Citations

Importance Gastroparesis is a condition of delayed gastric emptying in the absence of gastric outlet obstruction. Based on a 2018 US administrative health insurance claims database study, prevalence of definite gastroparesis (with documented delayed gastric emptying) was 21.5 per 100 000 persons. Observations Gastroparesis, which is caused by reduced contractions of the distal stomach or abnormal pyloric relaxation, is more common among females than males (ratio, 2:1-4:1) and typically causes nausea, vomiting, early satiety, bloating, and abdominal pain or discomfort. In a large US epidemiological study involving 82.6 million patients, the most common causes of gastroparesis were type 2 diabetes (51.7%), postsurgical effects (15%), medication-induced (11.8%), idiopathic (11.3%), type 1 diabetes (5.7%), and other (4.5%). Other risk factors include neurological disorders (eg, Parkinson disease), hypothyroidism, amyloidosis, connective tissue disorders (eg, scleroderma), and viral infections (eg, norovirus, cytomegalovirus, Epstein-Barr virus, SARS-CoV-2). The 2022 American College of Gastroenterology and the 2025 American Gastroenterological Association (AGA) guidelines define the criterion standard diagnostic test for gastroparesis as gastric emptying scintigraphy with more than 10% gastric retention at 4 hours in patients with symptoms of gastroparesis without mechanical obstruction based on upper endoscopy or abdominal imaging such as computed tomographic (CT) scan. The carbon 13 spirulina stable isotope breath test is also approved for diagnosing gastroparesis by the US Food and Drug Administration. Based on the percentage of gastric retention at 4 hours, gastroparesis is categorized in the 2022 AGA clinical practice update as mild (10%-15%), moderate (16%-35%), or severe (>35%). Treatment includes discontinuation of medications that delay gastric emptying such as opioids, cannabis, anticholinergics, and glucagon-like peptide-1 receptor agonists and for patients with diabetes, optimizing glycemic control. First-line therapies according to the AGA 2022 clinical practice update are a small particle diet (food that is blended or chopped into small pieces) that is low in fat and nondigestible fiber and antiemetics (eg, serotonin 5-hydroxytryptamine 3 [5-HT 3 ] receptor antagonists, histamine H 1 receptor antagonists) for mild gastroparesis; antiemetics and prokinetics (metoclopramide, erythromycin) for moderate gastroparesis, and liquid diet or jejunal enteral feeding for severe gastroparesis. Severe refractory gastroparesis may be treated with gastric peroral endoscopic myotomy (G-POEM), which involves endoscopic-guided incision of the pylorus sphincter muscle, or gastric electrical simulation, in which an implanted neurostimulator sends electrical pulses to the stomach muscle. Conclusions and Relevance Gastroparesis is a condition of delayed gastric emptying without gastric outlet obstruction that is diagnosed based on a gastric emptying study. First-line treatments include a small particle diet and antiemetics and prokinetics. Severe refractory gastroparesis may be treated with procedures such as G-POEM or gastric electrical simulation.

BACKGROUND: Primary aldosteronism (PA) is a common and treatable cause of hypertension, yet data on the durability of medical treatment response beyond the first year are limited. Using the PA medical treatment outcomes framework, we evaluated long-term biochemical and clinical outcomes and factors associated with treatment response. METHODS: We conducted an international, multicenter, observational cohort study across 27 centers on 4 continents. Adults with PA treated with mineralocorticoid receptor antagonists and/or epithelial sodium channel blockers between 2016 and 2021 were included if follow-up data were available at ≥12 months. Biochemical and clinical responses were classified as complete, partial, or absent using PA medical treatment outcomes criteria. Ordinal logistic regression identified determinants of a favorable treatment response. RESULTS: The cohort included 1292 patients (47.5% women, mean age 52 years) with a median follow-up of 34 months (interquartile range, 21–51). At ≥12 months, 58.3% achieved a complete biochemical response, and 20.8% achieved a complete clinical response, with only 5% showing no response. Determinants of a favorable biochemical response included lower aldosterone and lateralization index, and higher renin and potassium levels at baseline. In those taking spironolactone, a higher daily dose was also associated with a favorable biochemical response. Determinants of a favorable clinical response included female sex, lower body mass index, shorter duration of hypertension, and absence of hypertension-mediated organ damage. CONCLUSIONS: Targeted medical therapy for PA can deliver sustained biochemical and clinical benefits. Early disease detection and adequate dose titration are highly actionable determinants of long-term treatment success.

BACKGROUND: White matter hyperintensities (WMH) are widely used to assess cerebral small vessel disease but reflect late-stage injury. Diffusion magnetic resonance imaging (MRI) biomarkers have been proposed to capture earlier small vessel disease-related microstructural damage but their temporal progression relative to WMH and risk factors associated with progression remain unexplored. METHODS: We identified 2077 participants from the population-based cohort study of the Mayo Clinic Study of Aging in Olmsted County, Minnesota (aged 50–101 years) collected between 05/2005 and 09/2024 with longitudinal neuroimaging. Using multioutput nonlinear mixed-effects models in those with at least 2 fluid-attenuated inversion recovery-MRI and diffusion MRI scans, we characterized the temporal progression of WMH and 4 diffusion MRI biomarkers: fractional anisotropy of the genu of the corpus callosum, peak width of skeletonized mean diffusivity, free water, and Arteriolosclerosis-score, which were automatically estimated. Models incorporated participant-specific time shifts, correlations between biomarkers, and effects of risk factors (sex, education, APOE ε4 status, cardiometabolic conditions). RESULTS: The study population had a mean age of 78 years, 47% were women, 28% were APOE ε4 allele carriers, and 80% were cognitively unimpaired, with an average follow-up of 5.2 years (SD, 4.3 years) for fluid-attenuated inversion recovery-MRI and 4.3 years (SD, 3.9 years) for diffusion MRI. Arteriolosclerosis-score, fractional anisotropy of the genu of the corpus callosum, free water, and peak width of skeletonized mean diffusivity became abnormal in 50% of the study population 16, 12, 10, and 7 years before WMH become abnormal (half-width of CI <1 year), respectively. Global markers (Arteriolosclerosis-score, free water, peak width of skeletonized mean diffusivity, and WMH) were correlated, indicating shared substrates of widespread white matter injury. Fractional anisotropy of the genu of the corpus callosum, a vascular risk microstructural injury biomarker, was weakly coupled with WMH and had an earlier but more linear worsening across adulthood. Cardiometabolic conditions predicted earlier worsening of all biomarkers. Female participants showed earlier WMH, fractional anisotropy of the genu of the corpus callosum, and Arteriolosclerosis-score abnormalities, whereas male participants exhibited earlier peak width of skeletonized mean diffusivity and free water abnormalities. CONCLUSIONS: Diffusion MRI biomarkers were abnormal at least a decade before WMH become abnormal in the population, revealing a prolonged phase of early small vessel disease and highlighting their potential for small vessel disease prevention.

BACKGROUND Malignant peripheral nerve sheath tumors (MPNSTs) are malignant tumors that rarely demonstrate heterologous differentiation from angiosarcomatous components. These lesions can be hard to accurately diagnose. OBSERVATIONS A 25-year-old man with neurofibromatosis type 1 and a history of a left lumbar subcutaneous MPNST developed a lung metastasis of only the angiosarcoma component of the MPNST. Prior to H3K27me3 staining of the lung mass, there was no association of the angiosarcoma with the MPNST. Reinterpretation of the lumbar subcutaneous MPNST led to the identification of a previously unrecognized angiosarcomatous portion in that tumor as well. LESSONS This case highlights the importance of using H327me3 staining for accurate diagnosis of biopsies only capturing the heterologous components of MPNST. https://thejns.org/doi/10.3171/CASE251012

PURPOSE Systematic integration of tobacco cessation treatment within cancer centers is needed to improve smoking cessation outcomes among cancer patients and survivors. The current study characterizes baseline rates of tobacco use, use of cessation support, and changes in tobacco use over time among 756 participants diagnosed with cancer and enrolled in 9 ECOG-ACRIN Cancer Research Group trials. MATERIALS AND METHODS Participants completed surveys at trial enrollment and at 3- and 6-month follow-ups. Descriptive statistics were used to characterize patient characteristics and selected items from the Cancer Patient Tobacco Use Questionnaire (C-TUQ). Generalized estimating equations were used to examine the time point effect on tobacco product use. RESULTS At baseline, 11% of participants (n = 740) currently smoked cigarettes. Among participants with data available at all time points (n = 443), prevalence of current smoking was stable over time, with 7.2% of participants (n = 32) reporting current smoking at baseline, 7.0% (n = 31) at the 3-month follow-up assessment, and 6.8% (n = 30) at the 6-month follow-up assessment. Most participants (n = 77/104) who smoked cigarettes within the year prior to their cancer diagnosis continued smoking after their diagnosis, and during (n = 44/72) and following completion (n = 30/46) of their treatment. Sixty-two percent of participants (n = 81) who were currently smoking at baseline reported using smoking cessation medication and 32.1% reported use of nonpharmacologic smoking cessation support since their cancer diagnosis. In longitudinal analyses, the odds of using cigarettes since their cancer diagnosis, 3-month follow-up, and 6-month follow-up was higher than the odds of using cigarettes for the past 30 days at baseline (odds ratio [OR] = 1.97, OR = 1.62, and OR = 1.50, respectively; all p s < .01). CONCLUSION Smoking persists over time among patients with cancer enrolled in therapeutic cancer trials. Findings highlight the importance of increasing access to integrated and longitudinal smoking cessation support.

Abstract Background and Objectives: Neurosurgery is a distinctive realm with a tight and strict margin of error. IRRAflow (IRRA flow ) is a US Food and Drug Administration–approved active cerebrospinal fluid exchange system that can irrigate up to 180 mL/h. The system is tightly secured, safe, and continuously monitors intracranial pressure, using a 9F dual-lumen catheter. Inserting an IRRAflow catheter is more complex than standard external ventricular drains, with a higher risk of cerebrospinal fluid leak or catheter displacement. Particularly, the extracranial component of the IRRAflow catheter insertion is prone to errors and necessitates dedicated training. We aimed to design an affordable, reusable, and easy-to-use 3-dimensional printed model that simulates the extracranial component of the IRRAflow catheter insertion. Methods: The IRRAsert simulator was designed according to recent publications. The skull was printed with polylactic acid, and the Kocher point was drilled. A mold was cast to make the scalp, and Dragon Skin FX-Pro Part A and Part B (Smooth-On, Inc) was used to create a skin flap to cover the drilled Kocher point. Results: The IRRAsert simulator replicated the external parts of the skull starting from the bone outward. It allowed measurements for designating the Kocher point, incising the skin to reveal the drilled Kocher point, tunneling under the scalp, and creating a 5-cm posterior exit incision. The endogenous property of the mixed 1:1 ratio between parts A and B allowed adhesion with the underlying skull due to the attraction between polylactic acid and silicone in a stick-and-peel fashion. This adhesion allowed for dissection of skin from the bone during tunneling for the catheter under the scalp, as well as lifting and rotating the scalp for the next user. The final cost of our simulator was $20 to print the skull permanently, with another $5 to produce the skin that can be rotated 3 times for 3 different users. Conclusion: IRRAsert is the result of multidisciplinary efforts to produce an affordable simulator for the extracranial component of IRRAflow catheter insertion.

ABSTRACT Purpose We studied histologic Ewing sarcoma (ES) tumor response at local control surgery to explore associations between histologic response and chemotherapy practice changes over time and confirm its prognostic significance in the modern era. Methods We reviewed clinical data for 126 patients with ES treated at Mayo Clinic from 1977 to 2022, analyzing the percentage necrosis as a prognostic factor across chemotherapy regimens (including modern interval‐compressed VDC‐IE). Results In the historical cohort, 5‐year event‐free survival (EFS) and overall survival (OS) for patients with ≤5% versus greater than 5% viable tumor were 76% versus 59% ( p = 0.01) and 83% versus 62% ( p = 0.01). Review of 104 specimens by two pathologists identified the percentage remaining viable tumor as more reproducible than the percentage necrosis and/or fibrosis. On multivariable analysis of patients with localized disease ( n = 87), pelvic tumors and greater than 5% viable tumor remained independent risk factors for poor survival (EFS: hazard ratio [HR] 3.1, p < 0.01; OS: HR 2.1, p = 0.048). The modern cohort consisted of 22 patients. No patients with tumor size less than 8 cm at diagnosis and 100% necrosis after surgery had events; four of seven with tumors greater than 8 cm had events despite 100% necrosis. Conclusions Our results validate the historical threshold of greater than 5% viable tumor with older chemotherapy regimens but not with modern interval‐compressed VDC‐IE. In addition, inter‐rater reliability for the percentage viable is more reproducible than the percentage necrosis. Although numbers are small, tumors less than 8 cm with no viable tumor appear to be a favorable subgroup and suggest risk stratification using a combination of tumor size and any viable tumor should be evaluated in ES.

Background: Atezolizumab plus bevacizumab (A + B) and durvalumab plus tremelimumab (D + T) are approved first-line systemic therapy options for advanced hepatocellular carcinoma (HCC), with no head-to-head comparison. In this propensity-matched analysis, we compared the survival of patients with advanced HCC who received either A + B or D + T therapy. Methods: Patients with advanced HCC who received A + B or D + T treatment in the first-line setting were identified using the TriNetX platform, a health research network that provides access to electronic health record data from 112 healthcare organizations. Propensity-score-matched (PSM) analysis was conducted, and the median overall survival (OS) was estimated using the Kaplan–Meier method. Results: We identified 2819 patients with HCC who were treated with A + B or D + T: 2031 patients received A + B and 788 received D + T. Compared to patients in the A + B cohort, those who received D + T were more likely to be older (median age: 68.4 vs. 66.9 years), have lower platelet counts (186.8 vs. 201.3), higher prevalence of hypoalbuminemia with levels < 2.7 g/dL (35.2% vs. 28.4%), higher prevalence of bilirubin levels between 2.0 and 2.9 mg/dL (28.8% vs. 23.8%), and decreased INR with levels between 0.0 and 1.6 (92.1% vs. 86.3%). After PSM, 1536 patients were included in the survival analyses, with all variables adequately matched. There was no significant difference in the median OS between those receiving A + B or D + T [16.3 vs. 22.5 months, hazard ratio (HR) 0.89, 95% confidence interval (CI) 0.76–1.0]. Higher rates of immune-mediated colitis were noted in the D + T group. Conclusions: Similar survival rates were observed among patients with advanced HCC who received A + B and D + T in the first-line setting. Our study suggests that both A + B and D + T are valid treatment options, and that therapy can be tailored based on comorbidities, adverse effects, and patient preferences.