Faculty Bibliography

OBJECTIVE:Limited evidence guides the optimal timing of treatment after the detection of tumor growth during the observation of sporadic vestibular schwannoma (VS). The current work aimed to inform the timing of radiosurgical intervention based on an analysis of patient outcomes among those who ultimately failed stereotactic radiosurgery (SRS) and underwent salvage microsurgery. STUDY DESIGN/METHODS:A historical cohort study. SETTING/METHODS:Seven centers across the United States and Norway. METHODS:Adults with sporadic VS who underwent salvage microsurgery following failed primary SRS were included. The primary outcome of interest was the association between tumor size at the time of primary SRS and the ability to achieve gross total resection (GTR) and maintain postoperative House-Brackmann (HB) facial nerve grade I at the last follow-up after salvage microsurgery. RESULTS:Among 96 patients, the median (interquartile range [IQR]) cerebellopontine angle (CPA) tumor size at primary SRS was 14.5 mm (10.0-19.0). Each 1-mm increase in CPA tumor size at the time of primary SRS was associated with a 13% increased likelihood of near-total/subtotal resection or most recent postoperative HB grade >I (odds ratio [OR] 1.13, 95% confidence interval [CI] 1.05-1.21, P = .001), with an optimal tumor size threshold to distinguish this outcome of 12 mm of CPA extension (c-index 0.73). Similarly, for each 1-mm increase in CPA tumor size at the time of primary SRS, a 9% increase in any postoperative complication with salvage microsurgery was observed (OR 1.09, 95% CI 1.02-1.15, P = .009). CONCLUSION/CONCLUSIONS:Corroborated by size threshold surveillance data informing the timing of primary microsurgical resection, the current study suggests that VS outcomes are optimized when primary radiosurgical intervention is undertaken on growing tumors when they harbor 10-15 mm of cerebellopontine angle extension or less.

Psychiatric disorders are a common source of disease morbidity with high rates of refractoriness to first-line treatments. As such, many have investigated the utility of neurosurgical interventions for treatment-resistant forms of these conditions. More recently among these, functional neurosurgical techniques using high- and low-intensity focused ultrasound (FUS) have emerged as promising options in this arena, largely due to their minimally-invasive nature and encouraging early safety and efficacy data. Existing clinical data have thus far demonstrated FUS to be a potentially useful intervention for treatment-refractory forms of obsessive-compulsive disorder, major depressive disorder, various anxiety disorders, substance-use disorder, and schizophrenia. This report presents a comprehensive review of existing clinical trial data, summarizing key findings, study specifications, and providing critical analysis. In addition to giving the most complete summary of modern clinical research on this topic to date, this report characterizes the current state of this body of literature using bibliometric analysis, succinctly highlighting the most investigated topics and the most promising areas of modern investigation. Based on our review of the literature, current work on this topic is highly heterogeneous with regard to specific treatment protocols and anatomic targets for FUS - targeting multiple nuclei at a wide variety of intensities. We recommend that future studies aim to clarify more precise therapeutic targets and specific treatment protocols which optimize the efficacy of these techniques.

BACKGROUND:Left atrial appendage occlusion (LAA-O) with Amulet and Watchman FLX are approved for reducing stroke risk in patients with atrial fibrillation when oral anticoagulation is not tolerated. Real world clinical outcomes reported along with imaging data are needed to help clinicians choose between these two technologies and manage device-related complications. METHODS:The study retrospectively analyzed clinical, transesophageal (TEE), and available computed tomography (CT) data from 364 FLX and 292 Amulet procedures performed at an academic medical center over a 4-year period. RESULTS:were included. TTE LAA-orifice area correlated with CT-derived measurements. There were more late pericardial effusions for Amulet (3.1%) compared to FLX (0.3%), though the majority were conservatively managed. Mean procedure times were similar (FLX 64 ± 24, Amulet 65 ± 21 min) as were the rates of device related thrombus (FLX 1% and Amulet 1.4%). Clinically relevant peridevice leak (PDL) on follow-up TEE imaging was greater for FLX (16%) compared to Amulet (10%). Combined AF ablation-LAA-occlusion procedures exhibited lower rates of PDL and late pericardial effusions compared to solo procedures. CONCLUSIONS:Based on retrospective analysis, an initial strategy with Watchman FLX in patients with favorable LAA anatomy would reduce the risk of late pericardial effusions at the expense of a higher rate of clinically relevant PDL compared to Amulet. Combined AF ablation and LAA-O procedures exhibit less PDL.

Hypertrophic cardiomyopathy is a common but underrecognized cardiac disorder characterized by a heterogenous phenotype that includes increased left ventricular thickness, outflow obstruction, diastolic dysfunction, and arrhythmia. Hypertrophic cardiomyopathy is often heritable and associated with pathogenic variants in sarcomeric genes. While not curable, an integrated approach involving medical, interventional, and surgical care can have a considerable impact on disease burden, quality of life, and mortality. This review provides a practical overview of important topics in hypertrophic cardiomyopathy, including evaluation of differential diagnosis, imaging, provocation of left ventricular outflow obstruction, treatment of obstructive and nonobstructive hypertrophic cardiomyopathy with negative inotropic therapy and myosin inhibition, as well as surgical and interventional approaches to septal reduction and mitral valve intervention.

INTRODUCTION/UNASSIGNED:Hemodialysis has an essential role in the treatment of certain poisoned patients, both by enhancing the elimination of select poisons and correcting underlying fluid, electrolyte, and acid-base disturbances. We sought to identify barriers to the performance of hemodialysis when it was recommended by our poison center. METHODS/UNASSIGNED:Data from a single United States poison center were retrospectively queried for adult patients for whom the poison center recommended intermittent hemodialysis for poison removal. The primary outcome was the performance of intermittent hemodialysis within 12 h of the poison center recommendation, which we defined as timely hemodialysis. Univariable and multivariable logistic regressions were performed to assess the effect of the following variables on this outcome: age group, patient sex, time of day of the recommendation, day of week of the recommendation, year of the recommendation, hospital location, and poison category. RESULTS/UNASSIGNED:A total of 535 patient encounters were analyzed. The majority (72%) of patients had intermittent hemodialysis performed within 12 h of when it was recommended. The multivariable analyses showed that the odds of receiving recommended intermittent hemodialysis within 12 h were significantly lower when the recommendation was made during the nighttime (OR: 0.660; 95% CI: 0.442-0.987) compared to daytime and during the weekend (OR: 0.605; 95% CI: 0.398-0.918) compared to weekdays. DISCUSSION/UNASSIGNED:Intermittent hemodialysis is resource-intensive and requires specialized equipment and personnel, which is likely less available outside of regular business hours. This study is limited by its retrospective nature and may not be generalizable to other poison centers. CONCLUSION/UNASSIGNED:Patients for whom our poison center recommended intermittent hemodialysis during non-weekday times had lower odds of receiving timely hemodialysis. Hospital administrators and healthcare providers should be aware of this potential treatment obstacle for poisoned patients and identify the specific barriers involved in order to facilitate timely hemodialysis.

Lipid processing in the retinal pigment epithelium (RPE) is important for maintaining the health and function of the neural retina and the RPE itself. One mode of en mass lipid transport from the RPE is apolipoprotein B-containing lipoproteins (Blps), the assembly of which is regulated by microsomal triglyceride transfer protein (MTP). To gain an initial understanding of how the loss of MTP and, thereby, Blp secretion alters other lipid processing pathways in the RPE, we measured the expression of proteins associated with β-oxidation and lipid droplets in mice lacking MTP expression in the RPE (RPEΔMttp) and age-matched controls. Expression of perilipin 2, a lipid droplet-associated protein, nearly doubled in the RPE of RPEΔMttp, and its localization with neutral lipids also increased. Meanwhile, expression of CPT1A, which mediates the transport of fatty acids into the mitochondria for β-oxidation, was unaffected. These results suggest that the loss of Blp assembly alters intracellular lipid storage patterns. Future studies will examine the effects of the loss of RPE-specific MTP expression and Blp secretion on additional lipid processing pathways.

INTRODUCTION/BACKGROUND:There is an unmet need for tools to quantify dementia risk during its multi-decade preclinical/prodromal phase, given that current biomarkers predict risk over shorter follow-up periods and are specific to Alzheimer's disease. METHODS:Using high-throughput proteomic assays and machine learning techniques in the Atherosclerosis Risk in Communities study (n = 11,277), we developed the Dementia SomaSignal Test (dSST). RESULTS:In addition to outperforming existing plasma biomarkers, the dSST predicted mid-life dementia risk over a 20-year follow-up across two independent cohorts with different ethnic backgrounds (areas under the curve [AUCs]: dSST 0.68-0.70, dSST+age 0.75-0.81). In a separate cohort, the dSST was associated with longitudinal declines across multiple cognitive domains, accelerated brain atrophy, and elevated measures of neuropathology (as evidenced by positron emission tomography and plasma biomarkers). DISCUSSION/CONCLUSIONS:The dSST is a cost-effective, scalable, and minimally invasive protein-based prognostic aid that can quantify risk up to two decades before dementia onset. HIGHLIGHTS/CONCLUSIONS:The Dementia SomaSignal Test (dSST) predicts 20-year dementia risk across two independent cohorts. dSST outperforms existing plasma biomarkers in predicting multi-decade dementia risk. dSST predicts cognitive decline and accelerated brain atrophy in a third cohort. dSST is a prognostic aid that can predict dementia risk over two decades.