Faculty Bibliography

RATIONALE & OBJECTIVE/UNASSIGNED:The prevalence of chronic kidney disease (CKD) is known to increase with age; however, creatinine may be a less reliable filtration marker in older adults. Few studies have investigated the prevalence and progression of CKD using different filtration markers for estimating glomerular filtration rate (GFR). STUDY DESIGN/UNASSIGNED:A prospective observational cohort study. SETTING & PARTICIPANTS/UNASSIGNED:6,393 White and African American participants aged 65-100 years from the Atherosclerosis Risk in Communities Study (ARIC) at Visit 5, followed longitudinally at Visits 6 and 7. EXPOSURE AND OUTCOME/UNASSIGNED:The eGFR was estimated either by creatinine (eGFRcr), cystatin C (eGFRcys), creatinine and cystatin C (eGFRcr-cys), or using creatinine, cystatin C, and β-2-microglobulin (eGFRcr-cys-b2m). CKD progression was defined as 30% decline in eGFR at follow-up visits. ANALYTICAL APPROACH/UNASSIGNED:Logistic regression models, adjusted for sex, race and study center, diabetes, blood pressure, body mass index, prevalent cardiovascular disease, and heart failure. RESULTS/UNASSIGNED:when using eGFRcys (33%) compared with eGFRcr-cys (12%) or eGFRcr-cys-b2m (18%). The proportion with 30% eGFR decline was lowest with eGFRcr and highest with eGFRcys, with greater incidence in older age groups for all markers. LIMITATIONS/UNASSIGNED:No direct measurement of GFR. Not all participants survived or attended subsequent follow-up visits. CONCLUSIONS/UNASSIGNED:The prevalence and progression of CKD increase with age, but estimates vary with the filtration marker used. The eGFRcr gave the lowest estimate of CKD at 15% for people aged 65-69 years at Visit 5 while eGFRcys gave the highest estimates of CKD at 26% for that same population.

Systemic mastocytosis (SM) is a rare hematologic condition characterized by the proliferation and accumulation in tissue of clonal mast cells in multiple organ systems. The release of mast cell mediators in the indolent disease type and the predominant mast cell infiltration of tissues in advanced disease contribute to the heterogeneous clinical presentation. The disease driver in >90% of adult cases is an activating KIT mutation, with D816V being the most frequent. Here we describe a case of a young adult male presenting with osteoporosis with associated symptoms of reflux and a history of bee sting anaphylaxis. A multidisciplinary approach to the diagnosis and management was required to minimize morbidities and prevent complications. Current best supportive care was inadequate to control the patient's disease, and a selective KIT D816V inhibitor (avapritinib) was initiated. Conventional, and advanced therapies, including those in the treatment pipeline for SM are discussed.

BACKGROUND/UNASSIGNED:Spontaneous coronary artery dissection (SCAD) is a disease entity that often occurs in young, healthy women and can cause life-threatening ventricular arrhythmias and sudden cardiac arrest. However, the characteristics and outcomes of SCAD with cardiac arrest are not well characterized. METHODS/UNASSIGNED:This study investigated the baseline characteristics of SCAD patients with cardiac arrest using the National Inpatient Sample (NIS) database between 2016 and 2020. In addition, we also sought to determine the potential impact that implantable cardioverter defibrillator (ICD) therapy had on morbidity and mortality in SCAD patients presenting with cardiac arrest. RESULTS/UNASSIGNED:Our findings showed that the SCAD with cardiac arrest population had significantly higher comorbidities, including cardiac arrhythmias, congestive heart failure, pulmonary circulation disorders, liver diseases, solid tumors, coagulopathy, fluid disorders, chronic kidney disease (CKD), anemia secondary to deficiency, psychosis, neurological disorders, carotid artery disease, atrial fibrillation, ventricular arrhythmias (ventricular tachycardia (VT), ventricular fibrillation (VF)), and acute myocardial infarction (AMI), compared to the SCAD without cardiac arrest population. Likewise, for SCAD patients who did not have an ICD in place, we found increasing age, fluid and electrolyte disorders, uncomplicated diabetes, neurological disorders, peripheral vascular disease, pulmonary circulatory disorders, cardiac arrhythmias, and congestive heart failure to be associated with greater mortality. CONCLUSIONS/UNASSIGNED:SCAD patients with certain comorbidities (e.g., pulmonary diseases, liver diseases, cancers, coagulopathy, and CKD) who presented with AMI or congestive heart failure should be monitored closely for ventricular arrhythmias as they have a higher chance of progressing to cardiac arrest. ICD therapy can be considered for these patients, but data on the success of this treatment option are limited, and more research needs to be performed to determine whether the benefits of this outweigh the risks.

OBJECTIVE/UNASSIGNED:Families or loved ones of adolescents and young adults (AYA) with a poor cancer prognosis who preserved fertility and did not survive treatment may choose to pursue posthumous assisted reproduction (PAR; i.e., use of preserved reproductive material for future family-building attempts). Decisions about PAR may be occurring in the context of grief and bereavement, which is associated with ethical and psychological considerations because grief can complicate a person's capacity for informed decision-making. METHODS/UNASSIGNED:Through the use of a five-step ethical decision-making model, the American Psychological Association's Ethical Principles of Psychologists and Code of Conduct, and a blended case example, the ethical and psychological considerations for families of AYA with poor prognosis who pursue PAR is discussed with an ethical analysis. RESULTS/UNASSIGNED:Ethical and psychological considerations included assessing the potential for harm to involved parties, navigating PAR decision-making with responsibility and honesty, examining the accessibility of PAR, and considering informed consent/assent and autonomy. CONCLUSIONS/UNASSIGNED:Clinical recommendations for supporting families and loved ones exploring PAR in the context of grief were discussed, with considerations for improving clinicians' comfort and competence with PAR, incorporating grief into informed consent conversations, standardizing conversations about PAR, and promoting an interdisciplinary approach to PAR-related decisions.

Carcinoid heart disease (CHD) is a rare cardiac complication that occurs most commonly in patients with advanced neuroendocrine tumors and is a known sequela of carcinoid syndrome. Neuroendocrine tumors most widely associated with CHD include tumors in the small bowel, followed by lung, large bowel, pancreatic, appendiceal, and ovarian neoplasms. Carcinoid syndrome is a paraneoplastic syndrome caused by the release of serotonin and other substances from neuroendocrine tumors. It results in a spectrum of symptoms, including diarrhea, flushing, bronchospasm, and symptoms of congestive heart failure. Without treatment and for patients with advanced heart failure, the prognosis of CHD can be less than a year. Management of CHD is often challenging as patients typically present late, and the disease can progress rapidly. Therefore, optimal management of these patients requires close collaboration among various specialties to quantify disease burden, delay the progression of valvular disease, and determine the most effective surgical and medical management strategies depending on the cardiac manifestations to improve quality of life and reduce mortality. This involves a collaborative team, including cardiology and oncology, and often involves many other disciplines, including hepatobiliary and cardiovascular surgeons, endocrinologists, anesthesiologists, and gastroenterologists.

PURPOSE OF REVIEW/OBJECTIVE:Current biological findings provide new insights into the genetics driving growth of low-grade gliomas in pediatric patients. This has provided new targets for novel therapies. The purpose of this paper is to review novel therapies for pediatric low-grade gliomas that have been published in the past 24 months. RECENT FINDINGS/RESULTS:Low-grade gliomas are often driven by mitogen activated protein kinase (MAPK) alterations either with BRAF V600E point mutations or BRAF fusions. Current advances have also highlighted novel fusions of fibroblast growth factor receptor (FGFR), myeloblastosis family of transcription factors (MYB), meningioma 1 tumor suppressor (MN1), neurotrophic receptor kinase family of receptors (NTRK), Kristen RAS (Rat Sarcoma Virus) oncogene homolog in mammals (KRAS), Receptor tyrosine kinase ROS proto oncogene 1 (ROS1), protein kinase C alpha (PRKCA), and platelet derive growth factor receptor (PDGFR) amplification. Novel therapies have been employed and are showing encouraging results in pediatric low-grade gliomas. Current trials are underway with newer generation pan RAF inhibitors and mitogen activated protein kinase - kinase (MEK) inhibitors. Other early phase clinical trials have provided safety data in pediatric patients targeting FGFR fusion, NTRK fusion, PDGFR amplification and ROS1 mutations. SUMMARY/CONCLUSIONS:Historical treatment options in pediatric low-grade gliomas have utilized surgery, radiation therapy and conventional chemotherapy. Recently greater insight into their biology has found that alterations in MAPK driven pathways are often the hallmark of tumorigenesis. Targeting these novel pathways has led to tumor control and shrinkage without the use of conventional chemotherapy. Caution should be taken however, since these treatment options are still novel, and we do not fully appreciate the long-term effects. Nonetheless a new era of targeted medicine is here.

BACKGROUND/UNASSIGNED:A deeper understanding of acute rejection in vascularized composite allotransplantation is paramount for expanding its utility and longevity. There remains a need to develop more precise and accurate tools for diagnosis and prognosis of these allografts, as well as alternatives to traditional immunosuppressive regimens. METHODS/UNASSIGNED:Twenty-seven skin biopsies collected from 3 vascularized composite allotransplantation recipients, consisting of face and hand transplants, were evaluated by histology, immunohistochemistry staining, and gene expression profiling. RESULTS/UNASSIGNED:significantly predicted inflammation specific to vascularized composite allografts that required therapeutic intervention. CONCLUSIONS/UNASSIGNED:The mechanism of vascularized composite allograft-specific inflammation and rejection appears to be conserved across different patients and skin on different anatomical sites. A concise gene signature can be utilized to ascertain graft status along with a continuous scale, providing valuable diagnostic and prognostic information to supplement current gold standards of graft evaluation.

The morbidity and mortality for patients having a cardiac arrest is substantial. Even if optimally performed, conventional cardiopulmonary resuscitation is an inadequate substitute for native cardiac output and results in a 'low-flow' perfusion state. Venoarterial extracorporeal membrane oxygenation during cardiac arrest, also known as extracorporeal cardiopulmonary resuscitation (eCPR), has been proposed as an alternative to restore systemic perfusion. However, conflicting results regarding its efficacy compared to routine advanced cardiac life support have left its role in clinical practice uncertain. In this article, the merits and limitations of the existing data for eCPR are reviewed in a 'point- counterpoint' style debate, followed by potential considerations for future trials.

Coronary artery anomalies encompass a spectrum of congenital abnormalities affecting the origin, course, or termination of the major epicardial coronary arteries. Despite their rarity, coronary artery anomalies represent a significant burden on cardiovascular health due to their potential to disrupt myocardial blood flow and precipitate adverse cardiac events. While historically diagnosed postmortem, the widespread availability of imaging modalities has led to an increased recognition of coronary artery anomalies, particularly in adults. This review synthesizes current knowledge on the classification, mechanisms, and clinical implications of coronary anomalies, focusing on prevalent variants with significant clinical impact. We discuss strategies for medical and surgical management, as well as contemporary screening recommendations, acknowledging the evolving understanding of these anomalies. Given the breadth of possible variants and the limited data on some presentations, this review provides a framework to aid clinicians in the recognition and management of coronary anomalies, with a particular emphasis on their stratification by anatomical location. By consolidating existing knowledge and highlighting areas of uncertainty, this review aims to enhance clinical decision-making and improve outcomes for individuals with coronary anomalies.