Publications by Year: 2026

One of the key pillars of Ending the HIV Epidemic is ensuring adherence to oral HIV pre-exposure prophylaxis (PrEP). Men who have sex with men (MSM) who also have substance use disorders experience multiple challenges to maintaining PrEP adherence. We developed a digital pill system (DPS) linked to a personalized adherence intervention, PrEPSteps, to address barriers to PrEP adherence, and tested the feasibility and acceptability of this system, as well as its potential for an effect on PrEP adherence. We enrolled MSM with moderate to severe substance use disorder who were on oral PrEP in a two-arm pilot randomized controlled trial. Both arms received the DPS co-encapsulated with oral PrEP. Participants in the intervention arm also received "PrEPSteps" - a personalized cognitive-behavioral adherence intervention. Primary outcomes were feasibility and acceptability of DPS + PrEPSteps. To explore potential intervention effects, adherence changes from baseline to 3-month follow-up were compared across arms. At 6-month follow-up, adherence was assessed via self-report. Thirty-six participants were enrolled, 32, completed the run-in period, 28 were randomized, and 27 completed the 3-month intervention period. Of those, 26 completed six-month follow-up. Operation of the DPS and PrEPSteps was feasible, with consistent data recording throughout the 3-month intervention period. Qualitative interviews in the intervention arm at 3 months demonstrated PrEPSteps was acceptable. Intervention arm participants had 14% higher PrEP adherence (b = 13.67, 95%CI [.77-26.57], p = .039) at 3 month follow up. This effect persisted at six months, suggesting that PrEPSteps has the potential to improve PrEP adherence and help individuals sustain adherence benefits over time.Trial registration: www.ClinicalTrials.gov identifier: NCT03512418.

IMPORTANCE: Early and accurate identification of clinical warning signs in young infants may help avert sepsis morbidity and mortality in resource-limited settings.

OBJECTIVE: To systematically review evidence on the association and accuracy of clinical signs to diagnose sepsis or predict mortality in young infants aged 0 to 59 days to inform management in settings with limited laboratory diagnostics.

DATA SOURCES: MEDLINE, Embase, CINAHL, Global Index Medicus, and Cochrane CENTRAL Register were searched from inception through May 2023, with updated searches on September 5, 2024. An umbrella search of systematic reviews was conducted in January 2024.

STUDY SELECTION: Included studies reported data on 24 infant clinical signs informed by current World Health Organization (WHO) Integrated Management of Childhood Illness (IMCI) and hospital-based algorithms for the care of sick young infants reporting odds ratios (OR), risk ratios, or sensitivity and specificity.

DATA EXTRACTION AND SYNTHESIS: Data were extracted independently by 2 reviewers. Quality assessment used the Newcastle-Ottawa, Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2), and Quality Assessment of Prognostic Accuracy Studies (QUAPAS) scales. OR data were pooled using random-effects models. Data analysis was performed from July to September 2025.

MAIN OUTCOMES AND MEASURES: OR of all-cause mortality, culture-confirmed sepsis, or clinical sepsis (with access to laboratory investigations).

RESULTS: Of 7641 studies, 52 studies with 140 885 participants were included. A total of 16 clinical signs were significantly associated with mortality, 11 with culture-confirmed sepsis, and 13 with clinical sepsis. For mortality, the 5 strongest associations were weak, abnormal, or absent cry (OR, 20.48; 95% CI, 6.59-63.67); not able to feed at all (OR, 18.32; 95% CI, 6.00-55.97); not feeding well (OR, 13.39; 95% CI, 6.97-25.72); drowsiness or unconsciousness (OR, 12.46; 95% CI, 6.06-25.62); and prolonged capillary refill (OR, 12.06; 95% CI, 2.77-52.53). The top 5 signs associated with culture-confirmed sepsis were not feeding well (OR, 4.52; 95% CI, 1.10-18.59); prolonged capillary refill (OR, 3.59; 95% CI, 2.05-6.28); lethargy (OR, 3.44; 95% CI, 1.89-6.26); drowsiness or unconsciousness (OR, 3.07; 95% CI, 2.01-4.68); and feeding intolerance (OR, 2.95; 95% CI, 1.67-5.21).

CONCLUSIONS AND RELEVANCE: All current WHO IMCI clinical signs were significantly associated with mortality or culture-confirmed sepsis. Several signs not in IMCI were identified that may improve identification of life-threatening illness in young infants in resource-limited settings where clinical sign algorithms are the primary diagnostic tool.

Cardiovascular adverse effects of drugs have significant practical implications for patient management. While cardiovascular adverse effects have commonly been associated with oncologic therapeutics, a growing body of evidence suggests that non-oncologic medications can also be associated with significant cardiovascular harm. These adverse effects range from arrhythmias, conduction abnormalities, QT prolongation, heart failure, myocardial infarction, or structural cardiomyopathy. Non-oncologic drugs that have been implicated include antibiotics (e.g. macrolides, fluoroquinolones), antidiabetics (e.g. thiazolidinediones), non-steroidal anti-inflammatory drugs, drugs for gastrointestinal and urological conditions, and most importantly, cardiovascular drugs. In this narrative review, we focus on the most common non-oncologic drugs that cause cardiovascular adverse effects, their proposed underlying mechanisms with particular emphasis on their clinical manifestations and clinical implications for everyday cardiovascular practice.

The molecular pathways linking genetic variants to Parkinson's disease (PD) onset and progression remain incompletely defined; however, risk alleles in multiple genes, including GBA1, strongly implicate lipid metabolism. To systematically identify causal biomarker signatures, we analyzed comprehensive metabolome profiles from blood plasma in 149 PD patients and 150 controls, along with complementary genetic, RNA-sequencing, and metabolic data from other available clinical and pathologic cohorts. Using colocalization and summary-data-based Mendelian randomization, we tested whether expression and metabolic quantitative trait loci mediate the association between implicated genetic variants and PD risk. We further integrated differential metabolomics and proteomics from blood and brain to reveal pertinent mechanisms. We show that common PD risk variants at the serine palmitoyltransferase small subunit B (SPTSSB) locus, a key regulator of de novo sphingolipid biosynthesis, are associated with increased SPTSSB brain expression and elevated plasma ceramides. Additional analyses strongly support our hypothesis that a common SPTSSB causal variant is responsible for PD risk as well as the expression and metabolic quantitative trait loci. Multiple sphingolipids and fatty acid derivatives were perturbed in PD, and we identified both unique and shared features with the Alzheimer's disease metabolome. A PD acylcarnitine signature was further replicated in human postmortem brain tissue, when comparing those with or without preclinical Lewy body pathology. Integrated analysis of complementary brain proteomic profiles revealed dysregulation of mitochondrial processes dependent on acylcarnitines, including fatty acid beta-oxidation, the tricarboxylic acid cycle, and oxidative phosphorylation. Our results identify promising biomarkers and reveal a causal chain linking genetic variation to altered gene/protein expression, lipid dysmetabolism, and the manifestation of PD.

Neuronal signaling requires large amounts of ATP, making neurons particularly sensitive to defects in energy homeostasis. Mitochondrial movement and energy production are therefore regulated to align local demands with mitochondrial output. Here, we report a pathway that arrests mitochondria in response to decreases in the ATP-to-AMP ratio, an indication that ATP consumption exceeds supply. In neurons and cell lines, low concentrations of the electron transport chain inhibitor antimycin A decrease the production of ATP and concomitantly arrest mitochondrial movement without triggering mitophagy. This arrest is accompanied by the accumulation of actin fibers adjacent to the mitochondria, which serve as an anchor that resists the associated motors. This arrest is mediated by activation of the energy-sensing kinase AMPK, which phosphorylates TRAK1. This mechanism likely helps maintain cellular energy homeostasis by anchoring energy-producing mitochondria in places where they are most needed.

AIMS: Obesity, particularly visceral adiposity, is a key driver of cardiovascular mortality (CVM), yet conventional measures such as body mass index (BMI) inadequately capture fat distribution. The Body Roundness Index (BRI) is a novel anthropometric measure integrating waist circumference and height to better reflect body shape and visceral fat. This study examined the association between BRI and CVM in U.S. adults and across sociodemographic subgroups.

METHODS: We analyzed data from 31,351 adults (median age 43 yrs, 50% females) aged >20 years in NHANES 1999-2018, excluding those with prior cardiovascular disease or cancer. BRI was computed using a validated equation and categorized into quintiles (Q3 as reference). The primary outcome was CVM; secondary outcomes included all-cause, heart disease, and cerebrovascular mortality. Weighted Cox proportional hazards and restricted cubic spline (RCS) models evaluated associations after adjustment for demographic, behavioral, and clinical factors. Subgroup and sensitivity analyses tested consistency and effect modification.

RESULTS: During a median follow up of 10.1 years (IQR: 5.3-14.9 years), 883 cardiovascular deaths occurred. In fully adjusted models, participants in the highest BRI quintile had a 54% higher risk of CVM (HR, 1.54; 95% CI, 1.13-2.08; p=0.006) versus Q3. This risk remained high even among those with normal BMI. RCS analysis indicated a modest U-shaped association. Stronger effects were observed among middle-aged adults (45-64 years) and those with higher educational attainment.

CONCLUSIONS: Higher BRI is independently associated with increased cardiovascular mortality, particularly among middle aged adults and those with normal BMI, underscoring its potential as a practical, noninvasive tool for cardiovascular risk stratification. Incorporating BRI into clinical and public health assessment may improve identification of individuals at elevated risk.

BACKGROUND: Solid organ transplant (SOT) recipients face increased colorectal cancer (CRC) risk due to chronic immunosuppression and comorbidities such as primary sclerosing cholangitis, inflammatory bowel disease, and cystic fibrosis. Despite this elevated risk, CRC screening and treatment guidelines specific to transplant recipients remain limited. This systematic review and meta-analysis evaluated the prevalence, clinical characteristics, risk factors, and outcomes of CRC in SOT recipients.

METHODS: A comprehensive search across major databases identified studies reporting CRC incidence and outcomes in kidney, liver, heart, and lung transplant recipients. Study quality was assessed using validated risk-of-bias tools. Pooled estimates were calculated using a random-effects model; heterogeneity and organ-specific subgroup analyses were also conducted.

RESULTS: The pooled incidence of CRC in SOT recipients was 0.95% (95% CI: 0.35%-1.55%). Incidence was highest in heart transplant recipients (1.27%), followed by kidney (1.12%), lung (0.56%), and liver (0.53%) recipients. The mean time to CRC diagnosis was 8.8 years (95% CI: 5.94-11.82). A total of 41.13% of patients presented with stage III/IV or metastatic disease, and right-sided tumors predominated (46.34%). Surgical resection was performed in 62.74% of patients. The mortality rate among CRC patients post-transplant was 61.13% (95% CI: 39.55%-82.7%).

CONCLUSION: CRC in SOT recipients is associated with increased incidence, delayed diagnosis, and poor prognosis. The predominance of right-sided tumors and late-stage presentation underscore the need for tailored screening and surveillance protocols. Future clinical guidelines should incorporate organ-specific risk stratification and long-term monitoring to optimize outcomes in this high-risk population.

OBJECTIVE: We developed a culturally-grounded intervention to promote healthy beverage consumption among Navajo children aged 2-5 years. This study, which took place from 2021-2023, evaluated prepost changes in beverage habits and caregiver knowledge and attitudes.

METHODS: Prospective cohort study with prepost evaluation. Children attending participating early child education sites and their primary caregivers were enrolled. Survey data were collected at baseline, during the school year, and immediately after completion of the 4-month intervention.

RESULTS: Average daily water intake increased significantly from 17.0 to 22.3 fl oz, P = 0.003. There was no significant change in consumption of other specific beverages, nor in the consumption of all sugar-sweetened beverages combined (P = 0.94). The proportion of caregivers who agreed or strongly agreed that they were knowledgeable about Diné traditions about water increased from 59.3% to 87.0% (P = 0.001). Similarly, those who agreed that Diné traditions about water influenced what drink they offered their children increased from 46.3% to 81.5% (P < 0.001).

CONCLUSIONS AND IMPLICATIONS: Our pilot study suggests that a culturally-grounded water promotion program for Navajo families may have a positive impact on strengthening cultural connections among caregivers and increasing water intake among children aged 2-5 years. Further research is needed to evaluate effectiveness.

Sankey diagram of agreement between dischareg summary, discharge instructions, and patient provided reasoning for chronic medication changes made during hospitalization.