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.

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.

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.

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.

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.

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.

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.

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.

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.

Obesity in Adults: A 2022 Adapted Clinical Practice Guideline for Ireland.

BACKGROUND: This Clinical Practice Guideline (CPG) for the management of obesity in adults in Ireland, adapted from the Canadian CPG, defines obesity as a complex chronic disease characterised by excess or dysfunctional adiposity that impairs health. The guideline reflects substantial advances in the understanding of the determinants, pathophysiology, assessment, and treatment of obesity. SUMMARY: It shifts the focus of obesity management toward improving patient-centred health outcomes, functional outcomes, and social and economic participation, rather than weight loss alone. It gives recommendations for care that are underpinned by evidence-based principles of chronic disease management; validate patients' lived experiences; move beyond simplistic approaches of "eat less, move more" and address the root drivers of obesity. KEY MESSAGES: People living with obesity face substantial bias and stigma, which contribute to increased morbidity and mortality independent of body weight. Education is needed for all healthcare professionals in Ireland to address the gap in skills, increase knowledge of evidence-based practice, and eliminate bias and stigma in healthcare settings. We call for people living with obesity in Ireland to have access to evidence-informed care, including medical, medical nutrition therapy, physical activity and physical rehabilitation interventions, psychological interventions, pharmacotherapy, and bariatric surgery. This can be best achieved by resourcing and fully implementing the Model of Care for the Management of Adult Overweight and Obesity. To address health inequalities, we also call for the inclusion of obesity in the Structured Chronic Disease Management Programme and for pharmacotherapy reimbursement, to ensure equal access to treatment based on health-need rather than ability to pay.

Medication following bariatric surgery for type 2 diabetes mellitus (BY-PLUS) study: rationale and design of a randomised controlled study.

INTRODUCTION: Bariatric surgery is an effective method of controlling glycaemia in patients with type 2 diabetes mellitus (T2DM) and obesity. Long-term studies suggest that although glycaemic control remains good, only 20%-40% of patients will maintain remission according to the American Diabetes Association criteria. PURPOSE: This trial aims to examine the safety and efficacy of combining Roux-en-Y gastric bypass or sleeve gastrectomy with goal-directed medical therapy to improve long-term glycaemic control of T2DM. METHODS AND ANALYSIS: This prospective, open-label multicentre randomised controlled trial (RCT) will recruit 150 patients with obesity and T2DM from tertiary care obesity centres. Patients will be randomised 1:1 to receive either bariatric surgery and standard medical care or bariatric surgery and intensive goal-directed medical therapy, titrated to specific targets for glycated haemoglobin (HbA1c), blood pressure (BP) and low-density lipoproteins (LDL) cholesterol. The primary endpoints are the proportion of patients in each arm with an HbA1c<6.5% (48 mmol/mol) at 1 year and the proportion of patients in each arm achieving the composite endpoint of HbA1c<6.5% (48 mmol/mol), BP<130/80 mm Hg and LDL<2.6 mmol/L at 5 years. ETHICS AND DISSEMINATION: The local institutional review board approved this study. This study represents the first RCT to examine the safety and efficacy of combining bariatric surgery with intensive medical therapy compared with bariatric surgery and usual care for long-term diabetes control. TRIAL REGISTRATION NUMBER: NCT04432025.

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.

The Relationship Between Percentage Weight Loss and World Health Organization-Five Wellbeing Index (WHO-5) in Patients Having Bariatric Surgery.

PURPOSE: The association between bariatric surgery outcome and depression remains controversial. Many patients with depression are not offered bariatric surgery due to concerns that they may have suboptimal outcomes. The aim of this study was to investigate the relationship between baseline World Health Organization-Five Wellbeing Index (WHO-5) and percentage total weight loss (%TWL) in patients after bariatric surgery. MATERIALS AND METHODS: All patients were routinely reviewed by the psychologist and screened with WHO-5. The consultation occurred 3.5 ± 1.6 months before bariatric surgery. Body weight was recorded before and 1 year after surgery. A total of 45 out of 71 (63.3%) patients with complete WHO-5 data were included in the study. Data analysis was carried out with IBM SPSS Statistics (version 27) to determine the correlation between baseline WHO-5 and %TWL in patients having bariatric surgery. RESULTS: Overall, 11 males and 34 females were involved with mean age of 47.5 ± 11.5 and BMI of 46.2 ± 5.5 kg/m2. The %TWL between pre- and 1-year post-surgery was 30.0 ± 8.3% and the WHO-5 Wellbeing Index mean score was 56.5 ± 16.8. We found no correlation between %TWL and the WHO-5 Wellbeing Index (r = 0.032, p = 0.83). CONCLUSION: There was no correlation between the baseline WHO-5 Wellbeing Index and %TWL 1-year post-bariatric surgery. Patients with low mood or depression need to be assessed and offered appropriate treatment but should not be excluded from bariatric surgery only based on their mood.

Innate PD-L1 limits T cell-mediated adipose tissue inflammation and ameliorates diet-induced obesity.

Obesity has become a major health problem in the industrialized world. Immune regulation plays an important role in adipose tissue homeostasis; however, the initial events that shift the balance from a noninflammatory homeostatic environment toward inflammation leading to obesity are poorly understood. Here, we report a role for the costimulatory molecule programmed death-ligand 1 (PD-L1) in the limitation of diet-induced obesity. Functional ablation of PD-L1 on dendritic cells (DCs) using conditional knockout mice increased weight gain and metabolic syndrome during diet-induced obesity, whereas PD-L1 expression on type 2 innate lymphoid cells (ILC2s), T cells, and macrophages was dispensable for obesity control. Using in vitro cocultures, DCs interacted with T cells and ILC2s via the PD-L1:PD-1 axis to inhibit T helper type 1 proliferation and promote type 2 polarization, respectively. A role for PD-L1 in adipose tissue regulation was also shown in humans, with a positive correlation between PD-L1 expression in visceral fat of people with obesity and elevated body weight. Thus, we define a mechanism of adipose tissue homeostasis controlled by the expression of PD-L1 by DCs, which may be a clinically relevant finding with regard to immune-related adverse events during immune checkpoint inhibitor therapy.

Suppressive effects of the obese tumor microenvironment on CD8 T cell infiltration and effector function.

Obesity is one of the leading preventable causes of cancer; however, little is known about the effects of obesity on anti-tumor immunity. Here, we investigated the effects of obesity on CD8 T cells in mouse models and patients with endometrial cancer. Our findings revealed that CD8 T cell infiltration is suppressed in obesity, which was associated with a decrease in chemokine production. Tumor-resident CD8 T cells were also functionally suppressed in obese mice, which was associated with a suppression of amino acid metabolism. Similarly, we found that a high BMI negatively correlated with CD8 infiltration in human endometrial cancer and that weight loss was associated with a complete pathological response in six of nine patients. Moreover, immunotherapy using anti-PD-1 led to tumor rejection in lean and obese mice and partially restored CD8 metabolism and anti-tumor immunity. These findings highlight the suppressive effects of obesity on CD8 T cell anti-tumor immunity, which can partially be reversed by weight loss and/or immunotherapy.

The impact of ursodeoxycholic acid on gallstone disease after bariatric surgery: a meta-analysis of randomized control trials.

BACKGROUND: Ursodeoxycholic acid (UDCA) is a bile acid that has been shown to reduce the formation of gallstones after significant weight loss. OBJECTIVE: This study aimed to evaluate the impact of UDCA on the incidence of gallstones after bariatric surgery. SETTINGS: An electronic search of PubMed (Medline), Cochrane Central Register of Controlled Studies (CENTRAL), Scopus (Elsevier) databases, EMBASE, CINAHL, Clinicaltrials.gov, and Web of Science. METHODS: A meta-analysis of randomized control trials was performed. The primary outcome was the incidence of gallstones after bariatric surgery. Secondary outcomes included type of operation and time interval to and characteristics associated with gallstone formation. RESULTS: Ten randomized control trials including 2583 patients were included, 1772 patients (68.6%) receiving UDCA and 811 (31.4%) receiving placebo. There was a significant reduction in gallstone formation in patients who received UDCA postoperatively (risk ratio [RR] .36, 95% confidence interval [CI] .22-.41, P < .00001). The overall prevalence of gallstone formation was 24.7% in the control group compared to 7.3% in the UDCA group. A dose of ≤600 mg/day had a significantly reduced risk of gallstone formation compared to the placebo group (risk ratio .35; 95% CI .24-.53; P < .001). The risk reduction was not significant for the higher dose (>600 mg/day) group (risk ratio .30; 95% CI, .09-1.01, P = .05). CONCLUSIONS: UDCA significantly reduces the risk of both asymptomatic and symptomatic gallstones after bariatric surgery. A dose of 600 mg/day is associated with improved compliance and better outcomes regardless of type of surgery. UDCA should be considered part of a standard postoperative care bundle after bariatric surgery.

Assessment of baseline rates of functional and absolute iron deficiency in bariatric surgery candidates: a retrospective study.

BACKGROUND: Preoperative optimization of iron status is a priority in candidates for bariatric surgery. Inflammation is strongly associated with obesity, and as a consequence, functional iron deficiency (ID) is potentially an underreported issue in surgical candidates. OBJECTIVES: In light of updated practice guidelines, to retrospectively review preoperative iron status in an Irish cohort of bariatric surgery candidates, taking account of the relative incidence rate of functional ID. SETTING: A tertiary care obesity service with bariatric surgery referral in Ireland. METHODS: Baseline nutritional biochemistry records were reviewed between February 2017 and February 2020 in a hospital, Dublin, Ireland. Absolute ID was defined as serum ferritin <30 µg/L; functional ID was defined as ferritin, 30 to 100 µg/L, in the presence of C-reactive protein >5 mg/L. Anemia was indexed with reference to hemoglobin and qualified by vitamin B12 and folate status to rule out anemia unrelated to primary ID. RESULTS: The analysis included 120 patients, 68% female, 49.6 ± 9.3 years, and body mass index, 52.0 ± 9.6 kg/m2. The prevalence of absolute and functional ID was 11.7% and 30.8%, respectively (P = .0003). Anemia was associated with absolute ID and functional ID in 14.3% and 10.8% of patients (P = .29). Folate and vitamin B12 deficiency occurred in <5% of patients. CONCLUSION: In patients seeking bariatric surgery for severe obesity, the prevalence of baseline functional ID is substantial and can be associated with anemia. These findings raise queries with regard to how best to optimize preoperative iron status in the context of ongoing inflammation.