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Item Author Correction: Nod2 and Nod2-regulated microbiota protect BALB/c mice from diet-induced obesity and metabolic dysfunction(SpringerNature, 2018-04-16) Rodriguez-Nunez, Ivan; Caluag, Tiffany; Kirby, Kori; Rudick, Charles N.; Dziarski, Roman; Gupta, Dipika; Medicine, School of MedicineA correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.Item Body Mass Index Trajectories, Weight Gain, and Risks of Liver and Biliary Tract Cancers(Oxford University Press, 2022-08-12) Yang, Wanshui; Zeng, Xufen; Petrick, Jessica L.; Danford, Christopher J.; Florio, Andrea A.; Lu, Bing; Nan, Hongmei; Ma, Jiantao; Wang, Liang; Zeng, Hongmei; Sudenga, Staci L.; Campbell, Peter T.; Giovannucci, Edward; McGlynn, Katherine A.; Zhang, Xuehong; Epidemiology, Richard M. Fairbanks School of Public HealthBackground: Little is known about the role of early obesity or weight change during adulthood in the development of liver cancer and biliary tract cancer (BTC). Methods: We investigated the associations of body mass index (BMI) and weight trajectories with the risk of liver cancer and BTC in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO). BMI was self-reported at ages 20, 50, and at enrollment. BMI trajectories were determined using latent class growth models. Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: During a median follow-up of 15.9 years among 138,922 participants, 170 liver cancer and 143 BTC cases were identified. Compared with those whose BMI does not exceed 25 kg/m2, participants with BMI exceeding 25 kg/m2 at age 20 had increased risks of liver cancer (HR = 2.03, 95% CI: 1.26-3.28) and BTC (HR = 1.99, 95% CI: 1.16-3.39). Compared to participants maintaining normal BMI until enrollment, trajectory of normal weight at age 20 to obesity at enrollment was associated with increased risk for liver cancer (HR = 2.50, 95% CI: 1.55-4.04) and BTC (HR = 1.83, 95% CI: 1.03-3.22). Compared to adults with stable weight (+/-5kg) between age 20 to 50 years, weight gain ≥20 kg between ages 20 to 50 years had higher HRs of 2.24 (95%CI: 1.40-3.58) for liver cancer and 1.86 (95% CI: 1.12-3.09) for BTC. Conclusions: Being overweight/obese at age 20, and BMI trajectories that result in being overweight and/or obese, may increase risk for both liver cancer and BTC.Item Efavirenz Pharmacogenetics and Weight Gain Following Switch to Integrase Inhibitor-Containing Regimens(Oxford University Press, 2021) Leonard, Michael A.; Cindi, Zinhle; Bradford, Yuki; Bourgi, Kassem; Koethe, John; Turner, Megan; Norwood, Jamison; Woodward, Beverly; Erdem, Husamettin; Basham, Rebecca; Baker, Paxton; Rebeiro, Peter F.; Sterling, Timothy R.; Hulgan, Todd; Daar, Eric S.; Gulick, Roy; Riddler, Sharon A.; Sinxadi, Phumla; Ritchie, Marylyn D.; Haas, David W.; Medicine, School of MedicineBackground: Unwanted weight gain affects some people living with human immunodeficiency virus (HIV) who are prescribed integrase strand transfer inhibitors (INSTIs). Mechanisms and risk factors are incompletely understood. Methods: We utilized 2 cohorts to study pharmacogenetics of weight gain following switch from efavirenz- to INSTI-based regimens. In an observational cohort, we studied weight gain at 48 weeks following switch from efavirenz- to INSTI-based regimens among patients who had been virologically suppressed for at least 2 years at a clinic in the United States. Associations were characterized with CYP2B6 and UGT1A1 genotypes that affect efavirenz and INSTI metabolism, respectively. In a clinical trials cohort, we studied weight gain at 48 weeks among treatment-naive participants who were randomized to receive efavirenz-containing regimens in AIDS Clinical Trials Group studies A5095, A5142, and A5202 and did not receive INSTIs. Results: In the observational cohort (n = 61), CYP2B6 slow metabolizers had greater weight gain after switch (P = .01). This was seen following switch to elvitegravir or raltegravir, but not dolutegravir. UGT1A1 genotype was not associated with weight gain. In the clinical trials cohort (n = 462), CYP2B6 slow metabolizers had lesser weight gain at week 48 among participants receiving efavirenz with tenofovir disoproxil fumarate (P = .001), but not those receiving efavirenz with abacavir (P = .65). Findings were consistent when stratified by race/ethnicity and by sex. Conclusions: Among patients who switched from efavirenz- to INSTI-based therapy, CYP2B6 genotype was associated with weight gain, possibly reflecting withdrawal of the inhibitory effect of higher efavirenz concentrations on weight gain. The difference by concomitant nucleoside analogue is unexplained.Item Long-term outcomes in patients with adult-onset craniopharyngioma(Springer, 2022) Dogra, Prerna; Bedatsova, Lucia; Van Gompel, Jamie J.; Giannini, Caterina; Donegan, Diane M.; Erickson, Dana; Medicine, School of MedicinePurpose: Craniopharyngiomas are nonmalignant sellar and parasellar tumors exhibiting a bimodal age distribution. While the outcomes following treatment in patients with childhood-onset craniopharyngiomas are well characterized, similar information in adult-onset craniopharyngiomas is limited. We aimed to describe the long-term outcomes (weight and metabolic parameters, mortality) in patients with adult-onset craniopharyngioma following treatment. Methods: Patients with adult-onset craniopharyngioma with initial treatment (1993-2017) and >6 months of follow-up at our institution were retrospectively identified. Body mass index (BMI) categories included obese (BMI ≥ 30 kg/m2), overweight (BMI 25-29.9 kg/m2), and normal weight (BMI < 25 kg/m2). Results: For the 91 patients with adult-onset craniopharyngioma (44% women, mean diagnosis age 48.2 ± 18 years) over a mean follow-up of 100.3 ± 69.5 months, weight at last follow-up was significantly higher than before surgery (mean difference 9.5 ± 14.8 kg, P < 0.001) with a higher percentage increase in weight seen in those with lower preoperative BMI (normal weight (20.7 ± 18%) vs. overweight (13.3 ± 18.0%) vs. obese (6.4 ± 15%), P = 0.012). At last follow-up, the prevalence of obesity (62 vs. 40.5%, P = 0.0042) and impaired glucose metabolism (17.4% vs. 34%, P = 0.017) increased significantly. All-cause mortality was 12%, with the average age of death 71.9 ± 19.7 years (average U.S. life expectancy 77.7 years, CDC 2020). Conclusion: Patients with adult-onset craniopharyngioma following treatment may experience weight gain, increased prevalence of obesity, impaired glucose metabolism, and early mortality. Lower preoperative BMI is associated with a greater percentage increase in postoperative weight.Item Maternal weight gain among individuals with Type 2 diabetes and associated perinatal outcomes(2023-02-10) Izewski, Joanna; Crites, Kundai; Tang, Rachel; Saiko-Blair, Morgan; Campbell, Meredith; Pelton, Sarah; Scifres, ChristinaObjective The prevalence of type 2 Diabetes Mellitus (T2DM) in pregnancy is increasing, and adverse perinatal outcomes are common. We sought to assess whether higher or lower weight gain is associated with adverse perinatal outcomes in T2DM. Study Design This was a retrospective cohort study of patients with T2DM and a singleton gestation who delivered at 2 health systems between 2018-2020. Demographics, markers of health care utilization, and various perinatal outcomes were abstracted from the medical record. Race and ethnicity were self-reported. Our primary exposure was weight gain < 5 kilograms(kg) across gestation compared to those who gained ≥5kg. We excluded patients for whom weight gain could not be calculated. We assessed multiple perinatal outcomes, and we used multinomial logistic regression to adjust for covariates. Results We included 341 individuals with T2DM. There were 216/341 (63%) in the ≥5kg group, and 125/341 (37%) in the < 5kg group. The < 5kg group was more likely to be of Black race. The ≥5kg group initiated prenatal care earlier in gestation, were more likely to have ≥12 total prenatal visits, and be on insulin at the time of delivery. There were no significant differences in other demographics or markers of healthcare utilization (Table 1). Perinatal outcomes are shown in Table 2. Those with < 5kg of weight gain were less likely to develop a hypertensive disorder of pregnancy (aOR 0.3, 95% CI 0.2-0.5), or undergo a cesarean delivery (aOR 0.6, 95% CI 0.4-0.9). Stillbirth was more common among those who gained < 5kg (7 vs. 2%, p=0.02). There was a statistical difference in neonatal birthweight category (AGA vs. SGA vs. LGA) (p=0.04) between the 2 groups that did not persist after adjusting for covariates. Conclusion Weight gain is associated with adverse perinatal outcomes among individuals with T2DM. While weight gain < 5kg is associated with a reduced risk for certain outcomes, the increased risk for stillbirth deserves further study.Item Modification and Assessment of the Bedside Pediatric Early Warning Score in the Pediatric Allogeneic Hematopoietic Cell Transplant Population(Wolters Kluwer, 2018-05) Cater, Daniel T.; Tori, Alvaro J.; Moser, Elizabeth A.S.; Rowan, Courtney M.; Pediatrics, School of MedicineOBJECTIVES: To determine the validity of the Bedside Pediatric Early Warning Score system in the hematopoietic cell transplant population, and to determine if the addition of weight gain further strengthens the association with need for PICU admission. DESIGN: Retrospective cohort study of pediatric allogeneic hematopoietic cell transplant patients from 2009 to 2016. Daily Pediatric Early Warning Score and weights were collected during hospitalization. Logistic regression was used to identify associations between maximum Pediatric Early Warning Score or Pediatric Early Warning Score plus weight gain and the need for PICU intervention. The primary outcome was need for PICU intervention; secondary outcomes included mortality and intubation. SETTING: A large quaternary free-standing children's hospital. PATIENTS: One-hundred two pediatric allogeneic hematopoietic cell transplant recipients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 102 hematopoietic cell transplant patients included in the study, 29 were admitted to the PICU. The median peak Pediatric Early Warning Score was 11 (interquartile range, 8-13) in the PICU admission cohort, compared with 4 (interquartile range, 3-5) in the cohort without a PICU admission (p < 0.0001). Pediatric Early Warning Score greater than or equal to 8 had a sensitivity of 76% and a specificity of 90%. The area under the receiver operating characteristics curve was 0.83. There was a high negative predictive value at this Pediatric Early Warning Score of 90%. When Pediatric Early Warning Score greater than or equal to 8 and weight gain greater than or equal to 7% were compared together, the area under the receiver operating characteristic curve increased to 0.88. CONCLUSIONS: In this study, a Pediatric Early Warning Score greater than or equal to 8 was associated with PICU admission, having a moderately high sensitivity and high specificity. This study adds to literature supporting Pediatric Early Warning Score monitoring for hematopoietic cell transplant patients. Combining weight gain with Pediatric Early Warning Score improved the discriminative ability of the model to predict the need for critical care, suggesting that incorporation of weight gain into Pediatric Early Warning Score may be beneficial for monitoring of hematopoietic cell transplant patients.Item MON-266 The Association Between Prolactinomas and Weight Gain(Endocrine Society, 2020-05-08) Tariq, Zunera; Sabie, Farah Al; Donegan, Diane; Medicine, School of MedicineIntroduction: The prevalence of obesity is increasing worldwide and treatment remains challenging. Certain endocrine disorders may contribute to weight gain. These are important to recognize as treatment may have beneficial impact on weight. Studies have reported an increased prevalence of obesity in patients with prolactinomas. While several studies have examined the association between weight gain and prolactinomas, the results are conflicting. Therefore, the aim of this study was to determine if BMI is higher among those with a prolactinoma compared to those without. Methods: We identified all patients ≥18 years of age referred to endocrinology between 2008–2018 with a newly diagnosed prolactinoma (defined as a prolactin levels ≥40 ng/ml on 2 separate occasions and a pituitary adenoma evident on MRI without secondary causes for hyperprolactinemia). We extracted the following variables from the medical record: patient demographics, presenting symptoms, prolactin level and tumor size at diagnosis. Comparative data was obtained from the National Health and Nutrition Examination Survey (NHANES) 2015–2016, from which we included only those ≥18 years of age who had BMI data. Results: In total 34 patients with a newly diagnosed prolactinoma (female: 27 /34, 79%, mean age at diagnosis: 35.4 ± 10.7 years) met inclusion criteria. The majority of patients (23/34, 68 %) had microadenomas defined as <1cm. The median prolactin level at diagnosis was 103.3 (IQR 51.3- 249.25). Although the most common presenting symptoms were those consistent with hypogonadism (27/34, 79%) and galactorrhea (16/34, 47%), 1/3 patients also described weight gain. In comparison, 5662 individuals from NHANES (48 ± 18 years, female: 2955/5662, 52%) reported their BMIs. BMI was significantly increased among those with a prolactinoma compared to survey population [median BMI 30.9 kg/m2 (IQR, 24.9- 39) vs 28.3 kg/m2 (24.3- 33), P= 0.02]. This difference persisted even when adjusted for age and sex (P= 0.0002). In addition the prevalence of class II obesity (BMI ≥35 kg/m2) was higher in those with a prolactinoma compared to survey population (38% vs 18%, P=0.005). Among prolactinoma patients, there was a correlation between BMI and log-transformed prolactin levels (R2= 0.24, P=0.003). Conclusion: Weight gain is a presenting symptom for many patients with a newly diagnosed prolactinoma. When compared to a large cohort of adults in the US, those with a prolactinoma have higher BMI and an increased prevalence of class II obesity. Based on the correlation between BMI and log-transformed prolactin levels, we hypothesize that this weight difference may be related to hyperprolactinemia. These findings suggest that, in the appropriate context, hyperprolactinemia should be considered when a patient presents with weight gain.Item Nod2 and Nod2-regulated microbiota protect BALB/c mice from diet-induced obesity and metabolic dysfunction(SpringerNature, 2017-04-03) Rodriguez-Nunez, Ivan; Caluag, Tiffany; Kirby, Kori; Rudick, Charles N.; Dziarski, Roman; Gupta, Dipika; Department of Medicine, School of MedicineGenetics plays a central role in susceptibility to obesity and metabolic diseases. BALB/c mice are known to be resistant to high fat diet (HFD)-induced obesity, however the genetic cause remains unknown. We report that deletion of the innate immunity antibacterial gene Nod2 abolishes this resistance, as Nod2 -/- BALB/c mice developed HFD-dependent obesity and hallmark features of metabolic syndrome. Nod2 -/- HFD mice developed hyperlipidemia, hyperglycemia, glucose intolerance, increased adiposity, and steatosis, with large lipid droplets in their hepatocytes. These changes were accompanied by increased expression of immune genes in adipose tissue and differential expression of genes for lipid metabolism, signaling, stress, transport, cell cycle, and development in both adipose tissue and liver. Nod2 -/- HFD mice exhibited changes in the composition of the gut microbiota and long-term treatment with antibiotics abolished diet-dependent weight gain in Nod2 -/- mice, but not in wild type mice. Furthermore, microbiota from Nod2 -/- HFD mice transferred sensitivity to weight gain, steatosis, and hyperglycemia to wild type germ free mice. In summary, we have identified a novel role for Nod2 in obesity and demonstrate that Nod2 and Nod2-regulated microbiota protect BALB/c mice from diet-induced obesity and metabolic dysfunction.Item Pre-Treatment and During-Treatment Weight Trajectories in Black and White Women(Elsevier, 2022) Schneider-Worthington, Camille R.; Kinsey, Amber W.; Tan, Fei; Zhang, Sheng; Borgatti, Alena; Davis, Andrea; Dutton, Gareth R.; Mathematical Sciences, School of ScienceIntroduction: Black participants often lose less weight than White participants in response to behavioral weight-loss interventions. Many participants experience significant pretreatment weight fluctuations (between baseline measurement and treatment initiation), which have been associated with treatment outcomes. Pretreatment weight gain has been shown to be more prevalent among Black participants and may contribute to racial differences in treatment responses. The purpose of this study was to (1) examine the associations between pretreatment weight change and treatment outcomes and (2) examine racial differences in pretreatment weight change and weight loss among Black and White participants. Methods: Participants were Black and White women (n=153, 60% Black) enrolled in a 4-month weight loss program. Weight changes occurring during the pretreatment period (41 ± 14 days) were categorized as weight stable (±1.15% of baseline weight), weight gain (≥+1.15%), or weight loss (≤-1.15%). Recruitment and data collection occurred from 2011 to 2015; statistical analyses were performed in 2021. Results: During the pretreatment period, most participants (56%) remained weight stable. Pretreatment weight trajectories did not differ by race (p=0.481). At 4-months, those who lost weight before treatment experienced 2.63% greater weight loss than those who were weight stable (p<0.005), whereas those who gained weight before treatment experienced 1.91% less weight loss (p<0.01). Conclusions: Pretreatment weight changes can impact weight outcomes after initial treatment, although no differences between Black and White participants were observed. Future studies should consider the influence of pretreatment weight change on long-term outcomes (e.g., weight loss maintenance) along with potential racial differences in these associations.Item Preswitch Regimens Influence the Rate of Weight Gain After Switch to Tenofovir Disoproxil Fumarate, Lamivudine, and Dolutegravir (TLD): Study From an East African Cohort(Oxford University Press, 2023-12-12) Bourgi, Kassem; Ofner, Susan; Musick, Beverly; Wools-Kaloustian, Kara; Humphrey, John M.; Diero, Lameck; Yiannoutsos, Constantin T.; Gupta, Samir K.; Medicine, School of MedicineBackground: Switching from non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens to dolutegravir (DTG) has been associated with greater weight gain. Methods: We conducted our analysis using a longitudinal cohort of people with HIV (PWH) in Western Kenya. We evaluated changes in the rate of weight gain among treatment-experienced, virally suppressed PWH who switched from NNRTI to tenofovir disoproxil fumarate, lamivudine, and dolutegravir (TLD). We modeled the weights pre- and postswitch using a 2-phase model with linear trend preswitch and an inverted exponential function postswitch. We estimated an 18-month excess weight gain by comparing the projected weight with that expected using the preswitch rate. Results: A total of 18 662 individuals were included in our analysis, with 55% switching from efavirenz (EFV) and 45% from nevirapine (NVP). Of the studied individuals, 51% were female, and the median age and body mass index (BMI) were 51 years and 22 kg/m2, respectively. For the overall population, the rate of weight gain increased from 0.47 kg/year preswitch to 0.77 kg/year, with higher increases for females (0.57 kg/year to 0.96 kg/year) than males (0.34 kg/year to 0.62 kg/year). The rate of weight gain for individuals switching from EFV-based regimens significantly increased from 0.57 kg/year preswitch to 1.11 kg/year postswitch but remained stable at 0.35 kg/year preswitch vs 0.32 kg/year postswitch for individuals switching from NVP-based regimens. Conclusions: Switching from NNRTI-based regimens to TLD is associated with a modest increase in the rate of weight gain, with the preswitch NNRTI being the key determinant of the amount of weight gain experienced postswitch.