle index (44 ±â€Š8 vs 39 ±â€Š8, P = 0.007) were significantly decreased at 18 to 24 months. CONCLUSIONS: Malabsorption and malnutrition are prevalent in survivorship of esophageal and stomach cancer. This may be underappreciated, and both gut and pancreatic insufficiency represent modifiable targets in the interdisciplinary approach to recovery of HR-QL.

Impact of antidepressant use on post-operative weight loss following bariatric surgery.

BACKGROUND: Antidepressant medication can be associated with weight gain. Consideration should be given to the specific agent prescribed to optimize bariatric surgery outcomes. AIM: The aim of this study is to investigate if patients treated with antidepressants stratified by risk of weight gain are associated with less weight loss at 1 year postbariatric surgery. METHOD: A single centre, retrospective analysis of all patients who underwent bariatric surgery between July 2018 and 2021 within St Vincent's University Hospital group. The exposure was antidepressant use, stratified for risk of weight gain, and the control group was patients who underwent surgery but no antidepressant use. The primary outcome was % TWL (total weight loss) at 6 weeks, 6 months and 12 months post-surgery. Multivariate linear regression analysis was used to estimate the impact of antidepressant treatment on post-surgery weight loss at 12 months using the variables of age, gender and pre-operative BMI. RESULTS: Of the total cohort (n = 315), 70 patients (22.2%) were taking antidepressants. At 12 months, post-operatively patients taking medium risk for weight gain antidepressants had significantly less mean %TWL compared to those not taking antidepressants (p = 0.015). Overall, taking any antidepressant was not found to be a significant predictor of %TWL at 12 months after surgery (ß = - 2.590, p = 0.0836). CONCLUSION: Many patients undergoing bariatric surgery have concurrent psychiatric conditions. Given the complex relationship between bariatric surgery and mental health, psychotropic medications may be best managed by a specialist in the field such as a bariatric psychiatrist in order to optimize patient outcomes.

Adolescent bariatric surgery-a survey of referring practitioners.

BACKGROUND: Recent guidelines, supported by large, well-designed studies, suggest that bariatric surgery is a safe and effective treatment for adolescents living with severe obesity to improve health and psychosocial functioning. The aim of this study was to assess the opinions and referral practices of general practitioners (GPs) and paediatricians in Ireland. METHODS: A cross-sectional survey was circulated online to practising paediatricians and GPs. The survey consisted of a short introduction about childhood obesity and 12 questions on adolescent bariatric surgery and obesity medications. RESULTS: There were 45 unique responses to the survey from 22 GPs (48%), 8 paediatricians (17%), and 15 others. Most GPs (72%) would not consider referring an adolescent for bariatric surgery. Paediatricians were significantly more likely to refer (72% vs. 28%, p = 0.034). A minimum BMI of 40 kg/m2 was the most common response, which GPs (45%) and paediatricians (37.5%) suggested should be a pre-requisite for surgery. There was strong support for family psychological assessment and a reported deficit in the community support needed to manage obesity. GPs were more likely than paediatricians to respond that anti-obesity medications should be made available to adolescents, specifically liraglutide (45% vs. 25%), semaglutide (45% vs. 37.5%), and orlistat (22% vs. 0%). DISCUSSION: There is a reluctance among GPs to refer adolescents with severe obesity for consideration of bariatric surgery. Concerns regarding the different obesity treatments held by medical professionals should be addressed through education and engagement and should be fundamental to the development of child and adolescent obesity services.

Evaluating the Impact of Enhanced Recovery After Surgery Protocols on Surgical Outcomes Following Bariatric Surgery-A Systematic Review and Meta-analysis of Randomised Clinical Trials.

BACKGROUND: Enhanced recovery after surgery (ERAS) programmes are evidence-based care improvement processes for surgical patients, which are designed to decrease the impact the anticipated negative physiological cascades following surgery. AIM: To perform a systematic review and meta-analysis of randomised clinical trials (RCTs) to evaluate the impact of ERAS protocols on outcomes following bariatric surgery compared to standard care (SC). METHODS: A systematic review was performed in accordance with PRISMA guidelines. Meta-analysis was performed using Review Manager version 5.4 RESULTS: Six RCTs including 740 patients were included. The mean age was 40.2 years, and mean body mass index was 44.1 kg/m2. Overall, 54.1% underwent Roux-en-Y gastric bypass surgery (400/740) and 45.9% sleeve gastrectomy (340/700). Overall, patients randomised to ERAS programmes had a significant reduction in nausea and vomiting (odds ratio (OR): 0.42, 95% confidence interval (CI): 0.19-0.95, P = 0.040), intraoperative time (mean difference (MD): 5.40, 95% CI: 3.05-7.77, P < 0.001), time to mobilisation (MD: - 7.78, 95% CI: - 5.46 to - 2.10, P < 0.001), intensive care unit stay (ICUS) (MD: 0.70, 95% CI: 0.13-1.27, P = 0.020), total hospital stay (THS) (MD: - 0.42, 95% CI: - 0.69 to - 0.16, P = 0.002), and functional hospital stay (FHS) (MD: - 0.60, 95% CI: - 0.98 to - 0.22, P = 0.002) compared to those who received SC. CONCLUSION: ERAS programmes reduce postoperative nausea and vomiting, intraoperative time, time to mobilisation, ICUS, THS, and FHS compared to those who received SC. Accordingly, ERAS should be implemented, where feasible, for patients indicated to undergo bariatric surgery. Trial registration International Prospective Register of Systematic Reviews (PROSPERO - CRD42023434492.

Impact of Simulation Training on Core Skill Competency of Undergraduate Medical Students.

INTRODUCTION: Simulation based medical training (SBMT) is gaining traction for undergraduate learning and development. We designed, implemented, and independently assessed the impact of an SBMT programme on competency in surgical history taking and clinical examination for senior clinical students. METHODS: With institutional ethical approval and initial pilot study of student volunteers that ensured format appropriateness, we implemented an SBMT programme weekly for ten weeks during the core surgery module of our Medicine degree programme. Groups of 5 students collaboratively undertook an observed focused history and physical examination while simultaneously directing care on a simulated surgical patient (actor) with acute abdominal pain. This was conducted in a nonclinical, standardised, tutor-supervised environment and followed by a group debriefing led by both the simulated patient and tutor discussing student interaction and competency. All students undertook Southampton Medical Assessment Tool (SMAT) on a surgical inpatient prior to (baseline) and within 2 weeks after SBMT. Students without simulation training functioned as a control group and randomized cluster sampling was utilised for group selection. Second assessments were by independent surgical academics blinded to student group. Feedback was collected via anonymous questionnaire from those who undertook SBMT. RESULTS: One hundred students took part, fifty of whom undertook SBMT. Global mean SMAT scores were similar between the control and intervention group at baseline (p > 0.05). Scores on the second assessment were significantly higher (p = 0.0006) for those who had undertaken SBMT vs. controls; 94% of students taking SBMT reported benefit via questionnaire with 85% stating increased confidence in history-taking and 78% reporting improved abdominal examination. CONCLUSIONS: Undergraduate simulation training at scale is feasible and positively impacts undergraduate student core task competency.

Perceived Benefits of Bariatric Surgery: Patient Perspectives.

BACKGROUND: Obesity is a chronic and complex disease characterized by the excessive accumulation of adipose tissue, which has detrimental effects on health. Evaluating the changes in quality of life (QoL) after bariatric surgery complements the medical benefits which are documented by healthcare professionals. PURPOSE: To study the perceived health benefits 1 year after substantial weight loss induced by bariatric surgery. METHODS: This pilot study evaluated patients 1 year after bariatric surgery using 13 questions related to the health domains of the KOSS: airway, body mass, cardiovascular risk, diabetes, economic impact, functional, gonadal impact, health status perceived, image, junction of the gastro-esophagus, kidney, liver, and medication. In addition, the patients were asked to score the most significant benefit as "1," while the least beneficial benefit was scored as "13." RESULTS: One hundred fourteen consecutive patients were evaluated (men = 37 and women = 77). The responses were divided into functional, metabolic, and mental/social benefits. Patients ranked the functional question, "I became more active, and I can do more things" as the most important (average score of 3.7 ± 0.2), followed by a question related to metabolic status: "I am less worried about my risk of heart disease" (4.5 ± 0.3), and then a social/mental question, "My clothes fit better" (5.4 ± 0.3). The three least valuable benefits for the cohort were sexual life improvements (8.9 ± 0.3), heartburn improvements (9.0 ± 0.3), and urinary incontinence improvements (9.8 ± 0.3). CONCLUSIONS: Our observational pilot study demonstrated that patients value functional benefits after substantial weight loss the most, but that metabolic benefits and social/mental health benefits are also considered important.

Ileal pouch anal anastomosis: analysis of outcome and quality of life in 3707 patients.

BACKGROUND: Ileal pouch anal anastomosis (IPAA) is the treatment of choice for chronic, medically refractory mucosal ulcerative colitis, indeterminate colitis, familial adenomatous polyposis (FAP), and a select group of patients with Crohn's disease. AIM: : We report outcomes, complications, and quality of life (QOL) in a cohort of 3707 patients treated at our institution from January 1984 to March 2010. METHODS: Data were collected from a prospectively maintained database and chart review of 3707 consecutive primary IPAA cases. Patient demographics, postoperative complications, functional outcomes, and QOL data were available. Follow-up consisted of clinical examination with assessment of pouch function and QOL. RESULTS: A total of 3707 patients underwent primary pouch and 328 underwent redo pouch surgery. Postoperative histopathological diagnoses were mucosal ulcerative colitis (n = 2953, 79.7%), indeterminate colitis (n = 63, 1.7%), FAP (n = 223, 6%), Crohn's disease (n = 150, 4%), cancer/dysplasia (n = 97, 2.6%), and others (n = 221, 6.0%). Early perioperative complications were encountered in 33.5% of patients with a mortality rate of 0.1%. Excluding pouchitis, late complications were experienced by 29.1% of patients. Of those patients who had IPAA at our institution, pouch failure occurred in 197 patients (5.3%). During a median follow-up of 84 months, 119 patients (3.2%) required excision of the pouch, 32 (0.8%) had a nonfunctioning pouch, and 46 patients (1.2%) had redo IPAA. Functional outcomes and QOL were good or excellent in 95% of patients and similar in each histopathological subgroup. CONCLUSIONS: IPAA is an excellent option for patients with MUC, IC, FAP, and select patients with Crohn's disease.

Obesity and outcomes in trauma - a systematic review and meta-analysis.

BACKGROUND: The physiological abnormalities relating to obesity and metabolic syndrome can contribute to worse outcomes following trauma especially in class 2 and 3 obesity. The aim of this systematic review was to determine whether patients with a higher class of obesity who suffer traumatic injury have a higher risk of worse outcomes including in-hospital mortality than normal-weight patients. METHODS: A systematic search of MEDLINE, EMBASE, CENTRAL, Web of Science and CINAHL was performed for studies that reported a comparison of in-hospital obesity-related outcomes against normal-weight individuals aged 15 years and older following trauma. Single or multiple injuries from either blunt and/or penetrating trauma were included. Burn-related injuries, isolated head injury and studies focusing on orthopaedic related perioperative complications were excluded. RESULTS: The search yielded 7405 articles; 26 were included in this systematic review. 945,511 patients had a BMI>30. A random-effects meta-analysis was performed for analysis of all four outcomes. Patients with class 3 obesity (BMI>40) have significantly higher odds of in-hospital mortality than normal-BMI individuals following blunt and penetrating trauma (OR, 1.75; 95% CI, 1.39-2.19, p=<0.00001), significantly longer hospital LOS (SMD, 0.23; 95% CI, 0.21-0.25; p<0.00001) and significantly longer ICU LOS (SMD, 0.19; 95% CI, 0.12-0.26; p<0.0001). In contrast, studies that examined blunt and penetrating trauma and classified obesity with a threshold of BMI>30 found no significant difference in the odds of in-hospital mortality (OR, 0.94; 95% CI, 0.86-1.02, p=0.13). CONCLUSIONS: There is a higher risk of in-hospital mortality in patients living with class 3 obesity following trauma when compared with individuals with normal BMI. The management of patients with obesity is complex and trauma systems should develop specific weight related pathways to manage and anticipate the complications that arise in these patients. Systematic review registration number PROSPERO registration: CRD42021234482 Level of Evidence: Level 3.

The Impact of Bariatric Surgery on the Incidence of Colorectal Cancer in Patients with Obesity-a Systematic Review and Meta-analysis of Registry Data.

PURPOSE: Cancer and obesity represent two of the most significant global health concerns. The risk of malignancy, including colorectal cancer (CRC), increases with obesity. The aim of this study was to perform a systematic review and meta-analysis to determine the value of bariatric surgery in reducing CRC risk in patients with obesity using registry data. MATERIALS AND METHODS: A systematic review and meta-analysis were performed as per PRISMA guidelines. The risk of CRC was expressed as a dichotomous variable and reported as odds ratios (OR) with 95% confidence intervals (CIs) using the Mantel-Haenszel method. A multi-treatment comparison was performed, examining the risk reduction associated with existing bariatric surgery techniques. Analysis was performed using RevMan, R packages, and Shiny. RESULTS: Data from 11 registries including 6,214,682 patients with obesity were analyzed. Of these, 14.0% underwent bariatric surgery (872,499/6,214,682), and 86.0% did not undergo surgery (5,432,183/6,214,682). The mean age was 49.8 years, and mean follow-up was 5.1 years. In total, 0.6% of patients who underwent bariatric surgery developed CRC (4,843/872,499), as did 1.0% of unoperated patients with obesity (54,721/5,432,183). Patients with obesity who underwent bariatric surgery were less likely to develop CRC (OR: 0.53, 95% CI: 0.36-0.77, P < 0.001, I2 = 99%). Patients with obesity undergoing gastric bypass surgery (GB) (OR: 0.513, 95% CI: 0.336-0.818) and sleeve gastrectomy (SG) (OR: 0.484, 95% CI: 0.307-0.763) were less likely to develop CRC than unoperated patients. CONCLUSION: At a population level, bariatric surgery is associated with reduced CRC risk in patients with obesity. GB and SG are associated with the most significant reduction in CRC risk. PROSPERO REGISTRATION: CRD42022313280.

Implementation of an on-site simulation programme during COVID-19 and the assessment of its impact on medical students' competence.

BACKGROUND: COVID-19 has greatly impacted medical students' clinical education. This study evaluates the usefulness of a rapidly implemented on-site simulation programme deployed to supplement our disrupted curriculum. METHODS: Students on surgical rotations received 4-hour tutor-led simulated patient sessions (involving mannikins with remote audio-visual observation) respecting hospital and public health protocols. Attitudes were questionnaire-assessed before and after. Independent, blinded, nonacademic clinicians scored students' clinical competencies by observing real patient interactions using the surgical ward assessment tool in a representative sample versus those completing same duration medicine clinical rotations without simulation (Mann-Whitney U testing, p < 0.05 denoting significance) with all students receiving the same surgical e-learning resources and didactic teaching. RESULTS: A total of 220 students underwent simulation training, comprising 96 hours of scheduled direct teaching. Prior to commencement, 15 students (7% of 191 completing the survey) admitted anxiety, mainly due to clinical inexperience, with only two (1%) anxious re on-site spreading/contracting of COVID-19. A total of 66 students (30%, 38 females and 29 graduate entrants) underwent formal competency assessment by clinicians from ten specialties at two clinical sites. Those who received simulation training (n = 35) were judged significantly better at history taking (p = 0.004) and test ordering (p = 0.01) but not clinical examination, patient drug chart assessment, or differential diagnosis formulation. Of 75 students providing subsequent feedback, 88% stated simulation beneficial (notably for history taking and physical examination skills in 63%) with 83% advocating for more. CONCLUSION: Our rapidly implemented simulation programme for undergraduate medical students helped mitigate pandemic restrictions, enabling improved competence despite necessarily reduced clinical activity encouraging further development.

Evaluating the Role of Circulating MicroRNAs in Predicting Long-Term Survival Outcomes in Breast Cancer: A Prospective, Multicenter Clinical Trial.

BACKGROUND: While long-term outcomes have improved for patients with breast cancer, 20% to 30% will still develop recurrence, and identifying these patients remains a challenge. MicroRNAs (miRNAs) are small, noncoding molecules that modulate genetic expression and affect oncogenesis. STUDY DESIGN: This prospective, multicenter trial (ICORG10/11-NCT01722851) recruited patients undergoing neoadjuvant chemotherapy across 8 Irish centers. Predetermined miRNAs were quantified from patient whole blood using quantitative reverse transcriptase polymerase chain reaction. Venous sampling was performed at diagnosis (timepoint 1) and midway during neoadjuvant chemotherapy (timepoint 2 [T2]). miRNA expression profiles were correlated with recurrence-free survival (RFS), disease-free survival (DFS), and overall survival. Data analysis was performed using R v3.2.3. RESULTS: A total of 124 patients were recruited with a median age of 55.0 years. The median follow-up was 103.1 months. Increased miR-145 expression at T2 was associated with improved RFS (hazard ratio 0.00; 95% confidence interval [CI] 0.00 to 0.99; p = 0.050). Using survival regression tree analysis, a relative cutoff of increased miR-145 expression greater than 0.222 was associated with improved RFS (p = 0.041). Increased miR-145 expression at T2 trended towards significance in predicting improved DFS (hazard ratio 0.00; 95% CI 0.00 to 1.42; p = 0.067). Using survival regression tree analysis, a relative cutoff of increased miR-145 expression greater than 0.222 was associated with improved DFS (p = 0.012). No miRNAs correlated with overall survival. CONCLUSIONS: ICORG10/11 is the first Irish multicenter, translational research trial evaluating circulatory miRNAs as biomarkers predictive of long-term survival and correlated increased miR-145 expression with enhanced outcomes in early-stage breast cancer. Validation of these findings is required in the next generation of translational research trials.

The effects of normalizing hyperhomocysteinemia on clinical and operative outcomes in patients with critical limb ischemia.

PURPOSE: To assess the outcome of patients with medically treated hyperhomocysteinemia (HHC) requiring intervention for critical limb ischemia (CLI). METHODS: A parallel observational study was conducted to compare the clinical and revascularization outcomes of CLI patients who received standardized treatment for HHC preoperatively (folic acid and vitamin B12) vs. contemporaneous patients with normal homocysteine levels. The threshold for HHC diagnosis was 13.0 µmol/L. From 2009 to 2011, 169 patients underwent revascularization procedures for CLI. Of these, all 66 patients (40 men; mean age 69.6 ± 11.2 years) with HHC (mean 17.3 µmol/L, range 13.5-34.9) were treated to normalize the homocysteine level prior to lower limb revascularization. The remaining 103 patients (58 men; mean age 72.7±8.1 years) had normal homocysteine levels (8.2 µmol/L, range 5-12.3) before revascularization. The primary endpoint was symptomatic and hemodynamic improvement in the treated HHC group. The secondary endpoints were all-cause survival, binary restenosis, reintervention, amputation-free survival, and major adverse events. The treated HHC cohort was compared to an age/sex-matched historical group of patients with untreated HHC from 2002 to 2006 before HHC pretreatment became routine. All interventions (endovascular, hybrid, and open) were performed by the same surgeon, and the groups were evenly matched. RESULTS: Patients with HHC were treated for a mean 12.2 days, which significantly reduced their mean homocysteine level after 3 weeks to 10.1 µmol/L (range 6.2-14.4, p<0.05). After revascularization, immediate clinical improvement was similar between normal homocysteine and medically corrected HHC groups. There was no significant difference in time to binary restenosis (p=0.822). Secondary endpoints and all-cause mortality were similar. Multivariate logistic regression showed that untreated HHC was a significant factor for graft occlusion and limb loss (p<0.0001), but medically corrected HHC was no longer predictive of adverse operative outcome. CONCLUSION: Patients with medically corrected HHC have similar outcomes compared to those with normal homocysteine levels. Thus, aggressively treating HHC with folic acid and vitamin B12 may help enhance the clinical outcome of CLI patients undergoing revascularization.