Faculty Bibliography

BACKGROUND:Carnobacterium maltaromaticum and Faecalibacterium prausnitzii induce de novo gut synthesis of vitamin D to inhibit colorectal carcinogenesis in mice. Magnesium (Mg) treatment increases circulating vitamin D and Mg homeostasis is dependent on TRPM7 genotype. OBJECTIVE:We hypothesize that Mg treatment increases gut C. maltaromaticum and F. prausnitzii and the effect differs by TRPM7 polymorphism. METHODS:The Personalized Prevention of Colorectal Cancer Trial is a double-blind, precision-based randomized controlled trial with 240 participants randomized by both treatment and TRPM7 genotype. Stool, rectal swabs, and rectal mucosa were collected. RESULTS:Of 239 participants that completed the trial, 226 with valid microbiome data were analyzed (treatment n=112, placebo n=114). The interaction between treatment and TRPM7 genotype was only significant for C. maltaromaticum (p=0.001) and F. prausnitzii (p=0.02) in rectal swabs. In a stratified analysis by TRPM7 genotype without the missense variant, Mg treatment compared to placebo significantly increased abundance of C. maltaromaticum (0.217±0.615 (23.01%) compared to -0.065±0.588 (-6.30%); P=0.006) and F. prausnitzii (0.105±0.817 (2.13%) compared to -0.095±0.856 (-1.92%); P =0.04) in rectal swabs. The effect on C. maltaromaticum remained after multiple comparisons (Q=0.05 for C. maltaromaticum across all sample types and genotypes). In those with the TRPM7 missense variant, Mg decreased C. maltaromaticum, but not F. prausnitzii, compared to placebo in rectal swabs (-0.065±0.511 (-6.54%) compared to 0.133±0.503 (13.30%); adjusted P=0.04). The effect did not remain after FDR correction. Mg treatment's effect on C. maltaromaticum in rectal swabs primarily appeared in females, and the treatment-genotype interaction remained significant. CONCLUSION/CONCLUSIONS:In individuals with adequate TRPM7 function, Mg supplementation increases abundance of C. maltaromaticum and F. prausnitzii. CLINICAL TRIAL REGISTRY/BACKGROUND:This trial was registered on ClinicalTrials.gov as NCT04229992 (https://clinicaltrials.gov/study/NCT04229992?term=NCT04229992&rank=1). The parent study is registered as NCT03265483, and another relevant study is registered as NCT01105169.

BACKGROUND/UNASSIGNED:Despite their efficacy, medications for opioid use disorder (MOUD) remain underutilized in patients with infections from intravenous opioid use (I-IOU). This study evaluates the impact of an Expanded MOUD Access Initiative (EMAI) on MOUD uptake and other clinical outcomes in patients hospitalized for I-IOU at an institution without addiction medicine consultation. METHODS/UNASSIGNED:We performed a retrospective pre-post study of hospital admissions for I-IOU before (January 2019-June 2021) and after (January 2022-December 2023) EMAI introduction. Data was collected via chart review. The EMAI eliminated restrictions on methadone use and established a new order set for buprenorphine inductions. The primary outcome was MOUD receipt; secondary outcomes included patient directed discharge (PDD) and 30-day re-hospitalization. RESULTS/UNASSIGNED:There were 129 hospitalizations prior to the intervention (control) and 98 after (EMAI). MOUD receipt was significantly higher in the EMAI group (75.5% vs 31.0%; OR, 6.86 [95% CI, 3.84-12.61]). In patients not receiving MOUD prior to admission (n = 176), new inductions occurred more frequently in the EMAI group (68.0% vs 11.9%; OR, 15.76 [95% CI, 7.50-35.78]). PDD was lower in the EMAI group (23.5% vs 48.8%; OR, 0.32 [95% CI, 0.10-0.57]), as was 30-day re-hospitalization (12.2% vs 22.5%; OR, 0.48 [95% CI, 0.22-0.98]). In a multivariable logistic regression model, the EMAI was the only variable to show a statistically significant association with MOUD receipt (aOR, 6.89 [95% CI, 3.75-13.11]). CONCLUSIONS/UNASSIGNED:The EMAI was associated with increased MOUD uptake, reduced PDD, and fewer 30-day re-hospitalizations despite the lack of addiction medicine consultation.

Socioeconomic position (SEP) in childhood and beyond may influence the gut microbiome, with implications for disease risk. Studies evaluating the relationship between life-course SEP and the gut microbiome are sparse, particularly among Hispanic/Latino individuals, who have a high prevalence of low SEP. We use the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), a population-based cohort study conducted in four field centers in the United States (U.S.), to evaluate the association between life-course SEP and gut microbiome composition. Life-course SEP indicators included parental education (proxy of childhood SEP), current SEP (n = 2174), and childhood (n = 988) and current economic hardship (n = 994). Shotgun sequencing was performed on stool samples. Analysis of Compositions of Microbiomes was used to identify associations of life-course SEP indicators with gut microbiome species and functions. Parental education and current SEP were associated with the overall gut microbiome composition; however, parental education and current education explained more the gut microbiome variance than the current SEP. A lower parental education and current SEP were associated with a lower abundance of species from genus Bacteroides. In stratified analysis by nativity, we found similar findings mainly among foreign-born participants. Early-life SEP may have long-term effects on gut microbiome composition underscoring another biological mechanism linking early childhood factors to adult disease.

PURPOSE OF REVIEW/UNASSIGNED:As the overdose crisis evolves, it is important to monitor fentanyl consumption patterns. This review provides an overview of recent findings regarding illegally manufactured fentanyl (IMF) availability, use, and associated harms in the US. RECENT FINDINGS/UNASSIGNED:Availability of IMF has increased, especially in pill form, and the increasing adulteration of IMF with veterinary tranquilizers such as xylazine complicates overdose response. Prevalence in the general population based on self-reported IMF use is rare, and likely underestimated. Transitions from injection to smoking have been documented in recent years, particularly in the western US. Fentanyl-stimulant polysubstance use has also been observed increasingly among IMF-related overdose deaths. SUMMARY/UNASSIGNED:Shifts in routes of administration, availability of counterfeit pills containing fentanyl, and common adulterants add complexity to the landscape of IMF use and related harms. Additional data is needed for monitoring changes in consumption patterns to inform prevention and harm reduction efforts.

People with HIV are at increased risk of cardiovascular events; thus, care delivery strategies that increase access to comprehensive cardiovascular disease (CVD) risk management are a priority. We report the results of a multi-component telemedicine-based strategy to improve blood pressure control among people with HIV-Assess and Adapt to the Impact of COVID-19 on CVD Self-Management and Prevention Care in Adults Living with HIV (AAIM-High). The AAIM High strategy is a virtual adaptation of our previously published EXTRA-CVD strategy and consisted of hypertension education and six components: nurse-led care coordination (delivered by teleconference or telephone), home systolic blood pressure (SBP) monitoring, evidence-based treatment algorithms, electronic health records tools, technology coach, and communication preferences assessment. People with HIV (n = 74) with comorbid hypertension at three academic medical centers were enrolled in a single arm implementation study from January 2021 to December 2022. Over 12 months, the average patient-performed home SBP decreased by 7.7 mmHg (95% CI -11.5, -3.9). The percentage of patients at treatment goal, defined as average SBP <130 mmHg, increased from 46.0% to 72.5% at 12 months. By adapting to the growing use of telemedicine in healthcare delivery, our study effectively improved hypertension control in people with HIV through a virtual, nurse-led intervention.

BACKGROUND AND OBJECTIVES/OBJECTIVE:While reductions in optical coherence tomography (OCT) pRNFL and ganglion cell-inner plexiform layer thicknesses have been shown to be associated with brain atrophy in adult-onset MS (AOMS) cohorts, the relationship between OCT and brain MRI measures is less established in pediatric-onset MS (POMS). Our aim was to examine the associations of OCT measures with volumetric MRI in a cohort of patients with POMS to determine whether OCT measures reflect CNS neurodegeneration in this patient population, as is seen in AOMS cohorts. METHODS:This was a cross-sectional study with retrospective ascertainment of patients with POMS evaluated at a single center with expertise in POMS and neuro-ophthalmology. As part of routine clinical care, patients with POMS are evaluated by a POMS expert and undergo volumetric brain MRI, including whole-brain (WB), subregional, and gray matter (GM) volume analyses. Patients with POMS are routinely referred to neuro-ophthalmology for evaluation that includes high-contrast visual acuity, color vision testing, and OCT. Generalized estimating equation (GEE) models, accounting for within-patient, intereye correlations (both eyes of each patient were included), MS disease duration, and disease-modifying therapy efficacy, were used to determine the relationship between visual pathway structure and function and volumetric MRI measures. RESULTS:= 0.015, respectively). DISCUSSION/CONCLUSIONS:Our results demonstrate that changes in visual pathway structures are associated with reductions in overall brain volume and GM volumes, as well as greater lesion and black hole burden. Collectively, our results emphasize the importance of visual assessment in POMS and suggest that OCT reflects overall CNS neurodegeneration in this cohort.

Children face an urgent threat in the form of hazards posed by plastics in the environment. Despite robust and rapidly accumulating evidence on the effects of plastic on children's health, plastic presents a paradox for child health providers: while plastic is a vehicle for so many interventions, robust evidence from laboratory and human studies show that chemicals used to produce plastics contribute to chronic conditions in multiple organ systems and disrupt hormone function, and exposure to plastic-derived toxins is associated with adverse birth outcomes, metabolic conditions, neurodevelopmental disease and disability, and reproductive conditions. Evidence-based, safe, simple, and low-cost steps exist for child health providers in primary care to help families limit children's exposure to plastic-derived toxins. Health-care providers also have a crucial opportunity to protect the health and wellbeing of future generations of children by supporting local and global campaigns for governments, industries, and the general public to reduce the accumulation of plastics in the environment and minimise the use of plastics within health-care systems.

BACKGROUND:Moral distress, which occurs when the ethically correct action cannot be taken because of internal or external constraints, is associated with depression, burnout, and the desire to leave the healthcare profession among healthcare workers. This study compares internal medicine (IM) residents’ experiences of moral distress while caring for patients with COVID-19 in the year prior to and during the first year of the COVID-19 pandemic. METHODS:This is a mixed methods prospective observational cohort study that enrolled IM residents on a rolling basis beginning December 2018. Moral distress was evaluated via the validated Moral Distress Score-Revised (MDS-R) and Measure of Moral Distress for Healthcare Professionals (MDD-HP) and open-ended questions every 4-months via online surveys and through five resident focus groups. The moral distress scores (MDS) before and during the COVID-19 pandemic were compared using paired t-tests. Transcripts and free text were independently coded by investigators and analyzed by major themes and sub-themes. RESULTS: < .05). Qualitive findings included the exacerbation of existing moral distress and the emergence of new drivers of moral distress, including personal protective equipment, visitor policies, lack of moral framework, and tension between protecting one’s own health and caring for others. CONCLUSIONS:The results of this preliminary analysis suggest that the COVID-19 pandemic exacerbated pre-existing experiences of moral distress and brought to light new and different morally distressing situations for trainees. This analysis of the impact of the pandemic is valuable not only for identifying leverage points for intervention, but also for informing future crisis preparedness and cultivating moral resilience in trainees and the healthcare workforce. SUPPLEMENTARY INFORMATION:The online version contains supplementary material available at 10.1186/s12910-025-01274-6.

Social media can benefit prostate cancer care through education and empowerment, but also have the potential for exposure to misinformation, leading to adverse health and/or economic impacts for patients and damaging the patient-physician relationship. Clinicians should promote digital health literacy and provide recommended sources of reliable online content for additional information.

RAGE and its intracellular effector molecule, the actin polymerase DIAPH1, mediate inflammation and the complications of diabetes. Using NMR spectroscopy and mass spectrometry, we built a structural model of the RAGE-DIAPH1 complex, revealing how binding of the cytoplasmic tail of RAGE (ctRAGE) to DIAPH1 stimulates its actin polymerization activity, which is inhibited by a small molecule antagonist of RAGE-DIAPH1 interaction, RAGE406R. The solution structure of the RAGE406R - ctRAGE suggests that RAGE406R prevents the formation of the RAGE-DIAPH1. FRET, actin polymerization assays, smooth muscle cell migration, and THP1 cell inflammation experiments, together with the in vivo interrogation of the effects of RAGE406R in mouse models of inflammation and diabetic wound healing, support this mode of RAGE-DIAPH1 antagonism. Finally, the treatment of macrophages differentiated from peripheral blood-derived mononuclear cells from humans with type 1 diabetes with RAGE406R reduces the mRNA expression of the chemokine CCL2, diminishing the expression of a key node in the inflammatory response.