Tag: pubmed

Biom J. 2026 Jun;68(3):e70124. doi: 10.1002/bimj.70124.

ABSTRACT

In this paper, we present a Monte Carlo method for estimating a nonlinear function of the mean of a multivariate normal distribution. Building on this method, we propose a parametric estimation procedure for unimodal regression models, assuming that the response variable follows a gamma distribution while some covariates are contaminated with normal measurement error. Compared to existing approaches, the proposed method accommodates multivariate covariates and features a tractable bias-corrected likelihood function, enabling faster computation and more accurate estimation when the data distribution is correctly specified. To enhance the applicability of the proposed method, we also explore various model adequacy diagnostic tools and evaluate its robustness against distributional misspecifications. Notably, we introduce a goodness-of-fit test based on a unique characterization of the gamma distribution, designed to assess the validity of the distributional assumption for the response variable. Numerical studies and real-world data applications are conducted to evaluate the finite-sample performance of the proposed methods.

PMID:42145084 | DOI:10.1002/bimj.70124

Clin Transl Med. 2026 May;16(5):e70687. doi: 10.1002/ctm2.70687.

ABSTRACT

BACKGROUND AND AIMS: Existing imaging and serum-marker assays miss many early liver cancers, especially in high-risk chronic liver disease carriers. We aimed to create a highly accurate, non-invasive, methylation-based liquid biopsy for early detection.

METHODS: We used a comprehensive, multi-platform, multi-cohort strategy for marker discovery, starting with methylation profiling of hepatocellular carcinoma samples from TCGA and in-house cohorts. From 30 initial candidates, nine highly liver-specific methylation markers were shortlisted, and three optimal cfDNA markers (RNF135, CHFR, PAX5) were selected to develop a robust diagnostic model, tuned in a training set (N = 280) and locked in an internal testing set (N = 124). The model was then validated in a prospective, large-scale trial conducted at four geographically distinct Chinese centres.

RESULTS: The clinical trial included 1097 participants from two groups, (i) a diagnosing group (N = 646) that prospectively enrolled individuals without prior diagnostic results and represented a real-world high-risk population, and (ii) a diagnosed group recruited after pathology confirmation. Overall, the model achieved 94.43% (95% confidence interval, 92.12-96.09%) sensitivity and 95.16% (92.78-96.78%) specificity for liver cancer, with stage-I sensitivity of 93.10% (89.78-95.40%). Within the diagnosing group, overall sensitivity was 93.99% (91.28-95.90%), and for the 267 stage-I cases, it reached 92.88% (89.15-95.39%). As for specificity, it remained high across confounders: 92.78% (85.84-96.46%) in cirrhosis, 91.74% (85.46-95.45%) in other-cancer interference samples. Besides, the model outperformed the traditional liver cancer biomarker AFP and showed changes in methylation signals before and after surgery, suggesting a possible role in perioperative monitoring. Each centre independently reported sensitivities and specificities exceeding 90%, demonstrating robust geographic performance.

CONCLUSIONS: Using a systematic marker-discovery pipeline and a multi-centre prospective cohort, we developed a methylation-based liquid biopsy that reliably detects early liver cancer in high-risk populations.

CLINICAL TRIAL NUMBER: Chictr.org identifier: ChiCTR2400092883.

KEY POINTS: Three cfDNA methylation markers, RNF135, CHFR and PAX5, were identified for liver cancer liquid biopsy. A three-marker diagnostic model based on qMSP was established for highly accurate non-invasive detection of liver cancer. The LC-HMC model achieved 94.43% sensitivity and 95.16% specificity in the clinical trial. The model detected stage-I liver cancer with a sensitivity of 93.10%.

PMID:42145083 | DOI:10.1002/ctm2.70687

Am J Clin Pathol. 2026 May 5;165(5):aqag033. doi: 10.1093/ajcp/aqag033.

ABSTRACT

OBJECTIVES: To study and classify electronic safety reports assigned to the clinical laboratory of a large academic medical center, focusing on types of reporters, event classification, and severity of reported events.

METHODS: We performed a retrospective review of laboratory/pathology safety reports in 2023 at the Massachusetts General Hospital. Data included types of events, where the error occurred, the level of harm to the patient, and reporting patterns.

RESULTS: A total of 2334 reports were filed, with nearly three-fourths involving specimen/testing errors (76%). Most events (72%) originated in the preanalytical phase of testing, including labeling, collection, and transport issues. Of all reports, 56.7% indicated they did not reach the patient, 36.4% caused no harm but impacted the patient, 6% led to minor harm, and 0.6% resulted in permanent or major harm/damage. One case was severity level 4 (death). Laboratory technologists/technicians submitted most reports, while nursing was the primary reporter for events that pathology was required to resolve.

CONCLUSIONS: A large number of safety reports are generated in our large academic medical center. Most involve the preanalytical phase but do not result in direct patient harm. Despite improvements in information technology to improve the reliability of the preanalytical phase of testing, most reports reflect incidents outside the clinical laboratory.

PMID:42145078 | DOI:10.1093/ajcp/aqag033

J Nurs Manag. 2026;2026(1):e9254720. doi: 10.1155/jonm/9254720.

ABSTRACT

OBJECTIVE: This study evaluated the competency of nursing leaders and managers in Spain regarding evidence-based practice (EBP) and identified factors that affect its implementation in clinical environments.

BACKGROUND: EBP is essential for enhancing healthcare quality; however, there are still gaps between theoretical knowledge and its practical application. Nursing leaders are crucial in promoting EBP, yet their competence levels and obstacles have not been thoroughly examined in Spain.

MATERIAL AND METHODS: A cross-sectional study surveyed 159 nurse managers across 16 autonomous communities in Spain, utilizing the validated EBP-COQ Prof tool. The questionnaire assessed four competency domains-attitude, knowledge, skills, and utilization-using a 1 to 5 Likert scale. Predictors of EBP competency, including training, mentorship, and organizational affiliation, were analyzed using multivariate linear regression.

RESULTS: Participants demonstrated a strong overall EBP competence, with an average total score of 143.77 out of 175. The highest scores were in the attitude domain (36.26/40) and knowledge (43.09/55), whereas utilization scores were relatively lower (37.57/50). This indicates that applying EBP in practice still lags behind positive attitudes and knowledge. Key factors predicting higher EBP competence included EBP training, consistent reading of scientific literature, mentoring nursing students, and working in a BPSO center. These results also imply that organizational constraints may continue to impede the integration of EBP competence into routine managerial practice.

CONCLUSIONS: Spanish nurse managers possess strong EBP knowledge but continue to encounter difficulties in applying it clinically. The study highlights four adjustable factors of EBP competency that could guide focused interventions.

IMPLICATIONS FOR NURSING MANAGEMENT: Healthcare institutions should implement (1) training programs for addressing knowledge-to-practice gaps, especially for nonspecialist managers; (2) mentorship systems pairing EBP-competent leaders with novices; (3) protected time for EBP activities; and (4) expanded BPSO accreditation to institutionalize evidence-based care. Future initiatives should include EBP metrics in performance evaluations, and research should explore factors such as leadership styles and the impact of resource allocation on patient outcomes through longitudinal designs.

PMID:42145075 | DOI:10.1155/jonm/9254720

Ann Pharmacother. 2026 May 18:10600280261447319. doi: 10.1177/10600280261447319. Online ahead of print.

ABSTRACT

OBJECTIVE: To describe nerandomilast, a preferential phosphodiesterase 4B inhibitor indicated for the treatment of idiopathic pulmonary fibrosis and progressive pulmonary fibrosis.

DATA SOURCES: A PubMed search was conducted from origin to mid-April 2026 using the terms nerandomilast, Jascyd, BI 1015550, idiopathic pulmonary fibrosis (IPF), progressive pulmonary fibrosis, and interstitial lung disease. Phase 2 and 3 clinical trials, prescribing information, pooled analyses, and relevant guideline documents were included.

STUDY SELECTION AND DATA EXTRACTION: Two phase 3 randomized controlled trials evaluating nerandomilast in IPF and progressive pulmonary fibrosis were reviewed, along with regulatory prescribing information.

DATA SYNTHESIS: In the FIBRONEER-ILD and FIBRONEER-IPF trials, nerandomilast reduced forced vital capacity decline at 52 weeks compared with placebo. Treatment effects were observed in patients receiving background antifibrotic therapy and those treated with nerandomilast alone. Secondary time-to-event outcomes were not statistically significant. Diarrhea was the most common adverse event and occurred more frequently with nerandomilast, while serious adverse events were similar across treatment groups.Relevance to Patient Care and Clinical Practice in Comparison to Existing Drugs:Nerandomilast targets inflammatory and profibrotic pathways distinct from currently available antifibrotic therapies and may be used as monotherapy or in combination with existing agents. Its role is best understood as disease stabilization rather than reversal of established fibrosis.

CONCLUSION AND RELEVANCE: Nerandomilast represents an additional therapeutic option for patients with IPF and progressive pulmonary fibrosis. Ongoing long-term and real-world data will further clarify its place in clinical practice.

PMID:42145068 | DOI:10.1177/10600280261447319

J Med Primatol. 2026 Jun;55(3):e70080. doi: 10.1111/jmp.70080.

ABSTRACT

BACKGROUND: Colon cancer death toll due to metastasis is expected to rise. Extracellular vesicles are signalling molecules which can regulate communication between cells and either inhibit or promote cancer metastasis.

METHODS: Extracellular vesicles from adipose mesenchymal stem cells of Macaca fascicularis were obtained from previous research. Various concentrations of extracellular vesicles (5 μg/mL, 10 μg/mL, and 20 μg/mL) were applied to colon cancer cell line WiDr in a transwell invasion assay. CXCR3 gene expression analysis was done using RT-qPCR.

RESULTS: Application of extracellular vesicles successfully inhibited colon cancer invasion with decrease of number of invasive cells with increase in concentration. There was no statistical difference between cells treated with 10 μg/mL and 20 μg/mL of extracellular vesicles. Colon cancer cells treated with extracellular vesicles show upregulation of CXCR3A and CXCR3B gene expression compared to negative control.

CONCLUSION: Extracellular vesicles inhibit colon cancer cell invasion through upregulation of CXCR3B expression.

PMID:42144563 | DOI:10.1111/jmp.70080

Neth Heart J. 2026 May 18. doi: 10.1007/s12471-026-02050-w. Online ahead of print.

ABSTRACT

AIM: To evaluate the clinical impact of a dedicated multidisciplinary spontaneous coronary artery dissection (SCAD) care pathway compared with standard acute coronary syndrome management, focusing on safety, treatment patterns, clinical outcomes, and recurrence rates in patients with SCAD.

METHODS: In this retrospective observational cohort study, 117 SCAD patients were included: 63 managed within a SCAD-specific care pathway and 54 receiving standard care prior to or independent of its implementation. The SCAD pathway included protocolized angiographic diagnosis, conservative management when feasible, individualized medical therapy, screening for fibromuscular dysplasia (FMD) and systemic disorders, and SCAD-specific rehabilitation with structured follow-up. The primary endpoint was major adverse cardiovascular events (MACE) at 1‑year follow-up.

RESULTS: Patients in the SCAD pathway group were more often managed conservatively in the acute setting (76% vs. 24%, p < 0.001), had significantly lower rates of stent implantation (8% vs. 65%, p < 0.001), and were less frequently prescribed dual antiplatelet therapy (19% vs. 96%, p < 0.001). At 12-month follow-up, beta-blocker adherence was higher (76% vs. 41%, p < 0.001), aspirin use was lower (38% vs. 59%, p < 0.001), and recurrent SCAD occurred numerically less often but not statistically significantly (3% vs. 9%, p = 0.231). MACE rates were similar between groups, and no deaths occurred. FMD screening was more common in the pathway group (92% vs. 17%, p < 0.001), facilitating diagnosis and tailored long-term therapy.

CONCLUSION: Implementation of a standardized SCAD care pathway was associated with a safe conservative approach, more targeted secondary prevention, improved beta-blocker adherence, and a trend toward fewer recurrent SCAD events. These findings support integration of SCAD-specific multidisciplinary care into routine clinical practice to improve diagnostic precision and long-term outcomes.

PMID:42144538 | DOI:10.1007/s12471-026-02050-w

Infect Dis Ther. 2026 May 17. doi: 10.1007/s40121-026-01352-1. Online ahead of print.

ABSTRACT

INTRODUCTION: The continual emergence of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants drives the need to update evidence on coronavirus disease 2019 (COVID-19) severity and disease burden, and better understand the impact on prevention, treatment, and healthcare systems.

METHODS: This systematic review aimed to determine relative disease severity, through comparative measures of hospitalization, intensive care unit admission and mortality, between SARS-CoV-2 variants of concern emerging since Omicron was first identified. A protocol was registered a priori (PROSPERO ID: CRD42024619193). Systematic searches of MEDLINE and EMBASE databases were conducted in November 2024 and supplemented by conference searches from 2022-2024. Population, Exposure, Comparisons, Outcomes (PECO) criteria were used to screen publications for inclusion. Critical appraisal tools published in the Joanna Briggs Institute (JBI) Handbook for Evidence Synthesis were used to assess the risk of bias of the primary studies included. The outcomes associated with Omicron variants, identified by sequencing or predominance periods, included hospitalization, admission to intensive care, death, and various composite endpoints.

RESULTS: Thirty-two studies fulfilled the eligibility criteria, most reported on relative disease severity for early Omicron BA.5 (n = 23) and XBB (n = 24) variants. Overall, COVID-19 severity appeared largely comparable across the various Omicron subvariants. Among the subset of studies that directly compared various severity outcomes to earlier SARS-CoV-2 variants (n = 7), some reported modest increases or decreases in severity. However, these differences were generally not statistically significant. Five studies stratifying outcomes by the presence of comorbid conditions noted that comorbidities were predictors of significantly worse COVID-19 disease outcomes (p = 0.000-0.027).

CONCLUSIONS: Overall, this systematic review found the severity of COVID-19 disease to be comparable among Omicron subvariants. As SARS-CoV-2 subvariants continue to emerge, these results highlight the continuing need for vaccination against SARS-CoV-2 infection alongside early antiviral intervention to support short-term management and long-term reduction of COVID-19-associated morbidity and mortality.

PMID:42144508 | DOI:10.1007/s40121-026-01352-1

Ir J Med Sci. 2026 May 18. doi: 10.1007/s11845-026-04444-6. Online ahead of print.

ABSTRACT

BACKGROUND: Necrotising enterocolitis (NEC) is a life-threatening gastrointestinal condition predominantly affecting preterm infants. The majority of patients with NEC are treated medically, however, approximately 25% of patients require surgical intervention.

AIMS: This study wished to assess the national outcomes for patients with surgical NEC in Ireland. The data was gathered from the only two centres in Ireland that perform this type of surgery.

METHOD: All patients in the Republic of Ireland who underwent a laparotomy for NEC were identified over a 10 year period (2012-2022). The following information was obtained for each patient: sex, gestational age, birth weight, medical co-morbidities, length of bowel resection in centimetres, presence/absence of ileocecal valve after surgery, stoma formation, time from maternity hospital referral to surgical procedure and mortality.

RESULTS: 133 patients underwent laparotomy for NEC over the 10 year study period. 101 (75.9%) patients were alive at the time of data collection and 32 patients died, resulting in a mortality rate of 24.1%. All 13 patients with NEC totalis died (phi correlation with mortality 0.555). 0 patients with spontaneous intestinal perforation (SIP) died (phi correlation-0.152). Loss of ileocaecal valve at surgery was statistically significantly associated with mortality (phi correlation 0.536).

CONCLUSION: The outcomes for neonates with surgical NEC in Ireland in our study are favourable compared to the published literature. Our outcomes may be better than published data as they may not reflect a subgroup of patients with NEC in Ireland that never made it to our tertiary institutions for surgical assessment.

PMID:42144499 | DOI:10.1007/s11845-026-04444-6

Ann Biomed Eng. 2026 May 17. doi: 10.1007/s10439-026-04159-w. Online ahead of print.

ABSTRACT

PURPOSE: Prosthetic clinics and philanthropic organizations are increasingly using additive manufacturing (AM) to manufacture upper-limb prostheses (ULP). However, a lack of documented use cases and guidelines hinders its broader implementation. Additional data are required to establish recommendations. This exploratory study aims to investigate the sociodemographics and expertise of individuals using AM to manufacture ULP.

METHODS: An international cross-sectional web-based survey was conducted from October 1st, 2023, to June 30th, 2024. Participants were recruited using non-probability sampling through specialized online channels. We collected sociodemographic data and explored AM ULP manufacturing workflows and outcomes. The survey was available in French, English, and Spanish. Survey data underwent descriptive analyses.

RESULTS: Of 111 participants who started the survey, 61 (55%) completed it. Participants included aid organizations members (40%), prosthetists (37%), and other related professions (23%), with up to 5 years (60%) of AM experience. Active (56%) ULP were predominantly manufactured using Fused Filament Fabrication (84%) with polylactic acid (77%) material. Poor digital customization skills represented the main barrier to 3D production. Functionality and reliability of AM ULP parts represent major limitations in 3D devices studied.

CONCLUSION: Although additive manufacturing offers significant technological advantages for the production of upper-limb prostheses, human (e.g., digital skills, training) and technical (e.g., mechanical performance of materials) barriers can hinder its implementation and clinical relevance. Further studies, endorsed by official institutions, are warranted to establish guidelines for each subgroup of stakeholders to manufacture optimal ULP using AM.

PMID:42144492 | DOI:10.1007/s10439-026-04159-w