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BACKGROUND: Williams syndrome (WS) is a genetic condition associated with neurodevelopmental disorders including intellectual disability and executive functioning (EF) deficits. Although neuroimaging methods may clarify the neural basis of these impairments, participant burden and frequent exclusion of individuals with lower cognitive abilities prevent generalizable studies in WS. Functional near-infrared spectroscopy (fNIRS), a low-burden neuroimaging method, may offer a more accessible way to study the neural correlates of EF in WS. This study examined the feasibility of measuring prefrontal cortex (PFC) activation using fNIRS during a behavioural inhibition task in individuals with WS compared to neural activation and behavioural performance in age-matched typically developing controls. METHODS: Thirty-seven individuals with WS and 21 healthy volunteers, aged 3-85, completed resting state and Go/No-Go (GNG) task fNIRS recordings. Feasibility was evaluated through behavioural validity and fNIRS data quality. Prefrontal activation was assessed using oxygenated haemoglobin (HbO) changes during the task. Behavioural performance was measured by commission error rate. One-sample t tests evaluated task-related activation during the 'Go' and 'No-Go' conditions, and Spearman correlations tested associations between activation and behavioural performance. RESULTS: Eighty-nine percent of individuals with WS completed the resting state portion of the assessment with valid behavioural data, suggesting strong tolerance of the fNIRS platform. Sixty-five percent completed the GNG task without behavioural concerns. Preprocessing was successful in all valid cases, with minimal signal loss. Individuals with WS made significantly more commission errors than healthy volunteers, suggesting impaired behavioural inhibition. fNIRS analyses revealed distinct patterns of PFC activation during inhibition in WS, with significant activation at multiple channels not observed in healthy volunteers. However, activation was not significantly related to behavioural performance across groups. CONCLUSIONS: These results support the feasibility of fNIRS in individuals with WS, including those with varying levels of intellectual disability. The GNG task captured inhibition deficits in WS and elicited differing prefrontal activation, though the rate of behavioural exclusions suggests the task may require adaptation. Overall, fNIRS shows promise as a tolerable and accessible neuroimaging tool in neurodevelopmental populations typically excluded from neuroscientific research.

A 23-year-old female was found unresponsive after 3 weeks of illness and presented to urgent care a day before her death with a complaint of nausea, vomiting, and abdominal cramping. She had a history of obesity and polyendocrine metabolic ovarian syndrome (PMOS). At autopsy, nonhemorrhagic acute pancreatitis and steatohepatitis were identified. During the exam, areas of fat congealing within pooled blood were noted. Tubes of blood drawn during the examination became grossly lipemic at room temperature. Toxicological and laboratory testing showed a triglyceride level of 5440 mg/dL, HDL 9 mg/dL, total cholesterol 740 mg/dL, 0.06% wt/vol acetone in peripheral blood, and therapeutic levels of fluconazole. Postmortem genetic testing revealed an LDLR mutation associated with familial hypercholesterolemia. Obesity, high cholesterol, and PMOS are all disturbances known to perpetuate further metabolic issues, including severe hypertriglyceridemia (HTG). Most causes of severe HTG are the result of multigenic or polygenic mutations and are further exacerbated by exposure to nongenetic secondary factors. The combination of the patient's familial dyslipidemia, PMOS, and obesity created a compounding effect of metabolic dysfunction leading to her sudden death. Overall, this case highlights the need for close follow-up in patients with these conditions and better education on the possible consequences of their interplay, which can prove lethal.

BACKGROUND: Many district general hospitals (DGHs) in the UK do not have resident on-call cardiology registrars overnight; in these situations, it is becoming more common for cardiac outreach practitioners (COPs) to provide specialist input for patients presenting with suspected cardiac events. The aim of this study is to evaluate the exact diagnostic concordance between the initial working diagnoses made independently by COPs and subsequent final discharge diagnoses in patients assessed out of hours and to assess the accuracy of identifying acute coronary syndrome (ACS). METHODS: A retrospective, single-centre service evaluation was conducted at a UK DGH between January and June 2025. Initial COP diagnoses were compared with final discharge diagnoses, with exact diagnostic concordance reported as percentage agreement. Diagnostic performance for identifying ACS was assessed using sensitivity, specificity, positive predictive value, negative predictive value, overall accuracy and Cohen's kappa (κ). RESULTS: A total of 779 cases were screened, with 233 patients meeting inclusion criteria following staged exclusions. The overall exact diagnostic concordance was 92.7% (216/233). The 216 exact concordant cases comprised 125 concordant cardiac diagnoses and 91 concordant non-cardiac diagnoses. 17 cases had discordant diagnoses, but none were associated with delayed escalation, investigation or management. COP sensitivity for identifying ACS was 96.0%, specificity was 92.4%, positive predictive value was 85.9%, negative predictive value was 98.0% and overall classification accuracy was 93.6%. Cohen's κ was 0.858 (95% CI 0.789 to 0.927), indicating almost-perfect agreement. CONCLUSION: COPs demonstrated a high level of exact diagnostic concordance when compared with discharge diagnosis made by consultant cardiologist. This new evidence suggests that COP-led assessments are reliable when working within a clinical pathway.

BACKGROUND: Dual antiplatelet therapy is indicated in the management of non-ST-elevation acute coronary syndrome (NSTE-ACS) and can be administered before coronary angiography (pre-treatment) or after coronary anatomy is known. Based on clinical trials with rapid access to inpatient coronary angiography, clinical guidelines recommend invasive assessment prior to commencing a second antiplatelet. We aimed to evaluate the impact of a change in clinical policy from routine P2Y12 inhibitor pre-treatment to no routine pre-treatment on in-hospital outcomes in a UK healthcare context. METHODS: A retrospective observational study of hospitalised NSTE-ACS patients with a planned invasive strategy at a tertiary cardiac centre in Northeast England was conducted. Two cohorts were identified: routine pre-treatment (1 January 2021 to 31 December 2021) and no routine pre-treatment (1 July 2022 to 30 June 2023). Primary endpoints were in-hospital ST-elevation myocardial infarction (STEMI) and actionable bleeding events, reported as propensity score-adjusted ORs (ORs) and 95% CIs. RESULTS: Of 2506 NSTE-ACS cases, 1219 presented before and 1287 after the policy change, which was adhered to in most cases (84.2%). Median time from admission to angiography was 3.6 days (IQR 1.9, 5.8). In comparison to a routine pre-treatment strategy, a no routine pre-treatment strategy was associated with greater risk of in-hospital STEMI (1.7% vs 0.4%, adjusted OR 4.40, 95% CI 1.78 to 13.3), but lower risk of actionable bleeding events (0.2% vs 0.9%, adjusted OR 0.18, 95% CI 0.03 to 0.70). There was evidence of pre-treatment effect modification by procedural waiting time on in-hospital STEMI incidence (p for interaction=0.026). CONCLUSION: We observed a greater risk of in-hospital STEMI but lower rates of bleeding following the change from a routine pre-treatment to a no routine pre-treatment strategy. UK waiting times for in-patient coronary angiography are typically considerably longer than the trials on which guidance is based, which may impact the risk/benefit balance in clinical practice.

Task-specific tremor is a clinically heterogeneous phenotype that remains difficult to accommodate within current tremor classification. Although defined by its occurrence during a specific motor task, the boundaries with position-specific and isometric tremors remain uncertain. Additional classificatory complexity arises when a task-specific tremor phenotype is accompanied by neurological signs that remain subtle, questionable, or uncertain, such as possible dystonic posturing, rest tremor, mild bradykinesia, or response to alleviating maneuvers, and do not clearly support classification as a combined tremor syndrome, but raise the question of whether additional descriptive categories are needed. However, as in other movement disorders, caution is warranted against using additive labels to formalize uncertainty (the "plus" suffix) without biological, prognostic, or therapeutic validation. Available data suggest that the same task-specific tremor phenotype may reflect different underlying pathophysiological processes, with variable overlap with essential tremor, dystonia, and Parkinson's disease. This article addresses three unresolved issues in task-specific tremor: the interpretation of subtle neurological signs without prematurely introducing a "task-specific tremor-plus" category; the blurred boundary between task-specific, position-specific, and isometric tremors; and the relationship between heterogeneous clinical phenotypes and the available pathophysiological evidence. Rather than introducing new descriptive labels, we propose that these phenotypes should be approached through precise phenomenological description, quantitative characterization, and longitudinal follow-up, with the aim of determining whether they represent stable clinical variants, evolving combined tremor syndromes, or different expressions within a broader tremor spectrum.