Category: Statistics

Naunyn Schmiedebergs Arch Pharmacol. 2026 Feb 27. doi: 10.1007/s00210-026-05148-5. Online ahead of print.

ABSTRACT

Trabectedin has been approved for treating adult patients with unresectable or metastatic liposarcoma or leiomyosarcoma who have previously received anthracycline. However, the long-term safety of trabectedin in a large-sample population remains unknown. We used a real-world pharmacovigilance database to assess adverse events (AEs) related to trabectedin. A disproportionality analysis was performed to evaluate the relationship between trabectedin and AEs. Data between January 2015 and March 2024 were collected from the United States Food and Drug Administration Adverse Event Reporting System (FAERS), an international pharmacovigilance database, to analyze the characteristics and onset time of trabectedin-related AEs. During the studied period, the FAERS database recorded 14,931,458 AE reports, of which 1,748 were related to trabectedin. Approximately 137 trabectedin-related AE signals were identified in 17 system organ classes. The most common AEs listed on the trabectedin label were neutropenia, anemia, thrombocytopenia, and hepatobiliary disorders. We identified twenty-four new and unexpected significant off-label AEs, including atrial flutter, supraventricular tachycardia, increased troponin, venous thromboembolism, hyponatremia, hypokalemia, hypocalcemia, and hypophosphatemia. The median onset time of trabectedin-related AEs was 18.5 (interquartile range, 5-55.25) days. The findings confirmed expected trabectedin-related AEs and identified new AEs.

PMID:41758346 | DOI:10.1007/s00210-026-05148-5

Eur Radiol. 2026 Feb 27. doi: 10.1007/s00330-026-12360-7. Online ahead of print.

NO ABSTRACT

PMID:41758345 | DOI:10.1007/s00330-026-12360-7

Eur Radiol. 2026 Feb 27. doi: 10.1007/s00330-026-12411-z. Online ahead of print.

NO ABSTRACT

PMID:41758344 | DOI:10.1007/s00330-026-12411-z

Eur Radiol. 2026 Feb 27. doi: 10.1007/s00330-025-12302-9. Online ahead of print.

ABSTRACT

OBJECTIVES: Assessing regional brain atrophy on 3D-T1w imaging is crucial for evaluating neurodegenerative disorders. However, high-quality volumetric imaging is not always available. Thus, AI-based algorithms were developed to generate “synthetic” 3D-T1w sequences using various clinical sequences as input. This retrospective study aims to investigate whether regional atrophy patterns are preserved in deep learning-based synthetic 3D-T1w sequences from different inputs.

MATERIALS AND METHODS: The study included patients with Alzheimer’s disease (AD), Frontotemporal dementia (FTD), and healthy controls (HC). Probands were scanned at 3 T, and deep learning-based synthetic 3D-T1w images were generated from various inputs (3D FLAIR, 4 mm axial FLAIR, 4 mm coronal T2) using FreeSurfer-based SynthSR. Real 3D-T1w images served as the reference standard. Brain volumetry was performed using SynthSeg+ in FreeSurfer and the AssemblyNet-AD-FTD pipeline in VolBrain.

RESULTS: Global and regional volumes differed significantly between deep learning-based synthetized sequences and the reference standard 3D T1 for all subgroups and inputs (total white matter volume AD p = 0.0002, FTD p < 0.0001, HC p = 0.0116; total gray matter volume for AD, FTD, and HC p < 0.0001), except for hippocampal volumes. This systematic error in overestimating volumes affected automated disease probability prediction in FTD for all inputs (p < 0.0001) and in HC for coronal T2 input (adj. p = 0.0054).

CONCLUSION: Deep learning-based synthetic 3D-T1w sequences introduce systematic errors in assessing global and regional brain volumetric measures, leading to overestimated volumes in controls and patients. Resulting synthetic images should be used cautiously, especially for volumetric analyses.

KEY POINTS: Question It remains unclear whether deep learning-based synthetic 3D-T1w images from various inputs preserve regional atrophy patterns sufficiently to serve as input for automated volumetry. Findings Deep learning-based synthetic T1w images overestimate regional and global brain volumes in neurodegenerative diseases and controls, increasing with lower quality inputs. Clinical relevance Deep learning-based synthetic images should only be used with caution for volumetric evaluation of brain MRI scans. If possible, 3D scans should be used as input.

PMID:41758343 | DOI:10.1007/s00330-025-12302-9

Eur Radiol. 2026 Feb 27. doi: 10.1007/s00330-026-12325-w. Online ahead of print.

ABSTRACT

OBJECTIVES: Myocarditis is a common disease with a risk of chronic progression. The aim of this study is to assess changes in MRI parameters during serial monitoring in patients with acute myocarditis (AM), and to evaluate their prognostic implications for the prediction of major adverse cardiac events (MACE).

MATERIALS AND METHODS: In this prospective multicenter study, patients with MRI-confirmed AM between 2016 and 2020 underwent serial MRI: at baseline (6 [interquartile range (IQR), 3-10] days after symptom onset), short-term (median 36 [IQR, 33-42] days) and long-term (392 [IQR, 358-435] days). Cardiac MRI parameters, including mapping, were evaluated. MACE at 5-year follow-up were collected.

RESULTS: A total of 105 patients (age 38 [IQR, 28-45 years]; men 75, 71%) were enrolled. Infarct-like clinical presentation (80, 76%) was the most common, followed by heart failure (18, 17%) and arrhythmia (7, 7%). MACE occurred in 20/105 patients (28.5%). Persistence of active disease using LLc 2018 was found in 91% (87) of patients at short-term and 61.5% (48) of patients at long-term MRI. Lateral LGE pattern was associated with better prognosis (HR [95% CI] = 0.19 [0.09; 0.38]; p-value < 0.0001), while scar burden at long-term MRI was associated with MACE (HR [95% CI] = 1.15 [1.07; 1.24]; p-value < 0.001). Native T1 at short-time MRI (HR [95% CI] = 1.02[1.01; 1.02]; p-value < 0.0001) and T2 mapping at long-term MRI (HR [95% CI] = 1.27[1.07; 1.52]; p-value = 0.006) resulted independent predictors of events at multivariate analysis. Changes of MRI parameters at different time points were not predictors of MACE.

CONCLUSION: Cardiac MRI allows for monitoring of the healing process. Persistence of inflammation after 1 year from onset is associated with unfavorable outcomes.

KEY POINTS: Question Serial cardiac MRI with mapping may provide information about myocarditis healing vs chronic progression that can be useful for risk stratification? Findings Cardiac MRI showed persistence of active disease using LLc 2018 in 91% (87/96) of patients at short-term MRI and in 61.5% (48/79) at long-term MRI. At the long term, altered T2 mapping resulted predictors of adverse events together with higher LGE burden, altered troponin and dyspnea. Clinical relevance In acute myocarditis, serial cardiac MRI allows to monitor the healing process and identify the persistence of inflammation, which is associated with chronic evolution and unfavorable outcome.

PMID:41758342 | DOI:10.1007/s00330-026-12325-w

Nicotine Tob Res. 2026 Feb 27:ntag041. doi: 10.1093/ntr/ntag041. Online ahead of print.

ABSTRACT

INTRODUCTION: This study assesses the Italian population’s support for innovative tobacco control policies, which aims at reducing use of nicotine-containing products and exposure to secondhand smoke and aerosol.

METHODS: A cross-sectional study was conducted in 2024 among a representative sample of 3125 Italian adults. We assessed support on banning tobacco sales to people born after a certain year (Smoke-Free Generation, SFG), raising the minimum age for purchasing tobacco to 21 years (Tobacco 21, T21), substantially increasing tobacco taxation, banning electronic cigarettes (e-cigarette) and heated tobacco products (HTP) in indoor public places and workplaces, and prohibiting tobacco and e-cigs advertising.

RESULTS: Support for tobacco control policies was 67.0% for the SFG policy, 72.9% for the T21 policy, 61.5% for a tax increase, 80.8% for a ban on indoor e-cigarette and HTP use in public places and 81.7% in workplaces respectively, and 78.2% for an advertising ban for all nicotine products. Support for all policies increased with age (p-values for trend ranging from <0.001 to 0.037) and was significantly lower among current smokers (support ranging from 17.9% to 59.7%). E-cigarette users showed lower support for a SFG (32.4%) and advertising bans (41.4%), while HTP users were less supportive of all policies except the T21 policy (support ranging from 13.2% to 43.9%).

CONCLUSION: In Italy, strong public support exists for new tobacco control laws, especially among never smokers and non-users of novel products. However, also a considerable proportion of current smokers, e-cigarette and HTP users support these policies. Policymakers can confidently advance these strategies, while public campaigns should target less supportive groups.

PMID:41757497 | DOI:10.1093/ntr/ntag041

J Bone Miner Res. 2026 Feb 27:zjag046. doi: 10.1093/jbmr/zjag046. Online ahead of print.

ABSTRACT

Fracture risk in mid-life (ages 35-65) is under-recognised despite its implications for long-term skeletal health. Using UK Biobank data, we aimed to characterize fracture epidemiology in this critical age group through two complementary approaches. We conducted two studies: a cross-sectional analysis of self-reported fractures (2006-2010) to estimate annualized incidence risk per 10,000 people, and a longitudinal cohort analysis using linked Hospital Episode Statistics (2001-2022) to calculate incidence rates per 10,000 person years, both stratified by sex, skeletal site, and 10-year age bands. Fracture incidence varied substantially by age and sex. Among women, risk increased from age 35 years and accelerated notably from the mid-40s, peaking at 246 per 10,000 people in the 56-65 age group. This female trajectory, emerging earlier than previously recognized, contrasts with men, whose highest fracture risk occurred in early mid-life (peak: 232 per 10,000 people, ages 35-45). Across both sexes and age bands, the most reported fracture sites were: “other” (including digits and facial bones), wrist, ankle, arm, leg, spine, and hip, in descending order. In HES-linked data, 43,572 fractures were identified. Incidence patterns mirrored those from self-report: higher early mid-life fracture rates in men, followed by a transition to female predominance from around age 45. This large-scale, dual-method analysis offers the first clear evidence that female fracture risk begins to rise from age 35, with a marked acceleration from 45 onward. These sex-specific trajectories in mid-life fracture incidence are not fully captured in current clinical models and indicate that further work is needed to determine whether earlier or tailored approaches to risk assessment could provide cost-effective benefit in reducing the burden of fracture in mid-life.

PMID:41757485 | DOI:10.1093/jbmr/zjag046

J Am Heart Assoc. 2026 Feb 27:e045151. doi: 10.1161/JAHA.125.045151. Online ahead of print.

ABSTRACT

BACKGROUND: Intravascular ultrasound (IVUS)-guided percutaneous coronary intervention improves patient outcomes, yet the impact of a center’s IVUS experience on long-term outcomes remains unclear. We evaluated whether the prognostic association of IVUS-guided percutaneous coronary intervention in patients with acute myocardial infarction differs based on a center’s level of IVUS use.

METHODS: We retrospectively analyzed 9752 patients with acute myocardial infarction treated with second-generation drug-eluting stents from the KAMIR-NIH (Korean Acute Myocardial Infarction Registry-National Institutes of Health). The primary outcome was 3-year major adverse cardiovascular events, defined as a composite of all-cause death, myocardial infarction, and coronary revascularization. The secondary outcome was target-lesion failure, defined as a composite of cardiac death, target-vessel myocardial infarction, and ischemia-driven target lesion revascularization. Centers were classified into higher- or lower-IVUS-use groups on the basis of median institutional usage (10.3%).

RESULTS: In higher-use centers, IVUS-guided percutaneous coronary intervention was associated with lower rates of major adverse cardiovascular events (15.3% versus 18.5%, P=0.016) and target-lesion failure (6.3% versus 8.3%, P=0.039) in propensity score-matched populations. Multivariate Cox analysis confirmed lower risks of major adverse cardiovascular events (hazard ratio [HR], 0.80 [95% CI, 0.69-0.93]; P=0.003) and target-lesion failure (HR, 0.75 [95% CI, 0.59-0.93]; P=0.01). Conversely, in lower-use centers, IVUS guidance was not associated with significant differences in major adverse cardiovascular events (15.7% versus 18.6%, P=0.422) or target-lesion failure (8.9% versus 10.4%, P=0.644).

CONCLUSIONS: The association of IVUS-guided percutaneous coronary intervention with lower adverse event rates was more apparent and statistically demonstrable in centers with higher IVUS use. These findings suggest that institutional experience may amplify the observable impact of IVUS guidance, underscoring the potential value of standardized IVUS implementation in acute myocardial infarction management.

PMID:41757462 | DOI:10.1161/JAHA.125.045151

J Am Heart Assoc. 2026 Feb 27:e045541. doi: 10.1161/JAHA.125.045541. Online ahead of print.

ABSTRACT

BACKGROUND: The ONCO PE (Optimal Duration of Anticoagulation Therapy for Low-Risk Pulmonary Embolism Patients With Cancer) trial demonstrated the superiority of 18-month compared with 6-month rivaroxaban treatment for cancer-associated low-risk pulmonary embolism in reducing recurrent venous thromboembolism. However, it was uncertain whether the results could be applicable to patients with different performance status (PS) scores, which evaluate the physical condition of patients with cancer undergoing anticancer treatment.

METHODS: In this post hoc subgroup analysis of the ONCO PE trial, we compared the 18-month and 6-month rivaroxaban treatment groups in 2 subgroups: the low PS score (no restricted physical activity: PS=0; n=79) and high PS score (restricted physical activity: PS ≥1; n=99) subgroups. The primary end point was recurrent venous thromboembolism, and the major secondary end point was major bleeding.

RESULTS: The rate of recurrent venous thromboembolism was lower in the 18-month rivaroxaban group than in the 6-month rivaroxaban group, significantly among the low PS score subgroup (2.7% versus 19.0%, P=0.049) and numerically among the high PS score subgroup without statistical significance (7.7% versus 19.1%, P=0.10). The rate of major bleeding was not different between the 2 groups among the low PS score subgroup (2.7% versus 7.1%, P=0.39), while it was numerically higher in the 18-month rivaroxaban group than in the 6-month rivaroxaban group among the high PS score subgroup, without statistical significance (11.5% versus 4.3%, P=0.20).

CONCLUSIONS: Extended anticoagulation therapy for patients with cancer-associated low-risk pulmonary embolism might have a potential benefit in reducing thrombotic risk irrespective of PS score, whereas there might be some concerns on an increased risk of major bleeding in patients with a high PS score.

REGISTRATION: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT04724460.

PMID:41757461 | DOI:10.1161/JAHA.125.045541

Anal Chem. 2026 Feb 27. doi: 10.1021/acs.analchem.5c07249. Online ahead of print.

ABSTRACT

The advancement of hydrogen energy is an urgent necessity for the global energy transition and the realization of carbon neutrality. In water electrolysis, the development of novel catalysts is pivotal, while continued innovation in in situ electrochemical characterization is equally essential. This work presents a high-throughput in situ total internal reflection imaging (TIRi) platform that provides a “one stone, three birds” solution-concurrently enabling visualization of catalyst spatial uniformity, rapid qualitative performance screening, and quantitative evaluation of compositional sets. The system integrates a redesigned optical architecture with a 4 × 4 electrode array, establishing a direct correlation between optical contrast and electrochemical response. Using representative catalysts (Pt/C, NiFe, MoS₂, and WS₂) patterned on the array, we verify spatial consistency and elucidate activity variations in the hydrogen evolution reaction (HER). Furthermore, a Mo-Ru compositional-gradient alloy was fabricated, through which the optimal composition (Mo:Ru = 1:0.339) was identified, revealing the intrinsic correlation between electrocatalytic performance and compositional ratio. This nondestructive, cost-efficient, and inherently scalable method enables statistically robust, high-throughput catalyst discovery without compromising mechanistic insight, while offering a broadly generalizable operando framework that accelerates the rational design and optimization of electrocatalysts for sustainable energy technologies.

PMID:41757444 | DOI:10.1021/acs.analchem.5c07249