Faculty Bibliography

BACKGROUND:Recently, the gene therapy eladocagene exuparvovec received accelerated approval from the US Food and Drug Administration (as eladocagene exuparvovec-tneq) for treatment of aromatic L-amino acid decarboxylase deficiency (AADCd), a rare, infantile-onset disorder characterized by developmental delays. OBJECTIVES/OBJECTIVE:To conduct a US, modified societal perspective cost-utility analysis comparing eladocagene exuparvovec versus best supportive care (BSC). METHODS:Multistate survival modeling was implemented tracking disease progression from a "no motor function" health state to achievement of motor-function improvements, measured by: (1) multiples of the meaningful score difference (MSD) of the Peabody Developmental Motor Scales-Second Edition (PDMS-2) total score and (2) motor milestones. Eladocagene exuparvovec trials informed clinical inputs. Health-state utilities were from a US time-trade-off study that valued AADCd quality-of-life impacts. Outcomes were discounted (3%); costs were reported in 2024 US dollars. Scenario analyses, characterizing alternative approaches of the multistate survival model analyses and probabilistic sensitivity analysis to assess the impact of parameter uncertainty, were conducted. RESULTS:Discounted incremental quality-adjusted life-years (QALYs) for eladocagene exuparvovec were 20.83 (multiples of the MSD of total PDMS-2) and 18.44 (motor milestones). Incremental cost per QALY ranged from $199,007-$224,104. The scenario and sensitivity analyses results supported the validity of the base case analysis. CONCLUSIONS:Eladocagene exuparvovec is associated with considerable QALY gains compared with BSC. Within the context of other ultra-rare and/or one-time treatments, eladocagene exuparvovec provides substantial clinical improvements at lower cost than many other rare-disease treatments. Findings from this study highlight that eladocagene exuparvovec is an important treatment option for patients with AADCd.

METHODS:We analyzed the Nuclear Regulatory Commission event notifications related to brachytherapy events that occurred between January 1, 2005, and December 31, 2024. The events were categorized and their distribution and time evolution analyzed. RESULTS:A total of 818 events (227 LDR, 203 HDR, 21 intravascular, 367 microsphere) were identified, excluding events that related purely to shipping. We analyzed the events for the whole period and in consecutive 5-year intervals. The total number of events rose by 27% from the first to the last interval (2005-09:179, 2020-24:227), with the LDR events decreasing by 81% (2005-2009:98, 2020-24: 19) and microsphere events increasing by 588% (2005-09:25, 2020-24:172). HDR events decreased by 15% (2005-09:53, 2020-24:45), while intravascular events increased (2005-09:3, 2020-2024:7) but stayed very rare. . For HDR, the three most frequent categories were treatment planning error (26%), transfer tube issues (13%) and other/unknown issues (13%); the frequency of treatment planning events decreased with time (2005-09: 38%, 2020-24: 18%). For LDR, the three most frequent categories were lost or leaking source (39%), other/unknown issues (24%) and permanent implant sources implanted into wrong tissue (18%). For microspheres, most events were related to the sphere remaining in the delivery apparatus and for intravascular brachytherapy, to the source not retracting. The radioisotopes of LDR events were I-125 (72%), Pd-103 (11%), Cs-137 (8%), Ir-192 (4%), Cs-131 (3%) and Sr-90 (2%); no events relating to Ir-192 or Cs-137 occurred in 2020-24. CONCLUSION/CONCLUSIONS:The reduction in the LDR events is probably explained by the decreased frequency of prostate implants and LDR gynecological procedures. Microspheres now account for most event reports.

Stereotactic body radiotherapy (SBRT) for prostate cancer is a generally well-tolerated treatment but can rarely lead to complications such as fistula formation. We report a 69-year-old male on maintenance ibrutinib for chronic lymphocytic leukemia who developed a fistula between his bladder and vas deferens in the setting of ascending scrotal infection. Despite his prior history of SBRT, the fistula was successfully treated with minimally invasive measures. A combination of abscess debridement, urinary diversion, and broad-spectrum antibiotics helped to achieve fistula resolution. The unique presentation described herein highlights the importance of early aggressive intervention for source control and infection management in patients with complex pelvic infections post-SBRT.

BACKGROUND:The COVID-19 pandemic had a significant impact on healthcare delivery. Older adults with multimorbidities were at risk of healthcare disruptions for the management of their chronic conditions. OBJECTIVE:To characterize healthcare disruptions during the COVID-19 healthcare shutdown and recovery period (March 7, 2020-October 6, 2020) and their effects on disease management among older adults with multimorbidities who were patients of NYC Health + Hospitals (H + H), the largest municipal safety-net system in the United States. DESIGN/METHODS:Observational. PATIENTS/METHODS:Patients aged 50 + with hypertension or diabetes and at least one other comorbidity, at least one H + H ambulatory visit in the six months before COVID-19 pandemic onset (March 6, 2020), and at least one visit in the post-acute shutdown period (October 7, 2020 to December 31, 2023). MAIN MEASURES/METHODS:We characterized disruption in care (defined as no ambulatory or telehealth visits during the acute shutdown) and estimated the effect of disruption on blood pressure control, hemoglobin A1c (HbA1c), and low-density lipoprotein (LDL) cholesterol using difference-in-differences models. KEY RESULTS/RESULTS:Out of 73,889 individuals in the study population, 12.5% (n = 9,202) received no ambulatory or telehealth care at H + H during the acute shutdown. Low pre-pandemic healthcare utilization, Medicaid insurance, and self-pay were independent predictors of care disruption. In adjusted analyses, the disruption group had a 3.0-percentage point (95% CI: 1.2-4.8) greater decrease in blood pressure control compared to those who received care. Disruption did not have a significant impact on mean HbA1c or LDL. CONCLUSIONS:Care disruption was associated with declines in blood pressure control, which while clinically modest, could impact risk of cardiovascular outcomes if sustained. Disruption did not affect HbA1c or LDL. Telehealth mitigated impacts of the pandemic on care disruption and subsequent disease management. Targeted outreach to those at risk of care disruption is needed during future crises.

OBJECTIVES/OBJECTIVE:There are few standards for what information about an infectious disease outbreak should be reported to the public and when. To address this problem, we undertook a consensus process to develop recommendations for what epidemiological information public health authorities should report to the public during an outbreak. STUDY DESIGN/METHODS:We conducted a Delphi study following the steps outlined in the ACcurate COnsensus Reporting Document (ACCORD) for health-related activities or research. METHODS:We assembled a steering committee of nine experts representing federal and state public health, academia, and international partners to develop a candidate list of reporting items. We then invited 45 experts, 35 of whom agreed to participate in a Delphi panel. Of those, 25 participated in voting in the first round, 25 in the second round, and 25 in the third round, demonstrating consistent engagement in the consensus-building process. The final stage of the Delphi process consisted of a hybrid consensus meeting to finalize the voting items. RESULTS:The Delphi process yielded nine core reporting items representing a minimum standard for public outbreak reporting: numbers of new confirmed cases, new hospital admissions, new deaths, cumulative confirmed cases, cumulative hospital admissions, and cumulative deaths, each reported weekly and at Administrative Level 1 (typically state or province), and stratified by sex, age group, and race/ethnicity. CONCLUSIONS:This minimum reporting standard creates a strong framework for uniform sharing of outbreak information and promotes consistency of data between jurisdictions, enabling effective response by promoting access to information about an unfolding epidemic.

BACKGROUND AND AIMS/OBJECTIVE:Endoscopic submucosal dissection (ESD) is preferred over endoscopic mucosal resection (EMR) for resection of colon cancer with suspected superficial invasion. Data on appropriate utilization of ESD such as rates of cancer and non-curative resection (NCR) are under-reported. METHODS:Retrospective multicenter study of 547 consecutive colonic lesions undergoing ESD was performed. Outcomes were rates of cancer, NCR, surgery and predictors of NCR. RESULTS:Of all lesions, histopathology demonstrated cancer in 12% (n = 66). Overall, NCR was seen in 59.1% (n = 39) patients and 24.6% (n = 135) lesions contained high-grade dysplasia. For NCR, patients underwent surgery in 7.6% (n = 3) and adverse events were observed in 8.8% (n = 48). CONCLUSIONS:In our large multicenter Western cohort, the pathology was found to be benign in most of the colon ESDs and there was high NCR for resected lesions with cancer. The overall surgery rate, however, remained low. This study highlights the need to refine lesion selection criteria while continuing to optimize ESD technique to match the efficiency and safety of EMR.

Sjögren's disease (SjD) exemplifies the intricate relationship between oral health and overall systemic wellness. Characterized by autoimmune-mediated destruction of exocrine glands, it commonly manifests as xerostomia (dry mouth) and keratoconjunctivitis sicca (dry eyes), yet its reach extends well beyond the salivary and lacrimal glands to involve musculoskeletal, renal, pulmonary, and neurological systems. Insights from national patient surveys underscore considerable unmet needs in SjD management, emphasizing the importance of early recognition of oral health challenges. Concurrently, advances in clinical and translational research deepen our understanding of SjD's underlying mechanisms, revealing novel diagnostic and therapeutic strategies that target immunological pathways, foster glandular regeneration, and may alter disease progression. By providing a cohesive synthesis of state-of-the-art evidence, this review aims to expand clinicians' and researchers' understanding of SjD pathogenesis, address new research areas and key gaps, highlight the critical role of medical partnerships in addressing both systemic and oral manifestations, and advance patient-centered strategies to improve detection, treatment, and long-term disease management of this multifaceted autoimmune disorder. We discuss immune-mediated tissue damage, the potential of emerging biomarkers, and innovative treatments, including biologic agents and regenerative techniques. Patient perspectives further illuminate the daily challenges posed by SjD, underscoring the need for interdisciplinary care models that integrate oral medicine, rheumatology, and other medical specialties. Taken together, these insights underscore the pressing need for heightened awareness and collaborative approaches to pave the way for precision medicine interventions that can transform current management paradigms and ultimately improve the lives of individuals affected by Sjögren's disease.