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BackgroundThe objective of this study was to evaluate Dietary Inflammatory Index (DII®) in the preoperative period as well as 3 and 12 months post-surgery and its association with cardiometabolic risk factors after RYGB.Materials and MethodsThis is a prospective cohort study of 50 patients (both sexes) who underwent RYGB. All data were collected in 3 phases: before surgery, 3, and 12 months post-surgery. To calculate DII scores, we utilized mean nutrients from three 24-h recalls at each time point.ResultsThe patients had median age of 39.1 ± 7.9 years (70% women). Mean preoperative DII® score of 0.39 ± 1.49 was slightly pro-inflammatory. Mean DII score reduced to − 1.52 ± 1.27 after 3 months post-surgery and was classified anti-inflammatory. This value rebounded to − 0.88 ± 1.49 at 12 months but was still anti-inflammatory. From the adjusted linear regression analysis, we observed that preoperative DII score was statistically associated with variations in neck circumference (β = − 0.50; p = 0.03), waist-hip ratio (β = 0.01; p = 0.02), total cholesterol (β = 6.47; p = 0.002), and LDL cholesterol (β = 6.42; p = 0.001) after 12 months post-surgery. Changes in DII® at 3 and 12 months were not associated with changes in cardiometabolic risk factors.ConclusionWe observe significant changes in the inflammation potential of diet after 3 and 12 months of RYGB. Patients with higher preoperative E-DII scores have a greater metabolic improvement after 12 months of surgery.

Background The aim of this study was to evaluate evolution of ultra-processed food intake and recurrent weight gain in patients who underwent Roux-en-Y gastric bypass. Materials and Methods This study is an observational longitudinal study that evaluated patients who underwent metabolic and bariatric surgery at four time points: before surgery and at 3, 12, and 60 months after surgery. Anthropometric and dietary intake data were collected through two 24-h dietary recalls. All foods consumed were classified according to degree of processing. Recurrent weight gain was considered the difference between current weight and nadir weight. Results The sample consisted of 58 patients with a mean age of 38.7 ± 8.9 years and 68% female. After 60 months, mean excess weight loss and recurrent weight gain were 73.6 ± 27.2% and 22.5 ± 17.4%. Calorie and macronutrient intake decreased significantly between the pre-surgery period, and 3 and 12 months post-surgery; however, there was no significant difference after 60 months. In relation to food groups or macronutrients, no difference was observed between the pre-surgery period and 60 months post-surgery. The contribution of unprocessed or minimally processed foods to calorie intake gradually decreased after 3 months post-surgery. Conclusion The profile of dietary intake after 60 months of metabolic and bariatric surgery tends to approach that of the pre-surgery period. The contribution of unprocessed and minimally processed foods to calorie intake decreased after 60 months, while ultra-processed food contribution increased. Graphical Abstract

Purpose Some patients do not have the expected weight loss, and the post-surgical diet may partially explain these differences.ObjectivesTo estimate the impact of macronutrient substitution on obesity remission after RYGB, considering the protein source.Materials and MethodsThis study included 58 patients undergoing RYGB. Data collection was performed preoperatively, 3 and 12 months after surgery. Eight participants dropped out of the study at 3 months, and the others remained for 12 months. The foods consumed were registered using a 24-h, 3-day food recall. For the isocaloric substitution analysis, foods were classified according to the protein source. The groups were compared using hypothesis tests, and Cox proportional hazard ratio regression was used to analyze isocaloric substitution.ResultsAt three months after surgery, every 5% energy from plant protein replaced by animal protein increased by 3.50 [CI 1.204 — 10.205; p = 0.021] the probability of obesity remission. Stratified analysis by protein groups indicated that replacing vegetable protein with white meat was positively associated with remission of obesity. Every 5% vegetable protein replaced with white meat increased by 3.20 [CI 1.026 — 9.981; p = 0.045] the probability of obesity remission. Both results were independent of age, body mass index (BMI), and the presence of comorbidities.ConclusionThe results suggest that the consumption of animal proteins after RYGB, mainly white meat, favors weight loss.

PurposeBariatric surgery is an effective method for the treatment of severe obesity, however, binge eating disorder (BED) and negative body image can interfere with post-surgical evolution.ObjectiveTo describe the factors associated with BED in bariatric patients with a minimum of 2 years post-surgery.Materials and MethodsA cross-sectional observational study conducted with patients who underwent bariatric surgery through the Unified Health System (Sistema Único de Saúde [SUS]) and presenting a minimum of 2 years post-surgery. BED, depression symptoms, anxiety symptoms, quality of life and body image concerns were assessed by the Binge Eating Scale, Beck Depression Inventory, Beck Anxiety Inventory, Bariatric Analysis and Reporting Outcome System, and Body Shape Questionnaire, respectively. Socioeconomic and anthropometric data were also collected.ResultsBased on the ninety-two (92) patients evaluated, 83.7% were female, and had a mean age of 43.3 ± 9 years. Symptoms of depression (p = 0.002), anxiety (p = 0.000), body image concerns (p = 0.000), poor quality of life (p = 0.010), and obesity (p = 0.008) were associated with the presence of BED. All the anthropometric variables were higher in patients with BED, except excess weight loss. Regression analysis predicted BED through the presence of body image concern and anxiety symptoms.ConclusionAnxiety symptoms and body image concerns are associated with BED in patients who underwent bariatric surgery a minimum of 2 years.

BackgroundEating habits are one of the factors that directly affect weight recurrence after bariatric surgery, and therefore, this study assessed the association between food consumption and weight recurrence in patients who underwent bariatric surgery a minimum of 2 years.MethodsA cross-sectional observational study was conducted with patients who underwent bariatric surgery a minimum of 2 years through SUS, in the city of Palmas, Tocantins. Food consumption was assessed through two 24-h dietary recalls (R24). The foods were classified into groups by degree of processing following the NOVA classification system. Also, macronutrients and fiber contents were quantified. Anthropometric variables were evaluated and weight recurrence (WR) was defined as 15%.ResultsNinety-three (93) patients participated in the study, being 83.9% female, with mean age of 43.5 ± 9.13 years, mean post-surgery time of 4 years, and 58% present WR. A lower total energy consumption was found in patients without WR compared to those with WR (p = 0.05). Among the WR group, calories from processed foods (p = 0.00) and culinary ingredients (p = 0.05) were higher. However, carbohydrate consumption (percentage) was lower in the WR group (p = 0.04). A positive correlation was found between total energy (p = 0.03), processed foods (p = 0.03) and weight recurrence (p = 0.03).ConclusionWeight recurrence is associated with total daily energy intake, carbohydrates and food groups classified according to NOVA.

ObjectiveThe role of carbohydrates in weight loss in patients undergoing bariatric surgery (BS) remains poorly understood. Therefore, this study aimed to verify the relationship of the carbohydrate quality index (CQI) with weight loss and cardiometabolic risk markers up to 1 year after BS.Material and MethodsThis study included 50 patients with obesity undergoing Roux-en-Y gastric bypass. Data collection was performed preoperatively and 3 and 12 months after surgery. The foods consumed were documented using a 24-h food recall in 3 days. The CQI was calculated considering the following parameters: dietary fiber intake, sugar level; whole grains: proportion of total grains; solid carbohydrate: total carbohydrate ratio.ResultsFrom the total study sample, 58 participants were followed up for 3 months, and eight participants dropped out of the study. The remaining 50 patients were followed up for 12 months. Subjects were classified into tertiles according to the index score. A 1-unit increase in CQI was associated with a −1.02 decrease in insulin concentrations at 12 months and a −1.04 decrease in HOMA-IR. Concerning the total sample, the median of the CQI was 8 points and did not change at 3 and 12 months after surgery, but there was an improvement in some components of the index.ConclusionThe data suggest that the quality of carbohydrates can interfere with markers of insulin resistance after BS and the quality of carbohydrates is a point to be guided in patients undergoing BS.

In order to improve the efficacy of conventional radiotherapy, attention has been paid to immune cells, which not only modulate cancer cell response to therapy but are also highly recruited to tumours after irradiation. Particularly, the effect of ionizing radiation on macrophages, using therapeutically relevant doses, is not well understood. To evaluate how radiotherapy affects macrophage behaviour and macrophage-mediated cancer cell activity, human monocyte derived-macrophages were subjected, for a week, to cumulative ionizing radiation doses, as used during cancer treatment (2 Gy/fraction/day). Irradiated macrophages remained viable and metabolically active, despite DNA damage. NF-kappaB transcription activation and increased Bcl-xL expression evidenced the promotion of pro-survival activity. A significant increase of pro-inflammatory macrophage markers CD80 , CD86 and HLA-DR, but not CCR7 , TNF and IL1B was observed after 10 Gy cumulative doses, while anti-inflammatory markers CD163 , MRC1 , VCAN and IL-10 expression decreased, suggesting the modulation towards a more pro-inflammatory phenotype. Moreover, ionizing radiation induced macrophage morphological alterations and increased their phagocytic rate, without affecting matrix metalloproteases (MMP)2 and MMP9 activity. Importantly, irradiated macrophages promoted cancer cell-invasion and cancer cell-induced angiogenesis. Our work highlights macrophage ability to sustain cancer cell activities as a major concern that needs to be addressed to improve radiotherapy efficacy.

Both cancer and tumour-associated host cells are exposed to ionizing radiation when a tumour is subjected to radiotherapy. Macrophages frequently constitute the most abundant tumour-associated immune population, playing a role in tumour progression and response to therapy. The present work aimed to evaluate the importance of macrophage-cancer cell communication in the cellular response to radiation. To address this question, we established monocultures and indirect co-cultures of human monocyte-derived macrophages with RKO or SW1463 colorectal cancer cells, which exhibit higher and lower radiation sensitivity, respectively. Mono- and co-cultures were then irradiated with 5 cumulative doses, in a similar fractionated scheme to that used during cancer patients' treatment (2 Gy/fraction/day). Our results demonstrated that macrophages sensitize RKO to radiation-induced apoptosis, while protecting SW1463 cells. Additionally, the co-culture with macrophages increased the mRNA expression of metabolism- and survival-related genes more in SW1463 than in RKO. The presence of macrophages also upregulated glucose transporter 1 expression in irradiated SW1463, but not in RKO cells. In addition, the influence of cancer cells on the expression of pro- and anti-inflammatory macrophage markers, upon radiation exposure, was also evaluated. In the presence of RKO or SW1463, irradiated macrophages exhibit higher levels of pro-inflammatory TNF, IL6, CCL2 and CCR7, and of anti-inflammatory CCL18. However, RKO cells induce an increase of macrophage pro-inflammatory IL1B, while SW1463 cells promote higher pro-inflammatory CXCL8 and CD80, and also anti-inflammatory VCAN and IL10 levels. Thus, our data demonstrated that macrophages and cancer cells mutually influence their response to radiation. Notably, conditioned medium from irradiated co-cultures increased non-irradiated RKO cell migration and invasion and did not impact on angiogenesis in a chicken embryo chorioallantoic membrane assay. Overall, the establishment of primary human macrophage-cancer cell co-cultures revealed an intricate cell communication in response to ionizing radiation, which should be considered when developing therapies adjuvant to radiotherapy.

Truncating pathogenic or likely pathogenic variants of CDH1 cause hereditary diffuse gastric cancer (HDGC), a tumour risk syndrome that predisposes carrier individuals to diffuse gastric and lobular breast cancer. Rare CDH1 missense variants are often classified as variants of unknown significance. We conducted a genotype–phenotype analysis in families carrying rare CDH1 variants, comparing cancer spectrum in carriers of pathogenic or likely pathogenic variants (PV/LPV; analysed jointly) or missense variants of unknown significance, assessing the frequency of families with lobular breast cancer among PV/LPV carrier families, and testing the performance of lobular breast cancer-expanded criteria for CDH1 testing. This genotype-first study used retrospective diagnostic and clinical data from 854 carriers of 398 rare CDH1 variants and 1021 relatives, irrespective of HDGC clinical criteria, from 29 institutions in ten member-countries of the European Reference Network on Tumour Risk Syndromes (ERN GENTURIS). Data were collected from Oct 1, 2018, to Sept 20, 2022. Variants were classified by molecular type and clinical actionability with the American College of Medical Genetics and Association for Molecular Pathology CDH1 guidelines (version 2). Families were categorised by whether they fulfilled the 2015 and 2020 HDGC clinical criteria. Genotype–phenotype associations were analysed by Student's t test, Kruskal-Wallis, χ2, and multivariable logistic regression models. Performance of HDGC clinical criteria sets were assessed with an equivalence test and Youden index, and the areas under the receiver operating characteristic curves were compared by Z test. From 1971 phenotypes (contributed by 854 probands and 1021 relatives aged 1–93 years), 460 had gastric and breast cancer histology available. CDH1 truncating PV/LPVs occurred in 176 (21%) of 854 families and missense variants of unknown significance in 169 (20%) families. Multivariable logistic regression comparing phenotypes occurring in families carrying PV/LPVs or missense variants of unknown significance showed that lobular breast cancer had the greatest positive association with the presence of PV/LPVs (odds ratio 12·39 [95% CI 2·66–57·74], p=0·0014), followed by diffuse gastric cancer (8·00 [2·18–29·39], p=0·0017) and gastric cancer (7·81 [2·03–29·96], p=0·0027). 136 (77%) of 176 families carrying PV/LPVs fulfilled the 2015 HDGC criteria. Of the remaining 40 (23%) families, who did not fulfil the 2015 criteria, 11 fulfilled the 2020 HDGC criteria, and 18 had lobular breast cancer only or lobular breast cancer and gastric cancer, but did not meet the 2020 criteria. No specific CDH1 variant was found to predispose individuals specifically to lobular breast cancer, although 12 (7%) of 176 PV/LPV carrier families had lobular breast cancer only. Addition of three new lobular breast cancer-centred criteria improved testing sensitivity while retaining high specificity. The probability of finding CDH1 PV/LPVs in patients fulfilling the lobular breast cancer-expanded criteria, compared with the 2020 criteria, increased significantly (AUC 0·92 vs 0·88; Z score 3·54; p=0·0004). CDH1 PV/LPVs were positively associated with HDGC-related phenotypes (lobular breast cancer, diffuse gastric cancer, and gastric cancer), and no evidence for a positive association with these phenotypes was found for CDH1 missense variants of unknown significance. CDH1 PV/LPVs occurred often in families with lobular breast cancer who did not fulfil the 2020 HDGC criteria, supporting the expansion of lobular breast cancer-centred criteria. European Reference Network on Genetic Tumour Risk Syndromes, European Regional Development Fund, Fundação para a Ciência e a Tecnologia (Portugal), Cancer Research UK, and European Union's Horizon 2020 research and innovation programme.

BackgroundObesity is a disease that may involve disrupted connectivity of brain networks. Bariatric surgery is an effective treatment for obesity, and the positive effects on obesity-related conditions may be enhanced by exercise. Herein, we aimed to investigate the possible synergistic effects of Roux-en-Y Gastric Bypass (RYGB) and exercise training on brain functional networks.MethodsThirty women eligible for bariatric surgery were randomly assigned to a Roux-en-Y gastric bypass (RYGB: n = 15, age = 41.0 ± 7.3 years) or RYGB plus Exercise Training (RYGB + ET: n = 15, age = 41.9 ± 7.2 years). Clinical, laboratory, and brain functional connectivity parameters were assessed at baseline, and 3 (POST3) and 9 months (POST9) after surgery. The 6-month, three-times-a-week, exercise intervention (resistance plus aerobic exercise) was initiated 3 months post-surgery (for RYGB + ET).ResultsExercise superimposed on bariatric surgery (RYGB + ET) increased connectivity between hypothalamus and sensorial regions (seed-to-voxel analyses of hypothalamic connectivity), and decreased default mode network (DMN) and posterior salience (pSAL) network connectivity (ROI-to-ROI analyses of brain networks connectivity) when compared to RYGB alone (all p-FDR < 0.05). Increases in basal ganglia (BG) network connectivity were only observed in the exercised training group (within-group analyses).ConclusionExercise training is an important component in the management of post-bariatric patients and may improve the hypothalamic connectivity and brain functional networks that are involved in controlling food intake.Trial registrationClinicaltrial.gov: NCT02441361.