Citations

Abstract Objective The objective of this study is to characterize contemporary surgical management practices and factors influencing surgical decision‐making in the management of Lennox–Gastaut Syndrome (LGS) across pediatric epilepsy centers in the United States. Methods A 45‐item cross‐sectional survey was developed and distributed to Pediatric Epilepsy Research Consortium centers. Domains included institutional demographics, surgical evaluation timing and goals, presurgical workup, procedural utilization and outcomes, and barriers to surgery. Descriptive statistics and thematic analysis were performed. Results Thirty‐two pediatric epilepsy centers participated (38% response), the majority comprising pediatric epileptologists at Level 4 National Association of Epilepsy Centers. Most centers (66%) considered surgery after failure of 3–4 antiseizure medications. Presurgical workup typically included brain magnetic resonance imaging (MRI), long‐term electroencephalography (EEG) monitoring, and neuropsychological assessment, while use of functional imaging, magnetoencephalography, and intracranial EEG varied considerably. All centers offered vagus nerve stimulation and corpus callosotomy; 80%–90% offered resection, hemispherectomy, responsive neurostimulation (RNS); 60%–65% offered deep brain stimulation (DBS) and laser ablation. Among centers offering RNS, half targeted thalamic structures exclusively, and the remainder targeted cortical or combined cortical‐thalamic structures; the centromedian nucleus was the preferred thalamic target for RNS and DBS. Surgical decision‐making was influenced by patient characteristics, procedural considerations, and systemic factors. Seizure frequency, family preference, and multidisciplinary input were highly rated across all interventions. Etiology was critical for resection and hemispherectomy, while financial constraints, insurance barriers, and the need for future neuroimaging impacted neuromodulation selection. Scenario‐specific trends included less frequent consideration of DBS and RNS in children under five years, less use of hemispherectomy in older children, preference for corpus callosotomy in children with predominantly drop seizures, and procedural selection based on MRI findings. Significance Substantial variability exists in the surgical management of LGS. These findings highlight critical opportunities to harmonize practices, reduce disparities, and guide comparative effectiveness research to optimize outcomes. Plain Language Summary Lennox–Gastaut Syndrome (LGS) is a severe form of epilepsy that may require surgery when medications are not effective. This study found that surgical care for LGS varies widely across pediatric epilepsy centers in the United States, including when surgery is recommended, how patients are evaluated, and which procedures are available. Newer approaches such as brain stimulation are being used more often, although access remains inconsistent. These findings highlight the need for clearer treatment pathways to ensure that children with LGS have equitable access to the best possible care.

Abstract Background Lung adenocarcinoma in never-smokers is a major public health burden, especially among East Asian women. Polygenic risk scores (PRSs) are promising for risk stratification but are primarily developed in European-ancestry populations. We aimed to develop and validate single- and multi-ancestry PRSs for East Asian never-smokers to improve lung adenocarcinoma risk prediction. Methods PRSs were developed using genome-wide association study summary statistics from East Asian (8002 cases; 20 782 controls) and European (2058 cases; 5575 controls) populations. Single-ancestry models included a PRS with 25 single nucleotide variants (PRS-25), PRS clumping and thresholding (CT), and LDpred2; multi-ancestry models included LDpred2 plus European PRS-128, PRS-CSx, and clumping and thresholding, super learning, empirical Bayes (CT-SLEB). Performance was evaluated in independent East Asian data from the Female Lung Cancer Consortium and externally validated in the Nanjing Lung Cancer Cohort. We assessed predictive accuracy via area under the curve operating procedure (AUC), with 10-year and (ages 30-80 years) absolute risks estimates. Results The best multi-ancestry PRS, using East Asian and European data via CT-SLEB, outperformed the best East Asian-only (LDpred2; AUC = 0.629, 95% confidence interval [CI] = 0.618 to 0.641), achieving an AUC of 0.640 (95% CI = 0.629 to 0.653) and odds ratio of 1.71 (95% CI = 1.61 to 1.82) per standard deviation increase. Nanjing Lung Cancer Cohort validation confirmed robust performance (AUC = 0.649, 95% CI = 0.623 to 0.676). The top 20% PRS group had a 3.92-fold higher lung adenocarcinoma risk than the bottom 20%. Further, the top 5% PRS group reached a 6.69% lifetime absolute risk. Notably, this group reached the average population 10-year lung adenocarcinoma risk at age 50 years (0.42%) by age 41 years, 9 years earlier. Conclusions Multi-ancestry PRS approaches enhance lung adenocarcinoma risk stratification in East Asian never-smokers, with consistent external validation, suggesting future clinical utility.

Background: Patients with acute ischemic stroke secondary to distal and medium vessel occlusion (AIS-DMVO) and minor strokes present a challenge in determining the most appropriate emergent treatment. Factors leading to early neurological deterioration (END) in this patient population are understudied, but END is known to result in poor functional outcomes. Therefore, we aimed to investigate the factors contributing to END in minor AIS-DMVO cases. Methods: We included patients with AIS-DMVO and minor strokes from 37 sites across North America, Asia, and Europe. Minor stroke was defined as a baseline National Institutes of Health Stroke Scale (NIHSS) score of ⩽5. The primary outcome measure, END, was defined as a shift of ⩾4 points in the NIHSS score at day one after treatment compared to baseline. Univariable and multivariable logistic regression analyses were performed to identify factors associated with END. Results: Among 559 consecutive patients with DMVO and minor strokes, END was reported in 68 patients. In multivariable analysis, mechanical thrombectomy (MT) was independently associated with higher odds of END (adjusted odds ratio [aOR] 2.37, 95% CI 1.12–5.02, p = 0.02), while intravenous thrombolysis (IVT) was associated with lower odds of END (aOR 0.46, 95% CI 0.26–0.81, p = 0.008). However, the association between MT and END was no longer statistically significant in the IPTW-adjusted analysis (OR 1.65, 95% CI 0.69–3.98, p = 0.26). Hypertension and antiplatelet use at baseline were also independently associated with END. Among MT-treated patients, successful and excellent recanalization and first-pass effect were protective against END. Conclusion: MT was associated with END in patients with minor AIS-DMVO, although this association was not significant after IPTW adjustment. IVT was independently associated with reduced risk of END. These findings support careful patient selection and further study in randomized trials.

ABSTRACTWith the global rollout of COVID‐19 vaccines, vaccine safety remains a priority. Emerging concerns have raised the potential risk of a long COVID‐like syndrome following vaccination, informally called long Vax and provisionally termed post‐COVID‐19 vaccination syndrome (PCVS). Our narrative review describes the putative manifestation, pathophysiology, and therapeutic approaches of PCVS based on the available evidence, mostly from case reports/series and observational studies. Our review noted that PCVS typically manifests within days to weeks post‐vaccination, with symptoms lasting months to years. PCVS may present as recognized diagnoses such as postural orthostatic tachycardia syndrome (POTS), small‐fibre neuropathy (SFN), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), or as long‐term sequelae of myocarditis, vaccine‐induced thrombotic thrombocytopaenia (VITT), or immune thrombocytopaenia purpura (ITP). Symptomatically, PCVS overlaps with long COVID, such as fatigue and brain fog, but PCVS may involve more frequent paraesthesia and less dyspnoea. We also review pathophysiological hypotheses of PCVS, focussing on the vaccine‐derived spike protein and related immune responses. Finally, we discuss potential therapies used to treat patients with PCVS or related conditions, primarily documented in case reports/series, which could guide future clinical research. Overall, PCVS remains a poorly understood condition that requires more research to elucidate its prevalence, prognosis, risk factors, and treatments.

Importance Multiparametric magnetic resonance imaging (MRI), with or without prostate biopsy, has become the standard of care for diagnosing clinically significant prostate cancer. Resource capacity limits widespread adoption. Biparametric MRI, which omits the gadolinium contrast sequence, is a shorter and cheaper alternative offering time-saving capacity gains for health systems globally. Objective To assess whether biparametric MRI is noninferior to multiparametric MRI for diagnosis of clinically significant prostate cancer. Design, Setting, and Participants A prospective, multicenter, within-patient, noninferiority trial of biopsy-naive men from 22 centers (12 countries) with clinical suspicion of prostate cancer (elevated prostate-specific antigen [PSA] level and/or abnormal digital rectal examination findings) from April 2022 to September 2023, with the last follow-up conducted on December 3, 2024. Interventions Participants underwent multiparametric MRI, comprising T2-weighted, diffusion-weighted, and dynamic contrast–enhanced (DCE) sequences. Radiologists reported abbreviated biparametric MRI first (T2-weighted and diffusion-weighted), blinded to the DCE sequence. After unblinding, radiologists reported the full multiparametric MRI. Patients underwent a targeted biopsy with or without systematic biopsy if either biparametric MRI or multiparametric MRI was suggestive of clinically significant prostate cancer. Main outcomes and measures The primary outcome was the proportion of men with clinically significant prostate cancer. Secondary outcomes included the proportion of men with clinically insignificant cancer. The noninferiority margin was 5%. Results Of 555 men recruited, 490 were included for primary outcome analysis. Median age was 65 (IQR, 59-70) years and median PSA level was 5.6 (IQR, 4.4-8.0) ng/mL. The proportion of patients with abnormal digital rectal examination findings was 12.7%. Biparametric MRI was noninferior to multiparametric MRI, detecting clinically significant prostate cancer in 143 of 490 men (29.2%), compared with 145 of 490 men (29.6%) (difference, −0.4 [95% CI, −1.2 to 0.4] percentage points; P = .50). Biparametric MRI detected clinically insignificant cancer in 45 of 490 men (9.2%), compared with 47 of 490 men (9.6%) with the use of multiparametric MRI (difference, −0.4 [95% CI, −1.2 to 0.4] percentage points). Central quality control demonstrated that 99% of scans were of adequate diagnostic quality. Conclusion and relevance In men with suspected prostate cancer, provided image quality is adequate, an abbreviated biparametric MRI scan, with or without targeted biopsy, could become the new standard of care for prostate cancer diagnosis. With approximately 4 million prostate MRIs performed globally annually, adopting biparametric MRI could substantially increase scanner throughput and reduce costs worldwide. Trial registration ClinicalTrials.gov Identifier: NCT04571840

Background Sex affects the prevalence of atherosclerotic cardiovascular disease (ASCVD) risk factors but whether sex differences exist in the associations between ASCVD risk burden and cognitive function is unclear. Methods This cross‐sectional study included participants from a population‐based cohort study in China that recruited community‐dwelling adults aged 50 to 75 years without baseline cardiovascular disease and stroke. The 10‐year ASCVD risk burden was quantified with 3 multivariate risk prediction equations. Cognitive domains of memory, attention, visuospatial function, executive function, and processing speed were assessed. Multivariable linear regression models were used to examine the interaction terms between sex and ASCVD risk scores on cognition. Results The final analytical sample included 2180 participants. Mean±SD age was 60.14 (6.38) and 52.1% were women. Men showed significantly higher ASCVD risk burden than women at baseline but the effect of ASCVD risk on 2‐year cognition were amplified in women compared with men, for the domains of memory (eg, β=−0.20 [95% CI, –0.26 to −0.13] versus β=−0.11 [95% CI, –0.16 to −0.07]), executive function (eg, β=−0.23 [95% CI, –0.31 to −0.16] versus β=−0.16 [95% CI, –0.21 to −0.10]), and processing speed (eg, β=−0.33 [95% CI, –0.39 to −0.27] versus β=−0.17 [95% CI, –0.21 to −0.13]). Sex‐stratified analyses showed different neuropsychological profiles at moderate ASCVD risk burden levels, suggesting sex‐specific ASCVD‐risk related cognitive phenotypes. Conclusions Sex differences in cognitive health affected by ASCVD risk underscore the importance of sex‐specific cognitive monitoring during ASCVD risk management and better vascular risk control in women to prevent cognitive decline.

Introduction and Objective: Kidney stone growth and new stone formation are common clinical trial endpoints and are associated with future symptomatic events. To date, a manual review of CT scans has been required to assess stone growth and new stone formation, which is laborious. We validated the performance of a software algorithm that automatically identified, registered, and measured stones over longitudinal CT studies. Methods: We validated the performance of a pretrained machine learning algorithm to classify stone outcomes on longitudinal CT scan images at baseline and at the end of the 2-year follow-up period for 62 participants aged >18 years in the Prevention of Urinary Stones with Hydration (PUSH) randomized controlled trial. Stones were defined as an area of voxels with a minimum linear dimension of 2 mm that was higher in density than the mean plus 4 standard deviations of all nonnegative HU values within the kidney. The four outcomes assessed were: (1) growth of at least one existing stone by ≥2 mm, (2) formation of at least one new ≥2 mm stone, (3) no stone growth or new stone formation, and (4) loss of at least one stone. The accuracy of the algorithm was determined by comparing its outcomes to the gold standard of independent review of the CT images by at least two expert clinicians. Results: The algorithm correctly classified outcomes for 61 paired scans (98.4%). One pair that the algorithm incorrectly classified as stone growth was a new renal artery calcification on end-of-study CT. Conclusions: An automated image analysis method validated for the prospective PUSH trial was highly accurate for determining clinical outcomes of new stone formation, stone growth, stable stone size, and stone loss on longitudinal CT images. This method has the potential to improve the accuracy and efficiency of clinical care and endpoint determination for future clinical trials.

Abstract Rationale High-attenuation area (HAA) is a computed tomography (CT) tool that correlates with lung inflammation and fibrosis. Systemic molecular correlates of HAA (e.g., plasma proteins) may inform biological processes involved in interstitial lung disease. Objectives To identify plasma proteins that associate with HAA and correlate with a higher probability of developing new-onset fibrotic or subpleural interstitial lung abnormalities (ILAs). Methods Plasma protein levels were measured using a semiquantitative aptamer-based platform in MESA (the Multi-Ethnic Study of Atherosclerosis; N = 5,486) and SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study; N = 1,781). Linear regression models identified HAA-associated proteins after adjustment for demographic and socioeconomic factors, CT scanner parameters, study center, and batch. Associations of HAA-related proteins with new-onset fibrotic or subpleural ILAs were examined in MESA participants with ILA assessments on full-lung CT 10 years later. Immunohistochemical staining of select proteins was performed in lung tissue from pulmonary fibrosis cases. Measurements and Main Results There were 75 proteins detected that were significantly associated with HAA in MESA and SPIROMICS. Gene Ontology analysis of these proteins identified processes involved in immune cell chemotaxis and cellular growth and apoptosis. Seven proteins were associated with a higher probability of new-onset fibrotic or subpleural ILAs in MESA, and two of these, junctional adhesion molecule-like protein and GTP cyclohydrolase 1 feedback regulatory protein, stained in areas of fibrosis in lung tissue from patients with interstitial lung disease. Conclusions Plasma proteins associated with more HAA are involved in immune and cellular processes and associate with new-onset fibrotic-subpleural ILA.