Faculty Bibliography

SARS-CoV-2 infection is associated with platelet hyperreactivity and increased rates of arterial and venous thrombosis. SARS-CoV-2 mutations have resulted in several variants with differences in transmissibility, infectivity, and patient outcomes. This study investigates the effects of the ancestral strain of SARS-CoV-2 (WA1) and two variants of concern, Delta and Omicron, on the human megakaryocyte (MK) phenotype and transcriptome. Human CD34⁺-derived MKs were incubated with WA1, Delta or Omicron SARS-CoV-2 variants for 24 hours. MK activation markers were measured under resting and thrombin-stimulated conditions. RNA-seq and cytokine release in response to the viruses were assessed. Plasma cytokines were measured in hospitalized COVID-19 patients. Treatment of MKs with WA1, Delta or Omicron variants of SARS-CoV-2 resulted in similar increases in classical activation markers. However, SARS-CoV-2 variants mediated distinct transcriptomic changes. Across variants, 60 genes overlapped, including CXCL8. Consistent with transcriptomic changes, SARS-CoV-2-incubated MKs secreted significantly elevated levels of IL-8. Among hospitalized COVID-19 patients, plasma IL-8 levels were highest in COVID-19 patients who subsequently experienced thrombotic events or died. In conclusion, WA1, Delta, and Omicron similarly induce classical MK activation responses while mediating distinct transcriptomic changes. Increased IL-8 levels may serve as a biomarker to inform platelet hyperreactivity and thrombotic events associated with COVID-19.

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:Prior studies showed worse outcomes in obese inflammatory bowel disease (IBD) patients, especially those related to hospitalizations, surgery and steroid-free remission. Glucagon-like peptide-1 receptor agonists (GLP1-RAs) have demonstrated significant metabolic benefits for patients with type 2 diabetes mellitus (T2DM) and obesity. Hence, GLP1-RAs may improve clinical outcomes in patients with IBD, especially those with obesity. The objective was to systematically evaluate the impact of GLP1-RAs on clinical outcomes in patients with IBD. METHODS:A comprehensive literature search was performed using the databases PubMed, Embase, Web of Science, and Cochrane Library from inception to 15-03-2025. Studies reporting outcomes related to GLP1-RAs in patients with IBD were included. Primary outcomes included weight loss and various IBD-related co-endpoints such as hospitalizations, surgery, corticosteroid use, and advanced therapy initiation. FINDINGS/RESULTS:In total, 11 studies with 16,242 patients with IBD treated with GLP1-RAs were included. Weight loss was achieved using semaglutide (-9.6 kg, CI-95% -12.0; -7.2), liraglutide (-9.4 kg, CI-95% -13.0; -5.8) and tirzepatide (-11.8 kg, CI-95% -18.3; -5.4) after 3 months of follow-up. In meta-analyses, GLP1-RAs were associated with lower risk of surgery for effect sizes (logHR: 0.61 [95%-CI 0.44-0.84], I2 = 0%) and event frequencies (OR: 0.46 [95%-CI 0.32-0.67], I2 = 42%). Sensitivity analysis for BMI showed lower risk of hospitalizations and surgery in patients with obesity (BMI≥30). INTERPRETATION/CONCLUSIONS:Patients with IBD and obesity using GLP1-RAs were able to achieve significant weight loss and had lower risks of surgery and hospitalizations. Our findings require confirmation in prospective trials of GLP1-RAs in IBD.

Infections are increasingly recognised as a major cause of morbidity and mortality in patients with vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome. We conducted a systematic review to characterise the infectious burden of VEXAS syndrome and propose preventive strategies. We included 57 studies (813 patients) showing that infections in patients with VEXAS syndrome were frequent, severe in 40-60% of cases, and fatal in 6-15% of cases. Pulmonary infections were most common, followed by cutaneous infections and bacteraemia. Opportunistic pathogens, such as Pneumocystis jirovecii, Legionella pneumophila, non-tuberculous mycobacteria, and varicella zoster virus, were frequently reported, even in patients not receiving immunosuppressive therapy, which suggests intrinsic immune dysfunction. Prophylaxis with co-trimoxazole (or other Pneumocystis prophylaxis, such as atovaquone or pentamidine) and valaciclovir should particularly be considered for patients at high risk of infection, including those receiving immunosuppressive therapy and those with lymphopenia, pMet41Val mutation, or previous severe or recurrent infections. Posaconazole might be appropriate in patients with neutropenia who are taking azacitidine. Vaccination against Streptococcus pneumoniae, varicella zoster virus, influenza, and SARS-CoV-2 is recommended. These data highlight the need to integrate infectious risk into VEXAS syndrome management and to evaluate preventive strategies in prospective studies.

Breast tumors harbor dynamic microenvironments, with multiple immune cell types playing opposing roles during tumor progression and/or response to therapy. Tumor-associated macrophages promote mammary tumorigenesis, whereas the role of mammary tissue macrophages (MTMs) remains incompletely understood. High-dimensional immunostaining of murine mammary tumor progression revealed that MTMs were localized in the peritumoral stroma and associated with eosinophils, which were previously shown to facilitate antitumor T cell responses. The depletion of MTMs accelerated tumorigenesis in both spontaneous and orthotopically transplanted mammary tumor models. Upon induction of a productive antitumor response via the depletion of regulatory T cells, MTMs assumed an alternatively activated state and expressed eotaxins, thereby attracting eosinophils to peritumoral regions. MTMs expressed the receptor for the alarmin IL-33, which induced both MTM activation and eosinophil recruitment. These results suggest that MTMs can sense IL-33 and recruit eosinophils to facilitate antitumor immunity, a mechanism that may operate during tumor progression and be further enhanced during productive antitumor responses.

BACKGROUND:Black communities, compared to White communities, are disproportionately targeted with more unhealthy food advertisements on television and social media. Exposure to unhealthy food and beverage marketing is associated with appetitive sensations, purchase intention, and intake behaviors, which may contribute to poor overall diet quality and worsening nutritional disparities in Black communities. Despite the negative effects, food and beverage companies are expanding their reach and harnessing advanced technology to create immersive experiences using virtual reality (VR). Black young adults may be uniquely vulnerable. OBJECTIVE:We aim to explore the effect of a VR-based fast-food marketing experience (compared with a VR-based nonfood control) on purchase intention, arousal, and hunger in a sample of Black and White young adults. METHODS:We will recruit 200 Black and White young adults (aged 18-24 years) from the New York City metropolitan area for a 1-time, 2-hour laboratory-based study. After screening and obtaining informed consent, eligible participants will be randomized to 1 of 2 VR conditions: a VR-based fast-food marketing experience (Wendyverse; experimental) or a VR-based nonfood control (Nikeland). In the Wendyverse, users can order from the restaurant operated by Wendy's, play games, meet others who may be visiting the Wendyverse, and access codes that can be used to obtain free food at physical restaurants. The control condition will be the Nikeland app, where participants can play sports, try on apparel, and engage with celebrity athletes. Study personnel will provide a 5-minute training session to participants before beginning the experiment to ensure that they feel comfortable in the VR environment. Participants will otherwise engage with the VR app independently. The primary outcomes will be fast-food purchase intention, assessed via a self-report questionnaire; arousal, assessed via electrodermal activity or skin conductance; and hunger, assessed via salivary reactivity. We will also conduct secondary analyses to examine interactions by race, ethnicity, and food or nutrition insecurity as a proxy for socioeconomic status. Analyses of covariance and multiple linear regressions will be conducted to examine the effects of VR-based fast-food marketing exposure on the relevant outcomes (compared to the control). RESULTS:This study was funded by the National Institute on Minority Health and Health Disparities in September 2024. Recruitment is expected to begin in September 2025. We expect to complete data collection by October 2026 and begin data cleaning and analysis in November 2026. CONCLUSIONS:On the basis of previous research and data, we anticipate that young adults randomized to view VR-based food and beverage marketing will self-report higher purchase intention and demonstrate stronger arousal and hunger. The data will be used to support future research and improve the understanding of the effects of digital forms of unhealthy food and beverage marketing on young people. TRIAL REGISTRATION/BACKGROUND:ClinicalTrials.gov NCT06917391; https://clinicaltrials.gov/study/NCT06917391. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID)/UNASSIGNED:PRR1-10.2196/69096.

BACKGROUND:There is emerging literature describing clinical characteristics and outcomes in patients with mpox treated with tecovirimat. METHODS:We analyzed retrospective deidentified data from healthcare systems in New York City with the highest number of tecovirimat prescriptions. Individuals with probable or confirmed mpox initiating tecovirimat from May-December 2022 were included. A chart abstraction instrument was used to extract demographic and clinical data from medical records. We examined factors associated with delay in treatment and hospitalization. RESULTS:A total of 708 individuals prescribed tecovirimat for mpox were included in the analysis; median age was 36 years (IQR 31-43); 566 (80%) were cisgender men who have sex with men; and 399 (56%) were living with HIV. Side effects (100, 14%) and severe adverse events (7, 1%) were rare. The most common long-term sequela was scarring (69, 10%). One hundred and one (14%) were hospitalized. Median time from symptom onset to treatment initiation was 8 days (IQR 6-11). Non-Hispanic Black patients had higher risk of initiating tecovirimat ≥8 days after symptom onset (relative risk [RR]=1.3, 95%CI: 1.2-1.7) and being hospitalized (adjusted relative risk [aRR]=2.2, 95%CI: 1.4-3.5) compared with Hispanic patients, after adjusting for HIV and insurance status. CONCLUSIONS:We described common reasons for tecovirimat initiation and hospitalization. There were racial inequities in hospitalization and treatment delays. More research and focused efforts to mitigate these inequities are needed. These findings may better inform decisions for treatment initiation and hospitalization for mpox.

BACKGROUND:Drug-coated balloon angioplasty (DCB) is an emerging alternative to percutaneous transluminal angioplasty (PTA) for below-the-knee (BTK) revascularization in patients with chronic limb-threatening ischemia (CLTI). DCBs deliver antiproliferative agents to reduce neointimal hyperplasia, but results are mixed. This review assessed the clinical outcomes of DCB vs. PTA in BTK interventions for CLTI. METHODS:This systematic review and meta-analysis was registered with PROSPERO (CRD420251073999). PubMed and CENTRAL were searched for randomized controlled trials and clinical trials comparing DCB and PTA in adult CLTI patients undergoing BTK intervention. Studies until June 2025 were included in the review. Outcomes included clinically driven target lesion revascularization (CD-TLR), major amputation, all-cause mortality, primary patency, and late lumen loss (LLL). Risk of bias was assessed using the Cochrane RoB 2 tool, with most studies judged to have low or some concerns but no critical sources of bias. Random-effects model was used to calculate pooled odds ratios (ORs) and standardized mean differences (SMDs). RESULTS:Ten studies were included in the review; seven were eligible for meta-analysis. DCB significantly reduced CD-TLR compared to PTA at 12 months (OR: 0.39; 95% CI: 0.04-0.73), but not at 5 years. No significant differences were observed in major amputations or all-cause mortality at 12 months or 5 years, though mortality trended lower with DCB in the long term (OR: 0.57; 95% CI: 0.13-1.01). No significant differences between DCB and PTA were found for 6-month primary patency or LLL. CONCLUSION/CONCLUSIONS:DCB reduces early revascularization compared to PTA, but shows no significant long-term benefit in amputation or mortality. DCB may be selectively useful in certain patients at high risk of restenosis. Further long-term, risk-stratified studies are needed to optimize DCB use in CLTI management.

IMPORTANCE/UNASSIGNED:The oral microbiota may be involved in the development of pancreatic cancer, yet current evidence is largely limited to bacterial 16S amplicon sequencing and small retrospective case-control studies. OBJECTIVE/UNASSIGNED:To test whether the oral bacterial and fungal microbiome is associated with the subsequent development of pancreatic cancer. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This cohort study used data from 2 epidemiological cohorts: the American Cancer Society Cancer Prevention Study-II Nutrition Cohort and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Among cohort participants who provided oral samples, those who prospectively developed pancreatic cancer were identified during follow-up. Control participants who remained free of cancer were selected by 1:1 frequency matching on cohort, 5-year age band, sex, race and ethnicity, and time since oral sample collection. Data were collected from August 2023 to September 2024, and data were analyzed from August 2023 to January 2025. EXPOSURES/UNASSIGNED:The oral bacterial and fungal microbiome were characterized via whole-genome shotgun sequencing and internal transcribed spacer (ITS) sequencing, respectively. The association of periodontal pathogens of the red complex (Treponema denticola, Porphyromonas gingivalis, and Tannerella forsythia) and orange complex (Fusobacterium nucleatum, F periodonticum, Prevotella intermedia, P nigrescens, Parvimonas micra, Eubacterium nodatum, Campylobacter shower, and C gracilis) with pancreatic cancer was tested via logistic regression. The association of the microbiome-wide bacterial and fungal taxa with pancreatic cancer was assessed by Analysis of Compositions of Microbiomes With Bias Correction 2 (ANCOM-BC2). Microbial risk scores (MRS) for pancreatic cancer were calculated from the risk-associated bacterial and fungal species. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Pancreatic cancer incidence. RESULTS/UNASSIGNED:Of 122 000 cohort participants who provided samples, 445 developed pancreatic cancer over a median (IQR) follow-up of 8.8 (4.9-13.4) years and were matched with 445 controls. Of these 890 participants, 474 (53.3%) were male, and the mean (SD) age was 67.2 (7.5) years. Three oral bacterial periodontal pathogens-P gingivalis, E nodatum, and P micra-were associated with increased risk of pancreatic cancer. A bacteriome-wide scan revealed 8 oral bacteria associated with decreased and 13 oral bacteria associated with increased risk of pancreatic cancer (false discovery rate-adjusted Q statistic less than .05). Of the fungi, genus Candida was associated with increased risk of pancreatic cancer. The MRS, based on 27 oral species, was associated with an increase in pancreatic cancer risk (multivariate odds ratio per 1-SD increase in MRS, 3.44; 95% CI, 2.63-4.51). CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this cohort study, oral bacteria and fungi were significant risk factors for pancreatic cancer development. Oral microbiota hold promise as biomarkers to identify individuals at high risk of pancreatic cancer, potentially contributing to personalized prevention.

BACKGROUND:Among the alternative solutions being tested to improve access to genetic services, chatbots (or conversational agents) are being increasingly used for service delivery. Despite the growing number of studies on the accessibility and feasibility of chatbot genetic service delivery, limited attention has been paid to user interactions with chatbots in a real-world health care context. OBJECTIVE:We examined users' interaction patterns with a pretest cancer genetics education chatbot as well as the associations between users' clinical and sociodemographic characteristics, chatbot interaction patterns, and genetic testing decisions. METHODS:We analyzed data from the experimental arm of Broadening the Reach, Impact, and Delivery of Genetic Services, a multisite genetic services pragmatic trial in which participants eligible for hereditary cancer genetic testing based on family history were randomized to receive a chatbot intervention or standard care. In the experimental chatbot arm, participants were offered access to core educational content delivered by the chatbot with the option to select up to 9 supplementary informational prompts and ask open-ended questions. We computed descriptive statistics for the following interaction patterns: prompt selections, open-ended questions, completion status, dropout points, and postchat decisions regarding genetic testing. Logistic regression models were used to examine the relationships between clinical and sociodemographic factors and chatbot interaction variables, examining how these factors affected genetic testing decisions. RESULTS:Of the 468 participants who initiated a chat, 391 (83.5%) completed it, with 315 (80.6%) of the completers expressing a willingness to pursue genetic testing. Of the 391 completers, 336 (85.9%) selected at least one informational prompt, 41 (10.5%) asked open-ended questions, and 3 (0.8%) opted for extra examples of risk information. Of the 77 noncompleters, 57 (74%) dropped out before accessing any informational content. Interaction patterns were not associated with clinical and sociodemographic factors except for prompt selection (varied by study site) and completion status (varied by family cancer history type). Participants who selected ≥3 prompts (odds ratio 0.33, 95% CI 0.12-0.91; P=.03) or asked open-ended questions (odds ratio 0.46, 95% CI 0.22-0.96; P=.04) were less likely to opt for genetic testing. CONCLUSIONS:Findings highlight the chatbot's effectiveness in engaging users and its high acceptability, with most participants completing the chat, opting for additional information, and showing a high willingness to pursue genetic testing. Sociodemographic factors were not associated with interaction patterns, potentially indicating the chatbot's scalability across diverse populations provided they have internet access. Future efforts should address the concerns of users with high information needs and integrate them into chatbot design to better support informed genetic decision-making.