Higher Baseline Body Mass Index Research Articles

Real-world experiences: Efficacy and tolerability of pirfenidone in clinical practice.

BackgroundThe safety of pirfenidone on pulmonary fibrosis patients with other kinds of interstitial lung diseases (ILDs) in addition to idiopathic pulmonary fibrosis (IPF) is unknown. Furthermore, its effectiveness-related factors on IPF patients are not quite explored.MethodsA retrospective study, on patients prescribed pirfenidone for pulmonary fibrosis, was conducted to assess effectiveness on IPF patients and tolerability of all patients with lung fibrosis. The effectiveness of pirfenidone was tested on 110 IPF subjects receiving treatment for ≥3 months by high-resolution computed tomography (HRCT). Response-linked factors and progression-free survival (PFS) were also analyzed. The data about safety outcomes and drug dose adjustments were collected from all included subjects.ResultsA total of 176 subjects were included: 117 were IPF, 19 connective tissue disease-associated interstitial lung disease (CTD-ILD), and 40 unclassifiable ILD. Out of the 110 IPF subjects, 89 subjects were assessed as stable and 21 as progressive, out of which 10 died of acute exacerbation and 11 progressed. The effectiveness was significantly related to their baseline body mass index (BMI). IPF subjects with BMI>25kg/m2 or diffusion capacity of carbon monoxide (DLco)>30% had higher PFS rate. The most common adverse events were skin-related and gastrointestinal-related. Drug discontinuation owing to adverse events occurred similarly in these three groups.ConclusionPirfenidone was well tolerated in most of the lung fibrosis patients besides IPF, with a similar pattern of adverse events. Nearly 80% of IPF subjects were assessed as stable. More benefits were seen in IPF patients with higher BMI or mild-to-moderate disease.

Obesity and Baseline Estradiol Levels Are Independent Predictors for Initiation of Anastrozole in Hypogonadal Men on Clomiphene Citrate.

PurposeTo assess the conversion rate from clomiphene citrate (CC) monotherapy to combination CC+anastrozole (AZ) therapy in hypogonadal men and the predictors associated with the initiation of AZ.Materials and MethodsA retrospective review of records from hypogonadal men treated with CC in a single fertility center was performed from 2013 to 2018. Patient age, body mass index (BMI), blood pressure, and reproductive hormones were obtained at baseline. Obesity was defined as BMI≥30 kg/m2. Cox proportional hazards models were used to identify predictors of switching to combination CC+AZ therapy.ResultsA total of 318 men on CC were included. Median (interquartile range) age was 34 years (30–39 years) and patients were followed for a median of 9 months (4–17 months). Of these, 97 (30.5%) were started on CC+AZ therapy. These patients had higher baseline BMI and estradiol, which in multivariable regression were significant predictors for switching to CC+AZ therapy. A threshold of 18.5 pg/mL for baseline estradiol provided the highest accuracy for predicting the addition of AZ after adjusting for baseline BMI and total testosterone levels.ConclusionsIn our practice, following CC monotherapy, 30% of men were initiated on CC+AZ. Obesity (BMI≥30 kg/m2) and baseline estradiol ≥18.5 pg/mL can predict the conversion to combination therapy with addition of AZ. This information can be used to counsel patients and also help to identify patients who can be started on combination therapy upfront.

Nutritional outcomes in head and neck cancer patients: is intensive nutritional care worth it?

ObjectiveThis study aimed to compare nutritional outcomes before and after implementation of weekly dietetic counseling (intensive nutritional care) in head and neck cancers patients. MethodsA retrospective study with all head and neck patients, who received radiotherapy between January 2010 and December 2017 were performed. The main outcome was significant weight loss. Compliance to caloric and protein recommendations were also evaluated. ResultsIn all, 472 patients were included. Weight loss was not different between before and after implementation (-6.7%; IQ -10.5/-1.9 vs -5.0%; IQ -9.8/-0.7;p=0.06).There were no significant difference in terms of meeting the recommended intake. Higher baseline body mass index and oral nutritional support predicted significant weight loss. ConclusionImplementation of intensive nutritional care did not have an impact on weight loss and energy and protein intake in head and neck cancer patients. Further research would be of value to determine the appropriate service-delivery model to achieve optimal patient outcomes.

Incidence and Risk Factors of Obesity in Childhood Solid-Organ Transplant Recipients.

Obesity is a significant public health concern; however, the incidence post solid-organ transplantation is not well reported. This study determined the incidence and risk factors of obesity among pediatric solid-organ transplant recipients (heart, lung, liver, kidney, multiorgan) at The Hospital for Sick Children (2002-2011), excluding prevalent obesity. Follow-up occurred from transplantation until development of obesity, last follow-up, or end of study. Incidence of obesity was determined overall, by baseline body mass index, and organ group. Risk factors were assessed using Cox proportional-hazards regression. Among 410 (55% male) children, median transplant age was 8.9 (interquartile range [IQR]: 1.0-14.5) years. Median follow-up time was 3.6 (IQR: 1.5-6.4) years. Incidence of obesity was 65.2 (95% confidence interval [CI]: 52.7-80.4) per 1000 person-years. Overweight recipients had a higher incidence, 190.4 (95% CI: 114.8-315.8) per 1000 person-years, than nonoverweight recipients, 56.1 (95% CI: 44.3-71.1). Cumulative incidence of obesity 5-years posttransplant was 24.1%. Kidney relative to heart recipients had the highest risk (3.13 adjusted hazard ratio [aHR]; 95% CI: 1.53-6.40) for obesity. Lung and liver recipients had similar rates to heart recipients. Those with higher baseline body mass index (z-score; 1.72 aHR; 95% CI: 1.39-2.14), overweight status (2.63 HR; 95% CI: 1.71-4.04), and younger transplant age (y; 1.18 aHR; 95% CI: 1.12-1.25) were at highest risk of obesity. Higher cumulative steroid dosage (per 10 mg/kg) was associated with increased risk of obesity after adjustment. Among all transplanted children at The Hospital for Sick Children, 25% developed obesity within 5-years posttransplant. Kidney recipients, younger children, those overweight at transplant, and those with higher cumulative steroid use (per 10 mg/kg) were at greatest risk. Early screening and intervention for obesity are important preventative strategies.

HEART FAILURE OUTCOMES IN PATIENTS WITH DIABETES WITH AND WITHOUT ATRIAL FIBRILLATION - DATA FROM THE EMPA-REG OUTCOME STUDY

Atrial fibrillation (AF) is a frequent comorbidity in heart failure (HF) that worsens outcomes, reflecting more advanced myocardial disease. AF confers an additional risk associated with HF, and HF treatments, such as beta blockers, have not reduced mortality in patients with AF. In the EMPA-REG OUTCOME study, empagliflozin (EMPA) reduced HF hospitalizations (HHF), cardiovascular (CV) death, HHF/CV death, and incident/worsening nephropathy in patients with type 2 diabetes (T2D) and established CV disease. This post-hoc analysis of EMPA-REG OUTCOME examined (1) classical and expanded HF outcomes in a T2D population with and without pre-existing AF, and (2) the effect of EMPA in patients with and without AF. In total, 7020 patients with T2D and CV disease were treated with EMPA 10 mg, 25 mg or placebo (PBO), with a median follow up of 3.1 years. We explored the association between investigator-reported history of AF at baseline and time to first HHF, CV death, HHF/CV death, introduction of loop diuretics, occurrence of edema and incident/worsening nephropathy. We also assessed the consistency of the effect of EMPA in patients with and without AF at baseline. Differences in risks between groups were assessed using a Cox proportional hazards model with factors for age, sex, baseline body mass index (BMI), baseline glycated hemoglobin, baseline estimated glomerular filtration rate (eGFR), region, treatment, AF and treatment by AF interaction. All analyses were performed on a nominal two-sided alpha of 0.05 without adjustment for multiplicity. Overall, 389 patients had investigator-reported AF at baseline. Patients with AF were more often male (78.1 vs 71.1%), older (mean age 68.4 vs 62.8 years), had higher BMI (mean 31.7 vs 30.6 kg/m2), and lower eGFR (mean 67.4 vs 74.4 ml/min/1.73 m2). Furthermore, in PBO and EMPA-treated patients, rates of HHF/CV death were higher in patients with vs without AF at baseline (PBO/EMPA 23.2/15.4% vs 7.5/5.1%). Increased risks were also detected for HHF (PBO/EMPA 12.7/8.5% vs 3.5/2.4%), introduction of loop diuretics (PBO/EMPA 25.6/18.5% vs 12.7/8.2%), first occurrence of edema (PBO/EMPA 16.2/5.7% vs 9.7/5.3%) and incident/worsening nephropathy (PBO/EMPA 24.6/12.6% vs 18.5/12.7%). EMPA consistently reduced HHF, CV death, HHF/CV death, introduction of loop diuretics, occurrence of edema and incident/worsening nephropathy in patients with and without AF (Figure). In patients with T2D and CV disease, AF is associated with an increased risk of CV and HF outcomes and mortality. The treatment effects of EMPA are consistent in patients with and without AF.

Chlorinated persistent organic pollutants and type 2 diabetes - a population-based study with pre- and post- diagnostic plasma samples

PDS 63: Chemicals and metals: health effects, Exhibition Hall (PDS), Ground floor, August 27, 2019, 10:30 AM - 12:00 PM Background: Persistent organic pollutants (POPs) have been associated with type 2 diabetes (T2D), but causality is uncertain. Objective: Within longitudinal population-based data from northern Sweden, we assessed how POPs associated with T2D prospectively and cross-sectionally, and further investigated factors related to individual changes in POP concentrations. Methods: For 129 case-controls pairs matched by age, sex and date of sampling, plasma concentrations of HCB, p,p´-DDE, dioxin-like PCBs (PCB-118, -156), and non-dioxin like PCBs (PCB-74, -99, -138 -153, -170, -180, -183 -187) were analyzed twice (baseline and follow-up, 9-20 years apart). The cases received their T2D diagnose between baseline and follow-up. Prospective (using baseline data) and cross-sectional (using follow-up data) odds ratios (ORs) for T2D on lipid standardized POPs (HCB, p,p´-DDE, ∑DL-PCBs, ∑NDL-PCBs) were estimated using conditional logistic regression, adjusting for body mass index (BMI) and plasma lipids. The influence of BMI, weight-change, and plasma lipids on longitudinal changes in POP concentrations were evaluated among non-diabetic individuals (n=306). Results: POPs were associated with T2D in both the prospective and cross-sectional assessments. Of a standard deviation increase in POPs, prospective ORs ranged 1.42 (95% CI: 0.99, 2.06) for ∑NDL-PCBs to 1.55 (95% CI: 1.01, 2.38) for HCB (p<0.05 only for HCB), and cross-sectional ORs ranged 1.62 (95% CI: 1.13; 2.32) for p,p´-DDE to 2.06 (95% CI: 1.29, 3.28) for ∑DL-PCBs (p<0.05 for all POPs). In analyses of non-diabetic individuals, higher baseline BMI, decreased weight and decreased plasma lipid concentrations were associated with a slower decrease of POPs. Cases had, besides a higher BMI, reduced cholesterol and weight gain at follow-up compared to controls, which can explain the higher ORs in the cross-sectional assessments. Discussion: The indication that individuals’ body fat history might influence POP-T2D associations through decreased elimination rate, weakens the epidemiological support for a causal association.

Associations of obesity with antidiabetic medication use after living kidney donation: An analysis of linked national registry and pharmacy fill records.

We examined a novel linkage of national US donor registry data with records from a pharmacy claims warehouse (2007-2016) to examine associations (adjusted hazard ratio, LCL aHRUCL ) of post-donation fills of antidiabetic medications (ADM, insulin or non-insulin agents) with body mass index (BMI) at donation and other demographic and clinical factors. In 28515 living kidney donors (LKDs), incidence of ADM use at 9years rose in a graded manner with higher baseline BMI: underweight, 0.9%; normal weight, 2.1%; overweight, 3.5%; obese, 8.5%. Obesity was associated with higher risk of ADM use compared with normal BMI (aHR, 3.36 4.596.27 ). Metformin was the most commonly used ADM and was filled more often by obese than by normal weight donors (9-year incidence, 6.87% vs 1.85%, aHR, 3.55 5.007.04 ). Insulin use was uncommon and did not differ significantly by BMI. Among a subgroup with BMI data at the 1-year post-donation anniversary (n=19528), compared with stable BMI, BMI increase >0.5kg/m2 by year 1 was associated with increased risk of subsequent ADM use (aHR, 1.03 1.482.14, P=.04). While this study did not assess the impact of donation on the development of obesity, these data support that among LKD, obesity is a strong correlate of ADM use.

Abstract 116: BMI is Not a Risk Factor for All-Cause Mortality and Cardiovascular Disease Among African American Women

Background: Across the age spectrum, obesity rates are higher among African Americans (AA) than Whites, particularly women. Previous findings from a large cohort study indicated that risk of all-cause mortality is only moderately elevated with increased weight among AA, but this relationship is a much stronger finding in Whites. In this study, we examined the relationship of baseline body mass index (BMI) to incident all-cause mortality and fatal and non-fatal cardiovascular and renal disease (CVRD) events. Methods: Between 1994 - 2006, 1723 AA (52% women, age: 44±7 yrs., BMI: 29 ± 6 kg/m 2 , 51% hypertensive) were recruited for genetic studies of hypertension. Height and weight were obtained at baseline in a standardized manner. Mortality data were obtained from the National Death Index in 2018 on all subjects. Incidence of fatal/non-fatal CVRD events was obtained and confirmed by review of paper and electronic medical records between 2015-2019 in a sub-sample. Subjects who had either a CVRD event or at least 10 years of follow-up data available with no event were included (n=788). Logistic regression (LR) was performed to determine if BMI predicted mortality or a CVRD event. Results: There were 325 deaths (19%, time-to-death: 12±3 yrs.) from all causes. During a follow-up of 14±4 yrs., 154 subjects had a CVRD (20%) event/death. There was no difference in age between sexes, but women had a higher BMI compared to men (30±7 vs. 27±5 kg/m 2 , p&lt;0.0001). Men had a higher mortality (23% vs. 15%, p&lt;0.0001) and more CVRD events (24% vs. 16%, p = 0.008). The odds ratio (OR) for death was 1.62 (CI: 1.3-2.1, p=0.0002) in men compared to women. Baseline BMI was not predictive of all-cause mortality in the total sample or in men or women separately. BMI predicted CVRD events in men with an OR of 1.08 (CI: 1.03-1.13), i.e. one-unit increase in BMI in men led to 8% increase in odds for CVRD events. However, BMI was not predictive of CVDR events in women (OR: 1.01 [0.98-1.05]). Conclusion: This is the first study to evaluate the effect of BMI longitudinally on incident CVRD events among AA. Although BMI is the most common metric to define obesity, it is not predictive of CVRD and/or mortality risk among AA women. This factor should be considered while determining cardiovascular disease risk status among AA.

Clinical Significance of Early Hospital Readmission in Continuous-Flow Left Ventricular Assist Device Patients.

Data on the clinical significance of early hospital readmission within 90 days following left ventricular assist device (LVAD) implantation in patients with continuous-flow LVAD are limited. We aimed to assess the incidence, predictors, and outcomes of 90-day readmission in LVAD patients. Hospital readmission or death was assessed within 90 days after hospital discharge in 177 patients with HeartMate II LVADs implanted between May 2008 and June 2014. Predictors of early readmission and risk of death were evaluated using multivariable Cox models following adjustment for clinical covariates. Hospital readmission or death rate was 37% within 90 days. Age at implantation (hazard ratio [HR] = 1.03 per 1 year increase, p = 0.016), diabetes (HR = 2.19, p = 0.031) and smoking at baseline (HR = 2.06, p = 0.034) predicted early hospital readmission, while a higher baseline body mass index was found to be protective (HR = 0.92 per each unit increase in body mass index, p = 0.003). One-year all-cause mortality was 19% in patients with early hospital readmission as compared to 1% with no early hospital readmission (HR 15.50, p = 0.01). One-year mortality was 35% in patients with 2 or more readmissions compared to 10% mortality in patients with one readmission and 1% mortality in patients with no readmissions (p < 0.001). In LVAD patients, there is a high incidence of hospital readmission within 90 days, which is associated with an increased mortality. Targeted interventions, such as closer follow-up to prevent early and recurrent hospital readmissions in LVAD recipients, are warranted to improve outcomes.

Effect of Body Mass Index on 5-FU-Based Chemotherapy Toxicity and Efficacy Among Patients With Metastatic Colorectal Cancer; A Pooled Analysis of 5 Randomized Trials

IntroductionWe conducted this study to assess the effect of baseline body mass index (BMI) on the toxicity and efficacy of systemic chemotherapy among patients with metastatic colorectal cancer (CRC). Patients and MethodsThis was a pooled analysis of 5 clinical trials (NCT00115765, NCT00364013, NCT00272051, NCT00305188, and NCT00384176), which were accessed from the Project Data Sphere (www.projectdatasphere.org) platform. Multivariable logistic regression analysis was used to assess the relationship between BMI and the probability of different toxicities. Kaplan–Meier survival estimates were used to assess the effect of BMI on overall and progression-free survival. Multivariable Cox regression analysis was additionally conducted to evaluate the effect of BMI on overall and progression-free survival. ResultsA total of 3155 patients were included in the current analysis. Within multivariable logistic regression analysis, higher BMI was associated with higher probability of all-grade nausea and vomiting (odds ratio [OR], 1.025; 95% confidence interval [CI], 1.009-1.042; P = .002) and peripheral neuropathy (OR, 1.018; 95% CI, 1.001-1.034; P = .036; analysis restricted to oxaliplatin-treated patients). Lower BMI was associated with a higher probability of all-grade anemia (OR, 0.975; 95% CI, 0.956-0.995; P = .015), high-grade anemia (OR, 0.941; 95% CI, 0.890-0.994; P = .030), all-grade neutropenia (OR, 0.983; 95% CI, 0.968-0.999; P = .034), and high-grade neutropenia (OR, 0.962; 95% CI, 0.945-0.979; P < .001). Higher BMI also seemed to correlate with better overall survival in a multivariable Cox regression model (hazard ratio as a continuous variable: 0.977; 95% CI, 0.967-0.988; P < .001). ConclusionLower BMI was associated with a higher risk of hematological toxicities (anemia and neutropenia) whereas higher BMI might be associated with a higher risk of nausea, vomiting, and peripheral neuropathy. Higher BMI also seemed to be associated with better overall survival among patients with metastatic CRC.

Fracture Risk in Women with Breast Cancer Initiating Aromatase Inhibitor Therapy: A Registry-Based Cohort Study.

Aromatase inhibitors (AIs) used in breast cancer induce loss in bone mineral density (BMD) and are reported to increase fracture risk. Using a population-based BMD registry, we identified women aged at least 40 years initiating AIs for breast cancer with at least 12 months of AI exposure (n = 1,775), women with breast cancer not receiving AIs (n = 1,016), and women from the general population (n = 34,205). Fracture outcomes were assessed to March 31, 2017 (mean, 6.2 years for AI users). At baseline, AI users had higher body mass index (BMI), higher BMD, lower osteoporosis prevalence, and fewer prior fractures than women from the general population or women with breast cancer without AI use (all p < .001). After adjusting for all covariates, AI users were not at significantly greater risk for major osteoporotic fractures (hazard ratio [HR], 1.15; 95% confidence interval [CI], 0.93-1.42), hip fracture (HR, 0.90; 95% CI, 0.56-1.43), or any fracture (HR, 1.06; 95% CI, 0.88-1.28) compared with the general population. Higher baseline BMI, BMD, and lower prevalence of prior fracture at baseline may offset the adverse effects of AI exposure. Although confirmatory data from large cohort studies are required, our findings challenge the view that all women with breast cancer initiating AI therapy should be considered at high risk for fractures. In a population-based observational registry that included 1,775 patients initiating long-term aromatase inhibitor therapy, risk for major osteoporotic fracture, hip fracture, or any fracture was similar to the general population. Higher baseline body mass index, bone mineral density, and lower prevalence of prior fracture at baseline may offset the adverse effects of aromatase inhibitor exposure.

Fruit and Vegetable Consumption in Overweight or Obese Individuals: A Meta-Analysis.

Researchers have shown that fruit and vegetable consumption (FVC) promotes weight loss and prevents weight gain, thereby reducing risks for chronic health conditions. We conducted a meta-analysis to examine the overall effects of FVC interventions on weight loss for those with body-mass index (BMI) >25; we follow-up with moderator analyses to determine if effects varied based on participants, interventions, methods, or source characteristics. Extensive literature searches were conducted, resulting in 16 studies and providing 17 comparisons, across 3,719 participants. The overall summary effect was large (-2.81kg; p<.001). Several moderators were significant for increased weight loss: low socio-economic status (-4.99kg; p<.001), higher baseline BMI (slope=-0.29; p=.047), longer interventions (slope=0.012; p<.001), and recruitment setting [health care/programs (-3.7kg; p<.001); work/academic settings (-5.2kg: p<.001)]. Future researchers should investigate varying intervention lengths and examine specific needs of subgroups-higher versus lower socio-economic status, and overweight versus obese.

The effects of weight loss and metformin on cognition among breast cancer survivors: Evidence from the Reach for Health study.

Breast cancer survivors experience problems with cognition that interfere with daily life and can last for years. In the general population, obesity and diabetes are risk factors for cognitive decline, and weight loss can improve cognition; however, the impact of intentional weight loss on cancer survivors' cognition has not been tested. We investigated the impact of weight loss and metformin on changes in cognitive function in a sample of breast cancer survivors. Overweight/obese postmenopausal breast cancer survivors (n=333) were randomized to a weight loss intervention versus control and metformin versus placebo in a 2×2 factorial design. Outcomes were changes in five cognitive domains from baseline to 6months measured by objective neurocognitive tests. There were no statistically significant intervention effects for the metformin or weight loss interventions in five neurocognitive domains. Baseline body mass index (BMI) was a significant effect modifier of the changes in verbal functioning for the weight loss (P=0.009) and metformin interventions (P=0.0125). These effect modifications were independent of percent weight loss achieved during the 6-month study period. This randomized controlled trial of weight loss and metformin interventions that examined changes to cognition among breast cancer survivors suggests that these interventions may not improve cognitive functioning among breast cancer survivors in general. However, weight loss may improve verbal functioning among individuals with a higher BMI.

Estimated 8-year cumulative incidence of diabetes mellitus among Sami and non-Sami inhabitants of Northern Norway - The SAMINOR Study

BackgroundThe aim of the study was to estimate and compare the 8-year cumulative incidence of diabetes mellitus (DM) among Sami and non-Sami inhabitants of rural districts in Northern Norway.MethodsLongitudinal study based on linkage of two cross-sectional surveys, the SAMINOR 1 Survey (2003–2004) and the SAMINOR 2 Clinical Survey (2012–2014). Ten municipalities in rural Northern Norway were included in the study. DM-free participants aged 30 and 36–71 years in SAMINOR 1 were followed from 2 years after SAMINOR 1 to attendance in SAMINOR 2. The average follow-up time was 8.1 years. Of 5875 subjects who had participated in SAMINOR 1 and could potentially be followed to SAMINOR 2, 3303 were included in the final analysis. Self-reported DM and/or HbA1c ≥ 6.5% were used to identify incident cases of DM.ResultsAt baseline, body mass index (BMI) and waist-to-height ratio (WHtR) were higher among Sami than among their non-Sami counterparts. After 8 years of follow-up, 201 incident cases of DM were identified (6.1% both Sami and non-Sami subjects). No statistically significant difference was observed in the cumulative incidence of DM between the Sami and non-Sami.ConclusionsNo statistically significant difference in the 8-year cumulative incidence of DM among Sami and non-Sami was observed, although Sami men and women had higher baseline BMI and WHtR.

Body Composition and Acquired Functional Impairment in Survivors of Pediatric Critical Illness.

To identify whether body mass and composition is associated with acquired functional impairment in PICU survivors. Retrospective dual-cohort study. Single multidisciplinary PICU. Two distinct PICU survivor cohorts: 432 unselected admissions from April 2015 to March 2016, and separately 92 patients with abdominal CT imaging at admission from January 2010 to December 2016. None. Admission body mass index and Functional Status Scale scores at admission, PICU discharge, and hospital discharge were obtained for all patients. Acquired functional impairment was defined as increase greater than or equal to 3 in Functional Status Scale from baseline. Patients were classified as having: "temporary acquired impairment" (acquired impairment at PICU discharge recovering by hospital discharge), "persistent acquired impairment" (acquired impairment at PICU discharge persisting to hospital discharge), and "no acquired impairment." CT scans were analyzed for skeletal muscle and fat area using National Institute of Health ImageJ software (Bethesda, MD). Multinomial logistic regression analyses were conducted to identify associations between body mass index, muscle and fat indices, and acquired functional impairment. High baseline body mass index was consistently predictive of persistent acquired impairment in both cohorts. In the second cohort, when body mass index was replaced with radiologic anthropometric measurements, greater skeletal muscle, and visceral adipose tissue indices were independently associated with persistent acquired impairment at hospital discharge (adjusted odds ratio, 1.29; 95% CI, 1.03-1.61; p = 0.024 and adjusted odds ratio, 1.13; 95% CI, 1.01-1.28; p = 0.042, respectively). However, this relationship was no longer significant in children with PICU stay greater than 2 days. In PICU survivors, baseline body mass and composition may play a role in the persistence of acquired functional impairment at hospital discharge. Characterization and quantification of skeletal muscle and fat deserves further study in larger cohorts of PICU children.

Association of baseline body mass index (BMI) with response and survival in patients (Pts) with advanced melanoma (MEL) receiving PD-1 inhibitors.

9579 Background: Obesity promotes PD-1–mediated T cell dysfunction but also improves tumor response to PD-1 blockade. Obesity has been linked with positive outcomes in pts treated with PD-1 blockade. To evaluate the prognostic utility of BMI, we performed a retrospective evaluation of BMI and other covariates in 172 pts with stage IV cutaneous MEL. Methods: Pts with stage IV cutaneous MEL who received anti PD-1 therapy at the University of Pittsburgh between 2014-2018 were included in this analysis. PD-1 blockade was continued until progression or intolerable toxicity. Tumor assessment was performed at baseline and every 12 weeks and response classified per RECIST v1.1. Clinical and demographic data were obtained. BMI was defined based on values at the first treatment date and dichotomized into two groups: ≥30 vs. &lt; 30. Fisher exact test was used to evaluate the correlation between BMI group and ORR. Kaplan Meier method and Cox proportional hazard models were performed to analyzed the time-to-event outcomes (OS and PFS). Results: 172 pts with advanced MEL were evaluated. Greater BMI was associated with greater ORR, PFS and OS across various BMI cutoffs (BMI≥28, BMI≥30 and BMI≥35) although this effect was most obvious at BMI≥30. Pts with BMI≥30 achieved higher ORR than those with BMI &lt; 30 (74% vs. 58%, p-value = 0.04). Concordantly, pts with BMI≥30 had improved PFS and OS: median PFS (BMI≥30 21.1 mos vs. BMI &lt; 30 10.7 mos) and median OS (BMI≥30 35.4 mos vs. BMI &lt; 30 22.8 mos). Higher BMI was independently associated with improved OS (p = 0.018) and PFS (p = 0.047) adjusting for age, Breslow thickness and sex. No significant interaction was observed between the effects of BMI and that of age, sex, or Breslow thickness. Conclusions: Increased BMI was associated with greater ORR in addition to previously reported associations with PFS/OS in a large retrospective series of advanced MEL pts treated with PD-1 blockade. This data was independent of other prognostic factors and underscore the “inflammaging” effects of obesity and age in relation to anti PD-1 therapy in advanced cancer.

Nutritional parameters associated with hospital admissions in patients being treated for head and neck cancer.

This study analysed nutritional parameters (baseline body mass index (BMI), weight changes and enteral nutrition (EN) use, and their association with hospital admissions during radiotherapy in patients with head and neck cancer (HNC)). A retrospective review of patients diagnosed with HNC and treated with radiotherapy between October 2012 and April 2014 was conducted. Data on each subject's diagnosis, age, sex, chemotherapy, previous surgery, EN use, weight changes, and BMI were examined for their association with hospital admissions during treatment. Eighty-three patients were included, mean age (±standard deviation) = 61 (± 11years). Thirty-four percent had self-reported weight loss at diagnosis, and mean BMI was 26.2 ± 5.3kg/m2. Mean weight change during treatment was - 5.1 ± 6.2%. Ten patients used EN, with mean weight stabilisation during EN use (0.3 ± 5.1%). Higher presenting BMI, younger age, and definitive radiotherapy ± chemotherapy predicted greater weight loss (p < 0.05). Critical weight loss ≥ 5% was associated with a higher number of hospital admissions for nutrition reasons (n = 10) (p = 0.011) compared with those without critical weight loss (n = 2). EN use was associated with a higher number of nutrition-related admissions; however, it did not predict length of stay among those admitted. Critical weight loss during radiotherapy was associated with unplanned nutrition-related hospital admissions. Higher BMI was associated with greater weight loss during radiotherapy, whilst EN use assisted in weight preservation. Further research around patient selection for nutritional interventions aimed at preventing critical weight loss and unplanned hospital admissions is needed.

Chlorinated persistent organic pollutants and type 2 diabetes - A population-based study with pre- and post- diagnostic plasma samples

BackgroundPersistent organic pollutants (POPs) have been associated with type 2 diabetes (T2D), but causality is uncertain. ObjectiveWithin longitudinal population-based data from northern Sweden, we assessed how POPs associated with T2D prospectively and cross-sectionally, and further investigated factors related to individual changes in POP concentrations. MethodsFor 129 case-controls pairs matched by age, sex and date of sampling, plasma concentrations of hexachlorobenzene (HCB), dichlorodiphenyl-dichloroethylene (p,p'-DDE), dioxin-like (DL) polychlorinated biphenyl congeners (PCB-118 and PCB-156), and non-dioxin like (NDL-PCB: PCB-74, -99, -138 -153, −170, −180, −183 and PCB-187) were analyzed twice (baseline and follow-up, 9–20 years apart). The cases received their T2D diagnose between baseline and follow-up. Prospective (using baseline data) and cross-sectional (using follow-up data) odds ratios (ORs) for T2D on lipid standardized POPs (HCB, p,p'-DDE, ∑DL-PCBs, ∑NDL-PCBs) were estimated using conditional logistic regression, adjusting for body mass index (BMI) and plasma lipids. The influence of BMI, weight-change, and plasma lipids on longitudinal changes in POP concentrations were evaluated among non-diabetic individuals (n = 306). ResultsPOPs were associated with T2D in both the prospective and cross-sectional assessments. Of a standard deviation increase in POPs, prospective ORs ranged 1.42 (95% CI: 0.99, 2.06) for ∑NDL-PCBs to 1.55 (95% CI: 1.01, 2.38) for HCB (p < 0.05 only for HCB), and cross-sectional ORs ranged 1.62 (95% CI: 1.13; 2.32) for p,p'-DDE to 2.06 (95% CI: 1.29, 3.28) for ∑DL-PCBs (p < 0.05 for all POPs).In analyses of non-diabetic individuals, higher baseline BMI, decreased weight and decreased plasma lipid concentrations were associated with a slower decrease of POPs. Cases had, besides a higher BMI, reduced cholesterol and weight gain at follow-up compared to controls, which can explain the higher ORs in the cross-sectional assessments. DiscussionThe association between POPs and T2D was confirmed, but an indication that individuals body fat history might influence POP-T2D associations weakens the epidemiological support for a causal association. It also warrants studies based on other exposure metrics than biomonitoring. In addition, we note that a cross-sectional design overestimates the ORs if T2D cases have successfully intervened on weight and/or blood lipids, as changes in these factors cause changes in POPs.

SAT-094 Overweight and Obesity Associated with Immune-Related Adverse Events in Patients on Immune Checkpoint Inhibitor Therapy

Background As immune checkpoint inhibitor (ICI) therapies (PD(L)1 and CTLA-4 inhibitors) are increasingly used for treating malignancy, immune-related adverse events (irAEs) are being encountered by clinicians more frequently. Obesity is a pro-inflammatory metabolic state that has been associated with a higher risk of developing autoimmune disease, but its role in irAEs in patients treated with ICIs is not well characterized. Hypothesis We hypothesized that patients on ICI therapy who were overweight or obese would be more likely to have a grade 2 or greater irAE compared to normal or underweight patients. Methods We retrospectively collected clinical data for 398 cancer patients with baseline body mass index (BMI) data who received ICIs between January 2011 and April 2017 at our institution. Patients were categorized as having lower BMI (low or normal weight, <25) or higher BMI (obese or overweight, ≥25). An irAE was defined as an AE during ICI therapy that was ≥ Grade 2 according to the Common Terminology Criteria for AEs. We compared patient demographic and clinical characteristics between BMI categories. To determine if BMI category was associated with irAEs, we used multivariate logistic regression. Demographics and variables significantly associated with irAEs were included in the model. Results 201 (50.5%) of patients had lower BMI and 197 (49.5%) had higher BMI. 98 patients (24.6%) had an irAE and median follow up time was 8.7 months. The most common malignancies were melanoma (19.6%), non-small cell lung cancer (23.7%), hepatocellular carcinoma (14.6%), and urothelial carcinoma (12.3%). Patients were treated with blockade of CTLA-4 (11.8%), PD1/PDL1, (77.9%), combination of CTLA-4 and PD(L)1 blockade concurrently (4.0%), and sequentially (6.3%). Patients with lower and higher BMI did not differ significantly in respect to age, gender, clinical stage, or category of ICI. Race differed significantly between high vs low BMI categories, (White 60.4% vs 47.3%, Black 8.1% vs 11.9%, Hispanic 11.7% vs 8%, Asian 3.6% vs 11.9%, Unknown/other 16.2% vs 20.9%, p<0.01). Patients with higher BMI were more likely to have a preexisting autoimmune disease (10.8% vs 7.5%, p=0.04). Higher BMI was significantly associated with irAEs (odds ratio (OR) 1.79, 95% confidence interval (CI) 1.09-2.96 in a model adjusted for age, gender, race, ICI category, and preexisting autoimmune disease. Other race (compared to white race) (OR 0.40, 95% CI 0.19-0.83, PD(L)1 blockade (compared to CTLA-4 blockade) (OR 0.49, 95% CI 0.24-0.99), and preexisting autoimmune disease (OR 2.8, 95% CI 1.4-5.7) were also significant predictors of irAEs in the adjusted model. Conclusions Being overweight or obese was associated with irAEs in patients on ICI therapy. Insights into how BMI mediates the immune effects of ICI therapy can potentially elucidate how inflammation plays a role in the metabolic sequelae of obesity and adiposity.

Untangling the obesity paradox in patients with acute myocardial infarction after primary percutaneous coronary intervention (detail analysis by age)

BackgroundObesity is associated with increased morbidity and mortality. However, obesity paradox has been discussed in some patients with cardiovascular disease. ObjectivesWe investigated the mechanisms of the obesity paradox in acute myocardial infarction (AMI) patients. MethodsWe evaluated 1634 AMI patients with primary percutaneous coronary intervention (PCI). Patients were divided into 6 subgroups according to baseline body mass index (BMI) (low BMI: <20 kg/m2, normal BMI: 20–24.9 kg/m2, high BMI: ≥25 kg/m2) and age (the younger and elderly groups consisting of patients <70 and ≥70 years old). The primary outcome was defined as all-cause mortality. ResultsDuring the follow-up periods (median, 620 days; range, 344 to 730 days), 8.7% of patients experienced all-cause death. According to the Kaplan-Meier survival analysis, the patients in the younger age group with high BMI demonstrated significantly higher all-cause mortality compared to the other patients in the same age group (P = 0.012). In contrast, patients in the elderly age group with low BMI demonstrated significantly higher all-cause mortality compared to the others in the same age group (P < 0.001). Multivariate cox regression analyses showed that low BMI in the elderly age group (HR 1.69, 95% CI 1.12 to 2.55, P = 0.012) and high BMI in the younger age group (HR 2.77, 95% CI 1.19 to 6.45, P = 0.018) were independent predictors of all-cause mortality. ConclusionsThe obesity paradox was recognized only in patients in the elderly age group and not in the younger age group. The prognostic impact of BMI may differ by age in AMI patients.