Citations

AbstractObjectiveEpilepsy management employs self‐reported seizure diaries, despite evidence of seizure underreporting. Wearable and implantable seizure detection devices are now becoming more widely available. There are no clear guidelines about what levels of accuracy are sufficient. This study aimed to simulate clinical use cases and identify the necessary level of accuracy for each.MethodsUsing a realistic seizure simulator (CHOCOLATES), a ground truth was produced, which was then sampled to generate signals from simulated seizure detectors of various capabilities. Five use cases were evaluated: (1) randomized clinical trials (RCTs), (2) medication adjustment in clinic, (3) injury prevention, (4) sudden unexpected death in epilepsy (SUDEP) prevention, and (5) treatment of seizure clusters. We considered sensitivity (0%–100%), false alarm rate (FAR; 0–2/day), and device type (external wearable vs. implant) in each scenario.ResultsThe RCT case was efficient for a wide range of wearable parameters, though implantable devices were preferred. Lower accuracy wearables resulted in subtle changes in the distribution of patients enrolled in RCTs, and therefore higher sensitivity and lower FAR values were preferred. In the clinic case, a wide range of sensitivity, FAR, and device type yielded similar results. For injury prevention, SUDEP prevention, and seizure cluster treatment, each scenario required high sensitivity and yet was minimally influenced by FAR.SignificanceThe choice of use case is paramount in determining acceptable accuracy levels for a wearable seizure detection device. We offer simulation results for determining and verifying utility for specific use case and specific wearable parameters.

Purpose: Mehta casting is a potentially curative intervention for early-onset scoliosis (EOS) that typically requires multiple anesthetics. The Food and Drug Administration (FDA) reported that >3 hours of anesthesia under the age of 3 years old may alter brain development; however, no standard exists for the duration of anesthesia during casting. The purpose of this study is to quantify the variability in anesthesia during Mehta casting. We hypothesize that significant institutional variability exists and may be attributed to modifiable factors. Methods: An EOS registry was used to identify patients who underwent at least one Mehta casting procedure. Anesthesia exposure was quantified, and site variability was assessed by patient characteristics, cast placement, procedure type, and equipment used. Results: Our cohort consisted of 208 patients from 5 institutions (age 2.6±1.4 y). There were 1097 Mehta casting procedures, with 5.4±3.6 castings per patient. Of these patients, 106 (51%) were female, with an average age of 2.11±1.29 years old at the time casting was initiated. Patient etiologies included 154 idiopathic (74.0%), 22 syndromic (10.6%), 18 congenital (8.7%), 11 neuromuscular (5.3%), and 3 unknown (1.4%). Anesthesia time was 69±31 minutes and varied significantly between sites (59±14 to 117±46 min; P<0.001). Cumulative anesthesia time for patients under 3 years was 320±197 minutes with 120/161 (74.5%) patients exceeding 3 hours. Anesthesia time was lower after the FDA warning in 2016 compared with pre-2016 (71±30 vs. 66±32, P=0.008). Conclusions: Patients undergoing Mehta casting are at significant risk of exceeding 3 hours of anesthesia, which the FDA has stated may be harmful for children <3 years. Significant site variability indicates that standardization protocols should be developed to encourage best practices and minimize anesthetic times. Level of Evidence: Prognostic Level II.

Context.— Primary thoracic neoplasms are rare in children, whereas nonneoplastic mass lesions or cysts and metastases are more common, and there is a relative paucity of comprehensive histopathologic and molecular data. Objective.— To define the clinicopathologic spectrum of neoplastic and nonneoplastic diseases observed in resected mass lesions in the chest of pediatric patients, and to identify somatic alterations observed in primary neoplasms. Design.— Clinicopathologic features of thoracic mass lesions (n = 385) resected from 373 patients aged ≤21 years in a 25-year period (1993–2018) were included. Primary neoplasms having sufficient material were tested by a laboratory-developed comprehensive genomic profiling assay that assesses tumor mutational burden, microsatellite instability, somatic sequence variants, gene amplifications, fusions, and specific transcript variants. Results.— The most commonly resected space-occupying lesions were nonneoplastic mass lesions and cysts or malformations, resected in 117 (31.4%) and 58 of 373 patients (15.5%) respectively. Metastatic neoplasms were observed in 169 of 373 patients (45.3%; mean age 14.4 years, range 1–21 years); the most common was osteosarcoma (68 of 169; 40.2% of metastases). Primary lung neoplasms occurred in 24 of 373 patients (6.4%; mean age 14.5 years, range 6 months–21 years), and 16 patients had primary extrapulmonary thoracic tumors. Carcinoid tumor was the most common primary lung neoplasm (7 typical, 3 atypical). Molecular testing showed a prevalence of somatic pathogenic or likely pathogenic mutations and copy-number alterations. No fusions or splice variants were identified. Tumors were microsatellite-stable with low tumor mutational burden. Conclusions.— Resected pediatric thoracic mass lesions are more likely to be metastatic lesions, congenital cysts or malformations, or nonneoplastic lesions compared to primary thoracic neoplasms, which are encountered at a low frequency and tend to have relatively simple genetic profiles.

Artificial intelligence, specifically advanced language models such as ChatGPT, have the potential to revolutionize various aspects of healthcare, medical education, and research. In this review, we evaluate the myriad applications of artificial intelligence in diverse healthcare domains. We discuss its potential role in clinical decision-making, exploring how it can assist physicians by providing rapid, data-driven insights for diagnosis and treatment. We review the benefits of artificial intelligence such as ChatGPT in personalized patient care, particularly in geriatric care, medication management, weight loss and nutrition, and physical activity guidance. We further delve into its potential to enhance medical research, through the analysis of large datasets, and the development of novel methodologies. In the realm of medical education, we investigate the utility of artificial intelligence as an information retrieval tool and personalized learning resource for medical students and professionals.

Abstract We evaluated whether spike ripples, the combination of epileptiform spikes and ripples, provide a reliable and improved biomarker for the epileptogenic zone compared with other leading interictal biomarkers in a multicentre, international study. We first validated an automated spike ripple detector on intracranial EEG recordings. We then applied this detector to subjects from four centres who subsequently underwent surgical resection with known 1-year outcomes. We evaluated the spike ripple rate in subjects cured after resection [International League Against Epilepsy Class 1 outcome (ILAE 1)] and those with persistent seizures (ILAE 2–6) across sites and recording types. We also evaluated available interictal biomarkers: spike, spike-gamma, wideband high frequency oscillation (HFO, 80–500 Hz), ripple (80–250 Hz) and fast ripple (250–500 Hz) rates using previously validated automated detectors. The proportion of resected events was computed and compared across subject outcomes and biomarkers. Overall, 109 subjects were included. Most spike ripples were removed in subjects with ILAE 1 outcome (P &lt; 0.001), and this was qualitatively observed across all sites and for depth and subdural electrodes (P &lt; 0.001 and P &lt; 0.001, respectively). Among ILAE 1 subjects, the mean spike ripple rate was higher in the resected volume (0.66/min) than in the non-removed tissue (0.08/min, P &lt; 0.001). A higher proportion of spike ripples were removed in subjects with ILAE 1 outcomes compared with ILAE 2–6 outcomes (P = 0.06). Among ILAE 1 subjects, the proportion of spike ripples removed was higher than the proportion of spikes (P &lt; 0.001), spike-gamma (P &lt; 0.001), wideband HFOs (P &lt; 0.001), ripples (P = 0.009) and fast ripples (P = 0.009) removed. At the individual level, more subjects with ILAE 1 outcomes had the majority of spike ripples removed (79%, 38/48) than spikes (69%, P = 0.12), spike-gamma (69%, P = 0.12), wideband HFOs (63%, P = 0.03), ripples (45%, P = 0.01) or fast ripples (36%, P &lt; 0.001) removed. Thus, in this large, multicentre cohort, when surgical resection was successful, the majority of spike ripples were removed. Furthermore, automatically detected spike ripples localize the epileptogenic tissue better than spikes, spike-gamma, wideband HFOs, ripples and fast ripples.

Background: Endovascular thrombectomy (EVT) and intravenous thrombolysis (IVT) outcomes are unclear in patients with pre-stroke dementia or cognitive impairment. Although these individuals make up ~12% of acute stroke patients, they are often excluded from both stroke trials and routine care. This systematic review and meta-analysis explored reperfusion therapy outcomes in this population. Methods: Using the Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines, this systematic review investigated studies on acute ischemic stroke patients with dementia or cognitive impairment treated with either IVT or EVT. Primary outcome was defined as favorable 90-day outcome (modified Rankin Scale (mRS) score 0-2). Secondary outcomes included 90-day mortality, radiographic intracranial hemorrhage (ICH) and symptomatic ICH (SICH). Results: 9 articles were included from 825 screened. 5 observational studies of IVT use in patients with (n=1078) and without dementia (n=2805) were selected for a meta-analysis. There were no significant differences in favourable 90-day mRS (adjusted OR 0.61, 95% CI 0.24 to 1.59), 90-day mortality (unadjusted OR of 1.19, 95% CI 0.86 to 1.64), ICH (unadjusted OR 1.32, 95% CI 0.79 to 2.19) and SICH (unadjusted OR of 0.94, 95% CI 0.70 to 1.25). EVT in dementia patients in one study found only increased odds of ICH (adjusted OR 1.57 95%CI 1.03 to 2.40). For patients with cognitive impairment, no significant association was found with assessed outcomes in a pooled analysis of 3 IVT studies and one EVT study found poorer 90-day mRS outcomes. Conclusions: This systematic review and meta-analysis suggests no considerable safety concerns for IVT or EVT use in patients with pre-existing dementia or cognitive impairment, compared to those without. Uncertainty remains in the efficacy of these therapies for these individuals. Rigorous, patient-caregiver informed design, and a more nuanced outcome approach are warranted for future studies. REGISTRATION: URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42021240499.

Background and Objectives: It is unclear whether induced hypertension in acute ischemic stroke (AIS) may improve long-term outcomes. We conducted a systematic review and meta-analysis to compare the safety and efficacy of induced hypertension vs standard medical care in patients presenting with acute ischemic stroke within 72 hours of symptom onset. Methods: Two reviewers systematically searched PubMed using the prespecified terms “induced hypertension” or “blood pressure augmentation” plus “ischemic stroke” for clinical trials that reported functional independence (mRS 0-2) at 90 days. The safety outcome was symptomatic intracranial hemorrhage (sICH). Pooled odds ratio (OR) and 95% CI across trials were synthesized using fixed-effect model based on Mantel-Haenszel methods. Forest plots were constructed. Results: Three clinical trials with 270 AIS patients treated with induced hypertension (n=126) or standard medical care (n= 144) were included. Mean age was 66.6 years, 35.2% were women, and the mean initial NIHSS was 7.5. The rate of functional independence at 90 days was higher in patients treated with induced hypertension (70.6%) versus control (54.9%) (OR 1.88; 95% CI 1.13-3.11; p=0.01). sICH did not differ between patients treated with induced hypertension (<1%) versus control (<1%) (OR 1.03; 95% CI 0.14-7.45; p=0.98). Discussion: Among patients presenting with acute ischemic stroke with 72 hours of symptoms onset, induced hypertension resulted in better functional outcome at 90 days than standard medical care and did not increase risk of sICH. Large RCTs to test this observation are ongoing and needed to guide clinical practice.

Objective: To determine whether first pass effect (FPE) after mechanical thrombectomy (MT) for anterior circulation large vessel occlusion acute ischemic stroke (LVO-AIS) is modified by procedural time (PT). Methods: The Stroke Thrombectomy and Aneurysm Registry (STAR), a multi-center international dataset, was retrospectively analyzed for anterior circulation LVO-AIS treated by MT who achieved excellent reperfusion (TICI 2c/3). The primary outcome was good functional outcome as defined by a 90-day modified Rankin Scale (mRS) 0-2. The primary study exposure was first pass success (FPS, 1 pass vs ≥2 passes) and the secondary exposure was PT. Logistic regression models were fit-adjusted and marginal effects used to assess the interaction of PT (≤30 vs >30 minutes) and FPS, adjusting for potential confounders including time from last known well to start of MT. Results: A total of 1,310 patients had excellent reperfusion. These patients were divided into two cohorts based on PT: ≤30 minutes (777 patients, 59.3%) and > 30 minutes (533 patients, 40.7%). Good functional outcome was observed in 658 patients (50.2%). The interaction term between FPS and PT was significant (p=0.018). Individuals with FPS in ≤30 minutes had 11.5% higher adjusted predicted probability of good outcome compared with those who required ≥2 passes (58.2% vs. 46.7%, p=0.001). However, there was no significant difference in the adjusted predicted probability of good outcome based on FPS in individuals with PT >30 minutes (p=0.763). This relationship appeared identical in models with PT treated as a continuous variable. Conclusion: In a large, real-world, multi-national dataset, we find that FPE is importantly modified by PT. The added clinical benefit of FPE is lost in longer procedures (>30 minutes). These data argue for a new metric for MT procedures, namely, FPE 30 , that better represents the ideal of fast, complete reperfusion with a single pass of a thrombectomy device.

Abstract Many germline BRCA2 missense variants of uncertain significance (VUS) remain to be clinically classified as pathogenic or benign. Here we identify 70 missense VUS in the DNA binding domain (DBD) of BRCA2 that partially reduced homologous recombination DNA repair activity of the protein in a homology directed DNA repair cell-based assay. CRISPR/cas9-based knockin of these variants reduced cell survival of haploid cells and conferred increased sensitivity to the PARP inhibitor Olaparib. Sequence alignment analysis found that the variants were highly conserved across species from pufferfish to human. Structural analysis showed that these variants are located predominantly in unstructured regions of the DBD. Case-control association studies showed that the hypomorphic variants conferred moderate risks of breast (OR:2.85; 95%CI:1.43-5.88) and ovarian cancer (OR:3.37; 95%CI:1.30-8.54) that were significantly different from risks associated with known pathogenic and benign variants. Cumulative lifetime risks of breast and ovarian cancer among carriers were estimated at 25% and 4.7%, respectively. Age at diagnosis of breast cancer among hypomorphs carriers was 55 years of age as opposed to 48 years of age for carriers of pathogenic variants. In addition, the combination of functional and other genetic data in an ACMG/AMP-like variant classification model reclassified 39 variants as likely pathogenic. This novel group of low penetrance missense variants further calibrate BRCA2 variant classification methods and have significant implications for the management of variant carriers. Citation Format: Huaizhi (Gilbert) Huang, Chunling Hu, Jie Na, Mohamed Abozaid, Amik Munankarmy, Tara Rao, Carolyn A. Dunn Lumby, Paulo Cilas Morais Lyra, Ronan E. Couch, Benjamin R. Persons, Eric C. Polley, Rachid Karam, Tina Pesaran, Siddhartha Yadav, Alvaro N.A. Monteiro, Nicholas J. Boddicker, Susan M. Domchek, Marcy E. Richardson, Fergus J. Couch. Functional and clinical characterization of hypomorphic missense variants in the BRCA2 cancer predisposition gene [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Breast Cancer Research; 2023 Oct 19-22; San Diego, California. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_1):Abstract nr PR09.

AbstractWe present three cases of acute coronary obstruction postsurgical repair of type A aortic dissection, which were successfully treated with percutaneous coronary intervention. We describe a step‐by‐step approach to performing percutaneous coronary intervention in selective cases of coronary obstruction related to type A aortic dissection.