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Large and giant intracranial aneurysms: outcomes from the multicenter prospective SMART coils registry
No full textBackground: Endovascular coiling for intracerebral aneurysms has been evolving. Yet, large and giant aneurysms (LAGA) remain a significant challenge in any treatment modality and carry high rates of morbidity and mortality.
Method: The SMART registry, a prospective, multicenter site-adjudicated trial, was used to identify patients with LAGA (Sac 10–25 mm for large and >25 mm for giant) treated with the Penumbra SMART COIL (SMART) system and compare their outcomes to patients with smaller aneurysms (SA; Sac ≤ 10 mm). Aneurysm occlusion per Raymond-Roy (RROC) scale, recanalization, retreatment, mortality, and serious device-related adverse events (SAEs) were analyzed.
Results: A total of 133/905 (14.7%) enrolled patients had LAGA with a mean (SD) aneurysm size of 13.7 (3.59) mm for LAGA and 5.8 (1.95) mm for SA. LAGA were more likely to be non-saccular (24.1% vs. 12.3%, p = 0.0007) and wide-necked (69.9% vs. 59.7%, p = 0.0268) compared to SA. Primary coiling was the main treatment modality for LAGA and SA (43.6% vs. 43.3%; p = 1.0). However, LAGA were more likely to be treated with flow diversion in addition to coiling (6.0% vs. 1.0%, p < 0.001). At 1-year follow-up: (i) RROC I-II was 82.7% in LAGA and 91.2% in SA; p = 0.0166, (ii) recanalization rates were 13.8% vs. 12.7%; p = 0.7417, and retreatment rates were 11.5% vs. 6.4%; p = 0.0648, for LAGA and SA, respectively, and (iii) all-cause mortality was 9.8% in LAGA vs. 4.7% SA; p = 0.0222. The device-related SAEs rates were low and comparable between the two study groups (4.5% vs. 4.1%; p = 0.8153).
Conclusion: The SMART registry demonstrated that endovascular coiling can be feasible and safe in patients with LAGA, however randomized controlled studies are needed for comparative effectiveness
Hydroxyurea pharmacokinetics in children with sickle cell anemia across different global populations
No full textHydroxyurea provides effective disease-modifying treatment for people with sickle cell anemia (SCA), especially when escalated to maximum tolerated dose (MTD), which has wide interpatient dosing variability due to pharmacokinetic (PK) differences. Whether hydroxyurea PK parameters differ among children with SCA in different global regions is unknown. We compared hydroxyurea PK parameters among children with SCA from 5 clinical trials: HUSTLE (United States), TREAT (United States), NOHARM (Uganda), REACH (Uganda and Kenya), and EXTEND (Jamaica). Key hydroxyurea PK parameters were determined using HdxSim, a validated hydroxyurea PK software program. The results were compared across regions by analysis of variance. PK profiles from 451 children with SCA (146 from the United States, 265 from Africa, and 40 from the Caribbean) were included. Children from Africa had slightly lower volumes of distribution, but absorption rate and clearance were similar across regions. The PK-recommended doses to achieve MTD were statistically different but clinically similar across the United States (26.6 ± 5.9 mg/kg per day), Africa (27.6 ± 6.5 mg/kg per day), and the Caribbean (25.2 ± 4.7 mg/kg per day) (P = .04). In multivariable regression, younger age and increased reticulocyte counts were associated with higher PK-recommended doses. Hydroxyurea PK parameters in children with SCA differ minimally across global populations, predicting clinically similar doses to achieve MTD. Individualized hydroxyurea dosing based on a PK-population model derived from US children with SCA can be used broadly to maximize the benefits of this critical medication in other global populations. These trials were registered at www.ClinicalTrials.gov as #NCT00305175 (HUSTLE), #NCT02286154 (TREAT), #NCT01976416 (NOHARM), #NCT01966731 (REACH), and #NCT02556099 (EXTEND)
High Rates of Defect Closure After Resection of Large Nonpedunculated Colorectal Lesions Using a Through‐The‐Scope Clip With Anchor Prongs
No full textBackground: Prophylactic complete closure of mucosal defects after resection of gastrointestinal lesions is key to reducing delayed bleeding, but complete closure for large defects can be challenging with conventional through-the-scope clips (TTSC). The introduction of a TTSC with anchor prongs offers ability to approximate margins of larger defects.
Objective: The study objective was to evaluate prophylactic complete closure after polypectomy, endoscopic mucosal resection (EMR), or endoscopic submucosal dissection (ESD) in large (≥ 20 mm) nonpedunculated colorectal lesions (LNPCLs).
Methods: We conducted a multicenter, single-arm prospective cohort study of the TTSC with anchor prongs for prophylactic closure after EMR/polypectomy or ESD for LNPCLs. Patients were followed for 30 days after the index procedure. The primary outcome was the rate of complete closure of the defect. Other outcomes were the rate of delayed (postprocedural) bleeding, and rate of serious adverse events (SAEs).
Results: One hundred five eligible patients were enrolled. Ninety-nine (94.3%) defects had complete closure, with rates of 93.0% (80/86) for EMR/polypectomy and 100.0% (19/19) for ESD procedures. Delayed bleeding occurred in 2 (1.9%) patients by 30 days after the index procedure. Eight (7.6%) patients had ≥ 1 SAE, including bleeding (2 patients), perforation (1), microperforation (1), aspiration (1), nausea (1), and post-polypectomy syndrome (1).
Conclusion: Prophylactic use of the TTSC with anchor prongs achieved a 94% rate of complete defect closure after EMR/polypectomy or ESD for LNPCLs. The rate of delayed bleeding after closure in this cohort was 1.9%. A prospective RCT is ongoing to further evaluate the clinical outcomes of a TTSC with anchor prongs used for prophylactic closure
Reply to Musch et al.
No full textA response to a letter regarding the original article “Effect of pre-exercise dietary nitrate on skeletal muscle blood flow in a rat model of pulmonary hypertension”
Building Bridges in School Sports: Parent, Player, and Coach Perspectives on Communication and Mental Health
No full textYouth sports offer growth and community, yet athletes, parents, and coaches often face misaligned communication and unmet mental health needs. This project piloted a partnership between Indiana University School of Social Work and local high school teams, embedding practicum students in athletic settings. Parent surveys (n=50+) and coach assessments (n=20+) revealed challenges with communication, burnout, injury recovery, and emotional well-being. Social work students provided one-on-one sessions, group meetings (e.g., mindfulness, resilience), and family supports like parent podcasts and webinars. Results show parents and coaches value clearer communication, mental health attention, and stronger cohesion. Findings highlight the promise of embedding social workers in sports to build bridges, strengthen resilience, and support early mental health intervention
P-1982. Negative Predictive Value of Methods to Identify Underlying Medical Conditions with and without Use of a Lookback Period among Adults with a Healthcare Encounter for Acute Respiratory Illness, September 2023 – August 2024
No full textBackground:
Vaccine effectiveness (VE) studies are necessary to understand how well vaccines work in the real world. Many VE studies rely on health records to capture underlying medical conditions (UMCs) from a single acute respiratory illness- (ARI) associated encounter, which may bias VE if UMCs are not fully captured. We assessed capture of UMCs from a single acute encounter and a lookback period.
Methods:
Data were used from MarketScan® Treatment Pathways, a healthcare claims dataset, between September 1, 2023 – August 31, 2024. We included beneficiaries aged ≥18+ years with ≥1 inpatient or emergency department (ED) claim containing an ICD-10 code for ARI who had 3 years of continuous enrollment in a participating insurance plan prior to the date of their first ARI claim (i.e., index encounter). The prevalence of UMCs was calculated using ICD-10 codes from 1) the index encounter, and 2) the 1-year lookback period; and the difference was reported. Negative predictive value (NPV) with 95% exact binomial confidence intervals was calculated for identification of UMCs on the index encounter date, using the 1-year lookback period to define true negatives. Results were stratified by age group and encounter setting.
Results:
Among 65,056 beneficiaries with ≥1 inpatient ARI event and 162,943 with ≥1 ED ARI event, the most prevalent UMC categories were cardiovascular, endocrine/metabolic, and respiratory (Tables 1-4). Among beneficiaries aged 18–64 years, NPV was 90% for UMC categories with the lowest overall prevalence (i.e., cerebrovascular, hematologic, and underweight categories) (Tables 1-4).
Conclusion:
NPV was < 80% for common UMCs when identified using a single ARI encounter compared to a 1-year lookback period. Misclassification may influence VE estimates if UMCs are confounders in VE studies
Genetic diversity of Collaborative Cross mice implicates FFAR3 as a target for ILC2 anti-inflammatory reprogramming
No full textPulmonary group 2 innate lymphoid cells (ILC2s) are key drivers of Type 2 inflammation in diseases like asthma, yet the molecular mechanisms regulating their function are incompletely understood. Using the genetically diverse Collaborative Cross (CC) mouse panel, we mapped a quantitative trait locus (QTL) that governs ILC2 prevalence in the lung after aeroallergen exposure. This QTL induces a large population of ILC2s in the lung that are resistant to activation and have diminished Type 2 effector function. We identified free-fatty acid receptor 3 (Ffar3) as a gene responsible for this effect and demonstrated that FFAR3 signaling reprograms ILC2s to an anti-inflammatory state by promoting their survival, reducing Type 2 cytokine production, and enhancing IL-10 expression. This anti-inflammatory state is dependent on IL-2 signaling, is characterized by decreased ST2 expression, and is distinct from previously described IL-10-producing ILC2 phenotypes. FFAR3-dependent reprogramming is mediated by epidermal growth factor receptor (EGFR) upregulation, and FFAR3's anti-inflammatory effect is partially conserved in human ILC2s
Are asynchronous or synchronous clinical decision support more likely to change provider behavior? A case study in dementia
No full textObjective: Describe the impact of synchronous vs asynchronous clinical decision support (CDS) on clinician behavior in a single-site randomized, controlled environment.
Materials and methods: Mixed effects binomial logistic regression was used to compare the impact of synchronous against asynchronous messaging on neurology orders in a three-arm study.
Results: Asynchronous messaging resulted in a significant increase in patient neurology orders for evaluation (Odds ratio, alert-only arm: 1.88; 95% CI: 1.39, 2.55; alert and questionnaire arm: 1.99; 95% CI: 1.52, 2.62).
Discussion: Alerts sometimes generate little action on the part of clinicians. In this case, asynchronous inbox messaging significantly increased neurology orders.
Conclusion: Depending on context, asynchronous messaging may be superior to synchronous messaging when recommending a referral in an outpatient setting
Evaluation of Pathogenic Variants Associated With Monogenic Disorders of Dyslipidemia in Patients With Well Characterised MASLD
No full textBackground and aims: Dyslipidemia is common in patients with MASLD, but the frequency and significance of inherited disorders of dyslipidemia are unclear. We investigated the prevalence and significance of pathogenic variants associated with selected monogenic disorders of dyslipidemia in 3358 patients with well-characterised MASLD.
Approach: We identified clinically relevant variants in APOB, MTTP, PCSK9, ANGPTL3, LDLR and LDLRAP1 genes which can cause hypobetalipoproteinemia (HBL) and familial hypercholesterolemia (FH). Using ClinVar annotations as initial variant selection, we identified 2027 variants in those 6 genes which are reported as 'pathogenic' or 'likely pathogenic' (P/LP). We first assessed for the presence of P/LP variants in the study cohort and then investigated the effect of carrying P/LP variants on liver histology, by comparing ~4 matched controls for each APOB and LDLR carrier. As interpretative analyses, we also looked at the difference between liver enzymes, lipid measures and outcomes between the carriers and matched controls.
Results: Twenty-two variants among these 2027 P/LP variants were present in 24 out of 3358 patients (12 ApoB, 10 LDLR, 1 ANGPTL3 and 1 MTTP variant carriers). Compared to controls, APOB carriers had higher steatosis grade (2.4 vs. 1.7, p-value 0.0028), higher NAFLD activity score (NAS) (4.9 vs. 3.8, p-value 0.04), and numerically higher but statistically not significant fibrosis stage (1.2 vs. 1.1, p-value 0.75) and ALT (87.4 vs. 58.1 U/L, p-value 0.06). Their LDL-c (51 vs. 147.8 mg/dL, p-value 6.1E-09) and triglycerides (91.5 vs. 160.6 mg/dL, p-value 2.8E-03) were significantly lower. Compared to controls, LDLR carriers had numerically higher steatosis grade, NAS, fibrosis stage and LDL-c levels, but these were not statistically different.
Conclusions: Monogenic disorders of dyslipidemia are rarely present in patients with MASLD and are sometimes associated with worse liver histology. Testing for these conditions may be considered on a case-by-case basis
Early Life Food Desert Status Is Associated With Alpha and Gamma‐Tocopherol Levels and Infant Lung Function
No full textBackground: Living in a food desert (an area with limited access to affordable and nutritious food) is associated with a higher prevalence of childhood asthma. There is a lack of information regarding the impact of spending the first year of life in a food desert on subsets of Vitamin E (α- and γ-tocopherol) levels and lung development.
Objective: Determine if living in a food desert at 3 months of life is associated with altered α- and γ-tocopherol, and infant lung measurements.
Design: Newborns recruited within 1 week of delivery and prospectively followed for 3 months. 32 infants had sedated lung function tests and 50 had food desert data for analysis along with serum for α-tocopherol and γ-tocopherol analysis.
Participants: Fifty (50) infants within the prospective Indiana High-risk for Atopy in Neonates Cohort through Early life (INHANCE) were analyzed.
Main outcome measures: Lung function, serum tocopherol concentration, and food desert status from the INHANCE cohort were analyzed. Because α-tocopherol and γ-tocopherol have opposing mechanistic functions, and the combination of high α-tocopherol with low γ-tocopherol have been shown to associate with better lung function in 2- to 3-year olds and in adults, in this study of 3-month old infants, quadrants of high and low α-tocopherol and γ-tocopherol were assessed for association with food deserts and lung function tests.
Statistical analyses performed: Fisher's Exact tests were used to compare food desert designations with quadrants, due to small counts. Analysis of Variance (ANOVA) models were used to compare lung function values across the four quadrants, and Student's t-tests were used to compare the lung function z-scores across the two-level quadrant groups.
Results: At 3 months of age, lung volumes were lower in children living in food deserts (FVC: p = 0.006; FEV0.5: p = 0.008). None of the infants (n = 50) with the ideal tocopherol combination lived in a food desert compared to the other three quadrants with less ideal tocopherol combinations (p = 0.04). The infants (n = 32) with the ideal tocopherol combination had higher FRC (p = 0.006) and FEV0.5 (p = 0.025) z-scores than infants in the other three quadrants.
Conclusion: Not living in a food desert is associated with the highest α- and lowest γ-tocopherol levels at 3 months of age. At 3 months of age, not living in a food desert was associated with higher lung function; with higher lung function associated with the highest α-tocopherol and lowest γ-tocopherol levels. Prospective trials are needed to determine if a lack of nutritious food during pregnancy and the first year of life is linked with decreased α-tocopherol and increased γ-tocopherol throughout this time period, and if this potential link is consistently associated with lower airway measurements that persist for the first few years of life