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Eduardo Sepúlveda,1,2 Rui Poínhos,2,3 Miguel Constante,4,5 José Pais-Ribeiro,1,2 Paula Freitas,6–8 Davide Carvalho6–8 1Faculty of Psychology and Educational Sciences, University of Porto, Porto, Portugal; 2Associação de Prevenção e Apoio à Diabetes, Porto, Portugal; 3Faculty of Nutrition and Food Sciences, University of Porto, Porto, Portugal; 4Institute of Psychiatry, King's College London, London, UK; 5Department of Psychiatry, Hospital Beatriz Ângelo, Loures, Portugal; 6Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar São João, Porto, Portugal; 7Faculty of Medicine, University of Porto, Porto, Portugal; 8Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal Background: The aim of this study was to assess the relationship between health-related quality of life (HRQoL) and the presence or absence of hypertension and diabetes-related chronic complications in type 2 diabetes, and also the association between HRQoL and the number of chronic complications. Methods: One hundred patients with type 2 diabetes were interviewed. HRQoL was evaluated using the age-adjusted Short-Form 36 dimensions (physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health). Results: The mean age of the study population was 62.7±8.7 years; 54.0% were male, and 51.0% were receiving only oral hypoglycemic agents. Chronic complications were related to worse HRQoL in different dimensions: peripheral neuropathy and cardiovascular disease (all, except bodily pain), retinopathy (physical functioning, general health, vitality, and mental health), peripheral arterial disease (physical functioning, role-physical, and general health), and nephropathy (general health and vitality). Hypertension was related to worse general health and vitality. An increased number of chronic complications was associated with worse HRQoL in all dimensions of Short-Form 36 except for the bodily pain dimension. Conclusion: The presence and increased number of diabetes-related chronic complications, and the presence of hypertension were related to worse age-adjusted HRQoL. Peripheral neuropathy and cardiovascular disease were more strongly related to age-adjusted HRQoL. Keywords: retinopathy, nephropathy, peripheral neuropathy, cardiovascular disease, peripheral arterial disease

Eduardo Sepúlveda,1,2 Rui Poínhos,2,3 Miguel Constante,4,5 José Pais-Ribeiro,1,2 Paula Freitas,6,7 Davide Carvalho6,71Faculty of Psychology and Educational Sciences, University of Porto, Porto, Portugal; 2Associação de Prevenção e Apoio à Diabetes, Porto, Portugal; 3Faculty of Nutrition and Food Sciences, University of Porto, Porto, Portugal; 4Institute of Psychiatry, King’s College London, London, UK; 5Department of Psychiatry, Hospital Beatriz Ângelo, Loures, Portugal; 6Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar São João, Porto, Portugal; 7Faculty of Medicine, University of Porto, Porto, PortugalBackground: Diabetes mellitus is a chronic metabolic disease, the prevalence of which has registered a considerable increase, mainly in adults and elderly. The purpose of this study was to assess the relationship between health-related quality of life in patients with diabetes and sex, body mass index, type of diabetes and treatment regimens (type 1 diabetes: intensive versus conventional treatment; type 2 diabetes: insulin use versus non-insulin use), and duration of diabetes.Methods: One hundred and twenty-four patients with diabetes were interviewed. Health-related quality of life was evaluated using the age-adjusted Short-Form 36 dimensions (physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health), and related to demographic and clinical variables. Independent samples t-tests and One-Way Analysis of Variance were used to compare means of independent samples. The degree of association between pairs of variables was measured by Pearson’s (r) or Spearman’s (rs) correlation coefficients.Results: The mean age of the study population was 55.7±16.4 years; 54.8% were male, and 77.4% had type 2 diabetes. Females reported worse quality of life than males in all dimensions of the Short-Form 36, except for role-physical and bodily pain. Obese patients had worse physical functioning than normal weight and overweight patients, and worse vitality than their normal weight counterparts. Type 2 diabetic patients taking insulin had lower physical functioning and vitality than those without insulin therapy. Longer duration of diabetes was associated with lower physical functioning, role-physical, general health, vitality, role-emotional, and mental health.Conclusion: Being female, obese, having type 2 diabetes and taking insulin, and having a longer disease duration are characteristics associated with worse age-adjusted quality of life in patients with diabetes.Keywords: clinical variables, demographic variables, diabetes mellitus, health-related quality of life

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Background & Aims: Intestinal epithelial cell (IEC) damage is a hallmark of celiac disease (CeD); however, its role in gluten-dependent T-cell activation is unknown. We investigated IEC-gluten-T-cell interactions in organoid monolayers expressing human major histocompatibility complex class II (HLA-DQ2.5), which facilitates gluten antigen recognition by CD4 + T cells in CeD., Methods: Epithelial major histocompatibility complex class II (MHCII) was determined in active and treated CeD, and in nonimmunized and gluten-immunized DR3-DQ2.5 transgenic mice, lacking mouse MHCII molecules. Organoid monolayers from DR3-DQ2.5 mice were treated with or without interferon (IFN)-γ, and MHCII expression was evaluated by flow cytometry. Organoid monolayers and CD4 + T-cell co-cultures were incubated with gluten, predigested, or not by elastase-producing Pseudomonas aeruginosa or its lasB mutant. T-cell function was assessed based on proliferation, expression of activation markers, and cytokine release in the co-culture supernatants., Results: Patients with active CeD and gluten-immunized DR3-DQ2.5 mice demonstrated epithelial MHCII expression. Organoid monolayers derived from gluten-immunized DR3-DQ2.5 mice expressed MHCII, which was upregulated by IFN-γ. In organoid monolayer T-cell co-cultures, gluten increased the proliferation of CD4 + T cells, expression of T-cell activation markers, and the release of interleukin-2, IFN-γ, and interleukin-15 in co-culture supernatants. Gluten metabolized by P aeruginosa, but not the lasB mutant, enhanced CD4 + T-cell proliferation and activation., Conclusions: Gluten antigens are efficiently presented by MHCII-expressing IECs, resulting in the activation of gluten-specific CD4 + T cells, which is enhanced by gluten predigestion with microbial elastase. Therapeutics directed at IECs may offer a novel approach for modulating both adaptive and innate immunity in patients with CeD., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Tryptophan is an essential amino acid transformed by host and gut microbial enzymes into metabolites that regulate mucosal homeostasis through aryl hydrocarbon receptor (AhR) activation. Alteration of tryptophan metabolism has been associated with chronic inflammation; however, whether tryptophan supplementation affects the metabolite repertoire and AhR activation under physiological conditions in humans is unknown. We performed a randomized, double blind, placebo-controlled, crossover study in 20 healthy volunteers. Subjects on a low tryptophan background diet were randomly assigned to a 3-wk l-tryptophan supplementation (3 g/day) or placebo, and after a 2-wk washout switched to opposite interventions. We assessed gastrointestinal and psychological symptoms by validated questionnaires, AhR activation by cell reporter assay, tryptophan metabolites by liquid chromatography and high-resolution mass spectrometry, cytokine production in isolated monocytes by ELISA, and microbiota profile by 16S rRNA Illumina technique. Oral tryptophan supplementation was well tolerated, with no changes in gastrointestinal or psychological scores. Compared with placebo, tryptophan increased AhR activation capacity by duodenal contents, but not by feces. This was paralleled by higher urinary and plasma kynurenine metabolites and indoles. Tryptophan had a modest impact on fecal microbiome profiles and no significant effect on cytokine production. At the doses used in this study, oral tryptophan supplementation in humans induces microbial indole and host kynurenine metabolic pathways in the small intestine, known to be immunomodulatory. The results should prompt tryptophan intervention strategies in inflammatory conditions of the small intestine where the AhR pathway is impaired. NEW & NOTEWORTHY We demonstrate that in healthy subjects, orally administered tryptophan activates microbial indole and host kynurenine pathways in the small intestine, the primary metabolic site for dietary components, and the richest source of immune cells along the gut. This study provides novel insights in how to optimally activate immunomodulatory AhR pathways and indole metabolism in the small intestine, serving as basis for future therapeutic trials using l-tryptophan supplementation in chronic inflammatory conditions affecting the small intestine.

Background: Mesh repair in incarcerated or strangulated groin hernia is controversial, especially when bowel resection is required. We aimed to perform a meta-analysis comparing mesh and non-mesh repair in patients undergoing emergency groin hernia repair., Methods: We performed a literature search of databases to identify studies comparing mesh and primary suture repair of patients with incarcerated or strangulated inguinal or femoral hernias who underwent emergency surgery. Postoperative outcomes were assessed by pooled analysis and meta-analysis. Statistical analysis was performed using RevMan 5.4. Heterogeneity was assessed with I 2 statistics., Results: 1095 studies were screened and 101 were thoroughly reviewed. Twenty observational studies and four randomized controlled trials comprising 12,402 patients were included. We found that mesh-based repair had reduced recurrence (OR 0.36; 95% CI 0.19, 0.67; P = 0.001; I 2  = 35%), length of hospital stay (OR - 1.02; 95% CI - 1.87, - 0.17; P = 0.02; I 2  = 94%) and operative time (OR - 9.21; 95% CI - 16.82, - 1.61; P = 0.02; I 2  = 95%) without increasing surgical site infection, mortality or postoperative complications such as seroma, chronic, ileus or urinary retention. In the subgroup analysis of patients that underwent bowel resection, we found that mesh repair was associated with an increased risk of surgical site infection (OR 1.74; 95% CI 1.04, 2.91; P = 0.04; I 2  = 9%)., Conclusions: Mesh repair for incarcerated and strangulated groin hernias reduces recurrence without an increase in postoperative complications and should be considered in clean cases. However, in the setting of bowel resection, mesh repair might increase the incidence of surgical site infection., (© 2023. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

Background: Obesity is associated with an increased risk of ventral hernia development and recurrence rates after ventral hernia repair (VHR). The metabolic derangements caused by obesity can also lead to many postoperative complications. Therefore, it is a common practice to attempt weight loss before VHR. However, there is still no consensus on optimal preoperative management for obese patients with a ventral hernia. This study aims to perform a meta-analysis to evaluate the effect of preoperative weight optimization on VHR outcomes., Methods: We performed a literature search of PubMed, Scopus, and Cochrane Library databases to identify studies comparing obese patients who underwent surgical or non-surgical weight loss interventions before undergoing hernia repair surgery to obese patients who underwent hernia repair surgery without prehabilitation. Postoperative outcomes were assessed by means of pooled analysis and meta-analysis. Statistical analysis was performed using RevMan 5.4. Heterogeneity was assessed with I 2 statistics., Results: One thousand six hundred nine studies were screened and 13 were thoroughly reviewed. Five studies comprising 465 patients undergoing hernia repair surgery were included. No differences in hernia recurrence [odds ratio (OR) 0.66; 95% CI 0.23-1.89; P =0.44; I 2 =20%], seroma (OR 0.70; 95% CI 0.25-1.95; P =0.50; I 2 =5%), hematoma (OR 2.00; 95% CI 0.5-7.94; P =0.45; I 2 =0%), surgical site infection (OR 1.96; 95% CI 0.52-7.40; P =0.32; I 2 =0%), and overall complication (OR 0.80; 95% CI 0.37-1.74; P =0.58; I 2 =40%) rates were noted when comparing patients who underwent a preoperative weight loss intervention (prehabilitation or bariatric surgery) versus those who did not. In the subgroup analysis of patients who underwent bariatric surgery, we found no difference in hernia recurrence (OR 0.64; 95% CI 0.12-3.33; P = 0.59; I 2 =41%) or overall complications (OR 1.14; 95% CI 0.36-3.64; P =0.82; I 2 =64%). In the subgroup analysis of patients who lost weight versus patients who did not, there was no significant difference in overall complication rates (OR 0.86; 95% CI 0.34-2.21; P =0.76; I 2 =55%)., Conclusions: We found similar hernia recurrence, seroma, hematoma, and surgical site infection rates in patients who underwent preoperative optimization. These findings underline the need for prospective studies to define the optimal role of preoperative optimization and weight loss in obese patients undergoing ventral hernia repair., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)