Improving perioperative acetaminophen administration for safer and cost-effective multimodal analgesia in pediatric surgery: A QI initiative.

BACKGROUND: The use of acetaminophen in the perioperative period has emerged as an attractive option for providing safer and cost-effective analgesia in children. AIMS: The primary aim of our project was to increase the use of acetaminophen (both oral and intravenous) in the perioperative period from a baseline of 39.5% to 50% for all surgical patients within 24 months. The secondary aim was to increase the use of enteral acetaminophen from 10% to 52.5% during the same period. METHODS: A multidisciplinary team was formed, and model for improvement was chosen as the QI methodology. The primary measure was the total percentage of surgical patients receiving any form of perioperative acetaminophen, while our secondary measure was the percentage use of oral acetaminophen administration. We also tracked the average maximum PACU (Post Anesthesia Care Unit) pain scores and the percentage of patients receiving IV opioids. Multiple interventions were conducted, including education, increasing the availability of acetaminophen, and optimizing the electronic medical record (EMR). Monthly data was collected using an automated report in the EMR. RESULTS: We successfully achieved our goal, increasing the use of acetaminophen from 39.5% to 70% within four months. Despite some fluctuations, by the end of 24 months, we not only met but surpassed our goal, with 63% of patients receiving perioperative acetaminophen. Similarly, the usage of oral acetaminophen increased from a baseline of 10% to 78%. Our average maximum PACU pain scores improved from 5.4 to 5.2, and the percentage of patients receiving rescue opioids decreased from 15.4 to 13.1. CONCLUSION: We successfully achieved and sustained our goals of improving acetaminophen use for our surgical patients without worsening pain scores or worsening use of intravenous opioids. Future directions include further refining our strategies and exploring additional opportunities to optimize pain management in pediatric perioperative settings.

Incidence of erectile dysfunction among middle-aged and aging sexual minority men living with or without HIV.

Introduction: Erectile dysfunction (ED) has been established as a comorbidity among men living with HIV, but comparisons by HIV serostatus of ED incidence in a longitudinal follow-up cohort of men are lacking. We sought to evaluate the incidence of ED spanning a period of 12 years in a longitudinal cohort of sexual minority men (SMM) living with and without HIV. Methods: We analyzed ED incidence data for 625 participants in the longitudinal Multicenter AIDS Cohort Study from visits spanning October 2006 to April 2019. Results: SMM living with HIV were more likely to have incident ED compared with those living without HIV (rate ratio: 1.41; 95% CI: 1.14-1.75). Older age, current diabetes, cumulative cigarette use, and cumulative antidepressant use were associated with increased incidence of ED in the entire sample. Self-identifying as Hispanic, current diabetes, and cumulative antidepressant use were positively associated with ED incidence among SMM living with HIV. Cumulative cigarette use was positively associated with greater ED incidence only among SMM living without HIV. Discussion: In summary, age (full sample/ with HIV), current diabetes (full sample/with HIV), cumulative cigarette use (full sample/without HIV), and cumulative antidepressant use (full sample/with HIV) were associated with increased ED incidence. Skillful management of diabetes and careful titration of antidepressants, along with smoking cessation practices, are recommended to mitigate ED in this population.

Proteomic Signature of HIV-Associated Subclinical Left Atrial Remodeling and Incident Heart Failure.

Background: People living with HIV (PLWH) are at higher risk of heart failure (HF) and preceding subclinical cardiac abnormalities, including left atrial dilation, compared to people without HIV (PWOH). Hypothesized mechanisms include premature aging linked to chronic immune activation. We leveraged plasma proteomics to identify potential novel contributors to HIV-associated differences in indexed left atrial volume (LAVi) among PLWH and PWOH and externally validated identified proteomic signatures with incident HF among a cohort of older PWOH. Methods: We performed proteomics (Olink Explore 3072) on plasma obtained concurrently with cardiac magnetic resonance imaging among PLWH and PWOH in the United States. Proteins were analyzed individually and as agnostically defined clusters. Cross-sectional associations with HIV and LAVi were estimated using multivariable regression with robust variance. Among an independent general population cohort, we estimated associations between identified signatures and LAVi using linear regression and incident HF using Cox regression. Results: Among 352 participants (age 55±6 years; 25% female), 61% were PLWH (88% on ART; 73% with undetectable HIV RNA) and mean LAVi was 29±9 mL/m 2 . Of 2594 analyzed proteins, 439 were associated with HIV serostatus, independent of demographics, hepatitis C virus infection, renal function, and substance use (FDR<0.05). We identified 73 of these proteins as candidate contributors to the independent association between positive HIV serostatus and higher LAVi, enriched in tumor necrosis factor (TNF) signaling and immune checkpoint proteins regulating T cell, B cell, and NK cell activation. We identified one protein cluster associated with LAVi and HIV regardless of HIV viral suppression status, which comprised 42 proteins enriched in TNF signaling, ephrin signaling, and extracellular matrix (ECM) organization. This protein cluster and 30 of 73 individual proteins were associated with incident HF among 2273 older PWOH (age 68±9 years; 52% female; 8.5±1.4 years of follow-up). Conclusion: Proteomic signatures that may contribute to HIV-associated LA remodeling were enriched in immune checkpoint proteins, cytokine signaling, and ECM organization. These signatures were also associated with incident HF among older PWOH, suggesting specific markers of chronic immune activation, systemic inflammation, and fibrosis may identify shared pathways in HIV and aging that contribute to risk of HF.

CROI 2023: Metabolic and Other Complications of HIV Infection.

Comorbid conditions have major impacts on the health, quality of life, and survival of people with HIV, particularly as they age. The 2023 Conference on Retroviruses and Opportunistic Infections (CROI) featured excellent science related to specific comorbidities, such as cardiovascular disease (CVD), cancer, and obesity. Studies investigating factors that may contribute to CVD, such as mental health disorders, antiretroviral therapies, and activation of hormonal pathways, were featured prominently. Other studies sought to understand the epidemiology of non-AIDS-defining cancers in people with HIV. As at previous CROI conferences, weight gain attributable to antiretroviral therapies was a major theme, and several abstracts focused on the important question of whether weight decreases after discontinuation of antiretroviral therapy (ART) regimens associated with weight gain. This review focuses on abstracts presented at CROI 2023 in these areas, highlighting those with the most clinical impact.

Coronary artery endothelial function and aging in people with HIV and HIV-negative individuals.

Coronary artery disease (CAD) is a common comorbidity in people with human immunodeficiency virus (HIV) (PWH) and impaired coronary endothelial function (CEF) plays a central role in the pathogenesis of CAD. Age-related impaired CEF among PWH, however, is not well characterized. We investigated the association between CEF and age in males and females with and without HIV using 3-T magnetic resonance imaging (MRI). We measured the changes in coronary cross-sectional area (CSA) and coronary blood flow during isometric handgrip exercise (IHE), an established endothelial-dependent stressor with smaller increases in CSA and coronary blood flow indicative of impaired CEF. We included 106 PWH and 82 individuals without HIV. Differences in demographic and clinical characteristics between PWH and individuals without HIV were explored using Pearson's χ2 test for categorical variables and Welch's t test for continuous variables. Linear regression models were used to examine the association between CEF and age. CEF was significantly lower in PWH as compared with individuals without HIV. Coronary endothelial dysfunction was also present at younger ages in PWH than in the individuals without HIV and there were significant differences in CEF between the PWH and individuals without HIV across age groups. Among the individuals without HIV, the percent changes in CSA were inversely related to age in unadjusted and adjusted models. There was no significant association between CEF and age in PWH. To the best of our knowledge, this is the first study to examine the relationship between age and CEF in PWH, and our results suggest that factors other than age significantly impair CEF in PWH across the life span.NEW & NOTEWORTHY This is the first study to examine the relationship between age and coronary endothelial function (CEF) in people with human immunodeficiency virus (HIV) (PWH). CEF was assessed using magnetic resonance imaging (MRI) in people with and without HIV. Although age and CEF were significantly inversely related in individuals without HIV, there was no association between age and CEF in PWH.

Plasma Glycomic Markers of Accelerated Biological Aging During Chronic HIV Infection.

People with HIV (PWH) experience an increased vulnerability to premature aging and inflammation-associated comorbidities, even when HIV replication is suppressed by antiretroviral therapy (ART). However, the factors that contribute to or are associated with this vulnerability remain uncertain. In the general population, alterations in the glycomes of circulating IgGs trigger inflammation and precede the onset of aging-associated diseases. Here, we investigate the IgG glycomes of cross-sectional and longitudinal samples from 1,216 women and men, both living with virally suppressed HIV and those without HIV. Our glycan-based machine learning models indicate that living with chronic HIV significantly accelerates the accumulation of pro-aging-associated glycomic alterations. Consistently, PWH exhibit heightened expression of senescence-associated glycan-degrading enzymes compared to their controls. These glycomic alterations correlate with elevated markers of inflammatory aging and the severity of comorbidities, potentially preceding the development of such comorbidities. Mechanistically, HIV-specific antibodies glycoengineered with these alterations exhibit reduced anti-HIV IgG-mediated innate immune functions. These findings hold significant potential for the development of glycomic-based biomarkers and tools to identify and prevent premature aging and comorbidities in people living with chronic viral infections.

Aging-Related Comorbidity Burden Among Women and Men With or At-Risk for HIV in the US, 2008-2019.

Importance: Despite aging-related comorbidities representing a growing threat to quality-of-life and mortality among persons with HIV (PWH), clinical guidance for comorbidity screening and prevention is lacking. Understanding comorbidity distribution and severity by sex and gender is essential to informing guidelines for promoting healthy aging in adults with HIV. Objective: To assess the association of human immunodeficiency virus on the burden of aging-related comorbidities among US adults in the modern treatment era. Design, Setting, and Participants: This cross-sectional analysis included data from US multisite observational cohort studies of women (Women's Interagency HIV Study) and men (Multicenter AIDS Cohort Study) with HIV and sociodemographically comparable HIV-seronegative individuals. Participants were prospectively followed from 2008 for men and 2009 for women (when more than 80% of participants with HIV reported antiretroviral therapy use) through last observation up until March 2019, at which point outcomes were assessed. Data were analyzed from July 2020 to April 2021. Exposures: HIV, age, sex. Main Outcomes and Measures: Comorbidity burden (the number of total comorbidities out of 10 assessed) per participant; secondary outcomes included individual comorbidity prevalence. Linear regression assessed the association of HIV status, age, and sex with comorbidity burden. Results: A total of 5929 individuals were included (median [IQR] age, 54 [46-61] years; 3238 women [55%]; 2787 Black [47%], 1153 Hispanic or other [19%], 1989 White [34%]). Overall, unadjusted mean comorbidity burden was higher among women vs men (3.4 [2.1] vs 3.2 [1.8]; P = .02). Comorbidity prevalence differed by sex for hypertension (2188 of 3238 women [68%] vs 2026 of 2691 men [75%]), psychiatric illness (1771 women [55%] vs 1565 men [58%]), dyslipidemia (1312 women [41%] vs 1728 men [64%]), liver (1093 women [34%] vs 1032 men [38%]), bone disease (1364 women [42%] vs 512 men [19%]), lung disease (1245 women [38%] vs 259 men [10%]), diabetes (763 women [24%] vs 470 men [17%]), cardiovascular (493 women [15%] vs 407 men [15%]), kidney (444 women [14%] vs 404 men [15%]) disease, and cancer (219 women [7%] vs 321 men [12%]). In an unadjusted model, the estimated mean difference in comorbidity burden among women vs men was significantly greater in every age strata among PWH: age under 40 years, 0.33 (95% CI, 0.03-0.63); ages 40 to 49 years, 0.37 (95% CI, 0.12-0.61); ages 50 to 59 years, 0.38 (95% CI, 0.20-0.56); ages 60 to 69 years, 0.66 (95% CI, 0.42-0.90); ages 70 years and older, 0.62 (95% CI, 0.07-1.17). However, the difference between sexes varied by age strata among persons without HIV: age under 40 years, 0.52 (95% CI, 0.13 to 0.92); ages 40 to 49 years, -0.07 (95% CI, -0.45 to 0.31); ages 50 to 59 years, 0.88 (95% CI, 0.62 to 1.14); ages 60 to 69 years, 1.39 (95% CI, 1.06 to 1.72); ages 70 years and older, 0.33 (95% CI, -0.53 to 1.19) (P for interaction = .001). In the covariate-adjusted model, findings were slightly attenuated but retained statistical significance. Conclusions and Relevance: In this cross-sectional study, the overall burden of aging-related comorbidities was higher in women vs men, particularly among PWH, and the distribution of comorbidity prevalence differed by sex. Comorbidity screening and prevention strategies tailored by HIV serostatus and sex or gender may be needed.

Estrogen-Based Gender-Affirming Hormone Therapy and Subclinical Cardiovascular Disease in Transgender Women with HIV.

Purpose: Transgender women (TW) are disproportionately affected by HIV infection and cardiovascular disease (CVD). This study evaluated whether estrogen-based gender-affirming hormone therapy (GAHT) in TW with HIV (TWH-GAHT) is associated with indices of subclinical CVD. Methods: Of the 40 HIV-seropositive persons enrolled, 20-60 years of age, on antiretroviral treatment with undetectable viral load, assessments were performed on 15 TWH; of these persons, 11 were GAHT treated. These TWH-GAHT were matched with HIV+ cisgender men and women based on age, ethnicity/race, body mass index, and antihypertensive medication use. Sex hormones, and cardiometabolic (waist circumference, blood pressure, insulin resistance, lipid profile, and C-reactive protein), vascular (flow-mediated dilation [FMD] and arterial stiffness), and proinflammatory measures were obtained. Results: TWH-GAHT displayed elevated estradiol and suppressed testosterone levels relative to normative ranges. Analyses indicated the TWH-GAHT displayed lower low-density lipoprotein compared with cisgender groups (p < 0.05). Although no difference was seen on FMD, the central augmentation index of aortic stiffness was higher in cisgender HIV+ women than cisgender HIV+ men (p < 0.05). No other group difference on subclinical CVD markers was observed. For TWH, partial correlations indicated associations of certain sex hormones with selected cardiometabolic outcomes and the inflammatory cytokine, interleukin-8. Conclusion: When well matched to HIV+ cisgender men and women, subclinical CVD pathophysiology did not appear elevated in TWH-GAHT, although tendencies emerged suggesting that some subclinical CVD indices may be higher, but others lower than cisgender groups. Longitudinal studies of TWH are needed to more precisely evaluate the moderating effect of GAHT on cardiometabolic pathophysiology.

Association of cumulative social risk and gestational diabetes mellitus in the US, 2007-2018.

AIMS: Little is known regarding the association of multiple social risk factors and gestational diabetes mellitus (GDM). METHODS: We analyzed the 2007-2018 National Health and Nutrition Examination Surveys including 10,439 women aged ≥20 years (8 % with history of GDM). We created a cumulative social risk score (CSR) by adding scores assigned to each of the following: race/ethnicity, citizenship status and country of birth, education, and family income (score of 0 used as reference group). Using logistic regression, we assessed the associations of individual social risk factors (education, income, race/ethnicity and citizenship status) and CSR score with GDM, adjusting for age, parity, insurance status, care access, smoking, diet, physical activity, and body mass index. RESULTS: Among individual social risk factors, being a non-U.S. citizen (OR:1.51, 95% CI: 1.06-2.15) or belonging to a minority racial/ethnic group (OR:1.30, 95% CI: 1.04-1.59) was significantly associated with a greater odds of GDM. When examining the combined effects of social risk factors, a CSR score ≥3 was associated with an increased odds of GDM (OR:1.64, 95% CI: 1.22-2.1). CONCLUSIONS: Women with a greater burden of social risk factors are more likely to have GDM, thus should be the focus of interventions to prevent and treat GDM.

Pulmonary Function and Quality of Life in Aging Men With and Without HIV from the Multicenter AIDS Cohort Study.

People living with HIV have greater pulmonary function impairments and decreased health-related quality of life (HRQoL) compared to uninfected peers. We examined whether pulmonary impairment was associated with HRQoL or respiratory health status. Using Multicenter AIDS Cohort Study data (2017-2019), associations between outcomes [HRQoL (36-Item Short Form Survey) and respiratory health status (St. George's Respiratory Questionnaire)] with pulmonary impairment [diffusing capacity for carbon monoxide (DLCO) and forced expiratory volume in 1 s (FEV1), defined as <80% predicted for both] were examined. Adjusted analyses utilized linear and zero-inflated beta regression, the latter summarized by odds ratio (OR) and quotient ratios (QRs). We also considered whether the subset of adjustment variables age, HIV serostatus, or smoking modified the relationships examined. Of 1048 men, 55% had HIV, with median age 57 [interquartile range (IQR) = 48, 64] years and 1.2 (IQR = 0, 18.1) smoking pack-years. Impaired DLCO, but not impaired FEV1, was significantly associated with lower physical HRQoL [-2.71 (-4.09, -1.33); -1.46 (-3.45, 0.54), respectively]. Pulmonary impairment was associated with higher odds of any St. George's Respiratory Questionnaire (SGRQ) (total score) limitation [DLCO OR = 1.53 (1.15, 2.04); FEV1 OR = 2.48 (1.16, 5.30)] and was elevated in individuals with more severe SGRQ limitations [DLCO QR = 1.13 (0.94, 1.36); FEV1 QR = 1.27 (0.98, 1.64)]. HIV did not modify any associations examined. Age modified the DLCO and any respiratory limitation (SGRQ symptom score) association for every 10 mL CO/min/mmHg decrease in DLCO [age 30 OR = 1.03 (0.51, 2.08); age 50 OR = 1.85 (1.27, 3.85); and age 70 OR = 3.45 (2.00, 5.88)]. Similarly, age modified the DLCO and any respiratory limitation (SGRQ total score) association. FEV1 associations with SGRQ and HRQoL scores were similar across all ages. Impaired pulmonary function was associated with lower HRQoL and greater respiratory impairments. Future studies can determine if interventions aimed at preserving pulmonary function are effective in improving HRQoL and respiratory health among aging men with and without HIV.

Hypertension and one-year risk of all-cause mortality among women with treated HIV in the United States.

OBJECTIVE: Hypertension is a critical cause of cardiovascular disease, and women with HIV have a higher prevalence of hypertension than women without HIV. The relationship between hypertension and mortality has not been well characterized in women with treated HIV. Here, we estimate the effect of hypertension on 1-year risk of all-cause mortality among women with HIV on antiretroviral therapy (ART) in the United States. DESIGN: An analysis of multicenter, observational cohort data from the Women's Interagency HIV Study (WIHS) collected between 1995 and 2019. METHODS: We included women with HIV who reported ever using ART. We used parametric g-computation to estimate the effect of hypertension (SBP ≥140  mmHg, DBP ≥90 mmHg, or use of hypertensive medication) on all-cause mortality within 1 year of a WIHS visit. RESULTS: Among 2929 unique women, we included 57 034 visits with a median age of 45 (interquartile range: 39, 52) years. Women had hypertension at 34.5% of visits, and 641 deaths occurred within 1 year of a study visit. Comparing women at visits with hypertension to women at visits without hypertension, the standardized 1-year risk ratio for mortality was 1.16 [95% confidence interval (95% CI): 1.01-1.33]. The risk ratios were higher in Hispanic (risk ratio: 1.23, 95% CI: 0.86-1.77) and non-Hispanic black women (risk ratio: 1.19, 95% CI: 1.04-1.37) and lower in non-Hispanic white women (risk ratio: 0.93, 95% CI: 0.58-1.48). CONCLUSION: Among women with treated HIV, those with hypertension, compared with those without, had an increased 1-year risk of all-cause mortality.

CROI 2022: metabolic and other complications of HIV infection or COVID-19.

Comorbid conditions have a major impact on the health, quality of life, and survival of people with HIV, particularly as this population ages. The 2022 Conference on Retroviruses and Opportunistic Infections (CROI) featured excellent science related to specific comorbidities, such as cardiovascular disease, type 2 diabetes, cancer, and frailty. The role of systemic inflammation in the pathogenesis of cardiovascular disease was an important theme, with strong evidence regarding the impact of microbial translocation. Other studies examined functional impairment, frailty, and potential important contributors, such as concomitant medications and sleep disturbances. The ANCHOR (Anal Cancer/High-grade Squamous Intraepithelial Lesions Outcomes Research) study provided crucial evidence that treatment of high-risk anal lesions reduces the incidence of anal cancer, which has important implications in the prevention of this devastating comorbidity. In addition, numerous presentations demonstrated the importance of comorbid conditions in COVID-19 outcomes in people with HIV and described persistent symptoms after acute SARS-CoV-2 infection has resolved. This review focuses on the abstracts presented at CROI 2022 in these areas, highlighting those with the most clinical impact.

Pulmonary and physical function limitations in aging men with and without HIV from the Multicenter AIDS Cohort Study (MACS).

PURPOSE: We examined the associations between pulmonary impairments and physical function and whether age, HIV serostatus, or smoking modified these relationships. METHODS: Using Multicenter AIDS Cohort Study data, we examined associations between pulmonary function (diffusing capacity for carbon monoxide [DLCO], one-second forced expiratory volume [FEV1]) and subsequent physical outcomes (gait speed, grip strength, frailty [non-frail, pre-frail, frail]) using mixed models. RESULTS: Of 1,048 men, 55% were living with HIV, median age was 57(IQR=48,64) and median cumulative pack-years was 1.2(IQR = 0,18.1); 33% and 13% had impaired DLCO and FEV1(<80% predicted), respectively. Participants with impaired DLCO had 3.5 kg (95%CI: -4.6, -2.4) weaker grip strength, 0.04 m/sec (95%CI: -0.06, -0.02) slower gait speed and 4.44-fold (95%CI: 1.81, 10.93) greater odds of frailty compared to participants with normal DLCO. Participants with impaired FEV1 had 3.1 kg (95%CI: -4.8, -1.4) weaker grip strength, similar gait speed (-0.001 m/sec [95%CI: -0.04, 0.03]) and 5.72-fold (95%CI: 1.90, 17.19) greater odds of frailty compared to participants with normal FEV1. Age, but not smoking or HIV, significantly modified the DLCO effect on gait speed and grip strength. CONCLUSIONS: Pulmonary impairment and decreased physical function were associated. Preserving pulmonary function may help preserve physical function in aging men with and without HIV.

Circulating biomarker correlates of left atrial size and myocardial extracellular volume fraction among persons living with and without HIV.

BACKGROUND: Infection with human immunodeficiency virus (HIV) is associated with higher risk for myocardial disease despite modern combination antiretroviral therapy (cART). Factors contributing to this excess risk, however, remain poorly characterized. We aimed to assess cross-sectional relationships between elevations of left atrial volume index (LAVI) and myocardial extracellular volume (ECV) fraction that have been reported in persons living with HIV and levels of circulating biomarkers of inflammation, fibrosis, and myocyte stretch among persons living with and without HIV (PLWH, PLWOH). METHODS: Participants from three cohorts of PLWH and PLWOH underwent cardiovascular magnetic resonance imaging for measurement of LAVI and ECV. Levels of circulating proteins (IL-6, sCD14, galectin-3, NT-proBNP, GDF-15, TIMP-2, MMP-2, and hsTnI) were measured using immunoassays. Associations were assessed using logistic and linear regression, adjusting for demographics, substance use, and clinical characteristics. RESULTS: Among 381 participants with and without HIV, median age (IQR) was 55.1 (51.2, 58.4) years, 28% were female, 69% were Black, and 46% were current smokers. Sixty-two percent were PLWH (n = 235), of whom 88% were receiving cART and 72% were virally suppressed. PLWH had higher levels of sCD14 (p = < 0.001), GDF-15 (p = < 0.001), and NT-proBNP (p = 0.03) compared to PLWOH, while levels of other biomarkers did not differ by HIV serostatus, including IL-6 (p = 0.84). Among PLWH, higher sCD14, GDF-15, and NT-proBNP were also associated with lower CD4 + cell count, and higher NT-proBNP was associated with detectable HIV viral load. NT-proBNP was associated with elevated LAVI (OR: 1.79 [95% CI: 1.31, 2.44]; p < 0.001) with no evidence of effect measure modification by HIV serostatus. Other associations between HIV-associated biomarkers and LAVI or ECV were small or imprecise. CONCLUSIONS: Our findings suggest that elevated levels of sCD14, GDF-15, and NT-proBNP among PLWH compared to PLWOH observed in the current cART era may only minimally reflect HIV-associated elevations in LAVI and ECV. Future studies of excess risk of myocardial disease among contemporary cohorts of PLWH should investigate mechanisms other than those connoted by the studied biomarkers.

Comparison of Hormonal Response to a Mixed-Meal Challenge in Hypoglycemia After Sleeve Gastrectomy vs Gastric Bypass.

CONTEXT: Exaggerated postprandial incretin and insulin responses are well documented in postbariatric surgery hypoglycemia (PBH) after Roux-en-Y gastric bypass (RYGB). However, less is known about PBH after sleeve gastrectomy (SG). OBJECTIVE: We sought to compare meal-stimulated hormonal response in those with PBH after SG vs RYGB. METHODS: We enrolled 23 post-SG (12 with and 11 without PBH) and 20 post-RYGB (7 with and 13 without PBH) individuals who underwent bariatric surgery at our institution. PBH was defined as plasma glucose less than 60 mg/dL on 4-hour mixed-meal tolerance test (MTT). Islet and incretin hormones were compared across the 4 groups. RESULTS: Participants (N = 43) were on average 5 years post surgery, with a mean age of 48 years, mean preoperative body mass index of 48.4, 81% female, 61% White, and 53% post SG. Regardless of PBH, the SG group showed lower glucose, glucagon, and glucagon-like peptide 1 (GLP-1) responses to MTT and similar insulin and glucose-dependent insulinotropic polypeptide (GIP) responses compared to the RYGB group. Among those with PBH, the SG group following the MTT showed a lower peak glucose (P = .02), a similar peak insulin (90.3 mU/L vs 171mU/L; P = .18), lower glucagon (P < .01), early GLP-1 response (AUC0-60 min; P = .01), and slower time to peak GIP (P = .02) compared to PBH after RYGB. CONCLUSION: Among individuals with PBH, those who underwent SG were significantly different compared to RYGB in meal-stimulated hormonal responses, including lower glucagon and GLP-1 responses, but similar insulin and GIP responses. Future studies are needed to better understand the differential contribution of insulin and non-insulin-mediated mechanisms behind PBH after SG vs RYGB.

Trans women have worse cardiovascular biomarker profiles than cisgender men independent of hormone use and HIV serostatus.

BACKGROUND: Feminizing hormonal therapy (FHT) and HIV potentially alter cardiovascular disease (CVD) risk in transgender women (TW). METHODS: TW were enrolled in Los Angeles, California and Houston, Texas and frequency-matched to Multicenter AIDS Cohort Study cisgender men (CM) on age, race, substance use, and abacavir use. Biomarkers of CVD risk and inflammation were assessed via ELISA. Wilcoxon rank sum and Fisher's exact tests compared TW and CM. Multivariable linear regression assessed factors associated with biomarker concentrations. RESULTS: TW (HIV+ n  = 75, HIV- n  = 47) and CM (HIV+ n  = 40, HIV- n  = 40) had mean age 43-45 years; TW/CM were 90%/91% non-Hispanic Black, Hispanic, or Multiracial, 26%/53% obese, and 34%/24% current smokers; 67% of TW were on FHT. Among people with HIV (PWH), TW had higher median extracellular newly-identified receptor for advanced glycation end-products (EN-RAGE), lipoprotein-associated phospholipase A2 (LpPLA2), oxidized low-density lipoprotein (oxLDL), soluble tumor necrosis factor receptor type (sTNFR) I/II, interleukin (IL)-8 and plasminogen activator inhibitor (PAI)-1, but lower soluble CD14, von Willebrand factor (vWF) and endothelin (ET)-1 levels than CM. Findings were similar for participants without HIV (all P  < 0.05). In multivariable analysis, TW had higher EN-RAGE, IL-6, IL-8, P selectin, PAI-1, oxLDL and sTNFRI/II concentrations, and lower vWF, independent of HIV serostatus and current FHT use. Both being a TW and a PWH were associated with lower ET-1. CONCLUSIONS: Compared to matched cisgender men, trans women have altered profiles of biomarkers associated with systemic inflammation and CVD. Further work is needed to decipher the contributions of FHT to CVD risk in TW with HIV.

GDF15 and Cortisol Response to Meal Tolerance Test in Post-Sleeve Gastrectomy Patients with Weight Regain.

BACKGROUND: Hormonal factors behind weight regain (WR) after surgical weight loss remain inadequately understood. Growth/differentiation factor 15 (GDF15) has emerged as a potential therapeutic target in obesity treatment. Cortisol, another stress hormone, has also been associated with weight gain at both low and high circulating concentrations. We aimed to compare meal-stimulated GDF15 and cortisol response in adults with and without WR after sleeve gastrectomy (SG). We hypothesized that GDF15 and cortisol response to meal tolerance test (MTT) will be lower in those with versus without WR after SG. METHODS: Cross-sectional study comprised 21 adults without diabetes, who underwent SG. WR was defined as 100 × (current weight - nadir)/(preoperative weight - nadir) > 10%. GDF15, cortisol, insulin, glucose, and incretins (total glucagon-like peptide (GLP)-1 and glucose-dependent insulinotropic polypeptide (GIP) circulating concentrations) were measured during MTT (0-240 min) after 3-6 years post-bariatric surgery. RESULTS: All participants were 48% White, 85% female, with mean (SD) age: 43(10) years, and BMI: 36.2(7.6) kg/m2. Compared to the non-WR group (n = 6), the WR group (n = 15) had significantly higher BMI (WR: 38.6 ± 7.6 kg/m2, non-WR: 30.3 ± 3.5 kg/m2, p = 0.02) and showed lower GDF15 response (WR AUC vs non-WR AUC (116143 ± 13973 vs 185798 ± 38884 ng*min/L, p = 0.047)) and lower cortisol response (WR AUC vs non-WR AUC (3492 ± 210 vs 4880 ± 655 µg*min/dL, p = 0.015)). Incretin response did not differ between the groups. CONCLUSIONS: GDF15 and cortisol responses to MTT were lower in those who regained the weight after SG compared to those who did not, suggesting that dysregulation in GDF15 and cortisol response following bariatric surgery.

Clonal hematopoiesis in men living with HIV and association with subclinical atherosclerosis.

OBJECTIVES: People with HIV (PWH) are at increased risk for premature cardiovascular disease (CVD). Clonal hematopoiesis is a common age-related condition that may be associated with increased CVD risk. The goal of this study was to determine the prevalence of clonal hematopoiesis and its association with chronic inflammation and CVD in PWH. DESIGN: Cross-sectional study utilizing archived specimens and data from 118 men (86 PWH and 32 HIV-uninfected) from the Baltimore-Washington DC center of the Multicenter AIDS Cohort Study (MACS) who had had coronary computed tomography angiography (CTA) and measurement of 34 serologic inflammatory biomarkers. METHODS: Clonal hematopoiesis was assessed on peripheral blood mononuclear cells utilizing targeted error-corrected next generation sequencing (NGS) focused on 92 genes frequently mutated in hematologic malignancies. Clinical and laboratory data were obtained from the MACS database. RESULTS: Clonal hematopoiesis with a variant allele frequency (VAF) greater than 1% was significantly more common in PWH [20/86 (23.3%)] than in HIV-uninfected men [2/32 (6.3%)] ( P  = 0.035). PWH with clonal hematopoiesis (VAF > 1%) were more likely to have coronary artery stenosis of at least 50% than those without clonal hematopoiesis [6/20 (30%) vs. 6/64 (9%); P  = 0.021]. Presence of clonal hematopoiesis was not significantly associated with serological inflammatory markers, except for significantly lower serum leptin levels; this was not significant after adjustment for abdominal or thigh subcutaneous fat area. CONCLUSION: Clonal hematopoiesis was more common in PWH and among PWH was associated with the extent of coronary artery disease. Larger studies are needed to further examine the biological and clinical consequences of clonal hematopoiesis in PWH.

Methods for home-based self-applied polysomnography: the Multicenter AIDS Cohort Study.

Study Objectives: Along with multiple chronic comorbidities, sleep disorders are prevalent in people living with human immunodeficiency virus (HIV) infection. The goal of this study was to establish methods for assessing sleep quality and breathing-related disorders using self-applied home polysomnography in people with and without HIV. Methods: Self-applied polysomnography was conducted on 960 participants in the Multicenter AIDS Cohort Study (MACS) using the Nox A1 recorder to collect data on the frontal electroencephalogram (EEG), bilateral electrooculograms, and a frontalis electromyogram during sleep. Breathing patterns were characterized using respiratory inductance plethysmography bands and pulse oximetry. Continuous recordings of the electrocardiogram were also obtained. All studies were scored centrally for sleep stages and disordered breathing events. Results: Successful home polysomnography was obtained in 807 of 960 participants on the first attempt and 44 participants on the second. Thus, a successful polysomnogram was obtained in 851 (88.6%) of the participants. Reasons for an unsuccessful study included less than 3 h of data on oximetry (34.6%), EEG (28.4%), respiratory inductance plethysmography (21.0%), or two or more of these combined (16.0%). Of the successful studies (N = 851), signal quality was rated as good, very good, or excellent in 810 (95.2%). No temporal trends in study quality were noted. Independent correlates of an unsuccessful study included black race, current smoking, and cocaine use. Conclusions: Home polysomnography was successfully completed in the MACS demonstrating its feasibility in a community cohort. Given the burden of in-lab polysomnography, the methods described herein provide a cost-effective alternative for collecting sleep data in the home.