Faculty Bibliography

Mutations that accumulate in the human male germline with age are a major driver of genetic diversity and contribute to genetic diseases. However, aging-related male germline mutation rates have not been measured directly in germline cells (sperm) at the level of individuals. We developed a study design in which we recalled 23 sperm donors with prior banked samples to provide new sperm samples. The old and new sequential sperm samples were separated by long timespans, ranging from 10 to 33 years. We profiled these samples by high-fidelity duplex sequencing and demonstrate that direct high-fidelity sequencing of sperm yields cohort-wide mutation rates and patterns consistent with prior family-based (trio) studies. In every individual, we detected an increase in sperm mutation burden between the two sequential samples, yielding individual-specific measurements of germline mutation rate. Deep whole-genome sequencing of sequential sperm samples from two individuals followed by targeted validation measured remarkably stable mosaicism of clonal mutations that likely arose during embryonic and germline development, suggesting that age did not substantially impact the diversity of spermatogonial stem cell pools in these individuals. Our application of high-fidelity and deep whole-genome sequencing to sequential sperm samples provides insight into aging-related mutation processes in the male germline.

BACKGROUND AND OBJECTIVES/OBJECTIVE:This study aimed to evaluate whether a 6-month (limited) course of early IVIG is an effective strategy for relapse prevention in children with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) versus only acute therapies or other early immunotherapies. METHODS:This was a retrospective multicenter observational study of pediatric MOGAD patients from the US Network of Pediatric Multiple Sclerosis Centers with disease onset between October 1996 and December 2022. Controls were matched to limited early IVIG subjects using a 3:1 ratio. Hazard ratios of time to relapse and rate ratios of annualized relapse rate were calculated. The cumulative probability of remaining relapse-free was evaluated with the Kaplan-Meier method. RESULTS:We identified 130 unique control subjects treated before second attack with acute treatments only used in matching, 18 subjects treated with limited early IVIG, and 23 subjects treated with other early immunotherapy. The time to relapse was not different between either the limited early IVIG group and control group (HR 0.60 [0.22, 1.66], p = 0.32) or other early immunotherapy group (HR 0.98 [0.27, 3.6], p = 0.98). The limited early IVIG group showed a lower annualized relapse rate, although not statistically significant (RR 0.44 [0.17, 1.14], p = 0.09) compared with controls and a similar annualized relapse rate compared with the other early immunotherapy group (RR 0.56 [0.19, 1.69], p = 0.30). DISCUSSION/CONCLUSIONS:Although underpowered, our results suggest that the use of a limited, 6-month course of early IVIG may reduce the risk of multiphasic disease in pediatric MOGAD.

BACKGROUND/UNASSIGNED:We investigated racial and ethnic disparities in telehealth counseling among Medicaid-insured patients in outpatient substance use disorder (SUD) treatment clinics and assessed whether the clinic-level proportion of Medicaid-insured patients moderated these disparities. METHODS/UNASSIGNED:Using New York State (NYS) Medicaid and statewide treatment registry data, we analyzed 24,814 admission episodes across 399 outpatient SUD clinics during the first 6 months of COVID-19 (April-September 2020). Our outcome measure was the number of tele-counseling sessions within the first 90 days of treatment. Key independent variables included beneficiary race/ethnicity and the clinic-level proportion of Medicaid-insured patients, divided into four quartiles: lowest, second, third, and highest. Mixed effects negative binomial models assessed the associations between race/ethnicity, Medicaid proportions, and telehealth use, with interaction terms evaluating the moderating role of Medicaid proportions. RESULTS/UNASSIGNED:Black and Latinx patients received fewer telehealth sessions than non-Latinx White patients, with adjusted incidence rate ratios (aIRRs) of 0.86 (95% CI: 0.82, 0.91) for Black patients and 0.93 (95% CI: 0.88, 0.98) for Latinx patients. Black patients at clinics with the highest Medicaid proportions had higher telehealth usage rates compared to those at clinics with the lowest Medicaid proportions (aIRR, 1.20; 95% CI, 1.03-1.41). Patients in clinics with the highest Medicaid proportions were more likely to use individual telehealth counseling (aIRR, 1.02-1.88; 95% CI, 1.01-3.04). CONCLUSIONS/UNASSIGNED:Significant racial disparities in telehealth use exist, with variations persisting across clinics with different Medicaid proportions. Targeted interventions are needed to address these access gaps.

BACKGROUND/UNASSIGNED:Hospital websites play a key role when patients seek specialist care. Patients may become overwhelmed with the number of search results generated by hospital websites when looking for facial aesthetics procedures. This study characterizes plastic surgeons' representation on major hospital system websites in the United States for facial aesthetic procedures. METHODS/UNASSIGNED:The "find a doctor" tool on the top 20 US hospitals, as described in the US News and World Report's Hospital Rankings 2020-2021, was queried for 6 facial aesthetic procedures: rhinoplasty, facial rejuvenation, face lift, neck lift, blepharoplasty, and brow lift. Physician information such as their sex, medical specialty, medical school location, and residency program was recorded. RESULTS/UNASSIGNED:Our study revealed 1189 healthcare professionals, with 1077 being physicians. Plastic surgeons were consistently underrepresented in the results for each of the six search terms. The search term "blepharoplasty" produced the greatest number of plastic surgeons (44%), whereas the term "facial rejuvenation" produced the lowest number of plastic surgeons (32%). Nonsurgeons represented 6% of queries. CONCLUSIONS/UNASSIGNED:This study highlights the underrepresentation of plastic surgeons on hospital websites when searching for common facial aesthetic procedures. Factors such as the prevalence of procedures performed outside of hospitals, overlapping procedural privileges, and search engine inaccuracies may contribute to this issue. Patients may face challenges locating a plastic surgeon and could benefit from more streamlined guidance when using hospital websites.

GENERAL PURPOSE/OBJECTIVE:To provide an evidence-based review of strategies for the prevention and management of wounds and postoperative scars following microsurgical autologous breast reconstruction. TARGET AUDIENCE/BACKGROUND:This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and registered nurses with an interest in skin and wound care. LEARNING OBJECTIVES/OUTCOMES/OBJECTIVE:After participating in this educational activity, the participant will: 1. Identify operative considerations to promote wound healing in microsurgical autologous breast reconstruction. 2. Synthesize management strategies for major flap complications following microsurgical autologous breast reconstruction. 3. Explain features in the assessment, prevention, and treatment of scars following microsurgical autologous breast reconstruction.

MRI is widely used for the diagnosis and management of various abdominal diseases involving organs such as the liver, pancreas, and kidneys. However, one major limitation of MRI is its relatively slow imaging speed compared to other modalities. In addition, respiratory motion poses a significant challenge in abdominal MRI, often requiring patients to hold their breath multiple times during an exam. This requirement can be particularly challenging for sick, elderly, and pediatric patients, who may have reduced breath-holding capacity. As a result, rapid imaging plays an important role in routine clinical abdominal MRI exams. Accelerated data acquisition not only reduces overall exam time but also shortens breath-hold durations, thereby improving patient comfort and compliance. Over the past decade, significant advancements in rapid MRI have led to the development of various accelerated imaging techniques for routine clinical use. These methods improve abdominal MRI by enhancing imaging speed, motion compensation, and overall image quality. Integrating these techniques into clinical practice also enables new applications that were previously challenging. This paper provides a concise yet comprehensive overview of rapid imaging techniques applicable to abdominal MRI and discusses their advantages, limitations, and potential clinical applications. By the end of this review, readers are expected to learn the latest advances in accelerated abdominal MRI and explore new frontiers in this evolving field. Evidence Level: N/A Technical Efficacy: Stage 5.

BACKGROUND:Withdrawal-of-life-sustaining-therapies (WLST) in patients with traumatic brain injury (TBI) is a complex decision-making process. The clinical factors related to WLST in older adults with TBI are currently poorly understood. The present study aims to determine the clinical predictors of WLST in older patients with TBI. METHODS:All patients ≥ 65 years old with TBI (Head Abbreviated Injury Scale Score ≥ 3) were identified from the Geriatric TBI Database, a prospective registry of patients admitted to 45 trauma centers nationwide with TBI between 2017-2019. We collected factors related to past medical history, baseline demographic data, clinical presentation, TBI sub-type, neurosurgical interventions, and do-not-attempt-resuscitation (DNAR) orders. The primary outcome measure was WLST. Binary logistic regression was subsequently performed to determine factors independently associated with WLST. RESULTS:A total of 1600 patients were identified. The median age was 80 years old and 48.6 % of patients were male. In this cohort, 120 patients (7.5 %) underwent WLST. A logistic regression model revealed that Glasgow Coma Scale (GCS) (OR 0.82; 95 %-CI 0.77--0.87), cerebral edema (3.2; 1.5-7.0), craniotomy/craniectomy (2.5; 1.4-4.4), and DNAR (8.8; 5.5-14.3) were all independently associated with WLST. This model demonstrated excellent discrimination ability with a concordance statistic of 0.935. CONCLUSIONS:This study demonstrates that patients ≥ 65 years old with poor initial GCS, cerebral edema, craniotomy/craniectomy, and DNAR were all independently associated with WLST. Pre-injury frailty was not associated with WLST. Further studies are needed to evaluate the prognostic value of frailty indices in the management of patients with TBI.

This report outlines the case of a 9-year-old girl with severe anti-nuclear matrix protein 2 antibody-positive juvenile dermatomyositis presenting with disease refractory to multiple traditional therapies. Treatment with an experimental monoclonal antibody inhibiting interferon beta (IFNβ) resulted in the rapid resolution of her muscle weakness and cutaneous and gastrointestinal ulcers. This case highlights the potential benefit of inhibiting IFNβ in the management of recalcitrant juvenile dermatomyositis.

BACKGROUND:Most donor hearts offered for heart transplant (HT) in the United States (US) are turned down. We aimed to understand the reasons for this - focusing on those related to the potential recipient and HT center (i.e. donor-unrelated reasons for refusal). METHODS:The Donor Heart Study (DHS) enrolled 4,333 adult potential heart donors in US from 2015 - 2020. Separately by donor, each HT center who refused an offer for that donor was surveyed on their reason(s) for refusal. We measured the prevalences of 18 distinct donor-unrelated reasons for refusal and their association with the timing of offers (weekend vs. weekday). RESULTS:Our analytic sample included 14,132 unique surveys, each representing a declined offer for one of 3083 donors (mean per donor: 2.56; range: 1 - 17). Donor-unrelated reasons were cited in 24.3% (n = 3441) of surveys; among these, recipient issues (i.e. "recipient ill) were most common (cited in 7%) while resource-related issues (e.g. "logistics", "surgeon unavailable") were rare (<1%). Neither showed a significant time trend; however, other reasons ("already considering another offer", "distance too far") did so, with an abrupt uptick after 2018. We found that several donor-related (but no donor-unrelated) reasons for refusal (e.g. left ventricular hypertrophy, social risk behaviors) were significantly more common on weekends. Their "weekend-predominance" was not explained by differences in objective donor characteristics. CONCLUSIONS:Nearly one quarter of donor heart offer refusals are due to donor-unrelated reasons. Weekend-predominant reasons for offer refusal signal the highly subjective nature of donor assessment and warrant further scrutiny.

OBJECTIVES/UNASSIGNED:We conducted a scoping review to identify barriers to telehealth use and uptake from the perspective of patient, provider, and system that were documented in the literature. In addition to identifying and categorizing the barriers, we aimed to assess how barriers differed for studies conducted during the COVID-19 pandemic, as well as how barriers differed between the United States vs internationally based studies. MATERIALS AND METHODS/UNASSIGNED:Comprehensive searches of the PubMed/MEDLINE, CINAHL, and Scopus databases conducted on December 29, 2021 yielded 17 887 results, with 11 221 potentially eligible documents after duplicates were removed. The team conducted an initial title and abstract review, followed by full text review. Data from the included sources were extracted and summarized into primary themes. RESULTS/UNASSIGNED:We identified 395 articles specifically related to barriers of telehealth use. The top 5 barriers, in order of frequency, were: lack of skills or ability (55%), lack of interest (49%), lack of access to technology (45%), limitations of technology infrastructure (45%), and lack of quality of care (42%). Roughly one-third (39%) of studies were related to the COVID-19 pandemic and 54% were US-based studies. The rank order of barriers between COVID-19 vs non-COVID-19 studies and US vs non-US studies was the same; however, patients in the United States and those using telehealth during COVID-19 were more likely to cite barriers related to the lack of access to technology (COVID = 56% vs 38%; United States = 51% vs 38%). DISCUSSION/UNASSIGNED:Interventions to address barriers need to consider the unique needs of specific populations and the ways in which different barriers may intersect. CONCLUSION/UNASSIGNED:This review found that barriers to telehealth uptake and use are multilayered and occur at several levels (individual, structural, technological).