Citations

Abstract Objective People living with HIV have an increased risk of heart failure (HF). There are different subtypes of HF. Knowledge about the factors differentiating HF subtypes in people with HIV is limited but necessary to guide preventive measures and treatment. Methods A retrospective review of medical records was undertaken in people with HIV aged ≥18 years who received care at the University of Miami/Jackson Memorial HIV Clinic between January 2017 and November 2019 ( N = 1166). Patients with an echocardiogram available for review ( n = 305) were included. HF was defined as a documented diagnosis of any HF subtype ( n = 52). We stratified those with HF by their ejection fraction (EF) into HF with preserved EF (HFpEF), HF with borderline EF, or HF with reduced EF (HFrEF). Results The prevalence of HF was 4.5%. The cohort included 46.2% females and 75% self‐identified African Americans. Those with HF had a higher prevalence of hypertension, prior myocardial infarction, angina, coronary artery disease, percutaneous coronary intervention, coronary artery bypass grafting, diastolic dysfunction, and left ventricle hypertrophy. People with HIV with HF with borderline EF exhibited more coronary artery disease than those with HFpEF. Conclusions We characterize HF in people with HIV in South Florida and report the prevalence of HF and HF subtypes. Only a small percentage of patients had echocardiograms performed, suggesting an ongoing need for recognition of the increased risk of HF in people living with HIV, and raising the concern about lack of awareness contributing to underdiagnosis and missed treatment opportunities in this population.

Abstract Context Mild autonomous cortisol secretion (MACS) is diagnosed based on postdexamethasone cortisol >1.8 µg/dL. Scarce evidence exists on steroid circadian secretion and steroid metabolome in MACS. Objective To characterize 24-hour (h) urine steroid metabolome in patients with MACS and determine circadian differences in urine steroid profiling and cortisol concentrations in patients with MACS vs referent subjects. Methods Cross-sectional study, 2018-2023, at a referral center. Patients with MACS and age-, sex-, body mass index–, and menopausal status–matched referent subjects were included. Urine was collected over a 24 hour period as separate daytime and nighttime collections. High-resolution mass spectrometry assay was used to measure 25 steroids. A subgroup of patients and referent subjects was admitted for serum measurements of free and total cortisol every 2 hours. Outcomes were steroids, steroid sums, and ratios. Results Patients with MACS (n = 72) had lower µg/24 hour median androgens (2084 vs 3283, P < .001), higher glucocorticoids (15 754 vs 12936, P < .001), and higher glucocorticoid/androgen ratio (8.7 vs 3.9, P < .001) than referent subjects. Patients also had lower steroid day/night ratios than referent subjects, reflecting a higher relative nocturnal steroid production in MACS. In a subgroup of 12 patients with MACS and 10 referent subjects, the 24-hour areas under the curve for total and free serum cortisol were similar. However, evening mean total (5.3 vs 4.0 µg/dL, P = .056) and free (0.2 vs 0.1 µg/dL, P = .035) cortisol was higher in patients vs referent subjects. Conclusion Patients with MACS demonstrate an abnormal urine steroid metabolome, with a high glucocorticoid to androgen ratio, and a higher nocturnal steroid production.

9508 Background: Outcomes for pts with mMEL remain sobering despite access to available immunotherapies as the majority of pts are resistant or become refractory to checkpoint blockade with no approved treatments. CXCR1 and CXCR2 (CXCR1/2) signaling mediate myeloid immunosuppression and MEL growth, inversely correlating with anti-PD-1 response and pt survival. SX-682 is an oral allosteric inhibitor of CXCR1/2. As a single agent, SX-682 increases tumor CD8+ T cell infiltration and inhibits tumor growth in mouse MEL. Methods: This phase 1 dose-escalation with expansion trial (NCT03161431) evaluated pem and escalating doses of SX-682 (25 - 400 mg orally BID) in pts with mMEL in a 21-day cycle. Pts must have had progressive disease (PD) on prior anti-PD-1. Mucosal MEL and asymptomatic brain metastases were allowed. Escalation cohorts had a 21-day SX-682 monotherapy (MONO) run-in. Response assessment by RECIST 1.1 was every 2 cycles during combination (COMBO) treatment. Primary endpoint was safety: adverse events (AEs), dose-limiting toxicity (DLT) and maximally-tolerated dose (MTD). Secondary endpoints included objective response rate (ORR; complete [CR] + partial [PR] response), disease control rate (DCR; CR + PR + stable disease [SD]) and overall survival (OS). Results: As of October 2023, 51 pts were enrolled and treated; median age of 65 (range 24-91), 55% male, 61% elevated LDH, 39% BRAF mutated. All pts received prior anti-PD-1, 37 (73%) received combined anti-PD-1 and anti-CTLA-4, and 23 (45%) had ≥ 3 prior therapies. Steady-state blood SX-682 was dose-proportional. No MONO DLT or MTD was identified. The 200 mg dose cohort was expanded in COMBO based on safety and pharmacodynamics: mg BID dose (n) = 25 (3), 50 (3), 100 (6), 150 (8), 200 (31). Any grade and grade 3/4 treatment-related AEs (TRAEs) occurred in 75% and 43%, respectively, and discontinuation (DC) due to TRAEs in 20% (when uncomplicated neutropenia, a permitted effect from CXCR2 inhibition on bone-marrow trafficking, was excluded there were 25% grade 3/4 TRAEs and 12% DC [rash, transaminitis]). There was no infectious signal. At the 200 mg dose, the ORR was 21% in 19 evaluable pts (4 PR + 0 CR) and the DCR was 63% (8 SD + 4 PR). DCR significantly depended on SX-682 dose ( P vs. ≤100 mg): 0% (0/9) at ≤100 mg, 50% (3/6) at 150 mg ( P = 0.0440) and 63% (12/19) at 200 mg ( P = 0.0028). All 15 pts with disease control had progressed on anti-PD-1 and anti-CTLA-4. Median OS was longer in pts in the 200 mg cohort (14.7 months; 95% CI, 10.5 – NR [not reached], n = 31) than in pts treated with ≤100 mg SX-682 (7.4 months; 95% CI, 5.0 – NR; n = 10). Conclusions: SX-682 combined with pem had a tolerable safety profile and activity reflected by objective responses and clinically meaningful disease control in heavily pretreated mMEL pts with progression on anti-PD-1 and anti–CTLA-4. Clinical trial information: NCT03161431 .

Background: Our institution implemented acute-care obstetric (OB) telemedicine (TeleOB) to address rural disparities across our health system. We sought to determine whether in situ simulations with embedded TeleOB consultation increase participants’ comfort managing OB emergencies and comfort with and likelihood of using TeleOB. Methods: Rural site care teams participated in multidisciplinary in situ OB emergency simulations. Physicians in OB and neonatology at the referral center assisted via telemedicine consultation. Participants were surveyed before and after the simulations and six months later regarding their experience during the simulations. Results: Participants reported increased comfort with TeleOB activation, indications, and workflow processes, as well as increased comfort managing OB emergencies. Participants also reported significantly increased likelihood of using TeleOB in the future. Conclusions: Consistent with previous work, in situ simulation with embedded telemedicine consultations is an effective approach to facilitate telemedicine implementation and promote use by rural clinicians.

Abstract To investigate the cellular and molecular mechanisms associated with targeting CD30-expressing Hodgkin lymphoma (HL) and immune checkpoint modulation induced by combination therapies of CTLA4 and PD1, we leveraged Phase 1/2 multicenter open-label trial NCT01896999 that enrolled patients with refractory or relapsed HL (R/R HL). Using peripheral blood, we assessed soluble proteins, cell composition, T-cell clonality, and tumor antigen-specific antibodies in 54 patients enrolled in the phase 1 component of the trial. NCT01896999 reported high (>75%) overall objective response rates with brentuximab vedotin (BV) in combination with ipilimumab (I) and/or nivolumab (N) in patients with R/R HL. We observed a durable increase in soluble PD1 and plasmacytoid dendritic cells as well as decreases in plasma CCL17, ANGPT2, MMP12, IL13, and CXCL13 in N-containing regimens (BV + N and BV + I + N) compared with BV + I (P < 0.05). Nonresponders and patients with short progression-free survival showed elevated CXCL9, CXCL13, CD5, CCL17, adenosine–deaminase, and MUC16 at baseline or after one treatment cycle and a higher prevalence of NY-ESO-1-specific autoantibodies (P < 0.05). The results suggest a circulating tumor-immune-derived signature of BV ± I ± N treatment resistance that may be useful for patient stratification in combination checkpoint therapy. Significance: Identification of multi-omic immune markers from peripheral blood may help elucidate resistance mechanisms to checkpoint inhibitor and antibody–drug conjugate combinations with potential implications for treatment decisions in relapsed HL.

ImportancePersistent symptoms and disability following SARS-CoV-2 infection, known as post–COVID-19 condition or “long COVID,” are frequently reported and pose a substantial personal and societal burden.ObjectiveTo determine time to recovery following SARS-CoV-2 infection and identify factors associated with recovery by 90 days.Design, Setting, and ParticipantsFor this prospective cohort study, standardized ascertainment of SARS-CoV-2 infection was conducted starting in April 1, 2020, across 14 ongoing National Institutes of Health–funded cohorts that have enrolled and followed participants since 1971. This report includes data collected through February 28, 2023, on adults aged 18 years or older with self-reported SARS-CoV-2 infection.ExposurePreinfection health conditions and lifestyle factors assessed before and during the pandemic via prepandemic examinations and pandemic-era questionnaires.Main Outcomes and MeasuresProbability of nonrecovery by 90 days and restricted mean recovery times were estimated using Kaplan-Meier curves, and Cox proportional hazards regression was performed to assess multivariable-adjusted associations with recovery by 90 days.ResultsOf 4708 participants with self-reported SARS-CoV-2 infection (mean [SD] age, 61.3 [13.8] years; 2952 women [62.7%]), an estimated 22.5% (95% CI, 21.2%-23.7%) did not recover by 90 days post infection. Median (IQR) time to recovery was 20 (8-75) days. By 90 days post infection, there were significant differences in restricted mean recovery time according to sociodemographic, clinical, and lifestyle characteristics, particularly by acute infection severity (outpatient vs critical hospitalization, 32.9 days [95% CI, 31.9-33.9 days] vs 57.6 days [95% CI, 51.9-63.3 days]; log-rank P < .001). Recovery by 90 days post infection was associated with vaccination prior to infection (hazard ratio [HR], 1.30; 95% CI, 1.11-1.51) and infection during the sixth (Omicron variant) vs first wave (HR, 1.25; 95% CI, 1.06-1.49). These associations were mediated by reduced severity of acute infection (33.4% and 17.6%, respectively). Recovery was unfavorably associated with female sex (HR, 0.85; 95% CI, 0.79-0.92) and prepandemic clinical cardiovascular disease (HR, 0.84; 95% CI, 0.71-0.99). No significant multivariable-adjusted associations were observed for age, educational attainment, smoking history, obesity, diabetes, chronic kidney disease, asthma, chronic obstructive pulmonary disease, or elevated depressive symptoms. Results were similar for reinfections.Conclusions and RelevanceIn this cohort study, more than 1 in 5 adults did not recover within 3 months of SARS-CoV-2 infection. Recovery within 3 months was less likely in women and those with preexisting cardiovascular disease and more likely in those with COVID-19 vaccination or infection during the Omicron variant wave.

Abstract The requirement of community outreach and engagement (COE) as a major component of the National Cancer Institute (NCI) Cancer Center Support Grant has had an enormous impact on the way NCI-designated cancer centers identify, investigate, and address the needs of their catchment area (CA) communities. Given the wide-ranging diversity of our nation, COE’s scope of work (SOW) is extremely demanding and complex. Yet, COE is often marginalized and viewed as void of scientific methods when, in fact, it requires specialized scientific knowledge and a broad range of proficiencies. Black COE scientific directors may be particularly attuned to this marginalization as they have often confronted workplace inequities that resemble the health inequities observed within their cancer center’s CA. Thus, Black COE leaders are uniquely positioned to offer insight on the past, present, and future of COE. Key areas discussed include the low involvement of minoritized group members and those with appropriate expertise in national COE leadership; the lack of established, consistent criteria for evaluation of COE components and qualifications of evaluators; the need for substantial financial investment in COE; potential misalignment of community priorities and cancer center objectives; professional development and growth of COE staff and leaders; the expanding scope of COE across their respective cancer centers and CAs; and the need for center-wide involvement in COE and an “all-hands-on-deck” approach. These areas warrant thoughtful dialogue as COE evolves, for the benefit and success of all COE leaders. However, this dialogue must include diverse voices representing similarly diverse stakeholders at every level.

Abstract Context Patients with nonfunctioning adenomas (NFAs), adenomas with mild autonomous cortisol secretion (MACS) and Cushing syndrome (CS) demonstrate an increased cardiovascular risk. Objective This work aimed to determine the extent of lipoprotein abnormalities in NFA, MACS, and CS. Methods We conducted a single-center, cross-sectional study of patients with NFA (n = 167), MACS (n = 213), CS (n = 142), and referent individuals (n = 202) between January 2015 and July 2022. Triglyceride-rich lipoprotein particles (TRLP), low-density lipoprotein particles (LDLP), high-density lipoprotein particles (HDLP), their subclasses and sizes were measured using nuclear magnetic resonance spectroscopy. Multivariable logistic analyses were adjusted for age, sex, body mass index, smoking, hypertension, diabetes and lipid-lowering drug therapy. Results In age- and sex-adjusted analysis, all patients categories demonstrated increased very large TRLP, large TRLP, and greater TRLP size (odds ratio [OR], 1.22-2.08) and total LDLP (OR, 1.22-1.75) and decreased LDL and HDL size compared to referent individuals. In fully adjusted analysis, LDLP concentrations remained elevated in all patient categories (OR, 1.31-1.84). Total cholesterol, LDL cholesterol, triglycerides, and apolipoprotein B (ApoB) were also higher in all patient categories in age- and sex-adjusted analysis, with ApoB remaining elevated in all patient categories in fully adjusted analysis. Similar LDLP and ApoB elevations were observed in all patient categories after excluding individuals on lipid-lowering therapy. Conclusion Patients with overt, mild, and even absent cortisol excess demonstrate lipoprotein profile abnormalities, in particular, high LDLP and ApoB concentrations, which conceivably contribute to high cardiometabolic risk.