Obesity Cohort Research Articles

Prenatal Fine Particulate Matter Exposure and Childhood Anxiety Symptoms

Background: Air pollution has been linked to neurotoxic effects; however, there is limited research on mental health, particularly in younger populations in which symptoms often first arise. We studied the association between prenatal fine particulate matter (PM2.5) exposure and symptoms of anxiety in a cohort of 8-9 year olds in Mexico City.Methods: Participants included 173 mother-child pairs from the Programming Research in Obesity, Growth, Environment and Social Stressors longitudinal birth cohort in Mexico City. Daily PM2.5 predictions were estimated using a 1km satellite-based exposure model and averaged over trimesters and the entire pregnancy. Symptoms of anxiety were assessed using the Revised Children’s Manifest Anxiety Scale (RCMAS-2) (Spanish Version) administered by psychologists during the face-to-face interview at the 8-9 year study visit. Linear regression models were used to estimate the change in continuous anxiety symptoms with each 5-µg/m3 increase in PM2.5, for each trimester and the entire pregnancy. Models were adjusted for maternal education, maternal SES, maternal depression, maternal age, child’s age at study visit, and season of conception. We additionally assessed sex-specific effects by including an interaction term between PM2.5 and sex.Results: Higher levels of PM2.5 exposure averaged over the entire pregnancy was associated with increases in childhood anxiety symptoms at age 8-9, in males only (β for males = 2.06, 95% CI: 0.20, 3.91; β for females = -0.45, 95% CI: -2.38, 1.48; p-int: 0.02). This sex-specific effect was primarily seen for exposures during the 1st trimester (β for males= 1.13, 95% CI: -0.06, 2.32, p-int: 0.06).Conclusions: PM2.5 exposure in early pregnancy may be a critical window for elevated symptoms of anxiety in the mid/late childhood period. Future analyses will use distributed lag models to further define time and sex-specific effects, as well as adjust for other urban stress correlates such as environmental noise.

Prenatal Exposure to Stress and Lung Function in 8-10 year old Children

Background Exposure to stress during pregnancy can have long term effects on children’s lung function. This association appears to be sex dependent and has been previously demonstrated in 4-6 year old children. The aim of this study was to evaluate sex dependent associations between pre-natal stress exposure and lung function in 8-10 year old children. Methods Data is from 182 mother-child pairs of the ongoing Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) cohort in Mexico City. Stress levels in mothers were assessed as negative life events using the Crisis in Family Systems Revised (CRISYS) questionnaire during pregnancy. The score (0-11) was dichotomized at the median (3). We visited the child’s home and performed spirometry tests according to American Thoracic Society guidelines. Results were overread by a pediatric pulmonologist. Spirometry results were analyzed using linear regression. Models were stratified by child’s sex, and adjusted for maternal pregnancy exposure to PM 2.5, age at birth and child’s gestational age, height and age at time of spirometry. Results We found significant positive associations between higher stress and improved lung function. The associations were stronger in girls compared to boys. For percent predicted FVC and FEV1 higher vs lower stress in boys (β:3.81, 95% CI [-1.60, 9.24]) and (β:2.33 , 95% CI [-3.42, 8.08]) vs girls (β:5.76 , 95% CI [0.92, 10.59]) and (β:5.00 , 95% CI [0.57, 9.43]). Conclusions Prenatal stress is positively associated with children’s lung function and appears to be sex-dependent with females demonstrating improved lung function compared to males. Results highlight the importance of considering susceptibility by sex in studies of chemical and stress co-exposures.

Urinary fluoride patterns among children in Mexico and Canada

Background: New research suggesting fluoride is a developmental neurotoxicant highlights the importance of characterizing fluoride exposure in children. Fluoride is added to salt in Mexico and to drinking water in Canada to prevent dental caries. We examined the association of childhood urinary fluoride (CUF) with food and water fluoride levels in Mexico and Canada, respectively. Methods: We included 551 children (ages 4-6) from the Programming Research in Obesity, Growth, Environment and Social Stress (PROGRESS) cohort in Mexico City, and 522 children (ages 2-6) from the Maternal-Infant Research on Environmental Chemicals (MIREC) cohort in Canada. We applied Spearman correlations, T-tests or covariate adjusted linear regression to examine associations of CUF (mg/L; adjusted for specific gravity) with demographics and food or water fluoride concentrations. We used equivalence testing to compare cohort means. Results: Median (IQR) CUF concentrations were 0.67 (0.36) in PROGRESS, 0.56 (0.76) in fluoridated Canadian communities, and 0.35 (0.53) in non-fluoridated Canadian communities. Mean+/-SD CUF was equivalent in PROGRESS (0.74+/-0.42) and fluoridated Canadian communities (0.79+/-0.71), but lower in non-fluoridated Canadian communities (0.55+/-0.60, t (276)=-6.02, p≤.001). CUF tended to increase with age in PROGRESS (ρ=.10, p=.02) and MIREC (ρ=.17, p≤.001). In MIREC, CUF was higher in males (0.79+/-0.74) than females (0.54+/-0.58, p<.001); however, no sex differences were observed in PROGRESS (p=.97). In MIREC, water fluoride concentrations (median=0.2 mg/L) were significantly associated with CUF after covariate adjustment for age and sex (B=0.36, 95%CI: 0.11, 0.61, p=.005). Daily food and beverage fluoride intake (median=624.41 mcg/day) was not associated with CUF in PROGRESS (p=.89). Conclusion: Our findings suggest that the magnitude of fluoride exposure is comparable among children in Mexico City and fluoridated Canadian communities, despite different sources of exposure. Further studies are needed to clarify whether higher CUF among older children reflects different exposure patterns, sources of exposure or age-related toxicokinetics. Keywords: Fluoride, exposure, intake, development, epidemiology.

Untargeted metabolomic profiles of air pollution exposure during pregnancy and postpartum depression risk: a pilot study

Background. Postpartum depression (PPD) impacts 18% of mothers globally, adversely affecting the health of mothers and children. Evidence from the Programming Research on Obesity, Growth, Environment, and Social Stress (PROGRESS) cohort in Mexico City suggests that exposure to air pollution, namely PM2.5 (particulate matter < 2.5 μm in diameter), in pregnancy is associated with increased PPD risk. Untargeted metabolomics, in which hundreds to thousands of metabolites are identified without specifying these metabolites a priori, offers a data-driven approach to identify mechanisms linking PM2.5 and PPD.Aim. To characterize metabolomic profiles associated with PM2.5 exposures and PPD in maternal serum collected during the second and third trimesters of pregnancy.Methods. We randomly selected 100 mothers from PROGRESS in a pilot study, estimated PM2.5 exposures during pregnancy using a satellite-based spatiotemporally-resolved prediction model, and measured maternal depression at 6 months postpartum using the Edinburgh Postnatal Depression Scale (EPDS). In maternal serum, we performed liquid chromatography-mass spectrometry (LC-MS)-based untargeted metabolomic profiling of polar, semi-polar, and non-polar metabolites.Results. After filtering, 202 putatively-identified metabolites were analyzed in linear models adjusted for maternal age, education, BMI, and laboratory batch. Of these, 20 and 29 metabolites in the second and third trimesters, respectively, were associated (p<0.05) with average trimester PM2.5 levels in the respective trimester. Two third trimester metabolites (itaconate and nervonate) passed multiple testing correction (FDR<0.05). Itaconate was also negatively associated with PM2.5 in second trimester (p=0.003) and marginally associated with lower PPD risk (EPDS ≥ 13; p=0.08).Conclusions. In maternal serum collected during pregnancy, we identified metabolites associated with PM2.5 exposure. Itaconate, which was negatively associated with both PM2.5 exposure and PPD, is a mitigator of inflammation and oxidative stress, consistent with processes known to be involved in both PM2.5 exposure and depression.

Does Obesity and Procedure Type Increase the Risk of in-Hospital Mortality in Laparoscopic Hysterectomy?

Study Objective To assess the differences in demographics and laparoscopic hysterectomy type by comorbid obesity and to assess the risk of in-hospital mortality due to obesity and other comorbidities. Design We conducted a cross-sectional data analysis using the healthcare cost and utilization project's (HCUP) nationwide inpatient sample (NIS) data from 2012 to 2014. Setting In-patient data using the NIS that provides patient records from about 4,400 non-federal hospitals and covers 45 states in the US. Patients or Participants We identified 119,890 adult females undergoing laparoscopic hysterectomies based on ICD-9 procedure codes. We identified differences in demographic, comorbidities and procedure types between obesity (N=17,370) and non-obesity (N=102,520) cohorts. Further, we used logistic regression model adjusted for confounders to assess the odds ratio (OR) of obesity on in-hospital mortality. Interventions Total laparoscopic hysterectomy (TLH), laparoscopic assisted vaginal hysterectomy (LAVH), and laparoscopic supracervical hysterectomy (LSH). Measurements and Main Results Majority of the inpatients underwent TLH (51.3%), followed by LAVH (25.8%) and LSH (12.9%). Majority of the inpatients were middle-age adults 36 to 50 years (83.1%) and White (67.7%) with obesity cohort older than non-obesity (51.3y vs. 48.8y, P Conclusion Analysis of national-level data shows that obese patients have increased perioperative mortality with a higher prevalence of co-morbidities. More research studies should focus on improving these outcomes in obese patients.

Early-Life Dietary Cadmium Exposure and Kidney Function in 9-Year-Old Children from the PROGRESS Cohort.

Cadmium (Cd) is a toxic metal associated with adverse health effects, including kidney injury or disease. The aims of this study were to estimate dietary Cd exposure during childhood, and to evaluate the association of early-life dietary Cd with biomarkers of glomerular kidney function in 9-year-old Mexican children. Our study included 601 children from the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) cohort with up to five follow-up food frequency questionnaires from 1 to 9 years of age; and 480 children with measures of serum creatinine, cystatin C, and blood nitrogen urea (BUN), as well as 9-year-old estimated glomerular filtration rate. Dietary Cd was estimated through food composition tables. Multiple linear regression models were used to analyze the association between 1 and 9 years, cumulative dietary Cd, and each kidney parameter. Dietary Cd exposure increased with age and exceeded the tolerable weekly intake (TWI = 2.5 µg/kg body weight) by 16–64% at all ages. Early-life dietary Cd exposure was above the TWI and we observed inverse associations between dietary Cd exposure and kidney function parameters. Additional studies are needed to assess kidney function trajectories through adolescence. Identifying preventable risk factors including environmental exposures in early life can contribute to decreasing the incidence of adult kidney disease.

S0030 Roux-En-Y Gastric Bypass Is Associated With Higher Rates of Pancreatic Cysts and Pancreatic Adenocarcinoma When Compared to Laparoscopic Sleeve Gastrectomy: Findings of a Nationwide Analysis With Long-Term Follow-Up

INTRODUCTION: Although obesity is associated with several gastrointestinal malignancies, the association between obesity and pancreatic adenocarcinoma (PAC) remains controversial. We aim to evaluate the rates of pancreatic cysts (PC) and PAC in obesity and in those who underwent roux-en-y gastric bypass (RYGB), laparoscopic sleeve gastrectomy (LSG) and laparoscopic adjustable gastric banding (LAGB) using a large national database. METHODS: A commercial database (Explorys Inc, Cleveland, OH, USA), consisting of electronic health record data from 26 US healthcare systems, was surveyed. After excluding bariatric surgery, a cohort of patients with Systematized Nomenclature of Medicine-Clinical Terms (SNOMED-CT) diagnosis of “obesity” from 1999 to 2020 was identified. Within the obesity cohort, patients who developed new diagnoses of PC and PAC were identified. Subsequently, several cohorts of patients who underwent RYGB, LSG and LAGB were identified. The rates of new diagnoses of PC and PAC after at least 30 days of RYGB, LSG or LAGB were calculated. Risks of selected malignancies were compared amongst the obesity, RYGB, LSG and LAGB cohorts. RESULTS: Of the 72,531,460 patients in the database, 4,699,470 (6.5%), 40,250 (0.06%), and 58,520 (0.08%) with obesity, PC and PAC were identified respectively. There were 24,630 (0.03%) RYGB, 32,360 (0.09%) LSG and 8,650 (0.12%) LAGB cases in the database. There were 40 (0.16%), 30 (0.06%), and 10 (0.12%) of PC cases after at least 30 days of RYGB, LSG and LAGB respectively. Similarly, 140 (0.57%), 20 (0.06%) and 5 (0.06%) of PAC were identified after at least 30 days of RYGB, LSG and LAGB respectively. Patients who underwent RYGB were more likely to develop PC and PAC when compared to patients who underwent LSG (Table 1). Prevalence rates of PC and PAC overtime after bariatric surgery are presented in Figures 1 and 2 respectively. CONCLUSION: Patients who underwent RYGB had a higher risk of developing PC and PAC when compared to LSG and obese patients who did not undergo any bariatric procedure. This is the largest study to date to evaluate this topic. The underlying pathophysiology is unclear but is likely related to the permanent physiological and anatomical changes present in RYGB patients as compared to other types of bariatric interventions.Figure 1.: Proportion rates of pancreatic cyst (PC) after roux-en-y gastric bypass (RYGB), laparoscopic sleeve gastrectomy (LSG) and laparoscopic adjustable gastric banding (LAGB) over a 10 year follow up. Please note that Explorys rounds to closet 0 or 10.Figure 2.: Proportion rates of pancreatic adenocarcinoma (PAC) after roux-en-y gastric bypass (RYGB), laparoscopic sleeve gastrectomy (LSG) and laparoscopic adjustable gastric banding (LAGB) over a 10 year follow up. Please note that Explorys rounds to closet 0 or 10.Table 3.: Risk of pancreatic cyst (PC) and pancreatic adenocarcinoma (PAC) in roux-en-y gastric bypass (RYGB) vs. obesity (no bariatric surgery), RYGB vs. laparoscopic sleeve gastrectomy (LSG), RYGB vs. laparoscopic adjustable gastric banding (LAGB), LSG vs. obesity (no bariatric surgery), LSG vs. LAGB, and LAGB vs. obesity (no bariatric surgery). *P-value not significant. Please note that Explorys rounds to closet 0 or 10.

S1200 Roux-En-Y Gastric Bypass Is Associated With Higher Rates of Barrett’s Esophagus and Esophageal Adenocarcinoma When Compared to Laparoscopic Sleeve Gastrectomy: Findings of a Nationwide Analysis With Long-Term Follow-Up

INTRODUCTION: Obesity is thought to be a risk factor for esophageal malignancy. The association between bariatric interventions and esophageal malignancy remains unclear. We aim to examine the rates of Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC) in obese patients and in those who underwent roux-en-y gastric bypass (RYGB), laparoscopic sleeve gastrectomy (LSG) and laparoscopic adjustable gastric banding (LAGB). METHODS: A commercial database (Explorys Inc, Cleveland, OH, USA), consisting of EHR data from 26 US healthcare systems, was surveyed. After excluding bariatric surgery, a cohort of patients with Systematized Nomenclature of Medicine-Clinical Terms (SNOMED-CT) diagnosis of obesity (1999–2020) was identified. Within the obesity cohort, patients who developed new diagnoses of BE and EAC were identified. Subsequently, several cohorts of patients who underwent RYGB, LSG and LAGB were identified. The rates of new diagnoses of BE and EAC after at least 30 days of RYGB, LSG or LAGB were calculated. Risks were compared using univariable analysis. RESULTS: Of 72,531,460 patients in the database, 4,699,470 (6.5%), 230,300 (0.31%), and 10,950 (0.02%) with obesity, BE and EAC were identified respectively. There were 24,630 (0.03%) RYGB, 32,360 (0.05%) LSG and 8,650 (0.01%) LAGB. A total of 240 (0.97%), 110 (0.34%) and 70 (0.81%) of BE were identified after at least 30 days of RYGB, LSG and LAGB. A total of 20 (0.08%), 5 (0.02%), and 5 (0.06%) of EAC cases were identified after at least 30 days of RYGB, LSG and LAGB. Patients who underwent RYGB were more likely to develop BE and EAC when compared to patients who underwent LSG. Patients who underwent LSG were less likely to develop BE when compared to obese patients (Table 1). History of baseline GERD (prior to surgery) and cholecystectomy were associated with increased risk of BE after surgery (Table 2). Prevalence rates of BE over time after surgery are presented in Figure 1. CONCLUSION: Explorys rounds to the closest 0 or 10 to protect patient identity. This did not allow for further analysis of EAC. There is also potential selection and confounding biases. However, this is the largest study to evaluate the risk of BE and EAC in RYGB, LSG and LAGB. RYGB patients had higher risks of BE and EAC when compared to LSG. Longer duration of GERD in the RYGB population prior to surgery may explain this finding. The significant anatomical alteration and physiological changes may also contribute to these findings.Table 1.: Risk of Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC) in roux-en-y gastric bypass (RYGB) vs. obesity (no bariatric surgery), RYGB vs. laparoscopic sleeve gastrectomy (LSG), RYGB vs. laparoscopic adjustable gastric banding (LAGB), LSG vs. obesity (no bariatric surgery), LSG vs. LAGB, and LAGB vs. obesity (no bariatric surgery). *P-value not significantTable 2.: Underlying risk factors of Barrett’s esophagus (BE) after roux-en-y gastric bypass (RYGB), laparoscopic sleeve gastrectomy (LSG), and laparoscopic adjustable gastric banding (LAGB). *P-value not significantFigure 1.: Prevalence of Barrett’s esophagus (BE) after roux-en-y gastric bypass (RYGB), laparoscopic sleeve gastrectomy (LSG) and laparoscopic adjustable gastric banding (LAGB) over a 10 year follow up. *Explorys rounds to the nearest zero or 1.

Association between indicators of systemic inflammation biomarkers during puberty with breast density and onset of menarche

BackgroundSystemic inflammation may play a role in shaping breast composition, one of the strongest risk factors for breast cancer. Pubertal development presents a critical window of breast tissue susceptibility to exogenous and endogenous factors, including pro-inflammatory markers. However, little is known about the role of systemic inflammation on adolescent breast composition and pubertal development among girls.MethodsWe investigated associations between circulating levels of inflammatory markers (e.g., interleukin-6 (IL-6), tumor necrosis factor receptor 2 (TNFR2), and C-reactive protein (CRP)) at Tanner stages 2 and 4 and breast composition at Tanner stage 4 in a cohort of 397 adolescent girls in Santiago, Chile (Growth and Obesity Cohort Study, 2006–2018). Multivariable linear models were used to examine the association between breast composition and each inflammatory marker, stratifying by Tanner stage at inflammatory marker measurement. Accelerated failure time models were used to evaluate the association between inflammatory markers concentrations at each Tanner stage and time to menarche.ResultsIn age-adjusted linear regression models, a doubling of TNFR2 at Tanner 2 was associated with a 26% (95% CI 7–48%) increase in total breast volume at Tanner 4 and a 22% (95% CI 10–32%) decrease of fibroglandular volume at Tanner 4. In multivariable models further adjusted for body fatness and other covariates, these associations were attenuated to the null. The time to menarche was 3% (95% CI 1–5%) shorter among those in the highest quartile of IL-6 at Tanner 2 relative to those in the lowest quartile in fully adjusted models. Compared to those in the lowest quartile of CRP at Tanner 4, those in the highest quartile experienced 2% (95% CI 0–3%) longer time to menarche in multivariable models.ConclusionsSystemic inflammation during puberty was not associated with breast volume or breast density at the conclusion of breast development among pubertal girls after adjusting for body fatness; however, these circulating inflammation biomarkers, specifically CRP and IL-6, may affect the timing of menarche onset.

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

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. 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. National registries, Sweden. In this prospective cohort study, the Swedish Childhood Obesity Treatment Register was linked to several national registers. 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. 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.

Characteristics of adults with overweight and obesity who have not attempted weight loss in the prior 12 months

ObjectiveTo determine weight-related characteristics of adults with overweight or obesity who had not attempted weight loss in the prior 12 months. MethodsAdults from the obesity cohort of the PORTAL clinical data research network were randomly selected to complete a survey in 2015. It included topics of experiences with health care providers, weight history, and health-promoting behaviors. ResultsA total of 2811 adults completed the survey, of whom 24% reported not attempting weight loss in the previous 12 months. Controlling for sociodemographic characteristics and body mass index, respondents who reported that their health care provider never talked about weight were more likely to not attempt weight loss in the previous 12 months compared with respondents who reported providers frequently brought up weight (OR: 0.45; 95% CI: 0.24, 0.66). Respondents who perceived themselves as normal weight or underweight were 4.22 times more likely (95% CI: 3.53, 5.05) to not attempt weight loss compared with respondents who perceived themselves as overweight. Respondents who reported that they never tried to lose at least 10 lbs, ate 0−2 servings of fruits and vegetables daily, or engaged in 0−29 min of physical activity weekly were less likely to attempt weight loss. ConclusionsReceiving advice on weight loss from health care providers to improve awareness of overweight and obesity status may be important factors for a person’s weight management. Provider discussions about weight may be a strategy to motivate weight loss attempts.

Impact of Obesity on Outcomes of Patients With Coronavirus Disease 2019 in the United States: A Multicenter Electronic Health Records Network Study

Impact of Obesity on Outcomes of Patients With Coronavirus Disease 2019 in the United States: A Multicenter Electronic Health Records Network Study

β-Carotene Oxygenase 1 Activity Modulates Circulating Cholesterol Concentrations in Mice and Humans

Plasma cholesterol is one of the strongest risk factors associated with the development of atherosclerotic cardiovascular disease (ASCVD) and myocardial infarction. Human studies suggest that elevated plasma β-carotene is associated with reductions in circulating cholesterol and the risk of myocardial infarction. The molecular mechanisms underlying these observations are unknown. The objective of this study was to determine the impact of dietary β-carotene and the activity of β-carotene oxygenase 1 (BCO1), which is the enzyme responsible for the conversion of β-carotene to vitamin A, on circulating cholesterol concentration. In our preclinical study, we compared the effects of a 10-d intervention with a diet containing 50mg/kg of β-carotene on plasma cholesterol in 5-wk-old male and female C57 Black 6 wild-type and congenic BCO1-deficient mice. In our clinical study, we aimed to determine whether 5 common small nucleotide polymorphisms located in the BCO1 locus affected serum cholesterol concentrations in a population of young Mexican adults from the Universities of San Luis Potosí and Illinois: A Multidisciplinary Investigation on Genetics, Obesity, and Social-Environment (UP AMIGOS) cohort. Upon β-carotene feeding, Bco1-/- mice accumulated >20-fold greater plasma β-carotene and had ∼30mg/dL increased circulating total cholesterol (P <0.01) and non-HDL cholesterol (P <0.01) than wild-type congenic mice. Our results in the UP AMIGOS cohort show that the rs6564851 allele of BCO1, which has been linked to BCO1 enzymatic activity, was associated with a reduction in 10mg/dL total cholesterol concentrations (P=0.009) when adjusted for vitamin A and carotenoid intakes. Non-HDL-cholesterol concentration was also reduced by 10mg/dL when the data were adjusted for vitamin A and total carotenoid intakes (P=0.002), or vitamin A and β-carotene intakes (P=0.002). Overall, our results in mice and young adults show that BCO1 activity impacts circulating cholesterol concentration, linking vitamin A formation with the risk of developing ASCVD.

Does Obesity and Procedure Type Increase the Risk of In-Hospital Mortality in Laparoscopic Hysterectomy: A Report From the United States Hospitals.

ObjectivesTo assess the differences in demographics and laparoscopic hysterectomy type by comorbid obesity and to assess the risk of in-hospital mortality due to obesity and other comorbidities.MethodsWe conducted a cross-sectional study using the Nationwide Inpatient Sample (NIS, 2012-2014), and included 119,890 adult females undergoing total laparoscopic hysterectomy (TLH), laparoscopic-assisted vaginal hysterectomy (LAVH), and laparoscopic supracervical hysterectomy (LSH). We used a logistic regression model adjusted for confounders to assess the odds ratio (OR) of obesity on mortality in study inpatients.ResultsThe majority of the inpatients were middle-age 36-50 years (83.1%) and White (67.7%). Comorbidities were seen in a higher proportion of obesity cohort with most prevalent being hypertension (53.6%) and diabetes (23.9%), followed by depression and hypothyroidism (15.8% and 15.4%, respectively). Inpatients with comorbid obesity had 4.6 times (95% CI 2.79-7.69) higher odds for in-hospital mortality compared to non-obesity cohort. There was statistically no significant association between type of laparoscopic hysterectomy and in-hospital mortality.ConclusionAnalysis of national-level data shows that obese patients have a higher risk of in-hospital mortality by 364% compared to non-obese patients. There was no significant association between the laparoscopy procedure type and in-hospital mortality. More studies should focus on improving hospital outcomes and quality of life post-surgery in obese patients.

Differential Outcomes and Clinical Challenges of NAFLD With Extreme Obesity.

Nonalcoholic fatty liver disease (NAFLD) is closely associated with obesity. The prevalence of extreme obesity, defined as body mass index (BMI) of 50 kg/m2 or higher, is rising more rapidly than overall obesity. We aimed to compare the clinical outcomes and performance of noninvasive fibrosis assessment tools in NAFLD with or without extreme obesity. A retrospective analysis was performed in 304 patients with NAFLD with extreme obesity and compared them to patients with NAFLD with BMI of 40 kg/m2 or less, matched for age, gender, race, and liver fibrosis stage. The mean age of the NAFLD with extreme obesity cohort was 55.9 years, BMI 55 kg/m2, and 49.7% had cirrhosis at initial evaluation. Baseline cirrhosis and coronary artery disease were associated with increased risk of death, and dyslipidemia with decreased risk of mortality. Age, insulin use, hypertension, albumin and platelet count were associated with cirrhosis. Fifteen percent of patients had weight‐loss surgery, but this was not associated with survival or risk of cirrhosis. Of the 850 abdominal ultrasound scans performed in 255 patients, 24.1% were deemed suboptimal for hepatocellular carcinoma screening. The mean NAFLD fibrosis score (NFS) in the extreme obesity cohort, versus a propensity‐matched cohort with BMI of 40 kg/m2 or less, was significantly different for both low fibrosis (F0‐F2) (0.222 vs. −1.682, P < 0.0001) and high fibrosis (F3‐F4) (2.216 vs. 0.557, P < 0.001). Conclusion: NAFLD with extreme obesity is associated with increased risk of liver‐related and overall mortality. Accurate noninvasive assessment of liver fibrosis, low rates of weight loss surgery, and high failure rate of ultrasound were identified as clinical challenges in this population.

Dietary Patterns of Adolescents from the Chilean Growth and Obesity Cohort Study Indicate Poor Dietary Quality.

Diet during adolescence can have lasting effects on nutritional status, health, and development. We hypothesized that dietary patterns with low-quality nutrition are associated with overweightness. We collected data for 882 Chilean adolescents from the Growth and Obesity Cohort Study (mean age: 12 years). Dietary intake was assessed through 24-h recalls and weight status data were obtained during clinical visits. Dietary patterns were obtained through exploratory factor analysis. Multiple logistic regression models were used to examine cross-sectional associations between dietary patterns and overweight (BMI z-score ≥ 1 SD). Four dietary patterns were identified: “Breakfast/Light dinner”, “Natural foods”, “Western”, and “Snacking”. “Breakfast/Light dinner”, “Western”, and “Snacking” patterns provided higher energy and excess nutrients (sodium, saturated fat, and added sugar). Moreover, adolescents with higher adherence to “Western” or “ Snacking” patterns (third tertile) had higher odds of being classified as overweight (OR = 1.67; 95% CI: 1.103–2.522 and OR = 1.86; 95% CI: 1.235–2.792, respectively) than those with lower adherence (first tertile). “Natural foods” pattern was also associated with overweightness (OR = 1.83; 95% CI: 1.219–2.754). These dietary patterns were associated with overconsumption of nutrients of public health concern. Three of the four main dietary patterns were associated with overweightness. These results highlight the need of prioritizing adolescents on obesity prevention strategies.

Reproductive hormones during pubertal transition in girls with transient Thelarche

Transient thelarche (TT), that is, the appearance, regression and subsequent reappearance of breast buds, is a frequent phenomenon, but little is known about pubertal transition in these girls. To describe pubertal progression, growth, genotypes, reproductive hormones and growth factors in girls with TT compared to those who do not present TT (non-TT). Retrospective analysis of a longitudinal population-based study. Girls (n=508) of the Chilean Growth and Obesity cohort. Pubertal progression, reproductive hormones, follicle stimulating hormone (FSH) beta subunit/FSH receptor gene single nucleotide polymorphisms and growth. Thirty-seven girls (7.3%) were presented TT. These girls entered puberty by pubarche more frequently (51%) than girls with normal progression (non-TT; n=471; 23%, P=.005). Girls with TT who were under 8years old had lower androgens, anti-Müllerian hormone (AMH), luteinizing hormone (LH) and oestradiol (all P<.05) than older girls with TT. At the time of Tanner breast stage 2 (B2), girls with TT had higher androgens, LH, FSH, IGF1, LH, insulin and oestradiol (P<.01) than at the time of TT. TT girls were older at B2 (10.3±1.1 vs. 9.2±1.2years, P<.001) and menarche (12.3±0.8 vs. 12.0±1.0years, P=.040) than their counterparts (non-TT). No differences in anthropometric variables or FSHB/FSHR genotypes were detected. Transient thelarche is a frequent phenomenon that does not appear to be mediated by hypothalamic-pituitary-gonadal axis activation or by adiposity. Hormonal differences between earlier TT and later TT suggest that their mechanisms are different.

Identification of Aurora Kinase A as a Biomarker for Prognosis in Obesity Patients with Early Breast Cancer.

BackgroundObesity is associated both with a higher risk of developing breast cancer, particularly in postmenopausal women, and with worse disease outcome for women of all ages. Previous investigation suggested Aurora A kinase was able to partially restore the functionalities of obese adipose-derived mesenchymal stem cells by stabilizing their primary cilia and reestablishing a balance of multiple stemness-associated genes. The association between Aurora A and obesity breast cancer is still unclear. We hypothesized that overexpression of Aurora A was associated with poor survival in obesity breast cancer and the related axis mechanism was involved.MethodsA total of 517 primary breast cancer specimens were collected from the First Affiliated Hospital of China Medical University between January 2011 and November 2016. Our independent variable was BMI at baseline, categorized as overweight (BMI ≥25 kg/m2, as obesity cohort), and normal (18.5 ≤ BMI <25 kg/m2, as non-obesity cohort). The immunohistochemical (IHC) staining was performed with Aurora A, Survivin, MMP11, Cyclin B1, and Cathepsin L. Kaplan–Meier curve was used to analyze overall survival in our cohorts and TCGA-BRCA data (GSE3494). Log rank test was used to calculate P values. Protein–protein interaction (PPI) network analysis and MCODE model were used to analyze the Aurora-altered signal pathway from GSE78958.ResultsAmong 517 breast patients, Aurora A-positive (staining scores ≥4) was significantly higher in obesity breast carcinoma compared with non-obesity cancer carcinoma (χ2=9.79, P=0.002), with more frequency in hormone receptor-negative (68.4% vs 77.9%, P=0.015) and HER2-positive patients (28.7% vs 17.9%, P=0.003). High Aurora A expression was remarkably and significantly associated with overall survival (OS) (8-year OS ratio: 69.5% vs 81.1%, OR=1.76, 95% CI: 1.03~3.02, P=0.041) in obesity cohort. Interestingly, higher expression of Aurora A was not associated with a shorter overall survival time among the non-obesity breast cancer (8-year OS ratio: 81.4% vs 85.8%, OR=1.40, 95% CI: 0.79~2.45, P=0.229). As for RFS, the expression levels of Aurora A expression genes have no significance with RFS statistically in non-obesity and obesity patients. Aurora A and lymph node metastases were significantly poor prognostic factors for OS, and borderline significance was noted for high BMI. Kaplan–Meier survival analysis from TCGA database confirmed that the high Aurora A expression group had worse prognosis (HR=1.47, 95% CI: 1.14–1.90, P=0.003). The KEGG pathway enrichment results were consistent with GO biological process term analysis, in which CCNB1 was enriched for upregulated Aurora A. In our samples, Aurora A level on tumor cytoplasm had broad connections with Cyclin B1 by IHC correlation analysis (correlation coefficient = 0.227, P=0.001).ConclusionOur finding demonstrates here for the first time that high expression of Aurora A was notably correlated with early recurrence and poor overall survival in obesity patients with early breast cancer. The Aurora A-Cyclin B1 axis could be a potential promising therapeutic target for cancer intervention and therapy.

Association of childhood obesity with risk of early all-cause and cause-specific mortality: A Swedish prospective cohort study

BackgroundPediatric obesity is associated with increased risk of premature death from middle age onward, but whether the risk is already increased in young adulthood is unclear. The aim was to investigate whether individuals who had obesity in childhood have an increased mortality risk in young adulthood, compared with a population-based comparison group.Methods and findingsIn this prospective cohort study, we linked nationwide registers and collected data on 41,359 individuals. Individuals enrolled at age 3–17.9 years in the Swedish Childhood Obesity Treatment Register (BORIS) and living in Sweden on their 18th birthday (start of follow-up) were included. A comparison group was matched by year of birth, sex, and area of residence. We analyzed all-cause mortality and cause-specific mortality using Cox proportional hazards models, adjusted according to group, sex, Nordic origin, and parental socioeconomic status (SES). Over 190,752 person-years of follow-up (median follow-up time 3.6 years), 104 deaths were recorded. Median (IQR) age at death was 22.0 (20.0–24.5) years. In the childhood obesity cohort, 0.55% (n = 39) died during the follow-up period, compared to 0.19% (n = 65) in the comparison group (p < 0.001). More than a quarter of the deaths among individuals in the childhood obesity cohort had obesity recorded as a primary or contributing cause of death. Male sex and low parental SES were associated with premature all-cause mortality. Suicide and self-harm with undetermined intent were the main cause of death in both groups. The largest difference between the groups lay within endogenous causes of death, where children who had undergone obesity treatment had an adjusted mortality rate ratio of 4.04 (95% CI 2.00–8.17, p < 0.001) compared with the comparison group. The main study limitation was the lack of anthropometric data in the comparison group.ConclusionsOur study shows that the risk of mortality in early adulthood may be higher for individuals who had obesity in childhood compared to a population-based comparison group.

Anxiety and depression in children and adolescents with obesity: a nationwide study in Sweden

BackgroundAnxiety and depression are more common in children with obesity than in children of normal weight, but it is unclear whether this association is independent of other known risk factors. Interpretation of results from previous studies is hampered by methodological limitations, including self-reported assessment of anxiety, depression, and anthropometry. The aim of this study was to investigate whether obesity increases the risk of anxiety or depression independently of other risk factors in a large cohort of children and adolescents, using robust measures with regard to exposure and outcome.MethodsChildren aged 6–17 years in the Swedish Childhood Obesity Treatment Register (BORIS, 2005–2015) were included (n = 12,507) and compared with a matched group (sex, year of birth, and area of residence) from the general population (n = 60,063). The main outcome was a diagnosis of anxiety or depression identified through ICD codes or dispensed prescribed medication within 3 years after the end of obesity treatment. Hazard ratios (HRs) with 95% confidence intervals (CIs) from Cox proportional models were adjusted for several known confounders.ResultsObesity remained a significant risk factor for anxiety and depression in children and adolescents after adjusting for Nordic background, neuropsychiatric disorders, family history of anxiety/depression, and socioeconomic status. Girls in the obesity cohort had a 43% higher risk of anxiety and depression compared to girls in the general population (adjusted HR 1.43, 95% CI 1.31–1.57; p < 0.0001). The risk in boys with obesity was similar (adjusted HR 1.33, 95% CI 1.20–1.48; p < 0.0001). In sensitivity analyses, excluding subjects with neuropsychiatric disorders and a family history of anxiety/depression, the estimated risks in individuals with obesity were even higher compared with results from the main analyses (adjusted HR [95% CI]: girls = 1.56 [1.31–1.87], boys = 2.04 [1.64–2.54]).ConclusionsResults from this study support the hypothesis that obesity per se is associated with risk of both anxiety and depression in children and adolescents.