Visceral fat and clinical outcome in patients receiving first-line chemotherapy with bevacizumab for metastatic colorectal cancer.

BACKGROUND: Visceral fat produces angiogenic factors such as vascular endothelial growth factor that promote tumoral growth. However, its influence on outcome for patients with advanced cancer treated with anti-angiogenic agents is controversial. AIMS: The aim of this study was to determine whether visceral fat volume, visceral fat area and body mass index are associated with outcome in patients receiving first-line bevacizumab-based treatment for metastatic colorectal cancer. METHODS: This multicenter prospective study included 103 patients with metastatic colorectal cancer who received first-line bevacizumab-based chemotherapy. Computed tomography was used to measure visceral fat volume and visceral fat area. Endpoints were tumoral response at 2 months, progression free survival and overall survival. RESULTS: Visceral fat volume and visceral fat area, but not body mass index, were significantly associated with better outcome. Using sex-specific median values progression free survival was significantly longer in patients with high visceral fat volume (13.2 versus 9.4 months; p = 0.0043). In the same way, high visceral fat volume and visceral fat area were associated with a significantly better overall survival: 31.3 versus 20.5 months (p = 0.0072) and 29.3 versus 20.5 months (p = 0.0078), respectively. By multivariate analysis, visceral fat volume was associated with longer progression free survival and overall survival. CONCLUSION: This study demonstrates that a high visceral fat volume is associated with better outcome in patients receiving first-line bevacizumab-based chemotherapy for metastatic colorectal cancer.

Changes in adipose tissue distribution and relation to cardiometabolic risk factors after Roux-en-Y gastric bypass in adolescents.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) among adolescents with obesity results in significant weight loss; however, depot-specific changes have been understudied. OBJECTIVE: We hypothesized that visceral adipose tissue (VAT) reduction in adolescents undergoing RYGB would be greater than other depots and associated with improvement in cardiometabolic risk factors. SETTING: Three specialized treatment centers in Sweden. METHODS: Fifty-nine adolescents underwent dual x-ray absorptiometry before surgery and at 1, 2, and 5 years after RYGB. Changes in body composition in multiple depots (total fat, lean body, gynoid fat, android fat, subcutaneous adipose tissue, and VAT) and cardiometabolic risk factors were assessed using multiple linear regression analysis and generalized estimating equations adjusting for age, sex, and baseline risk factor levels. Data are presented as percent change (95% CI) with regression models showing slopes and estimated P values. RESULTS: At 1 year post-RYGB, a significant reduction was observed across all body composition measures (P < .001) with the greatest reduction observed in VAT (-65.1% [-68.7, -61.8]). From year 1 to 5 years post-RYGB, a regain was observed in all depots except lean body mass (1.2% [.3, 2.7], P = .105). A sex-specific difference in overall trajectories was only observed in lean body mass with males consistently having higher mean levels. Change in VAT at 1 year correlated with change in triglycerides (slope: .21 mg/dL/kg, P = .034) and fasting plasma insulin (slope: 44 pmol/L/kg, P = .027). CONCLUSIONS: Adiposity measures all decreased after RYGB but poorly predicted change in cardiometabolic risk. Despite significant reductions at 1 year, a steady regain was observed out to 5 years, with values still well below baseline. Further research should consider control group comparison and extended follow-up.

Child and adolescent obesity.

The prevalence of child and adolescent obesity has plateaued at high levels in most high-income countries and is increasing in many low-income and middle-income countries. Obesity arises when a mix of genetic and epigenetic factors, behavioural risk patterns and broader environmental and sociocultural influences affect the two body weight regulation systems: energy homeostasis, including leptin and gastrointestinal tract signals, operating predominantly at an unconscious level, and cognitive-emotional control that is regulated by higher brain centres, operating at a conscious level. Health-related quality of life is reduced in those with obesity. Comorbidities of obesity, including type 2 diabetes mellitus, fatty liver disease and depression, are more likely in adolescents and in those with severe obesity. Treatment incorporates a respectful, stigma-free and family-based approach involving multiple components, and addresses dietary, physical activity, sedentary and sleep behaviours. In adolescents in particular, adjunctive therapies can be valuable, such as more intensive dietary therapies, pharmacotherapy and bariatric surgery. Prevention of obesity requires a whole-system approach and joined-up policy initiatives across government departments. Development and implementation of interventions to prevent paediatric obesity in children should focus on interventions that are feasible, effective and likely to reduce gaps in health inequalities.

Opioid Use After Gastric Bypass, Sleeve Gastrectomy or Intensive Lifestyle Intervention.

OBJECTIVE: To compare opioid use in patients with obesity treated with bariatric surgery versus adults with obesity who underwent intensive lifestyle modification. SUMMARY OF BACKGROUND DATA: Previous studies of opioid use after bariatric surgery have been limited by small sample sizes, short follow-up, and lack of control groups. METHODS: Nationwide matched cohort study including individuals from the Scandinavian Obesity Surgery Registry and the Itrim health database with individuals undergoing structured intensive lifestyle modification, between August 1, 2007 and September 30, 2015. Participants were matched on Body Mass Index, age, sex, education, previous opioid use, diabetes, cardiovascular disease, and psychiatric status (n = 30,359:21,356). Dispensed opioids were retrieved from the Swedish Prescribed Drug Register from 2 years before to up to 8 years after intervention. RESULTS: During the 2-year period before treatment, prevalence of individuals receiving ≥1 opioid prescription was identical in the surgery and lifestyle group. At 3 years, the prevalence of opioid prescriptions was 14.7% versus 8.9% in the surgery and lifestyle groups (mean difference 5.9%, 95% confidence interval 5.3-6.4) and at 8 years 16.9% versus 9.0% (7.9%, 6.8-9.0). The difference in mean daily dose also increased over time and was 3.55 mg in the surgery group versus 1.17 mg in the lifestyle group at 8 years (mean difference [adjusted for baseline dose] 2.30 mg, 95% confidence interval 1.61-2.98). CONCLUSIONS: Bariatric surgery was associated with a higher proportion of opioid users and larger total opioid dose, compared to actively treated obese individuals. These trends were especially evident in patients who received additional surgery during follow-up.

Long-term changes in dietary intake and its association with eating-related problems after gastric bypass in adolescents.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) surgery is an established, effective treatment for severe adolescent obesity. Long-term dietary intake and the relationship to eating-related problems are scarcely evaluated in this population. OBJECTIVES: Assess changes in dietary intake in adolescents after RYGB and explore associations between dietary intake and eating-related problems. SETTING: Multicenter study in Swedish university hospitals. METHOD: Diet history, binge eating scale (BES), and Three-Factor Eating Questionnaire were assessed preoperatively and 1, 2, and 5 years after RYGB in 85 adolescents (67% female) aged 16.5 ± 1.2 years with a body mass index (BMI) of 45.5 ± 6.0 kg/m2 and compared with control individuals at 5 years. RESULTS: Five-year BMI change was -28.6% ± 12.7% versus +9.9% ± 18.9% in RYGB patients versus control individuals (P < .001). Through 5 years, RYGB adolescents reported reduced energy intake, portion size of cooked meals at dinner, and milk/yoghurt consumption (P < .01). The BES scores were 9.3 ± 8.3 versus 13.4 ± 10.5 in RYGB patients versus control individuals (P = .04). Association between BES score and energy intake was stronger in control individuals (r = .27 versus r = .62 in RYGB patients versus control individuals, P < .001). At 5 years, lower energy intake was associated with greater BMI loss in all adolescents (r = .33, P < .001). Higher scores in BES and uncontrolled and emotional eating were associated with higher energy intake, cooked meals, candies/chocolates, cakes/cookies, desserts, and sugary drinks (r > .23, P < .04) and lower intake of fruits/berries (r = -.32, P = .044). A higher score in cognitive restraint was associated with a higher intake of cereals and fruits/berries (r > .22, P < .05) and a lower intake of sugary drinks (r = -.24, P < .03). CONCLUSION: To support optimization of long-term outcomes in adolescent RYGB patients, it is important to provide management strategies to reduce energy intake. Monitoring eating-related problems could identify potential individuals at risk of poor weight loss and to initiate treatment interventions.

Recurrent massive hemoptysis from distal pulmonary pseudoaneurysms complicating invasive aspergillosis in a teenager.

Invasive pulmonary aspergillosis in children rarely complicates life-threatening massive hemoptysis. Here, we report the case of a 15-year-old girl with acute lymphoblastic leukemia who was hospitalized for fever and medullary aplasia 1 month after beginning chemotherapy for invasive pulmonary aspergillosis. Despite voriconazole and caspofungine treatment, excavation of some lesions caused a unilateral small pneumothorax and bilateral pleural effusion, justifying intensive care management. The massive hemoptysis that occurred on day 23 was complicated with heart failure, and the patient was promptly resuscitated. Fibroscopy and computed tomography angiography (CTA) did not reveal the origin or cause of the bleeding. A second massive bleeding event occurred on day 32, and heart failure resolved after 10min of low flow. A new CTA showed 2 pseudoaneurysms of the subsegmental pulmonary arteries that were treated with embolization. Sedation was gradually decreased owing to improvement in respiratory status, but the patient did not regain consciousness because of deep brain sequelae. A limitation of care was decided upon, and the patient died in the following weeks. Massive hemoptysis is a rare life-threatening complication of invasive pulmonary aspergillosis, especially in children. Pulmonary artery pseudoaneurysms are unusual and should be detected as soon as possible to guide therapy. Intensive care management should be followed by embolization if the patient is stable; otherwise, surgery is indicated, ideally after identifying the source of bleeding by CTA or bronchoscopy. Early CTA follow-up can be proposed if the source of bleeding is still unknown as pseudoaneurysms can appear or grow rapidly.

Comparison of Sleeve Gastrectomy vs Intensive Lifestyle Modification in Patients With a BMI of 30 to Less Than 35.

Importance: There is a lack of studies evaluating sleeve gastrectomy compared with intensive lifestyle treatment in patients with class 1 obesity (body mass index [BMI] 30 to <35 [calculated as weight in kilograms divided by height in meters squared]). Objective: To compare outcomes and safety of sleeve gastrectomy compared with intensive nonoperative obesity treatment in patients with class 1 obesity. Design, Setting, and Participants: This matched, nationwide cohort study included patients with class 1 obesity who underwent a sleeve gastrectomy or intensive lifestyle treatment between January 1, 2012, and December 31, 2017, and who were registered in the Scandinavian Obesity Surgery Registry or the Itrim health database. Participants with class 1 obesity were matched 1:2 using a propensity score including age, sex, BMI, treatment year, education level, income, cardiovascular disease, and use of antibiotic drugs, antidepressants, and anxiolytics. Interventions: Sleeve gastrectomy or intensive lifestyle treatment. Main Outcomes and Measures: Outcomes included weight loss after intervention, changes in metabolic comorbidities, substance use disorders, self-harm, and major cardiovascular events retrieved from the National Patient Register, Prescribed Drug Register, and Cause of Death Register as well as the Scandinavian Obesity Surgery Registry and the Itrim health database. Data were analyzed from December 1, 2021 until May 31, 2022. Results: The study included 1216 surgery patients and 2432 lifestyle participants with similar mean (SD) BMI (32.8 [1.4] vs 32.9 [1.4]), mean (SD) age (42.4 [9.7] vs 42.6 [12.7] years), and sex (1091 [89.7%] vs 2191 [90.1%] women). Surgery patients had greater 1-year weight loss compared with controls (22.9 kg vs 11.9 kg; mean difference, 10.7 kg; 95% CI, 10.0-11.5 kg; P < .001). Over a median follow-up of 5.1 years (IQR, 3.9-6.2 years), surgery patients had a lower risk of incident use of diabetes drugs (59.7 vs 100.4 events per 10 000 person-years; hazard ratio [HR], 0.60; 95% CI, 0.39-0.92; P = .02) and greater 2-year diabetes drug remission (48.4% vs 22.0%; risk difference 26.4%; 95% CI, 11.7%-41.0%; P < .001), but higher risk for substance use disorder (94 vs 50 events per 10 000 person-years; HR, 1.86; 95% CI, 1.30-2.67; P < .001) and self-harm (45 vs 25 events per 10 000 person-years; HR, 1.81; 95% CI, 1.09-3.01; P = .02). No between-group difference in occurrence of major cardiovascular events was observed (23.4 vs 24.8 events per 10 000 person-years; HR, 0.96; 95% CI, 0.49-1.91; P = .92). Conclusions and Relevance: In this cohort study, compared with intensive nonoperative obesity treatment, sleeve gastrectomy in patients with class 1 obesity was associated with greater weight loss, diabetes prevention, and diabetes remission but a higher incidence of substance use disorder and self-harm.

Response to Induction Therapy in Pediatric Hodgkin's Lymphoma: Performance of First-Order Texture Parameters of CT Images.

Objectives: The aim of this study was to examine whether texture analysis features on pretreatment contrast-enhanced CT images could predict adequate response (AR) or inadequate response (IR) after two cycles of chemotherapy in pediatric Hodgkin's lymphoma (PHL). Materials and methods: This retrospective single-center study included 32 children and adolescents with HL. Texture analysis was independently performed by two radiologists using pretreatment CT scans. The mean gray level, standard deviation, entropy, kurtosis, and skewness were derived from pixel distribution histograms before and after spatial filtration ranging from two (fine texture) to six (coarse texture). Interobserver reliability was studied using interobserver correlation coefficients (ICCs) to select texture parameters. Relationships between early response assessment (ERA) to induction therapy and associated factors were studied using Student's t-tests and a lasso penalized logistic regression analysis. Results: Of the 32 patients, IR was observed in 13 and AR in 19. Inter-reader agreement was good to excellent (ICC > 0.75) for all parameters except skewness and kurtosis without filtration and at spatial scale filtration (SSF) = 2. These parameters were excluded from the analysis. The t-test identified only entropy at SSF = 2 (p value = 0.039) as a potential predictor of ERA. No parameters were significantly associated with ERA, according to a lasso penalized logistic regression. Conclusion: No textural parameters were identified as predictors of ERA after two cycles of chemotherapy in PHL.

Physical activity in early childhood: a five-year longitudinal analysis of patterns and correlates.

BACKGROUND: Knowledge on longitudinal patterns and related factors of young children's physical activity (PA) is still scarce. Therefore, the aim of this study was to examine patterns and changes of accelerometer-measured PA over time in two to six-year-old children. Furthermore, the aim was to investigate if parental PA, socioeconomic status, sex, weight status, and motor skills are related to child PA over time, using prospective cohort data from a clustered randomized controlled trial. METHODS: One hundred and six children (52% girls) and their parents had PA measured yearly from age two to six with an Actigraph GT3X. The actigraph was worn on the non-dominant wrist for one week; anthropometric data and motor skills, as well as background information, was collected simultaneously. The outcome was counts per minute from the vector magnitude, and linear mixed-effect models were used to answer the research questions. RESULTS: Among the children, accelerometer-measured PA increased on average by 11% per year from two years of age (mean 3170 cpm (3007-3334 95% CI)) onwards to six years of age (mean 4369 cpm (4207-4533 95% CI)). From three years of age, children were more active on weekdays than on weekend days. The rate of difference varied across low, medium, and highly active children (based on tertiles). No significant differences in weekdays/weekend PA among the lowest active children was found. Despite this, they were still significantly less active on weekend days than the most active children. Maternal, but not paternal PA was found to be significantly positively related to child PA over time, with a medium to large effect size. But no significant relationships were found between child PA and sex, weight status, or socioeconomic status. CONCLUSIONS: PA increased on average with 11% per year, similarly for boys and girls. From three years of age children were more active during weekdays than weekend days. These results indicate that child PA benefits from active stimulation by parents and care takers already from early ages. It is important to identify attributes of possible intervention designs for weekend days for families with young children as well as characterize the least active children. TRIAL REGISTRATION: Early STOPP was prospectively registered in the clinical trials registry: clinicaltrials.gov , ID NCT01198847.

Prevalence of insufficient weight loss 5 years after Roux-en-Y gastric bypass: metabolic consequences and prediction estimates: a prospective registry study.

OBJECTIVE: The study aimed to investigate the heterogeneity of weight loss 5 years after Roux-en-Y gastric bypass (RYGB) and the association with cardiometabolic health as well as to model prediction estimates of surgical treatment failure. DESIGN: Retrospective analysis of prospectively collected data from the Scandinavian Obesity Surgery Registry (SOReg). SETTING: 29 surgical units from the whole of Sweden contributed data. Inclusion was restricted to surgical units with a retention rate of >60% five years postsurgery. PARTICIPANTS: 10 633 patients were extracted from SOReg. In total 5936 participants were included in the final sample, 79.1% females. The mean age of participants before surgery was 39.4±9 years and mean body mass index (BMI) 42.9±5.1. 2322 were excluded (death before the 5-year follow-up (n=148), other types of surgery or reoperations (n=637), age at surgery <18 or >55 years (n=1329), presurgery BMI <35 kg/m2 (n=208)). In total, 2375 (29%) of eligible individuals were lost to the 5-year follow-up. MAIN OUTCOME: The occurrence of surgical treatment failure 5 years after surgery was based on the three previously published definitions: per cent excess BMI loss <50%, total weight loss <20% or BMI >35 where initial BMI was <50, or >40 where initial BMI was >50. In addition, we report the association between surgical treatment failure and biochemical markers of obesity-related comorbidity. We also developed predictive models to identify patients with a high risk of surgical treatment failure 5 years postsurgery. RESULTS: In total, 23.1% met at least one definition of surgical treatment failure at year 5 which was associated with (adjusted OR) with 95% CI): type 2 diabetes (T2D, OR 2.1; 95% CI 1.6 to 2.7), dyslipidaemia (OR 1.8; 95% CI 1.6 to 2.1) and hypertension (OR 1.9; 95% CI 1.6 to 2.2). Surgical treatment failure at 5 years was predicted by combined demographic and anthropometric measures from baseline, 1 and 2 years postsurgery (area under the curve=0.874). CONCLUSION: Laparoscopic RYGB leads to a marked and sustained weight loss with improvement of obesity-related comorbidity in most patients. However, 23% met at least one definition of surgical treatment failure, which was associated with a greater risk of relapse and a higher incidence of T2D, dyslipidaemia and hypertension 5 years after surgery. Poor initial weight loss and early weight regain are strong predictors of long-term treatment failure and may be used for early identification of patients who require additional weight loss support.

High estimated prevalence of bariatric surgery in young adults treated for pediatric obesity.

BACKGROUND: Despite the modest effects of behavioral treatment on obesity in adolescence, bariatric surgery is rarely performed. Obesity often persists from childhood to adulthood, but it is not known how many individuals proceed with bariatric surgery in young adulthood. OBJECTIVE: The aim of this study was to determine what proportion of individuals who received pediatric behavioral obesity treatment subsequently underwent bariatric surgery in early adulthood, and to identify predictors thereof. SETTING: National registries, Sweden. METHODS: In this prospective cohort study, the Swedish Childhood Obesity Treatment Register was linked to several national registers. RESULTS: The childhood obesity cohort included 6502 (45% females) with a median age at follow-up of 21.7 years (interquartile range [IQR] 5.2). Of these, 8.2% underwent bariatric surgery at a median age of 20.9 years (IQR 4.2). The estimated cumulative incidence of bariatric surgery at age 30 was 21.5%. Obesity-related co-morbidities were identified in 31.7% before bariatric surgery in the childhood obesity cohort. Predictors of bariatric surgery were female sex, high body mass index standard deviation score (BMI SDS) at the start and end of treatment, poor treatment response, as well as own or parental cardiometabolic disease. CONCLUSIONS: More than a fifth are estimated to undergo bariatric surgery in early adulthood, despite having received pediatric behavioral obesity treatment. Our results indicate that for many children, behavioral treatment is insufficient in reducing obesity and preventing obesity-related co-morbidity. Therefore, it is reasonable to assume that more effective treatment of adolescents with severe obesity, including more rigorous behavioral support and pharmacologic treatment, but also more frequent use of bariatric surgery, would benefit this group of patients.

Depression, anxiety, and suicidal ideation in young adults 5 years after undergoing bariatric surgery as adolescents.

PURPOSE: Metabolic and bariatric surgery (MBS) is increasingly used in adolescents. The aim was to explore symptoms of depression and anxiety in young adults over 5 years' follow-up after undergoing MBS. METHODS: Beck Depression Inventory-2 and the Beck Anxiety Inventory were used to assess symptoms of depression and anxiety in 62 patients 1, 2, and 5 years after having Roux-en-Y gastric bypass at 13-18 years of age. Mental health, eating-related problems, and weight outcomes were tested for association with suicidal ideation at the 5-year follow-up. RESULTS: At the 5-year follow-up, the mean score for depression was 11.4 (± 12.4), indicating minimal symptoms of depression. The mean score for anxiety was 12.82 (± 11.50), indicating mild anxiety symptoms. Still, several participants reported moderate or severe symptoms of depression (26%) and anxiety (32%). Women reported more symptoms than men (P = 0.03 and 0.04). No significant changes were found in self-reported symptoms of depression and anxiety between the 1-year and the 5-year follow-up (P = 0.367 and 0.934). Suicidal ideation was reported by 16% at the 5-year follow-up. Participants reporting suicidal ideation had lost significantly less excess weight than participants without suicidal ideation (P = 0.009). CONCLUSION: Five years after adolescent MBS, a substantial minority still struggles with mental health issues, and women are more burdened than men. Our results indicate an association between less optimal weight loss and suicidal ideation 5 years after MBS. The findings emphasize the importance of offering long-term follow-up and mental health treatment several years after MBS. LEVEL OF EVIDENCE: Level III, cohort study. CLINICAL TRIAL REGISTRATION: The study is registered with ClinicalTrials.gov (NCT00289705). First posted February 10, 2006.

Celiac disease can be predicted by high levels of tissue transglutaminase antibodies in children and adolescents with type 1 diabetes.

OBJECTIVES: Children with type 1 diabetes (T1D) are not included in guidelines regarding diagnosis criteria for celiac disease (CD) without a diagnostic biopsy, due to lack of data. We explored whether tissue transglutaminase antibodies (anti-tTG) that were ≥ 10 times the upper limit of normal (10× ULN) predicted CD in T1D. METHODS: Data from the Swedish prospective Better Diabetes Diagnosis study was used, and 2035 children and adolescents with T1D diagnosed between 2005-2010 were included. Of these, 32 had been diagnosed with CD before T1D. The children without CD were repeatedly screened for CD using anti-tTG antibodies of immunoglobulin type A. In addition, their human leukocyte antigen (HLA) were genotyped. All children with positive anti-tTG were advised to undergo biopsy. Biopsies were performed on 119 children and graded using the Marsh-Oberhüber classification. RESULTS: All of the 60 children with anti-tTG ≥10x ULN had CD verified by biopsies. The degree of mucosal damage correlated with anti-tTG levels. Among 2003 screened children, 6.9% had positive anti-tTG and 5.6% were confirmed CD. The overall CD prevalence, when including the 32 children with CD before T1D, was 7.0% (145/2035). All but one of the children diagnosed with CD had HLA-DQ2 and/or DQ8. CONCLUSIONS: As all screened children and adolescents with T1D with tissue transglutaminase antibodies above 10 times the positive value 10x ULN had CD, we propose that the guidelines for diagnosing CD in screened children, when biopsies can be omitted, should also apply to children and adolescents with T1D as a noninvasive method.

5-year mental health and eating pattern outcomes following bariatric surgery in adolescents: a prospective cohort study.

BACKGROUND: Mental health problems are prevalent among adolescents with severe obesity, but long-term mental health outcomes after adolescent bariatric surgery are not well known. We aimed to assess mental health outcomes over 5 years of follow-up after Roux-en-Y gastric bypass surgery in adolescents who participated in the Adolescent Morbid Obesity Surgery (AMOS) study. METHODS: This was a non-randomised matched-control study in adolescents aged 13-18 years who had a BMI of 40 kg/m2 or higher, or 35 kg/m2 or higher in addition to obesity-related comorbidity; who had previously undergone failed comprehensive conservative treatment; and were of pubertal Tanner stage III or higher, with height growth velocity beyond peak. A contemporary control group, matched for BMI, age, and sex, who underwent conventional obesity treatment, was obtained from the Swedish Childhood Obesity Treatment Register. Data on dispensed psychiatric drugs and specialist treatment for mental disorders were retrieved from national registers with complete coverage. In the surgical group only, questionnaires were used to assess self-esteem (Rosenberg Self-Esteem [RSE] score), mood (Mood Adjective Checklist [MACL]), and eating patterns (Binge Eating Scale [BES] and Three-Factor Eating Questionnaire-R21 [TFEQ]). This study is registered with ClinicalTrials.gov (NCT00289705). FINDINGS: Between April 10, 2006, and May 20, 2009, 81 adolescents (53 [65%] female) underwent Roux-en-Y gastric bypass surgery, and 80 control participants received conventional treatment. The proportion of participants prescribed psychiatric drugs did not differ between groups in the years before study inclusion (pre-baseline; absolute risk difference 5% [95% CI -7 to 16], p=0·4263) or after intervention (10% [-6 to 24], p=0·2175). Treatment for mental and behavioural disorders did not differ between groups before baseline (2% [-10 to 14], p=0·7135); however, adolescents in the surgical group had more specialised psychiatric treatment in the 5 years after obesity treatment than did the control group (15% [1 to 28], p=0·0410). There were few patients who discontinued psychiatric treatment post-surgery (three [4%] receiving psychiatric drug treatment and six [7%] receiving specialised care for a mental disorder before surgery). In the surgical group, self-esteem (RSE score) was improved after 5 years (mixed model mean 21·6 [95% CI 19·9 to 23·4]) relative to baseline (18·9 [17·4 to 20·4], p=0·0059), but overall mood (MACL score) was not (2·8 [2·7 to 2·9] at 5 years vs 2·7 [2·6 to 2·8] at baseline, p=0·0737). Binge eating was improved at 5 years (9·3 [7·4 to 11·2]) relative to baseline (15·0 [13·5 to 16·5], p<0·0001). Relative changes in BMI were not associated with the presence or absence of binge eating at baseline. INTERPRETATION: Mental health problems persist in adolescents 5 years after bariatric surgery despite substantial weight loss. Although bariatric surgery can improve many aspects of health, alleviation of mental health problems should not be expected, and a multidisciplinary bariatric team should offer long-term mental health support after surgery. FUNDING: Swedish Research Council, VINNOVA, Västra Götalandsregionen, ALF VG-region, Region Stockholm, Swedish Child Diabetes Foundation, Swedish Heart and Lung Foundation, Tore Nilsson's Foundation, SUS Foundations and Donations, Capio Research Foundation, and Mary von Sydow's Foundation.

Micronutrient intake and biochemistry in adolescents adherent or nonadherent to supplements 5 years after Roux-en-Y gastric bypass surgery.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) is an effective obesity treatment in adults and has become established in adolescents. Lower adherence to supplementation in adolescents confers a risk for long-term nutritional deficiencies. OBJECTIVES: To assess adherence to supplementation, micronutrient intake, and biochemistry in adolescents through 5 years after RYGB. SETTING: University hospitals, multicenter study, Sweden. METHODS: Micronutrient intake and adherence to supplementation were assessed by diet history interviews and biochemistry preoperatively, 1, 2, and 5 years after RYGB in 85 adolescents (67% females), aged 16.5 years (± 1.2) with a body mass index of 45.5 kg/m2 (± 6.0). Adherence was defined as taking prescribed supplements ≥3 times a week. Micronutrient intake and biochemistry were compared with matched controls at 5 years. RESULTS: Over 75% completed the dietary assessments across 5 years after RYGB. Adherence ranged between 44-61% through 5 years. At 5 years, ferritin and hemoglobin decreased (P < .04) and 61% had iron deficiency (P ≤ .001). Among females with iron deficiency, most did not adhere to supplementation (P = .005), and 59% of these had anemia (P < .001). Vitamin D insufficiency continued after surgery and 80% of participants who did not adhere to supplementation had insufficiency (P = .002). Adolescents not adhering had lower levels of vitamin D, B12, and ferritin (females) compared with both adhering adolescents and the control group (all P < .04). CONCLUSIONS: Half of adolescents after RYGB reported sufficient long-term adherence to supplementation. Adhering to supplements and reporting a higher micronutrient intake were associated with more favorable biochemistry. Results support the recommendations for monitoring micronutrient intake and biochemistry in all patients who have undergone RYGB surgery, and the recommendation of higher preventive supplementation of vitamin D and iron in both sexes. As hypothesized, adolescents not adhering had a higher prevalence of long-term micronutrient deficiencies.

Five-year changes in dietary intake and body composition in adolescents with severe obesity undergoing laparoscopic Roux-en-Y gastric bypass surgery.

BACKGROUND: Information is scarce on long-term changes in energy intake (EI), dietary energy density (DED), and body composition in adolescents undergoing laparoscopic Roux-en-Y gastric bypass (RYGB). OBJECTIVES: To investigate long-term changes in EI, DED, and body composition in adolescents after LRYGB. SETTING: University hospitals, multicenter study, Sweden. METHODS: Eighty-five adolescents (67% girls; mean ± standard deviation, age 16.0 ± 1.2 yr, body mass index 45.5 ± 6.1 kg/m2) were assessed preoperatively (baseline) and 1, 2, and 5 years after LRYGB with diet history interviews and dual-energy x-ray absorptiometry. Matched obese adolescent controls receiving nonsurgical treatment were assessed only at 5 years. RESULTS: Weight decreased 31%, 33%, and 28% at 1, 2, and 5 years after LRYGB (P < .001) while controls gained 13% over 5 years (P < .001). Dietary assessments were completed in 98%, 93%, 87%, and 75% at baseline and 1, 2, and 5 years, respectively, and in 65% of controls. Baseline EI (2558 kcal/d), decreased by 34%, 22%, and 10% after 1, 2, and 5 years (P < .05). DED decreased at 1 year (P = .03). Macronutrient distribution was not different from controls at 5 years, but EI and DED were 31% and 14% lower (P < .015). Fat, fat-free, and muscle mass decreased through 5 years after LRYGB (P < .001). Boys preserved muscle mass more than girls (P < .01). Adequate protein intake was associated with preservation of muscle mass (P = .003). CONCLUSIONS: In adolescents undergoing LRYGB EI remained 10% lower 5 years after surgery. Decreased EI and DED, rather than macronutrient distribution, are important factors in weight loss after surgery. Higher protein intake may facilitate preservation of muscle mass.

European paediatric non-alcoholic fatty liver disease registry (EU-PNAFLD): Design and rationale.

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disorder in children and has the potential to progress to advanced fibrosis/cirrhosis, end-stage liver disease and hepatocellular carcinoma. However, the natural history of the condition is poorly understood and there are no approved treatments. The European Paediatric Non-Alcoholic Fatty Liver Disease Registry (EU-PNAFLD) is a multi-centre registry of paediatric NAFLD that will serve as a prospective, observational, natural history study and provide a tractable back-bone to support recruitment into subsequent interventional trials. Collection of samples into a bio-repository will facilitate translational studies, including genome sequencing and metabolomics. EU-PNAFLD will work closely alongside the existing adult European NAFLD Registry to obtain data on clinical outcomes after 20-30 years. Through an international, well-characterised large-scale cohort, EU-PNAFLD will address the key questions in paediatric NAFLD and benefit patients with the condition.

Binge eating and other eating-related problems in adolescents undergoing gastric bypass: results from a Swedish nationwide study (AMOS).

Bariatric surgery is established as a treatment option for adolescents with severe obesity. Little is known about binge eating (BE) and other eating-related problems in adolescents undergoing bariatric surgery. BE, emotional eating, uncontrolled eating, and cognitive restraint were assessed at baseline, and one and two years after gastric bypass using questionnaires in 82 adolescents (mean age 16.9 years, 67% girls). BE was assessed with the Binge Eating Scale (BES) and other eating-related problems with the Three Factor Eating Questionnaire. Change in eating-related problems over time, along with the relationship between eating behaviors and other aspects of mental health and weight outcome, were analyzed. At baseline, 37% of the adolescents reported BE (defined as a BES score >17). Two years after gastric bypass, adolescents reported less problems related to BE, emotional eating, and uncontrolled eating. Improvements were moderate to large. Adolescents reporting BE at baseline also reported more general mental health and psychosocial weight-related problems before and/or two years after surgery, compared to adolescents with no BE. After surgery adolescents with BE before surgery reported more suicidal ideation than those with no BE at baseline. None of the eating-related problems assessed at baseline was associated with weight outcome after surgery. More binge eating, emotional eating, and uncontrolled eating two years after surgery were associated with less weight loss. In conclusion, eating-related problems were substantially reduced in adolescents after undergoing gastric bypass. However, pre-operative BE seem to be associated with general mental health problems before and two years after surgery, including suicidal ideation. Pre-operative eating-related problems did not affect weight outcome, and our results support existing guidance that BE should not be considered an exclusion criterion for bariatric surgery in adolescents.

Risk of suicide and non-fatal self-harm after bariatric surgery: results from two matched cohort studies.

BACKGROUND: Bariatric surgery reduces mortality, but might have adverse effects on mental health. We assessed the risk of suicide and self-harm after bariatric surgery compared with non-surgical obesity treatment. METHODS: Suicide and non-fatal self-harm events retrieved from nationwide Swedish registers were examined in two cohorts. The non-randomised, prospective Swedish Obese Subjects (SOS) study compared bariatric surgery (n=2010; 1369 vertical-banded gastroplasty, 376 gastric banding, and 265 gastric bypass) with usual care (n=2037; recruitment 1987-2001). The second cohort consisted of individuals from the Scandinavian Obesity Surgery Registry (SOReg; n=20 256 patients who had gastric bypass) matched to individuals treated with intensive lifestyle modification (n=16 162; intervention 2006-13) on baseline BMI, age, sex, education level, diabetes, cardiovascular disease, history of self-harm, substance misuse, antidepressant use, anxiolytics use, and psychiatric health-care contacts. FINDINGS: During 68 528 person-years (median 18; IQR 14-21) in the SOS study, suicides or non-fatal self-harm events were higher in the surgery group (n=87) than in the control group (n=49; adjusted hazard ratio [aHR] 1·78, 95% CI 1·23-2·57; p=0·0021); of these events, nine and three were suicides, respectively (3·06, 0·79-11·88; p=0·11). In analyses by primary procedure type, increased risk of suicide or non-fatal self-harm was identified for gastric bypass (3·48, 1·65-7·31; p=0·0010), gastric banding (2·43, 1·23-4·82; p=0·011), and vertical-banded gastroplasty (2·25, 1·37-3·71; p=0·0015) compared with controls. Out of nine deaths by suicide in the SOS surgery group, five occurred after gastric bypass (two primary and three converted procedures). During 149 582 person-years (median 3·9; IQR 2·8-5·2), more suicides or non-fatal self-harm events were reported in the SOReg gastric bypass group (n=341) than in the intensive lifestyle group (n=84; aHR 3·16, 2·46-4·06; p<0·0001); of these events, 33 and five were suicides, respectively (5·17, 1·86-14·37; p=0·0017). In SOS, substance misuse during follow-up was recorded in 48% (39/81) of patients treated with surgery and 28% (13/47) of controls with non-fatal self-harm events (p=0·023). Correspondingly, substance misuse during follow-up was recorded in 51% (162/316) of participants in the SOReg gastric bypass group and 29% (23/80) of participants in the intensive lifestyle group with non-fatal self-harm events (p=0·0003). The risk of suicide and self-harm was not associated with poor weight loss outcome. INTERPRETATION: Bariatric surgery was associated with suicide and non-fatal self-harm. However, the absolute risks were low and do not justify a general discouragement of bariatric surgery. The findings indicate a need for thorough preoperative psychiatric history assessment along with provision of information about increased risk of self-harm following surgery. Moreover, the findings call for postoperative surveillance with particular attention to mental health. FUNDING: US National Institutes of Health and Swedish Research Council.

Value of Contrast-Enhanced Ultrasound Quantification Criteria for Identifying Patients not Responding to Bevacizumab-Based Therapy for Colorectal Liver Metastases.

PURPOSE: To evaluate changes in tumor vascularization parameters based on contrast-enhanced ultrasound (CEUS) quantification criteria of at least one visible liver metastasis as an early predictor of non-response to chemotherapy, including bevacizumab for colorectal cancer (CRC) liver metastases. MATERIALS AND METHODS: This multicenter prospective study included patients who received first-line bevacizumab-based chemotherapy. Tumor enhancement measured using CEUS within one liver metastasis and in relation to the surrounding healthy liver was quantified within 8 days before the first infusion of bevacizumab (E0), 24 hours after the end of the first infusion of bevacizumab (E1), in the 24 hours before the 2nd and 3 rd infusion of bevacizumab on day 15 (E2) and day 30 (E3), respectively, and after 2 months of treatment (E4). Endpoints were tumor response using RECIST criteria at 2 months, progression-free survival (PFS) and overall survival (OS). RESULTS: Among the 137 patients included in this study, 109 were analyzed. Only CEUS parameters calculated in relation to healthy liver were significant. High wash-in and wash-out rates at baseline were significantly associated with a better tumor response. Increases over time E2-E0 and E3-E0 for peak enhancement were significantly associated with shorter progression-free survival. Increases over time E2-E0 and E3-E0 for peak enhancement and wash-in area under the curve were significantly associated with a shorter overall survival. CONCLUSION: This large study demonstrated that early dynamic changes in the vascularity of liver metastases evaluated by quantified CEUS are associated with outcome in patients receiving first-line bevacizumab-based treatment for metastatic CRC.