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Background Randomized trials have shown equivocal outcomes between a direct aspiration as first-pass technique (ADAPT) and stent retriever (SR) stroke thrombectomy, yet whether specific patient subgroups benefit differentially from one technique over the other remains unknown. Methods In this retrospective multicenter cohort study, patients with large vessel occlusion were included, and those who underwent ADAPT versus SR first-pass thrombectomy (either as standalone or combined with aspiration) were compared. The primary outcome was a composite of first-pass effect (FPE, modified Thrombolysis In Cerebral Infarction (mTICI) 2c or better with one attempt) with no symptomatic intracranial hemorrhage (sICH). A causal forest model was used to estimate the conditional average treatment effect (CATE) for each patient, with larger CATEs indicating that ADAPT is expected to be more advantageous. Patients were stratified by CATEs, and outcomes were compared between treatment groups. Results Among 6700 included patients, ADAPT (n=3695, 55%) was associated with a higher rate of FPE with no sICH (39.9% vs 26.9%; adjusted OR (aOR) 2.07, 95% CI 1.77 to 2.41, P<0.001). The causal forest identified significant treatment effect heterogeneity (interaction P<0.001), where ADAPT was more advantageous in more recent years and among patients with M1 occlusions presenting in earlier time windows. Low-CATE patients showed no statistically significant difference between techniques (aOR 0.91, 95% CI 0.57 to 1.45, P=0.70), while medium- and high-CATE patients demonstrated progressively larger ADAPT advantages (aOR 2.06, 95% CI 1.67 to 2.55, and aOR 2.99, 95% CI 2.24 to 3.98, respectively, both P<0.001). Conclusions ADAPT may be superior to SR for a majority of patients, particularly in recent years, and among patients with M1 occlusions presenting in earlier time windows.

Heart rate variability (HRV) is a widely utilized approach for investigating cardiovascular health and human performance. Methodological approaches, analyses, and interpretations of HRV can vary extensively, and scientific debates on HRV reliability and utility remain. These debates have been amplified in recent years by the rapid growth and ubiquity of wearable devices, and their incorporation into scientific research studies. The present guidelines paper takes an evidence-based approach to propose more consistent and rigorous measurement and interpretation of HRV within human cardiovascular research and application. First, HRV has some utility as a cardiovascular risk stratification tool, but is not appropriate to employ as a specific marker of cardiac sympathetic outflow or sympathovagal balance. While time-domain and spectral analysis can more accurately reflect respiratory modulation of cardiac vagal (parasympathetic) activity, caution is necessary to avoid overinterpretation, particularly with respect to the concept of “vagal tone”. Numerous experimental, demographic, and environmental factors influence HRV assessment, interpretation, and reliability. Specifically, it is critical to account for non-modifiable (age, sex, race/ethnicity, etc.) and modifiable (i.e., exercise, physical fitness, etc.) factors within participant samples. Furthermore, technical approaches such as the HRV input signal (e.g., electrocardiography vs. photoplethysmography), length of recording, location of recordings (i.e., laboratory vs. field), respiratory rate and depth, and analytical approaches (i.e., time vs. frequency domain) can all impact rigor, reliability, and study interpretations. Finally, with respect to the rapid advancements of HRV assessment using wearable technology, investigators should interpret and contextualize findings within the limitations outlined in this guideline review.

An accurate differential diagnosis for diffuse lung disease can be confidently established by using a systematic approach to identify the predominant radiographic pattern, determine the distribution of disease, and assess for architectural or volume change.

Importance Limited granular data exist on breast cancer in transgender, nonbinary, and/or gender-diverse (TGD) individuals. Objective To describe patient demographic and tumor clinicopathological variables, clinically relevant risk factors, method of breast cancer detection, treatment characteristics, and locoregional outcomes and to estimate a 5-year breast cancer–specific survival (BCSS). Design, Setting, and Participants This cohort study obtained data on patients treated from 1990 to 2023 from 22 US academic medical centers using institutional databases, electronic medical records, and tumor registries. Included participants were TGD individuals 18 years or older with stage 0 to IV breast cancer. A comparative breast cancer cohort was selected from the 2016 to 2021 Surveillance, Epidemiology, and End Results Program (SEER) breast cancer dataset. Data were analyzed from January to October 2025. Exposure Breast cancer. Main Outcomes and Measures Estimated 5-year BCSS and locoregional recurrence rates. Wilcoxon rank sum and χ 2 tests were used to compare continuous and categorical variables. Kaplan-Meier analysis was used to estimate 5-year BCSS. Results A total of 112 TGD persons (median [IQR] age at diagnosis, 42.5 [36.5-51.0] years; 104 individuals [92.9%] were assigned female at birth) with breast cancer and 1 with bilateral disease were included in the analysis. Forty-three patients (38.4%) used gender-affirming hormone therapy before diagnosis. Among the entire cohort, 58 patients (51.8%) detected their own breast cancer, 68 (60.7%) had a familial breast cancer history, and 16 (14.3%) had a pathogenic germline variant. Tumors were predominantly hormone receptor positive (96 [85.7%]) and early stage (29 [25.7%] ductal carcinoma in situ [DCIS]; 51 [45.1%] stage I). The TGD cohort, compared with patients with breast cancer in the SEER dataset (N = 480 915), was younger (median [IQR] age, 42.5 [36.5-51.0] years vs 62.0 [52.0-72.0] years), had a higher proportion of persons assigned male at birth (8 [7.1%] vs 3522 [0.7%]), more often had progesterone receptor–positive disease (89 [79.5%] vs 335 491 [69.8%]), and presented with earlier-stage disease (eg, DCIS: 29 [25.9%] vs 79 604 [16.6%]). With a median (IQR) follow-up time for the TGD cohort of 38 (24-74) months, 5-year BCSS was favorable at 96.2% (95% CI, 85.3%-99.0%). Conclusions and Relevance This cohort study of TGD patients with breast cancer found that this population was young and often detected their own tumors via self-examination, suggesting opportunities to improve early detection through screening for individuals at elevated risk. Although short-term BCSS appeared favorable, prospective research is essential to define evidence-based guidelines and elucidate long-term outcomes.

<p class="MsoNormal"> <span lang="EN-US">The Semantic Web has the ultimate goal of making a machine understand Internet data. To enable the encoding of semantics with the data, well-known technologies are used such as RDF (Resource Description Framework) and OWL (Web Ontology Language). These technologies formally represent the meaning involved in information. For example, ontology can describe concepts, relationships between things, and categories of things. These embedded semantics offer significant advantages such as reasoning over data and dealing with heterogeneous data sources.<o:p></o:p></span> </p>

ABSTRACT Background Bile acid (BA) malabsorption (BAM) is a common cause of chronic diarrhoea and may occur in some patients due to abnormalities of the gut microbiota. Effects of probiotics on faecal secretory BAs, particularly the primary BA, chenodeoxycholic acid, are unclear. Aim/Methods We conducted a randomized, double‐blind, placebo‐controlled trial of the De Simone formulation 8‐strain probiotic in 24 patients previously diagnosed with BAM. Patients were randomized to 3 weeks of the probiotic (900 billion bacteria) or placebo (maltose), both administered three times daily. Symptoms, serum 7 α C4, faecal primary BAs, intestinal permeability by 13 C‐mannitol‐lactulose test (0.1 and 1 g of the sugars respectively) over 24 h, faecal short chain fatty acids (SCFA), microbiome, and metabolome were assessed at baseline and post‐intervention. Results Data from 22 patients were included. Probiotic supplementation was associated with a significant decrease in % faecal primary BAs (chenodeoxycholic acid and cholic acid) with median change from baseline −5.7 [IQR −10.3, 0.9]% compared to 9.8 [IQR 0.2, 20.6]% on placebo ( p = 0.012). The faecal microbiome was significantly different in the probiotic group after intervention, driven by probiotic‐specific species. There were no significant differences in symptoms, intestinal permeability, or SCFA. However, there was a numerical difference in the changes from baseline in 0‐2 h 13 C‐mannitol excretion −1.9 [−13.9, 4.2] mg for the probiotic and 1.0 (−0.5, 12.7) mg for placebo ( p = 0.084). Conclusions The De Simone formulation probiotic induced significant microbiome and metabolome changes in patients with BAM, ultimately leading to a decrease in % faecal primary BAs and possible reduction in intestinal permeability. Clinical Trials.gov registration NCT #06609148, January 2, 2025.

ABSTRACT Beta‐lactam antibiotics (beta‐lactams) are first‐line treatments for most major infectious syndromes in acutely ill patients, with in vitro activity against common pathogens, demonstrated efficacy in trials, and a perceived low risk of adverse effects. The current dosing approach, informed by population‐level data, tends to be simplistically reduced to a “one size fits all” dosing method which only accounts for body weight (i.e., in pediatrics) and end organ function to estimate drug clearance (e.g., estimated glomerular filtration rate); this approach results in substantial variability in observed serum concentrations in acutely ill patients, which can compromise real‐world effectiveness and safety. Beta‐lactam dose individualization, therefore, defined as a dosing regimen for one patient informed by measured concentrations from that patient, has been recommended in international clinical guidelines. Comprehensive guidance on best practices for beta‐lactam dose individualization is lacking. To address this knowledge gap and develop guidance, a multidisciplinary panel of international experts was assembled from the disciplines of infectious diseases, critical care, pharmacometrics, and laboratory medicine, representing both adults and pediatrics. The panel systematically evaluated the literature, using the GRADE approach where feasible, to address broad thematic questions pertaining to whether beta‐lactam dose individualization should be pursued, for what indications beta‐lactam dose individualization is warranted, and the most critical considerations and best practices for implementation of beta‐lactam individualization. The resultant consensus recommendations will equip healthcare professionals caring for acutely ill patients treated with beta‐lactam therapy with the evidence and tools necessary to guide optimal use of beta‐lactam dose individualization.

Abstract Background Immune dysregulation, immunosuppressive therapy and active inflammatory bowel disease (IBD) increase susceptibility to respiratory syncytial virus (RSV) infection. We evaluated the risk of RSV infection in patients with active and nonactive IBD. Methods Using the TriNetX Analytics Network from October 2024 through March 2025, we identified adult patients (aged ≥18 years) with IBD. Patients were classified as having active IBD if they had recent IBD complications, IBD-related surgery, or elevated inflammatory markers (within preceding 6 months); those without recent complications,surgeries, or elevated inflammatory markers were classified as having nonactive IBD within the same period. Outcomes were assessed within 180 days after the index date and included RSV infection, bacterial pneumonia, intensive care unit (ICU) admission, and mechanical ventilation. Results Among 141 763 patients (47 883 patients with active IBD, 93 880 patients with nonactive IBD), 2879 patients with active IBD and 3583 with nonactive IBD received the RSV vaccination. After matching, each cohort included 46 308 patients. Active IBD was associated with higher odds of RSV infection (adjusted odds ratio [aOR], 1.55; 95% CI, 1.18-2.04), bacterial pneumonia (aOR, 2.58; 95% CI, 2.08-3.19), ICU admissions (aOR, 2.07; 95% CI, 1.88-2.28), and mechanical ventilation (aOR, 2.41; 95% CI, 2.01-2.88). RSV risk remained higher among patients with active IBD both with and without systemic corticosteroid exposure. Among RSV-vaccinated patients, RSV infection rates were not significantly different between active and nonactive IBD (aOR, 1.26; 95% CI, 0.78-1.79). Conclusion Patients with active IBD had higher risk of RSV infection. Increased RSV risk was observed both among patients with active IBD with and without systemic corticosteroid exposure. Among RSV-vaccinated patients, RSV infection rates were not significantly different between active and nonactive IBD. Further prospective studies are needed to validate these findings.

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 (&amp;gt;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.