National 22-year epilepsy surgery landscape shows increasing open and minimally invasive pediatric epilepsy surgery.

OBJECTIVES: A surgical "treatment gap" in pediatric epilepsy persists despite the demonstrated safety and effectiveness of surgery. For this reason, the national surgical landscape should be investigated such that an updated assessment may more appropriately guide health care efforts. METHODS: In our retrospective cross-sectional observational study, the National Inpatient Sample (NIS) database was queried for individuals 0 to <18 years of age who had an International Classification of Diseases (ICD) code for drug-resistant epilepsy (DRE). This cohort was then split into a medical group and a surgical group. The former was defined by ICD codes for -DRE without an accompanying surgical code, and the latter was defined by DRE and one of the following epilepsy surgeries: any open surgery; laser interstitial thermal therapy (LITT); vagus nerve stimulation; or responsive neurostimulation (RNS) from 1998 to 2020. Demographic variables of age, gender, race, insurance type, hospital charge, and hospital characteristics were analyzed between surgical options. Continuous variables were analyzed with weight-adjusted quantile regression analysis, and categorical variables were analyzed by weight-adjusted counts with percentages and compared with weight-adjusted chi-square test results. RESULTS: These data indicate an increase in epilepsy surgeries over a 22-year period, primarily due to a statistically significant increase in open surgery and a non-significant increase in minimally invasive techniques, such as LITT and RNS. There are significant differences in age, race, gender, insurance type, median household income, Elixhauser index, hospital setting, and size between the medical and surgical groups, as well as the procedure performed. SIGNIFICANCE: An increase in open surgery and minimally invasive surgeries (LITT and RNS) account for the overall rise in pediatric epilepsy surgery over the last 22 years. A positive inflection point in open surgery is seen in 2005. Socioeconomic disparities exist between medical and surgical groups. Patient and hospital sociodemographics show significant differences between the procedure performed. Further efforts are required to close the surgical "treatment gap."

Preprocedural Computed Tomography Planning for Surgical Aortic Valve Replacement.

BACKGROUND: Selection of transcatheter valve size using preprocedural computed tomography (CT) is standardized and well established. However, valve sizing for surgical aortic valve replacement (SAVR) is currently performed intraoperatively by using sizers, which may result in variation among operators and risk for prosthesis-patient mismatch. This study evaluated the usefulness of CT annulus measurement for SAVR valve sizing. METHODS: This study included patients who underwent SAVR using Inspiris or Magna Ease and received preoperative electrocardiogram-gated CT imaging. Starting from June 2022, study investigators applied a CT sizing algorithm using CT-derived annulus size to guide minimum SAVR label size. The final decision of valve selection was left to the operating surgeon during SAVR. The study compared the appropriateness of valve selection (comparing implanted size with CT-predicted size) and prosthesis-patient mismatch rates without aortic root enlargement between 2 cohorts: 102 cases since June 2022 (CT sizing cohort) and 180 cases from 2020 to 2021 (conventional sizing cohort). RESULTS: Implanted size smaller than CT predicted size and severe prosthesis-patient mismatch were significantly lower by CT sizing than by conventional sizing (12% vs 31% [P = .001] and 0% vs 6% [P = .039], respectively). Interoperator variability was a factor associated with implanted size smaller than CT predicted with conventional sizing, whereas it became nonsignificant with CT sizing. CONCLUSIONS: Applying CT sizing to SAVR led to improved valve size selection, less prosthesis-patient mismatch, and less interoperator variability. CT sizing for SAVR could also be used to predict prosthesis-patient mismatch before SAVR and identify patients who need aortic root enlargement.

Asymptomatic trigger of adrenal crisis in a patient with Sheehan syndrome: importance of timely recognition and intervention.

Our patient is a female in her 70s who initially presented following an episode of bowel and bladder incontinence, as well as unresponsiveness. Her family denied any preceding illness or sick symptoms. During her workup, it was noted that she was wearing a medical bracelet, which listed prednisone as one of her daily medications, raising concern for an acute adrenal crisis (AC). Ultimately, our patient's condition improved with high-dose intravenous steroids before being tapered to her home regimen. Current literature highlights the pathophysiological complexity of an AC but fails to identify clear risk factors that trigger such events, especially in asymptomatic patients. Accordingly, our case highlights this gap, arguing the importance of appropriate patient education and timely intervention for such clinically ambiguous yet life-threatening presentations.

Clinical Trial-Ready Patient Cohorts for Multiple System Atrophy: Coupling Biospecimen and iPSC Banking to Longitudinal Deep-Phenotyping.

Multiple system atrophy (MSA) is a fatal neurodegenerative disease of unknown etiology characterized by widespread aggregation of the protein alpha-synuclein in neurons and glia. Its orphan status, biological relationship to Parkinson's disease (PD), and rapid progression have sparked interest in drug development. One significant obstacle to therapeutics is disease heterogeneity. Here, we share our process of developing a clinical trial-ready cohort of MSA patients (69 patients in 2 years) within an outpatient clinical setting, and recruiting 20 of these patients into a longitudinal "n-of-few" clinical trial paradigm. First, we deeply phenotype our patients with clinical scales (UMSARS, BARS, MoCA, NMSS, and UPSIT) and tests designed to establish early differential diagnosis (including volumetric MRI, FDG-PET, MIBG scan, polysomnography, genetic testing, autonomic function tests, skin biopsy) or disease activity (PBR06-TSPO). Second, we longitudinally collect biospecimens (blood, CSF, stool) and clinical, biometric, and imaging data to generate antecedent disease-progression scores. Third, in our Mass General Brigham SCiN study (stem cells in neurodegeneration), we generate induced pluripotent stem cell (iPSC) models from our patients, matched to biospecimens, including postmortem brain. We present 38 iPSC lines derived from MSA patients and relevant disease controls (spinocerebellar ataxia and PD, including alpha-synuclein triplication cases), 22 matched to whole-genome sequenced postmortem brain. iPSC models may facilitate matching patients to appropriate therapies, particularly in heterogeneous diseases for which patient-specific biology may elude animal models. We anticipate that deeply phenotyped and genotyped patient cohorts matched to cellular models will increase the likelihood of success in clinical trials for MSA.

Cardiac-sparing radiotherapy for locally advanced non-small cell lung cancer.

BACKGROUND: We have carried out a study to determine the scope for reducing heart doses in photon beam radiotherapy of locally advanced non-small cell lung cancer (LA-NSCLC). MATERIALS AND METHODS: Baseline VMAT plans were created for 20 LA-NSCLC patients following the IDEAL-CRT isotoxic protocol, and were re-optimized after adding an objective limiting heart mean dose (MDHeart). Reductions in MDHeart achievable without breaching limits on target coverage or normal tissue irradiation were determined. The process was repeated for objectives limiting the heart volume receiving ≥ 50 Gy (VHeart-50-Gy) and left atrial wall volume receiving ≥ 63 Gy (VLAwall-63-Gy). RESULTS: Following re-optimization, mean MDHeart, VHeart-50-Gy and VLAwall-63-Gy values fell by 4.8 Gy and 2.2% and 2.4% absolute respectively. On the basis of associations observed between survival and cardiac irradiation in an independent dataset, the purposefully-achieved reduction in MDHeart is expected to lead to the largest improvement in overall survival. It also led to useful knock-on reductions in many measures of cardiac irradiation including VHeart-50-Gy and VLAwall-63-Gy, providing some insurance against survival being more strongly related to these measures than to MDHeart. The predicted hazard ratio (HR) for death corresponding to the purposefully-achieved mean reduction in MDHeart was 0.806, according to which a randomized trial would require 1140 patients to test improved survival with 0.05 significance and 80% power. In patients whose baseline MDHeart values exceeded the median value in a published series, the average MDHeart reduction was particularly large, 8.8 Gy. The corresponding predicted HR is potentially testable in trials recruiting 359 patients enriched for greater MDHeart values. CONCLUSIONS: Cardiac irradiation in RT of LA-NSCLC can be reduced substantially. Of the measures studied, reduction of MDHeart led to the greatest predicted increase in survival, and to useful knock-on reductions in other cardiac irradiation measures reported to be associated with survival. Potential improvements in survival can be trialled more efficiently in a population enriched for patients with greater baseline MDHeart levels, for whom larger reductions in heart doses can be achieved.