Citations

ABSTRACTVarious cutaneous adnexal neoplasms have been associated with gene fusions as the main driver of their histogenesis, most of which showed poroid or hidradenomatous differentiation or represented other tumors of sweat glands. Recently, we encountered two cases of primitive basaloid neoplasms of predominantly folliculogenic/pilosebaceous origin, both surprisingly harboring recurrent EWSR1 rearrangements. Both tumors presented in young patients of either sex (1 F; 17 years; 1 M; 37 years) and involved the dermis and subcutaneous tissue of the abdominal wall (case 1) and the buttock (case 2). Histologically, the tumors were composed of primitive, basaloid cells with areas of keratinization (case 1) or foci of sebaceous differentiation (case 2) and stained strongly with keratins, p40 (case 1) or p63 (case 2), while lacking significant CD99 expression in both cases. Case 1 harbored an EWSR1::FLI1 fusion while case 2 harbored an EWSR1::PBX3 fusion. Clinical follow‐up was available for case 2 and showed no evidence of disease at 15 months of follow‐up. Methylation profiling showed case 1 to cluster with cutaneous squamous cell carcinoma, while case 2 was independent but positioned close to salivary gland epithelial‐myoepithelial carcinoma. These findings expand on the histopathologic and molecular genetic features of basaloid tumors with apparent adnexal differentiation and raise awareness to carefully interpret and correlate molecular findings with morphology and immunophenotype to avoid misinterpretation as a mesenchymal neoplasm.

Summary: Epilepsy neuromodulation treatment failure is a significant challenge, with multiple possible causes. The responsive neurostimulation (RNS) system delivers stimulation from a single current source, and the relative flow of the electrical current through each stimulating contact is inversely proportional to the relative impedance of each contact. Current shunting through low-impedance contacts (i.e., intraventricular contacts) can divert therapy away from the intended targets and may be a cause of treatment failure. We present a case of a patient with bitemporal epilepsy and bitemporal encephaloceles, with poor response to bilateral mesial temporal RNS, who completed stereotactic EEG (sEEG) monitoring to investigate the possible causes of treatment failure. The sEEG was safely completed without damaging the RNS device. The sEEG recorded independent bitemporal interictal epileptiform discharges and seizures, which did not arise from sampled encephalocele regions. The sEEG-recorded RNS stimulation artifact was reduced in the left mesial temporal region relative to the right, which suggested potential current shunting through the right-sided contacts. Impedance measurements confirmed several low-impedance contacts from the right lead, with associated intraventricular position on imaging. At last follow up, 161 days after replacement of the right lead, the patient experienced an additional 58% reduction in seizure burden. Effective therapy delivery by single-current-source neurostimulation systems, such as RNS, critically depends on relative electrode impedances. Current shunting through low-impedance contacts is an underappreciated potential cause of treatment failure. Routine impedance assessments and individualized stimulation programs are recommended to avoid unintended current diversion. Concurrent sEEG monitoring and active RNS are feasible and can characterize stimulation effects.

Purpose of review This review aims to synthesize current evidence on the expanding role of glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) beyond glycemic control, particularly in the context of critical illness. With growing recognition of their anti-inflammatory, immunomodulatory, and organ-protective properties, GLP-1RAs show promise in managing complications such as sepsis, acute respiratory distress syndrome (ARDS), acute kidney injury, and multiorgan dysfunction. This review explores their mechanisms across vital systems – including cardiovascular, pulmonary, renal, hepatic, neuropsychiatric, and gut-lung-microbiome axes – highlighting preclinical and clinical data. By consolidating emerging findings, this review aims to inform future translational research and support the integration of GLP-1RAs into critical care strategies. Recent findings Recent evidence highlights GLP-1RAs as promising adjuncts in critical illness due to their multiorgan protective effects. In cardiovascular systems, GLP-1RAs improve endothelial function, reduce ischemia-reperfusion injury, and modulate autonomic tone. In the CNS, they provide neuroprotection by reducing neuroinflammation and pyroptosis. In the lungs, they attenuate ARDS by decreasing cytokine production, enhancing surfactant secretion, and restoring alveolar-capillary integrity. Renally, they reduce acute injury and preserve filtration function. In the gut, GLP-1RAs modulate the microbiome, enhance barrier integrity, and lower systemic inflammation via the gut-lung axis. Additionally, they reduce hepatic inflammation and support pancreatic beta-cell survival, improving insulin sensitivity and metabolic stability in critical care. Summary GLP-1 receptor agonists hold promise as multiorgan protective agents in critical illness, offering benefits beyond glucose control. Their anti-inflammatory, metabolic, and vaso-protective properties may be harnessed to prevent or attenuate organ failure, support recovery, and improve long-term outcomes in critically ill patients. Further clinical trials are warranted to define their safety, efficacy, and optimal application across ICU populations.

INTRODUCTION Gastroesophageal reflux is common in respiratory disease, but the interplay between gastrointestinal mechanisms that expose individuals to reflux and potentially aspiration, and lung mechanics and function remain incompletely understood. Our aim was to investigate this in patients with chronic obstructive pulmonary disease (COPD) and non-idiopathic pulmonary fibrosis (IPF) interstitial lung disease (non-IPF ILD), and compare with our published findings in IPF. METHODS Fifty-seven patients with COPD (aged: 34–75 years) and 64 with non-IPF ILD (22–75 years) who underwent high-resolution impedance manometry and 24-hour pH impedance together with pulmonary function assessment were compared with 35 IPF patients (51–84 years). RESULTS COPD patients were less likely to exhibit ineffective esophageal motility (IEM) and/or absent contractility ( P = 0.009; P = 0.028), and tended to exhibit esophagogastric junction outflow obstruction (EGJOO) and/or hypercontractility ( P = 0.09, P = 0.14) than IPF and non-IPF ILD patients. Notably, integrated relaxation pressure correlated with esophageal length index (ELI) ( P = 0.048) and inspiratory LESP ( P = 0.003), with latter 2 correlating with each other ( P < 0.001). EGJOO patients tended to have fewer proximal reflux events and reduced pulmonary function, with the latter inversely correlating with ELI ( P < 0.05). Non-IPF ILD patients were less likely to exhibit EGJOO than COPD patients ( P = 0.27), and less likely to exhibit IEM ( P = 0.07) than IPF patients. However, those with IEM or EGJOO exhibited greater proportions of reflux events reaching the proximal esophagus than those with normal motility ( P < 0.03), which in contrast to IPF, seemed not to associate with worse pulmonary function. DISCUSSION Associations between esophageal motility, and lung mechanics and function, and consequently reflux, are very disease-specific.

BACKGROUND AND OBJECTIVES: This study aimed to investigate the clinical presentation, natural history, and long-term outcome of sporadic cerebral cavernous malformations (CCMs) based on initial Zabramski classification. METHODS: A prospective cohort of 285 patients with sporadic CCMs was analyzed. Patients were classified into Zabramski Types I-IV based on diagnostic MRI. Clinical presentation, lesion size, location, and developmental venous anomaly presence were recorded. Prospective symptomatic hemorrhage (SH) (censored at first hemorrhage, surgery, or last follow-up) and functional outcomes were assessed using Kaplan-Meier and Cox regression analyses. Functional outcomes were measured with the modified Rankin Scale (mRS) at baseline, annually, and at the last follow-up. RESULTS: The cohort included 58.9% women and 41.1% men, with a mean age at diagnosis of 44.5 years. Zabramski Types I-IV (n = 113, 125, 40, and 7, respectively) differed significantly in clinical presentation ( P < .001). Type I lesions were symptomatic in 97.3%, Types II and III in 34.4% and 22.5%, respectively, while all Type IV lesions were asymptomatic. Type I lesions had the highest annual hemorrhage rate (13.9% per year) and a 5-year cumulative risk of 50.6%. Types II and III had lower rates (2.9% and 1.8%), whereas no hemorrhages occurred in Type IV lesions. At baseline, 70.8% of Type I patients had mRS ≥2, which decreased to 35.4% at the last follow-up. Type III lesions had favorable outcomes, with 7.5% of patients having mRS ≥2 at the last follow-up. Type IV lesions remained asymptomatic throughout. Severe SH significantly increased the odds of poor outcomes (mRS ≥3; P < .001), whereas Zabramski type was not predictive of outcomes after adjustment. CONCLUSION: Zabramski classification aids in stratifying hemorrhage risk and guiding management in CCMs. Severe SH is a critical determinant of functional outcomes, underscoring the need for comprehensive risk assessments and individualized patient care strategies.