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Despite the progress made in understanding the management and outcomes of Moyamoya angiopathy (MMA), several aspects of the disease remain largely unknown. In particular, evidence on the disease history and management of MMA is lacking, mainly due to methodological and selection biases in the available studies and the lack of large, randomized prospective studies. Therefore, the care of MMA patients remains limited to a few expert centers worldwide, and management is often based on local expertise and available resources. Over the years, recommendations or expert opinions have been written to provide guidance to physicians in the treatment of this condition with the goal of reducing the risk of stroke recurrence and long-term disability. However, there is no complete agreement between the available guidelines and recommendations due to differences in the articles addressed, methodologies, expertise, and validated approaches to literature review. This lack of consensus on the management of MMA may confuse clinicians and highlight some important issues and points. The aim of this comprehensive review article is to critically examine three recent guidelines and recommendations on MMA, discussing their differences and similarities and highlighting gaps in MMA care that need to be covered.

AbstractIntroductionThe International Hidradenitis Suppurativa Severity Score System (IHS4) is a validated tool that measures inflammatory lesions, including draining tunnels, in hidradenitis suppurativa (HS).ObjectiveTo evaluate secukinumab efficacy using IHS4 in patients with moderate to severe HS.MethodsData from the SUNSHINE and SUNRISE trials, which assessed subcutaneous secukinumab 300 mg every 2 (SECQ2W) and 4 (SECQ4W) weeks in adults with moderate to severe HS, were analyzed. Assessments included changes from baseline in IHS4 and severity classification up to Week 52; IHS4‐55, IHS4‐75, IHS4‐90 responses (55%, 75% and 90% reduction in IHS4) and concordance between IHS4‐55 and HS clinical response (HiSCR), at Weeks 16 and 52.ResultsIn total, 1084 patients (SECQ2W = 361; SECQ4W = 360; placebo = 363) were analyzed. At Week 16, SECQ2W and SECQ4W demonstrated a numerically higher reduction in IHS4 from baseline versus placebo (adjusted mean [95% CI]: −10.80 [−12.30 to −9.30] and −9.46 [−10.96 to −7.96] vs. −4.92 [−6.43 to −3.41]); the reduction was maintained until Week 52 in both dose regimens. A greater proportion of patients achieved IHS4‐55 with SECQ2W (43.4%) and SECQ4W (39.5%) versus placebo (31.5%) at Week 16, with further improvement at Week 52. Similar trends were observed for IHS4‐75 and IHS4‐90 responses. While no patients had mild disease based on IHS4 (80.7% had severe and 19.3% had moderate HS) at baseline, a greater proportion of patients were categorized as having mild disease at Week 16 in the SECQ2W (25.9%) and SECQ4W (24.0%) groups versus placebo (16.4%); this trend continued up to Week 52 in both dose regimens. Strong concordance (>85%) was observed between IHS4‐55 and HiSCR.ConclusionsBoth SECQ2W and SECQ4W demonstrated efficacy in improving treatment response as measured by IHS4 and reducing disease severity versus placebo at Week 16 and these improvements were sustained through Week 52. These findings support that the dynamic and dichotomous IHS4 can efficiently detect treatment response changes in clinical trial settings.Clinical Trials RegistrationSUNSHINE (NCT03713619); SUNRISE (NCT03713632).

OBJECTIVE Smoking has been shown to negatively impact spinal health, as well as the outcomes of spinal fusion. Published reports show conflicting data regarding whether smoking negatively impacts patient outcomes following lumbar decompression. The objective of this study was to investigate whether smoking affects the outcomes of patients undergoing lumbar decompression for spinal stenosis or herniated disc. METHODS The Quality Outcomes Database was queried for patients with spinal stenosis or lumbar disc herniation who underwent one- or two-level lumbar decompression without fusion. All patients had preoperative and 12-month outcome measures and were divided into groups of nonsmokers and current smokers. Outcomes were compared between the two groups, as well as the percentage of patients reaching the minimal clinically important difference (MCID) threshold for numeric rating scale (NRS) back and leg pain scores and the Oswestry Disability Index (ODI). RESULTS Of 17,271 patients, 14,233 were nonsmokers and 3038 were current smokers. Smokers had worse baseline NRS back and leg pain, ODI, and EQ-5D scores and experienced slightly less improvement in all measures following lumbar decompression (p ≤ 0.009), although changes were largely similar, and a high percentage of patients achieved the MCID thresholds for NRS back pain (78% nonsmokers vs 75% smokers), NRS leg pain (79% nonsmokers vs 73% smokers), and ODI (74% nonsmokers vs 68% smokers). Comparison of propensity-matched cohorts did not identify any difference in outcomes in smokers versus nonsmokers. CONCLUSIONS In patients undergoing lumbar decompression for spinal stenosis or herniated disc, smokers demonstrated slightly less improvement in outcomes compared with nonsmokers, and a high proportion of both groups achieved meaningful improvement with surgery. While smoking cessation should be strongly encouraged in all patients, lumbar decompression procedures for spinal stenosis and herniated disc should not be denied to smokers.

OBJECTIVE Imaging surveillance with serial MRI, or a "wait-and-scan" approach, is a management option for patients with small or medium-sized vestibular schwannomas (VSs). Prior publications have indicated no distinct quality of life advantage to upfront treatment compared with initial wait-and-scan management. However, imaging surveillance is dependent on patient adherence to follow-up. In this study, the authors aimed to identify rates and predictors of patient loss to follow-up during wait-and-scan management of sporadic VS. METHODS A single-center study was conducted including all patients from 2013 to 2018 who had undergone upfront imaging surveillance of sporadic VS. Patient data were retrospectively obtained from the electronic medical record. Outcomes of interest included loss to follow-up unrelated to death and inconsistent adherence to imaging surveillance recommendations. Logistic regression analyses were conducted to evaluate factors associated with loss to follow-up. RESULTS Over a 6-year study period, 270 patients underwent initial imaging surveillance of a sporadic VS. The median tumor diameter was 8.6 mm (range 1–28.9 mm). At the time of censoring, 106 patients (39.3%) had received treatment, 157 (58.1%) had been advised to continue follow-up, and 7 (2.6%) had died of non–VS-related causes. In total, 73 patients (27.0%) were completely lost to follow-up prior to the first treatment or death. Additionally, 60 patients (22.2%) missed at least 1 MRI follow-up or imaging follow-up was delayed by more than 1 year. Multivariable logistic regression identified an out-of-state residence (OR 3.05, 95% CI 1.58–5.89, p = 0.0009) and a smaller tumor size (unit OR per 1-mm increase in size, OR 0.88, 95% CI 0.83–0.95, p = 0.0006) to be associated with loss to follow-up. Patients living ≥ 350 miles from the hospital or with tumors ≤ 3 mm at the time of initial clinic evaluation were most likely to be lost to follow-up. Only a smaller tumor size was associated with an increased risk of inconsistent imaging follow-up (unit OR per 1-mm increase in size, OR 0.92, 95% CI 0.87–0.98, p = 0.007). CONCLUSIONS Patients undergoing imaging surveillance of VS are at risk for loss to follow-up and inconsistent imaging surveillance. Patients with smaller tumors or those living farther away from the treating institution are at highest risk for being lost to follow-up.

Abstract Objectives Social support (SS) and social isolation (SI) are social determinants of health (SDOH) associated with psychiatric outcomes. In electronic health records (EHRs), individual-level SS/SI is typically documented in narrative clinical notes rather than as structured coded data. Natural language processing (NLP) algorithms can automate the otherwise labor-intensive process of extraction of such information. Materials and Methods Psychiatric encounter notes from Mount Sinai Health System (MSHS, n = 300) and Weill Cornell Medicine (WCM, n = 225) were annotated to create a gold-standard corpus. A rule-based system (RBS) involving lexicons and a large language model (LLM) using FLAN-T5-XL were developed to identify mentions of SS and SI and their subcategories (eg, social network, instrumental support, and loneliness). Results For extracting SS/SI, the RBS obtained higher macroaveraged F1-scores than the LLM at both MSHS (0.89 versus 0.65) and WCM (0.85 versus 0.82). For extracting the subcategories, the RBS also outperformed the LLM at both MSHS (0.90 versus 0.62) and WCM (0.82 versus 0.81). Discussion and Conclusion Unexpectedly, the RBS outperformed the LLMs across all metrics. An intensive review demonstrates that this finding is due to the divergent approach taken by the RBS and LLM. The RBS was designed and refined to follow the same specific rules as the gold-standard annotations. Conversely, the LLM was more inclusive with categorization and conformed to common English-language understanding. Both approaches offer advantages, although additional replication studies are warranted.

Precision medicine, which among other aspects includes an individual's genomic data in diagnosis and management, has become the standard‐of‐care for Mendelian cardiovascular disease (CVD). However, early identification and management of asymptomatic patients with potentially lethal and manageable Mendelian CVD through screening, which is the promise of precision health, remains an unsolved challenge. The reduced costs of genomic sequencing have enabled the creation of biobanks containing in‐depth genetic and health information, which have facilitated the understanding of genetic variation, penetrance, and expressivity, moving us closer to the genotype‐first screening of asymptomatic individuals for Mendelian CVD. This approach could transform health care by diagnostic refinement and facilitating prevention or therapeutic interventions. Yet, potential benefits must be weighed against the potential risks, which include evolving variant pathogenicity assertion or identification of variants with low disease penetrance; costly, stressful, and inappropriate diagnostic evaluations; negative psychological impact; disqualification for employment or of competitive sports; and denial of insurance. Furthermore, the natural history of Mendelian CVD is often unpredictable, making identification of those who will benefit from preventive measures a priority. Currently, there is insufficient evidence that population‐based genetic screening for Mendelian CVD can reduce adverse outcomes at a reasonable cost to an extent that outweighs the harms of true‐positive and false‐positive results. Besides technical, clinical, and financial burdens, ethical and legal aspects pose unprecedented challenges. This review highlights key developments in the field of genotype‐first approaches to Mendelian CVD and summarizes challenges with potential solutions that can pave the way for implementing this approach for clinical care.

Abstract In animal models, brain neurodegeneration biomarkers drain into cervical lymph nodes (CLNs), and this drainage function is reduced with ageing. If this occurred in humans, CLNs may provide a readily accessible measure of this aspect of protein clearance. We tested this hypothesis in people using ultrasound-guided fine needle aspiration. We measured amyloid-beta 40 and 42, phosphorylated tau 181 (pTau181), glial fibrillary acidic protein and neurofilament light using single molecule array in CLN aspirates and plasma from: (i) a discovery cohort of 25 autoimmune patients; and (ii) plasma, CLNs and capillary blood in four healthy volunteers, an optimization cohort. Ultrasound-guided fine needle aspiration was well-tolerated by all participants. In both cohorts, all biomarkers were detected in all plasma and CLN samples, other than neurofilament light (8/17 of discovery cohort). CLN biomarker concentrations were significantly greater than plasma concentrations for all except neurofilament light, most markedly for pTau181 (266-fold; P < 0.02), whose CLN concentrations decreased with age (Spearman r = −0.66, P = 0.001). This study presents the first evidence that neurodegenerative biomarkers are detectable in human CLNs. Raised CLN:plasma biomarker ratios suggest their concentration in CLNs may offer a distinct compartment for minimally-invasive measurement of brain clearance and lymphatic drainage, with potential applicability to study of ageing and future clinical trials.