Faculty Bibliography

Strain imaging, performed with echocardiography and cardiovascular magnetic resonance (CMR), is a noninvasive technique for detecting subclinical myocardial dysfunction across the heart failure spectrum, in various cardiomyopathies, and within the field of cardio-oncology. By quantifying myocardial deformation, strain enhances diagnosis, risk stratification, and treatment monitoring beyond traditional measures such as ejection fraction. While echocardiography remains the most accessible modality, ongoing advances in CMR techniques-including incorporation of artificial intelligence-promise to improve standardization, reproducibility, and clinical integration of strain imaging in the management of heart failure and cardiovascular care.

Apolipoprotein B (APOB) containing lipoproteins contribute to atherosclerosis by entering the arterial wall through the endothelial cell (EC) surface receptors scavenger receptor-BI (SR-BI) and activin receptor-like kinase 1 (ALK1). We used N-terminal fragments of APOB, molecular modeling, and site-directed mutagenesis to identify and block the binding of chylomicrons and LDL to these receptors in cells and mice. We discovered that different APOB regions interact with SR-BI and ALK1 expressed on ECs APOB48 lipoproteins were only internalized by SR-BI. A fragment of APOB, comprising 18% of the N-terminal sequence, APOB18, reduced the uptake and transport of both chylomicrons and LDL by ECs, whereas a shorter fragment, APOB12, only blocked ALK1 mediated uptake of APOB100 containing lipoproteins. Importantly, overexpressing APOB18 decreased atherosclerosis in hypercholesterolemic mice. These findings identify the N-terminal region of APOB as the cause of atherosclerosis and illustrate an approach to treating or preventing vascular disease.

OBJECTIVE:Fatigue and depression are common and disabling symptoms in people with Multiple Sclerosis (PwMS). This study aimed to examine the relationship between discordant fatigue measures and depression severity in PwMS. METHODS:A retrospective analysis was conducted on 712 PwMS evaluated over 14 years at a comprehensive MS center. All participants completed the Fatigue Severity Scale (FSS), Modified Fatigue Impact Scale (MFIS), and Beck Depression Inventory (BDI) as part of routine clinical care. Fatigue score concordance was defined as both FSS and MFIS being above or below the threshold; discordance was defined as one above and one below. Statistical analyses compared demographic, clinical, and depression-related variables between groups. RESULTS:Of the 712 patients (75.3% female; mean EDSS 2.8), 78.9% demonstrated concordant fatigue scores, while 21.1% showed discordance-most commonly with elevated MFIS and low FSS. The discordant group had significantly higher mean BDI scores (23.0 vs. 9.8; P < 0.0001) and elevated suicidality scores, despite similar clinical characteristics. CONCLUSIONS:PwMS with discordant fatigue profiles, particularly those with higher MFIS than FSS scores, exhibit significantly greater depressive symptoms. Discordance between fatigue measures may serve as a clinical marker for underlying depression, supporting the need for comprehensive psychosocial evaluation in this subgroup.

BackgroundOver 20 million people in the U.S. are behind on cervical cancer screenings (CCS). Sexual minority populations are 50% less likely to engage in routine screening, putting them at higher risk for cervical dysplasia and cancer due to undetected precancer and delayed diagnosis. Their barriers to speculum exams include access to care, sexual trauma, and provider bias. At-home HPV self-collection (SC) offers a clinically accurate, preferred alternative screening method.ObjectiveTo assess clinical agreement, usability, and screening experiences and preferences for an FDA-authorized at-home vaginal SC device among participants who identify as lesbian, gay, bisexual, pansexual, queer, or other non-heterosexual identities (LGBQ+).MethodsSELF-CERV was a prospective, multi-site method-comparison study conducted across 16 U.S. sites. Participants completed SC in a simulated at-home setting and underwent clinician collection with a speculum and cervical brush; paired specimens were tested for primary HPV using the Roche cobas. Surveys assessed barriers to screening, prior screening experiences, usability, and preferences. 609 participants were enrolled; 599 had paired samples, including 74 LGBQ+ participants.ResultsCompared with heterosexual participants, LGBQ+ participants more frequently delayed or avoided screening, had lower preventive care engagement, and described worse prior speculum-based screening experiences, including higher pain, discomfort, and aversion. Clinical agreement between self- and clinician-collected specimens was comparable, with no unanticipated safety concerns. The SC device was rated as easy to use and acceptable across groups; LGBQ+ participants reported greater comfort and empowerment and a stronger preference for at-home self-collection. Qualitative comments emphasized privacy and reduced distress, including trauma- and dysphoria-related concerns.ConclusionAt-home SC is a clinically valid, usable, and strongly preferred CCS option, particularly among LGBQ+ populations who experience disproportionate barriers to speculum-based CCS. Broader adoption of FDA-authorized at-home SC paired with telehealth will enable future impact assessment to reduce persistent disparities in CCS for LGBQ+ populations.

Dementia caregiving represents a major public health challenge, with spousal caregivers assuming the greatest burden. Spouses, themselves typically older adults, provide high intensity, long-term, and largely unpaid care across all stages of cognitive decline. Despite their central role in dementia care, the health consequences experienced by spousal caregivers remain insufficiently characterized in the literature and inadequately addressed in clinical and public health practice. This structured narrative review synthesizes current evidence on the multidimensional impact of dementia caregiving on the physical, psychological, cognitive, social, and financial health of spousal caregivers. It further contextualizes these consequences within the trajectory of dementia progression, and identifies interventions, support systems, and policy considerations necessary to mitigate caregiver burden. Spousal caregivers experience disproportionate burden due to continuous, escalating responsibilities that often mirror the progressive deterioration of their partners. Emotional burdens, including uncertainty during pre-diagnostic stages, role strain, conflict, loss of intimacy, and anticipatory grief. Physically, spouses endure musculoskeletal strain, sleep disruption, poor nutrition, and heightened frailty risk. Psychologically, spousal caregivers exhibit elevated rates of depression, anxiety, loneliness, and stress-related disorders. Socially, caregivers experience substantial isolation, stigma, and erosion of social networks. Financial hardship, including early retirement, reduced employment, and uncompensated care hours, further exacerbate stress. Evidence suggests that chronic caregiving stress contributes to biological changes such as immune dysregulation, inflammation, acceleration, aging, and potential cognitive decline in caregivers themselves. Caregiver burden influences patient outcomes as evidenced by increased emergency department use, falls, and earlier institutionalization in persons with dementia whose caregiver is subjected to a high burden. Current care models rarely include routine, caregiver assessment or structured guidance following diagnosis, resulting in substantial unmet needs. Effective mitigation requires integrated, stage-sensitive interventions, including psychosocial support, caregiver education, respite services, culturally tailored programs, and digital health tools, alongside broader policy reforms to reduce financial and structural barriers.

INTRODUCTION/BACKGROUND:Endoscopic retrograde cholangiopancreatography (ERCP) is essential for pancreaticobiliary disease management; however, there are risks associated with the procedure, particularly post-ERCP pancreatitis (PEP). Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), widely used in metabolic disease, possess anti-inflammatory and cytoprotective properties that may influence periprocedural outcomes. Their impact on ERCP adverse events remains unclear; therefore, we aimed to investigate whether GLP-1 influences short-term postprocedural outcomes using a large real-world database. METHODS:We conducted a retrospective cohort study using the TriNetX US Collaborative Network, identifying adults (18 y or older) who underwent ERCP between January 2015 and December 2024. Patients were categorized based on documented preprocedure GLP-1 receptor agonist exposure. Propensity score matching (1:1) was performed using demographic, clinical, procedural, and pharmacologic covariates to minimize confounding, yielding 2 well-balanced cohorts. Thirty-day post-ERCP outcomes-including acute pancreatitis, cholangitis, sepsis, gastrointestinal bleeding, biliary stricture, choledocholithiasis, and repeat ERCP-were assessed using ICD-10 and CPT codes. Risk ratios (RRs) and hazard ratios (HRs) with 95% CIs were calculated. RESULTS:Of 250,502 patients with ERCP screened, 21,818 propensity-matched individuals were included in the final analysis. Compared with matched nonusers, patients receiving GLP-1 receptor agonists had significantly lower 30-day rates of all major ERCP-related adverse events. GLP-1 RA exposure was associated with reduced risks of acute pancreatitis (RR: 0.47, 95% CI: 0.43-0.51), cholangitis (RR: 0.56, 95% CI: 0.50-0.62), sepsis (RR: 0.51, 95% CI: 0.46-0.57), gastrointestinal bleeding (RR: 0.49, 95% CI: 0.40-0.61), biliary stricture (RR: 0.52, 95% CI: 0.48-0.55), repeat ERCP (RR: 0.53, 95% CI: 0.48-0.58), and choledocholithiasis (RR: 0.66, 95% CI: 0.62-0.71). Results were consistent across time-to-event analyses over the 30-day follow-up period. CONCLUSIONS:In this large real-world analysis, preprocedure GLP-1 RA therapy was associated with markedly reduced 30-day ERCP-related adverse events, most notably PEP. These findings highlight a potential protective role of GLP-1 signaling in the periprocedural inflammatory response and support prospective studies evaluating GLP-1 RAs as adjunctive prophylactic agents in ERCP. Further prospective studies are needed.

Stereotactic body radiotherapy (SBRT) is established as standard therapy for organ-confined prostate cancer (PC) based on 5-yr phase 2-3 outcomes, but 10-yr data are lacking. Here, we report 10-yr results of a trial conducted at 21 centers. Patients were treated from January 2008 to April 2010. SBRT was delivered on a noncoplanar robotic platform with real-time motion management, to a total dose of 40 Gy in five fractions. Adjuvant hormone therapy was not allowed. Late toxicities (>90 d) were assessed with Common Terminology Criteria for Adverse Events version 3 (CTCAE v3). Biochemical failure is defined as nadir+2. Relapses are defined as biochemical or clinical failure or salvage/systemic PC therapy. Out of 310 evaluable patients, median age 68 yr; 172 were low-risk (LR), and 138 patients were intermediate-risk (IR). Median follow-up was 9 yr. Ten-yr cumulative grade 3 gastrointestinal (GI) or genitourinary (GU) toxicities were 1.4% and 1.5% in the LR and IR cohorts, respectively. There were no grade 4-5 events observed. Ten year grade 2+ GI and GU toxicity rates were 2.1% and 14% respectively. Overall survival in 10 yr was 84%. Overall, relapse-free survival (RFS) was 90%; 94% in the LR cohort, 86% in the IR cohort, and 92% versus 77% in the favorable vs unfavorable intermediate subgroups. In this multi-institutional trial, the 10-yr follow-up demonstrates that prostate SBRT yields minimal toxicity and favorable RFS.

INTRODUCTION/BACKGROUND:Early lymph node (LN) metastasis often precedes systemic metastasis and corresponds with significantly inferior survival for patients diagnosed with early-stage breast cancer (EBC). To understand the biological pathways involved in early LN metastasis, differential gene expression (DGE) analysis compared large tumors without evidence of LN metastasis (pT2-3pN0) to small tumors with LN metastasis (pT1pN+). METHODS:This study included 2,349 patients with EBC who underwent MammaPrint and BluePrint testing as part of the FLEX (NCT03053193). DGE was performed between pT2-3pN0/pT1pN + and across their MP/BP subtypes. Immune deconvolution was assessed using gene-signature-based methods, complemented by conventional tumor-infiltrating lymphocyte (TIL) analyses on a representative subset of patients. RESULTS:Greater DGE was observed within the MammaPrint High Risk and BluePrint Luminal B subgroups compared to pathological stages. MammaPrint High Risk tumors saw 73 differentially expressed genes (DEGs), while 34 were found for Luminal B tumors. Gene set enrichment analysis (GSEA) of MammaPrint High Risk/Luminal B tumors showed upregulated proliferation pathways and downregulated epithelial-to-mesenchymal transition (EMT) and immune profiles in pT2-3pN0 vs. pT1pN+, respectively. Immune deconvolution analyses showed a higher abundance of T gamma delta cells and CD4 + Th1 cells and a lower abundance of T regulatory cells, M2 macrophages, and cancer-associated fibroblasts within pT2-3pN0 tumors. Conventional histological assessment revealed no significant differences in TILs. CONCLUSION/CONCLUSIONS:This study lays the groundwork for exploring mechanisms of LN metastasis in EBC and their relation to MammaPrint High Risk and Luminal B subtypes. These data support previous studies' association of LN metastasis with EMT and immune dysregulation.

Prader-Willi syndrome (PWS) is a rare genetic disorder marked by metabolic, endocrine, and behavioral challenges, with hyperphagia as a central feature contributing to significant health risks. Diazoxide choline extended-release (DCCR; VYKAT™ XR) is a once-daily adenosine triphosphate (ATP)-sensitive potassium channel activator recently approved for the treatment of hyperphagia in individuals with genetically confirmed PWS aged 4 years and older. As this novel therapy enters clinical practice, clinicians require practical guidance on appropriate use. This manuscript provides actionable recommendations for patient selection, baseline assessments, and strategies for optimizing comorbid conditions prior to initiation. Structured, weight-based dosing and titration protocols are outlined, along with recommendations for monitoring glycemia and edema and managing common adverse events (AEs), including hyperglycemia, peripheral edema, and rash. Special considerations are discussed for patients with diabetes, cardiopulmonary risk factors, and those on concomitant medications with potential drug-drug interactions. The guidance is informed by data from the phase 3 DESTINY-PWS program, long-term extension studies, and real-world clinical experience. Emphasis is placed on early identification and management of AEs and the importance of a multidisciplinary approach to care. These recommendations aim to support clinicians in safely and effectively incorporating DCCR into the management of PWS, improving outcomes for affected individuals. Ongoing research and real-world evidence will continue to refine best practices and address remaining gaps in knowledge.