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Introduction To assess the within-class variation in kidney outcomes following initiation of sulfonylurea therapy. Research design and methods We used claims data of enrollees in commercial, Medicare Advantage, and traditional Medicare health plans between 2014 and 2021 to emulate a target trial including adults ≥21 years with type 2 diabetes at moderate cardiovascular risk to compare initiation of glimepiride, glipizide, or glyburide on the incidence of chronic kidney disease (CKD) stage 3 or worse, including initiation of kidney replacement therapy (primary outcome); secondary outcomes examined incident CKD stages 3-4, kidney failure (including kidney replacement therapy), all-cause mortality, and hypoglycemia requiring emergency department or hospital care. Random treatment assignment was emulated using propensity scores, estimated using the super learner ensemble method, and incorporated as inverse probability of treatment weights into proportional hazards models. Results The weighted study cohort included 295 092 individuals starting glimepiride (n=134 926), glipizide (n=145 984), and glyburide (n=14 182). One year after treatment initiation, stage 3 or worse CKD developed in 2.1% of patients in the glimepiride group, 2.2% in the glipizide group, and 1.8% in the glyburide group. Glyburide was associated with a lower risk of kidney complications compared with both glimepiride (HR 0.84, 95% CI 0.76 to 0.92) and glipizide (HR 0.81, 95% CI 0.73 to 0.89), despite a higher risk of severe hypoglycemia (HR 1.47, 95% CI 1.27 to 1.71 vs glipizide and HR 1.22, 95% CI 1.05 to 1.42 vs glimepiride). In contrast, the risk of kidney complications was modestly increased with glipizide compared with glimepiride use (HR 1.04, 95% CI 1.00 to 1.07). Conclusions Glyburide was associated with a modestly lower risk of kidney complications, despite a higher risk of hypoglycemia, while glipizide was associated with a higher risk of kidney complications. These hypothesis-generating findings suggest important within-class differences that warrant consideration in clinical decision-making and future research. Despite rigorous prespecified causal inference analytic methods, the risk of unmeasured confounding and bias by indication with the use of observational data remains. Trial registration number NCT05214573 .

BACKGROUND AND OBJECTIVES: Contralateral transfalcine approaches are widely used for interhemispheric/mesial cortical pathologies, even those extending beyond 2 cm lateral from the midline. Nevertheless, the superior limit of contralateral exposure through this approach is not defined. This anatomic study aims to characterize the maximal superior and lateral limits of contralateral exposure using a contralateral transfalcine approach. METHODS: Interhemispheric approaches in the anterior, middle, and posterior-thirds of the interhemispheric fissure were performed in 10 cadaveric head specimens. Rectangular falcine incisions were made and carried maximally superiorly. The contralateral hemisphere was maximally laterally resected from the superior point of visualization down to the level of the corpus callosum. Distances between the most superior point of visualization of the contralateral hemisphere and the superficial point of its cortex and between the midline and the most lateral point of visualization at the level of the corpus callosum were measured and are reported as averages. RESULTS: At the anterior-third of the interhemispheric fissure, the superior point of visualization was 4.8 mm inferior to the cortex. The lateral distance of visualization at the genu of the corpus callosum was 22.9 mm. At the middle-third, the superior point of visualization was 9.7 mm inferior to the cortex. The lateral distance visualized at the body of the corpus callosum was 22.4 mm. At the posterior-third, the superior point visualization of the mesial contralateral hemisphere was 12.6 mm inferior to the cortex. The lateral distance visualized at the splenium of the corpus callosum was 21.3 mm. CONCLUSION: Using the contralateral transfalcine approach, the superior limit of contralateral exposure progressively decreases more posteriorly along the interhemispheric corridor—ranging from 4.8 mm inferior to the cortex in the anterior-third to 12.6 mm inferior to the cortex in the posterior-third. The contralateral optimal view of exposure increases deeper along the interhemispheric corridor.

Abstract Aims Atrial fibrillation (AF) and chronic kidney disease (CKD) often coexist, and both increase the risk of thromboembolism and bleeding. We aim to investigate the impact of CKD in patients with AF undergoing left atrial appendage occlusion (LAAO). Methods and results We conducted a retrospective analysis using the TriNetX database, from April 2015 to February 2023. Patients aged ≥ 18 years with AF undergoing their first LAAO were included. We performed a comparative analysis of patients with CKD/end-stage renal disease (ESRD) vs. those without. Propensity Score Matching (PSM) (1:1) was employed based on baseline characteristics. The primary outcomes were ischaemic stroke/transient ischaemic attack (TIA)/systemic embolism (SE) and major bleeding over a three-year follow-up. We included 10 689 patients, of whom 4140 had CKD/ESRD, and 6549 had no CKD. PSM resulted in 3085 patients in each cohort. CKD/ESRD was significantly associated with a higher risk of major bleeding [HR: 1.179, 95% CI (1.080, 1.288), P < 0.001], acute myocardial infarction, acute heart failure, acute kidney injury, cardiac-related haemodynamic instability (CRHI), hospitalizations, and all-cause mortality (P < 0.001), with no significant difference in ischaemic stroke/TIA/SE [HR: 1.019, 95% CI (0.909, 1.141), P = 0.750]. Conclusion Our study suggests that CKD/ESRD was significantly associated with a higher risk of major bleeding, acute myocardial infarction, acute heart failure, acute kidney injury, CRHI, hospitalizations, and all-cause mortality, with no significant difference in ischaemic stroke/TIA/SE among patients with AF undergoing LAAO.

OBJECTIVE Intramedullary spinal cord tumors (IMSCTs) are typically treated with maximal safe resection, during which neurosurgeons often monitor for neurological injury using muscle motor evoked potential (mMEP) and direct wave (D-wave) neuromonitoring. The predictive value of changes in D-waves for identifying motor outcomes is underexplored. This study evaluated the utility of D-waves for predicting postoperative motor deficits. METHODS Patients who underwent resection of a primary IMSCT with mMEP neuromonitoring from 2003 to 2023 at a tertiary care hospital were identified. Patients who underwent D-wave monitoring in addition to mMEP monitoring were compared to those who underwent mMEP monitoring alone using the Mann-Whitney U-test, chi-square test, and Fisher’s exact test. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of D-wave and mMEP monitoring for identifying new neurological deficits immediately postoperatively and at 1 month, 6 months, and last follow-up were calculated. RESULTS After matching, 125 patients were included (median age 42.0 years; 57.6% male; median follow-up 34.0 months), of whom 88 had both mMEP and D-wave data. The most common pathologies were ependymoma (64.0%) and astrocytoma (17.6%). Patients who did and did not undergo D-wave neuromonitoring had similar preoperative neurological function, primary pathology, tumor grade, and tumor location. D-wave use was associated with increased gross-total resection (88.6% vs 64.9%, p = 0.002) and reduced mortality (5.7% vs 24.3%, p = 0.007), length of stay (5.0 vs 6.0 days, p = 0.033), and 30-day readmission (2.3% vs 13.5%, p = 0.013) and reoperation (1.1% vs 10.8%, p = 0.012). At the 6-month follow-up, D-wave monitoring alone was superior to mMEP and combination monitoring for detecting new motor deficits. D-wave monitoring had peak sensitivity (77.8%) and NPV (96.5%) at 6 months and peak specificity (95.8%) and PPV (76.9%) in the immediate postoperative period. CONCLUSIONS D-wave monitoring was associated with reduced mortality and was more accurate than mMEP monitoring alone or combination monitoring for detecting new postoperative neurological deficits. Further prospective studies are needed to validate these results.

Background and Objectives: Obstructive sleep apnea (OSA) is a heterogeneous disease with diverse clinical presentations and high global prevalence. Obesity is a common comorbidity in OSA, but its relationship with symptom subtypes remains unclear. This study aimed to evaluate the association between OSA symptom subtypes and obesity in a clinical cohort. Methods: This observational study analyzed data from the Santiago Obstructive Sleep Apnea (SantOSA) prospective clinical cohort, including adults with OSA confirmed by home sleep apnea testing. Symptom subtypes were identified using latent class analysis. Associations between obesity and symptom subtypes were evaluated using multivariable regression models adjusted for age, sex, tobacco use, RDI, T90%, TST, hypertension, and diabetes. Statistical significance was set at p < 0.05. Results: A total of 1167 patients were included (943 men). Latent class analysis identified three symptom subtypes: non-sleepy, disturbed sleep, and excessive daytime sleepiness. Among obese patients, 30.7%, 50.0%, and 19.3% were classified into these subtypes, respectively. Obesity prevalence was 50.2%, and compared with non-obese OSA patients, obese patients showed a higher prevalence of severe OSA (46.1% vs. 26.9%), hypertension (54.4% vs. 34.9%), and diabetes (37.2% vs. 19.4%), as well as higher ESS scores and higher RDI and T90% values (all p < 0.01). In adjusted analyses, obesity remained independently associated with the excessive daytime sleepiness subtype after controlling for age, sex, tobacco use, RDI, T90%, TST, and comorbidities. Conclusions: Obesity is highly prevalent in OSA and is associated with specific symptom-defined phenotypes, particularly excessive daytime sleepiness and disturbed sleep. These findings support the relevance of considering symptom profiles alongside traditional severity metrics.

BACKGROUND: Unruptured intracranial aneurysms (UIAs) affect up to 5% of the population, and rupture can lead to devastating subarachnoid hemorrhage. GLP-1RAs (glucagon-like peptide-1 receptor agonists) have anti-inflammatory and vasculoprotective effects, but their impact on aneurysm stability and subarachnoid hemorrhage outcomes is unexplored. This study evaluated whether GLP-1RA use is associated with reduced rupture risk and attenuated severity in the event of a rupture. METHODS: We conducted a retrospective cohort study using the TriNetX US Collaborative Network (2016–2024). Cohort 1 included patients with newly diagnosed, untreated UIA; cohort 2 included those who suffered aneurysm rupture. GLP-1RA exposure was defined as use before or within 3 months of UIA diagnosis (cohort 1) or before rupture (cohort 2). The primary outcome was aneurysm rupture risk in cohort 1. Secondary outcomes include presentation severity, vasospasm, and mortality in cohort 2. Propensity score matching balanced demographics, comorbidities, and medications. RESULTS: After propensity score match, cohort 1 of patients with untreated UIA included 8088 GLP-1RA users and 8088 nonusers. GLP-1RA use was associated with significantly lower probabilities of aneurysm rupture at 1-year (0.65% versus 1.51%; P <0.001), 3-year (1.18% versus 1.85%; P <0.001), and 5-year (1.49% versus 2.10%; P <0.001) timepoints, representing a 48% decrease in hazards (hazard ratio, 0.52 [95% CI, 0.38–0.69]). Among patients who suffered aneurysm rupture (cohort 2, N=298 after propensity score match), prerupture GLP-1RA use (n=149) was associated with lower rates of intraparenchymal hemorrhage (17.4% versus 33.6%; P <0.001), intraventricular hemorrhage (10.1% versus 23.5%; P <0.001), and clinically significant vasospasm (10.7% versus 24.2%; P =0.002), as well as numerically lower rates of 30-day mortality (9.4% versus 14.1%; P =0.21). CONCLUSIONS: For patients with untreated UIA, GLP-1RA use was associated with a 48% reduction in aneurysm rupture risk and, among those who suffered aneurysm rupture, milder clinical and radiographic severity. These findings suggest possible neuroprotective and vascular stabilizing effects of GLP-1RAs for patients with UIA.

ABSTRACT HLA‐B*08:345Q differs from HLA‐B*08:238 by one nucleotide substitution, introducing a premature stop codon in exon 5.