Faculty Bibliography

A 70-year-old male with a history of 3 prior median sternotomies and on anticoagulation presented with acute chest and back pain associated with a pseudoaneurysm of the ascending and aortic arch in the setting of residual dissection involving the innominate, proximal right carotid, and subclavian arteries. A physician-modified triple vessel fenestrated-branched arch endograft was deployed. The innominate branch stent was deployed from the right carotid cut down, while the left carotid and left subclavian branch stents were placed from a femoral approach. Postoperatively, the innominate branch was found to be deployed in the false lumen of the dissected native innominate artery, leading to continued pressurization of the pseudoaneurysm. This was rescued by placing a Gore Iliac Branch Endoprosthesis (IBE) into the innominate branch through a temporary conduit sewn to the right carotid artery with a right subclavian branch placed via a brachial artery cut down into the internal iliac gate. The use of IBE allowed branch stent extension past the dissected native vessels. The patient had an uneventful recovery without neurologic complications. At 3-month follow-up, the patient remains well with an excluded pseudoaneurysm, and patent bifurcated innominate, bilateral carotid, and subclavian artery branches. A Gore IBE can be utilized in a dissected innominate artery to create an innominate branch device during fenestrated-branched endovascular arch repair.

INTRODUCTION/BACKGROUND:Physician-modified fenestrated-branched endovascular aortic repair (PM-FBEVAR) for the aortic arch provides a minimally invasive treatment option for patients who are too high-risk for open repair. Improvements in technique are gained with ongoing experience with these complex repairs. This study aims to describe outcomes of arch PM-FBEVAR and technical lessons. MATERIALS AND METHODS/METHODS:A retrospective review of consecutive patients who underwent PM-FBEVAR with zone 0 proximal sealing at a single institution between January 2019 and July 2023 was performed. Cases completed using initial techniques (early technique) were compared with cases using the current techniques (current technique). Modification technique changed to include a self-orienting spine trigger wire and anatomically specific fenestrations or inner branches in the current group. The primary outcome was in-hospital mortality. Secondary outcomes included technical success and 30 day stroke. RESULTS:A total of 21 patients underwent arch PM-FBEVAR, with 7 in the early group and 14 in the current group. Severe comorbidities were present in both groups including chronic obstructive pulmonary disease (COPD) (43% vs 36%), prior open ascending aortic repair (57% vs 43%), and prior stroke (86% vs 21%), respectively. Technical success was the same (86% vs 86%, p=1.0). Fluoroscopy time (56 vs 24 min, p=0.012) and in-hospital death (43% vs 0%, p=0.026) were significantly lower in the current group. A 30 day stroke rate (29% vs 7%, p=0.247) was non-significantly decreased in the current group. All-cause mortality was 100% vs 7% during median follow-up of 8 and 6 months (p<0.001). Three deaths in the early group were related to their aortic arch repair including aortic rupture during endograft advancement and 2 postoperative strokes. CONCLUSION/CONCLUSIONS:There is a significant learning curve associated with aortic arch PM-FBEVAR. This study suggests that gained experience, use of the spine trigger wire technique, and precise creation of fenestrations or inner branches can lead to a shorter procedure time and lower complications.Clinical ImpactPhysician modified fenestrated branched endografting is feasible for the aortic arch. The high rate of stroke and perioperative mortality was reduced with incorporation of self-orienting spine trigger wire and anatomically specific inner branch creation.

Generative artificial intelligence (GenAI) is rapidly transforming various sectors, including healthcare and education. This paper explores the potential opportunities and risks of GenAI in graduate medical education (GME). We review the existing literature and provide commentary on how GenAI could impact GME, including five key areas of opportunity: electronic health record (EHR) workload reduction, clinical simulation, individualized education, research and analytics support, and clinical decision support. We then discuss significant risks, including inaccuracy and overreliance on AI-generated content, challenges to authenticity and academic integrity, potential biases in AI outputs, and privacy concerns. As GenAI technology matures, it will likely come to have an important role in the future of GME, but its integration should be guided by a thorough understanding of both its benefits and limitations.

PURPOSE:Genetic variants at the low end of the penetrance spectrum have historically been challenging to interpret because their high population frequencies exceed the disease prevalence of the associated condition, leading to a lack of clear segregation between the variant and disease. There is currently substantial variation in the classification of these variants, and no formal classification framework has been widely adopted. The Clinical Genome Resource Low Penetrance/Risk Allele Working Group was formed to address these challenges and promote harmonization within the clinical community. METHODS:The work presented here is the product of internal and community Likert-scaled surveys in combination with expert consensus within the Working Group. RESULTS:We formally recognize risk alleles and low-penetrance variants as distinct variant classes from those causing highly penetrant disease that require special considerations regarding their clinical classification and reporting. First, we provide a preferred terminology for these variants. Second, we focus on risk alleles and detail considerations for reviewing relevant studies and present a framework for the classification these variants. Finally, we discuss considerations for clinical reporting of risk alleles. CONCLUSION:These recommendations support harmonized interpretation, classification, and reporting of variants at the low end of the penetrance spectrum.

Free polymannose-type oligosaccharides (fOS) are processed by cytosolic enzymes to generate Man5GlcNAc which is transferred to lysosomes and degraded. Lysosomal fOS import was demonstrated in vitro but is poorly characterized in part due to lack of convenient substrates. As chitooligosaccharides (COS, oligomers β1,4-linked GlcNAc) block [3H]Man5GlcNAc transport into lysosomes, we asked if COS are themselves transported and if so, can they be chemically modified to generate fluorescent substrates. We show that COS are degraded by lysosomal hydrolases to generate GlcNAc, and robust ATP-dependent transport of [3H]COS2/4 di and tetrasaccharides into intact rat liver lysosomes was observed only after blocking lysosomal [3H]GlcNAc efflux with cytochalasin B. As oligosaccharides with unmodified reducing termini are the most efficient inhibitors of [3H]COS2/4 and [3H]Man5GlcNAc transport, the non-reducing GlcNAc residue of COS2-4 was de-N-acetylated using Sinorhizobium meliloti NodB, and the resulting amine substituted with rhodamine B (RB) to yield RB-COS2-4. The fluorescent compounds inhibit [3H]Man5GlcNAc transport and display temperature-sensitive, ATP-dependent transport into a sedimentable compartment that is ruptured with the lysosomotropic agent L-methyl methionine ester. Once in this compartment, RB-COS3 is converted to RB-COS2 further identifying it as the lysosomal compartment. RB-COS2/3 and [3H]Man5GlcNAc transports are blocked similarly by competing sugars, and are partially inhibited by the vacuolar ATPase inhibitor bafilomycin and high concentrations of the P-type ATPase inhibitor orthovanadate. These data show that Man5GlcNAc, COS2/4 and RB-COS2/3 are transported into lysosomes by the same or closely related mechanism and demonstrate the utility of COS modified at their non-reducing terminus to study lysosomal oligosaccharide transport.

BACKGROUND AND OBJECTIVE/UNASSIGNED:The study of resilience in youth with inflammatory bowel disease (IBD) is in early stages. The current review aims to illustrate how the use of a multisystemic framework may serve as a developmental and disease-appropriate framework for conceptualizing and designing resilience research for youth with IBD. METHODS/UNASSIGNED:This is a narrative review; therefore, a comprehensive and systematic literature search was not conducted. Rather, the current paper aims to map selected existing literature to a multisystemic model as exemplars of how the model may be used in youth with IBD. Relevant literature was reviewed, synthesized, and mapped onto the proposed multi-systemic framework. KEY CONTENT AND FINDINGS/UNASSIGNED:The current review considers existing literature across three proposed dimensions of resilience: contexts of risk exposure, protective and promotive factors/processes, and desired outcomes. Review of each dimension includes consideration of selected existing literature to explain what is known about each dimension currently, as well as to propose additional potential future areas to broaden understanding. Specific key takeaways include: (I) understanding risk exposure in young people with IBD requires consideration of disease-specific, demographic, and sociocultural factors; (II) protective and promotive factors and processes for these young people span individual, familial, peer, school, and community levels; and (III) desired outcomes encompass both the absence of negative and the presence of positive indicators. CONCLUSIONS/UNASSIGNED:A multisystemic approach to the study of resilience in young people with IBD may not only clarify current gaps in the field, but also allow for additional future considerations to best understand how and for whom outcomes characterized as resilient may occur in this population.

AIMS/OBJECTIVE:The atherosclerotic profile and advanced plaque subtype burden in symptomatic patients ≤45 years old have not been established. This study aimed to assess the prevalence and predictors of coronary artery calcium (CAC), plaque subtypes, and plaque burden by coronary computed tomography angiography (CCTA) in symptomatic young patients. METHODS AND RESULTS/RESULTS:We included 907 symptomatic young patients (18-45 years) from Montefiore undergoing CCTA for chest pain evaluation. Prevalence and predictors of CAC, plaque subtypes, and burden were evaluated using semi-automated software. In the overall population (55% female and 44% Hispanic), 89% had CAC = 0. The likelihood of CAC or any plaque by CCTA increased with >3 risk factors {RFs, odds ratio [OR] 7.13 (2.14-23.7) and OR 10.26 (3.36-31.2), respectively}. Any plaque by CCTA was present in 137 (15%); the strongest independent predictors were age ≥35 years [OR 3.62 (2.05-6.41)] and family history of premature coronary artery disease (FHx) [OR 2.76 (1.67-4.58)]. Stenosis ≥50% was rare (1.8%), with 31% of those having CAC = 0. Significant non-calcified plaque (NCP, 37.2%) and low-attenuation plaque (LAP, 4.24%) burdens were seen, even in those with non-obstructive stenosis. Among patients with CAC = 0, 5% had plaque, and the only predictor of exclusively NCP was FHx [OR 2.29 (1.08-4.86)]. CONCLUSION/CONCLUSIONS:In symptomatic young patients undergoing CCTA, the prevalence of CAC or any coronary atherosclerosis was not negligible, and the likelihood increased with RF burden. The presence of coronary stenosis ≥50% was rare and most often accompanied by CAC >0, but there was a significant burden of NCP and LAP even within the non-obstructive group.

Non-caseating granulomatous infiltration of the myocardium is the hallmark of cardiac sarcoidosis (CS). CS manifests clinically as conduction disturbance, ventricular arrhythmia, sudden cardiac death and/or heart failure with reduced ejection fraction. Other than confirmation through endomyocardial biopsy, a diagnosis of probable CS can be established by histological evidence of systemic sarcoidosis in addition to characteristic clinical or advanced imaging findings. Cardiac Magnetic Resonance imaging (CMR) and ¹⁸F-flurodeoxyglycose positron emission tomography (FDG-PET) are imaging modalities indispensable in the diagnosis and monitoring of CS. FDG-PET is the method of choice for identifying the active inflammatory phase of CS and in the monitoring and modifying of immunosuppressive treatment. CMR is better suited for assessing cardiac morphology and function. Both modalities are more effective in detecting CS when used in combination than either is alone. Management of CS is primarily based upon observational data of low quality due to a paucity of randomized controlled trials. Corticosteroid therapy and/or tiered-immunosuppression are the mainstays of treatment in reducing myocardial inflammation. Steroid-sparing agents aim to limit the unfavorable side-effects of a significant steroid burden. Antiarrhythmics and guideline-directed medical therapies are utilized for control of ventricular arrhythmia and left ventricular dysfunction respectively. CS necessitates multidisciplinary care in specialized centers to most effectively diagnose and manage the disease. Additional randomized trials are warranted to further our understanding of medical optimization in CS.