Tag: pubmed

Eur Urol. 2026 Mar 11:S0302-2838(26)02002-6. doi: 10.1016/j.eururo.2026.02.011. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: Studies reported to date indicate that local therapy may improve outcomes in men with de novo metastatic (M1) prostate cancer (PCa). The aim of this study was to evaluate the effect of local therapy to the primary tumor on progression-free survival (PFS) in men with M1 PCa.

METHODS: In a multicenter, randomized phase 2 trial, men with de novo M1 PCa, after receiving 6 mo of best systemic therapy (BST), were randomly assigned (1:1) to continue BST alone (arm 1) or BST with the addition of either radiotherapy or surgery to their primary tumor (arm 2). The primary endpoint was PFS, defined as the time from randomization to progression (Prostate Cancer Working Group 2) by prostate-specific antigen, radiographic or symptomatic progression, or the time to change systemic therapy as per physician discretion and/or clinical decision, or death, whichever occurred first. Immunohistochemistry for the tumor suppressors p53, RB1, and PTEN was performed on available prostate biopsies at baseline and 6 mo. The aggressive variant PCa molecular signature (AVPC-MS) was assigned if two or more of these tumor suppressors were abnormal. In the current intent-to-treat analysis, the Kaplan-Meier product-limit method was used to estimate the median PFS.

KEY FINDINGS AND LIMITATIONS: Between March 2013 and April 2018, 119 patients were randomized (arm 1: 59 and arm 2: 60). The median follow-up for patients who survived was 66 mo (64 mo for BST alone and 67 mo for BST plus local therapy groups). BST included androgen deprivation therapy (n = 119), with docetaxel (n = 37) or with androgen receptor pathway inhibitor agents (n = 9). Local therapy included surgery (n = 45), radiation (n = 13), or none (n = 2). At data analysis, 88 patients met Prostate Cancer Working Group 2 progression, and 53 patients had died. The median PFS was 17.9 mo (95% confidence interval [CI] 11.7-36.4) in arm 1 and 14.8 mo (95% CI 11.4-42.9) in arm 2 (hazard ratio [HR] 0.89, 95% CI 0.59-1.34, p = 0.6). Toxicity was limited in both arms, with grade 3 toxicities in four patients (6.7%) in arm 2 and zero patients in arm 1. Three patients required palliative intervention for symptomatic local progression in arm 1, while an additional six patients crossed over to receive local therapy after meeting castration-resistant PCa progression criteria. Predictors of worse overall survival (OS) for all comers included CHAARTED high-volume (HR 1.84, 95% CI 1.06-3.19) and clinical cT3b/T4 (HR 1.97, 95% CI 0.88-4.41) disease. Having the AVPC molecular profile (AVPC-MS) at baseline or 6 mo was significantly associated with worse PFS (HR 1.74, 95% CI 1.02-2.98, p = 0.04). However, there was no statistically significant association with OS (HR 1.83, 95% CI 0.94-3.56, p = 0.08).

CONCLUSIONS AND CLINICAL IMPLICATIONS: This phase 2 randomized study failed to demonstrate improved PFS in men with de novo M1 PCa treated with BST with the addition of local therapy to their primary tumor. Its effect on OS is being tested in an ongoing phase 3 trial (SWOG 1802). We identified biomarkers of potential prognostic value (CHAARTED volume status, cT3b/cT4 disease, and the AVPC-MS) that may serve to optimize therapy selection and stratification in this population, but these require further evaluation.

PMID:41833492 | DOI:10.1016/j.eururo.2026.02.011

Eur J Intern Med. 2026 Mar 14:106819. doi: 10.1016/j.ejim.2026.106819. Online ahead of print.

ABSTRACT

INTRODUCTION: Retinal vascular alterations were reported in patients with SSc suggesting a potential role for OCTA in the evaluation of SSc-related microangiopathy. The aim of the study is to evaluate the microangiopathic alterations in the retina of patients with SSc and to evaluate their correlation with the clinical manifestations of the disease and the capillaroscopic findings MATERIALS AND METHODS: This is a case-control study comparing SSc patients to healthy controls. OCTA acquisition consisted on scans of the superficial capillary plexus (SCP) and deep capillary plexus (DCP) of both the macula and the optic nerve, performed using Canon OCT. Vascular density (VD), vascular length density (VLD), foveal avascular zone (FAZ) and retinal thickness in the fovea and in the perifoveal region were obtained using dedicated software.

RESULTS: 41 SSc patients (11 were VEDOSS) were compared with 20 healthy controls. SSc patients showed reduced VD and VLD values ​​in all areas evaluated both in the SCP and DCP (p < 0.001 for both). At the optic nerve level, both VD and VLD values ​​were reduced at the SCP (p < 0.001 for both) and DCP levels (p = 0.009 and p < 0.001). Retinal thickness in the parafoveal region was increased in SSc patients (p = 0.013) and correlated with blood flow at nailfold videocapillascopy (p = 0.030). VD and VLD at the foveal level in DCP were associated with the presence of avascular areas (p = 0.018 and p = 0.019) and neoangiogenesis (p = 0.023 and p = 0.025).

CONCLUSION: Ocular microangiopathy is present in scleroderma patients since the early stages of the disease and is correlated with capillaroscopic alterations.

PMID:41833472 | DOI:10.1016/j.ejim.2026.106819

J Mass Spectrom. 2026 Apr;61(4):e70047. doi: 10.1002/jms.70047.

ABSTRACT

Mussel aquaculture has experienced substantial growth in recent decades, with global production exceeding 2.17 megatons (live weight), more than doubling since the early 21st century. Representing nearly 94% of the total mussel production, aquaculture plays a crucial economic and ecological role. Mussels accumulate xenobiotics through their filter-feeding behaviour, providing valuable insights into potential human exposure to the contaminants. However, the high lipid and protein content in their tissue can introduce analytical challenges, requiring rigorous clean-up procedures to mitigate matrix effects. Herein, we applied a QuEChERS-based extraction method coupled with high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) to investigate the occurrence of emerging contaminants (ECs) in raw and boiled Mytilus galloprovincialis samples. Samples were collected from three aquaculture farms supplying mussels to fish markets in Liguria (Italy), aiming to provide a representative overview of contamination across different geographical sources. A total of 36 samples were analysed, detecting ECs in 26 samples. Caffeine was the most frequently detected contaminant, consistent with its widespread consumption. Additionally, UV filters were also commonly found in the samples, likely due to the sampling period at the end of summer, when sunscreen use is highest. This is the first study to investigate the impact of cooking on the concentrations of different classes of ECs in mussels, reflecting real consumption conditions. Box and whisker plots revealed consistently higher contaminant concentrations in boiled samples, suggesting that thermal processing may influence contaminant release. This study aims to offer insights into contaminants distribution and preliminary information for human exposure assessment of potential risks to human health.

PMID:41833453 | DOI:10.1002/jms.70047

J Sch Psychol. 2026 Apr;115:101528. doi: 10.1016/j.jsp.2025.101528. Epub 2026 Feb 12.

ABSTRACT

This paper proposes new data-analysis reporting guidelines for researchers conducting single-case experimental design (SCED) research. Statistical analyses of SCED data are being used with higher frequency and across a wider range of disciplines in the health sciences, behavioral sciences, and education. Building on prior reporting standards for other domains of quantitative intervention research, we present the role of visual and statistical analysis of SCED data, with specific tabled recommendations for professional reporting guidelines. We expand the Journal Article Reporting Standards (JARS) presented by Appelbaum et al. (2018) and the Single-Case Reporting Guideline In Behavioral Interventions (SCRIBE) 2016 Checklist (Tate et al., 2016). In particular, we feature expanded guidelines for visual and statistical analysis of SCED intervention methodology, including guidelines within both nonrandomized and randomized design domains. These recommendations are intended as a guide for conducting original research to establish evidence-based practices.

PMID:41833442 | DOI:10.1016/j.jsp.2025.101528

Adv Sci (Weinh). 2026 Mar 15:e21637. doi: 10.1002/advs.202521637. Online ahead of print.

ABSTRACT

Conventional methods to control electromagnetic (EM) fields via digital coding metasurfaces are basically focused on generating deterministic EM responses, such as beam forming, holographic imaging, and harmonic modulation, by employing specific coding patterns or sequences. In contrast, controlling random EM fields aims to produce EM fields with target temporal statistical properties, such as spatial mean and variance distributions. Here, we propose a framework to control the spatial distribution of temporal statistical properties of EM fields via random time-space coding metasurfaces (RTCM). We establish a statistical model of RTCM in probability space and reveal that the spatial mean and variance distributions of EM fields are determined by the marginal and pairwise joint distributions of the random codes. Time-varying random EM fields with desired mean and variance distributions are generated by the sampling codes constrained by these distributions. We further show that simultaneously direct transmission and jamming can be achieved via the spatial mean and variance peaks, respectively. This work extends the metasurface paradigm into the probability domain, marking a shift from deterministic response design to probabilistic structuring, and paving the way for new approaches in communication, information security, and EM countermeasures.

PMID:41833001 | DOI:10.1002/advs.202521637

QJM. 2026 Mar 14:hcag077. doi: 10.1093/qjmed/hcag077. Online ahead of print.

ABSTRACT

BACKGROUND: Healthcare professionals working in hospitals during armed conflict are exposed to extreme psychological stress while maintaining clinical duties. Although psychological distress is well documented, the biological mechanisms linking wartime stress to functional outcomes such as workability remain insufficiently characterized.

OBJECTIVES: To investigate associations between psychological distress, perceived stress, workability, and inflammatory biomarkers among healthy hospital healthcare professionals working under acute wartime conditions.

METHODS: A prospective observational study was conducted among 90 healthy healthcare professionals employed at a hospital in central Israel during the October 2023 missile attacks. Participants completed validated questionnaires assessing psychological distress, perceived stress, and workability. Blood samples were collected to measure inflammatory biomarkers. Associations between psychological measures, workability indices, and biomarker levels were analyzed using multivariable statistical models.

RESULTS: Higher levels of psychological distress and perceived stress were significantly associated with reduced workability scores. Elevated stress measures correlated with increased levels of pro-inflammatory biomarkers, suggesting activation of inflammatory pathways. These biological changes partially mediated the relationship between psychological distress and impaired workability.

CONCLUSIONS: Acute wartime stress among hospital healthcare professionals is associated with both psychological impairment and measurable inflammatory responses, which may contribute to reduced functional capacity. These findings provide insight into the biological embedding of extreme occupational stress and underscore the need for targeted psychosocial and organizational interventions to protect healthcare workers operating under conflict conditions.

PMID:41832997 | DOI:10.1093/qjmed/hcag077

Oncologist. 2026 Mar 14:oyag081. doi: 10.1093/oncolo/oyag081. Online ahead of print.

ABSTRACT

BACKGROUND: Given the superior relapse-free survival (RFS) and different safety profiles of 1 year of adjuvant S-1 or uracil/tegafur (UFT) for stage II/III rectal cancer, the benefit-risk of these two regimens was formally assessed using the Net Treatment Benefit (NTB).

PATIENTS AND METHODS: Individual patient data from the JFMC 35-C1 trial were used. S-1 and UFT were compared regarding RFS, incidence of grade ≥3 symptoms, and incidence of grade ≥3 laboratory abnormalities reported as adverse events (AEs). Laboratory abnormalities and symptoms were analyzed as binary variables and as counts. Univariate and multivariate NTBs were computed for various ways of prioritizing the outcomes.

RESULTS: The univariate NTB for RFS was 9.2% (95% confidence interval [CI], 3.4% to 15.2%, P = 0.005) in favor of S-1. The univariate NTB was not statistically significant for any symptom. For grade ≥3 laboratory AEs, only thrombocytopenia was statistically significant in favor of UFT (NTB=-0.8%; 95% CI, -1.6% to -0.02%; P = 0.044). In the multivariate analysis considering RFS as the outcome of first priority, the incidence of grade ≥3 symptoms as second, and the incidence of grade ≥3 laboratory abnormalities as third, the multivariate NTB was 8.8% (95% CI, 2.7% to 14.9%, P = 0.014) in favor of S-1. In sensitivity analyses according to age group, the NTB was generally positive for patients <70 years but non-significant for those ≥70 years old.

CONCLUSION: The reanalysis of the JFMC 35-C1 trial suggests that S-1 has a superior benefit-risk to UFT when RFS is considered as the outcome of first priority, followed by the incidence of grade ≥3 symptoms and of grade ≥3 laboratory abnormalities.

PMID:41832993 | DOI:10.1093/oncolo/oyag081

Endocr Metab Immune Disord Drug Targets. 2026 Mar 9. doi: 10.2174/0118715303462423260125161230. Online ahead of print.

ABSTRACT

INTRODUCTION: Osteoporosis (OP) is a major public health burden; however, the role of SERPIN family proteins remains incompletely understood. This study aimed to investigate genetically inferred associations between SERPINs and OP and to explore potential regulatory relationships.

METHODS: Genome-wide association study (GWAS) summary statistics were used to perform two sample Mendelian randomization (MR) and summary-data-based Mendelian randomization (SMR) analyses. Primary MR estimates were derived using inverse-variance-weighted (IVW), MR-Egger, weighted median, simple mode, and weighted mode methods. Cancellous bone tissue from the greater trochanter of the femur was collected from three patients with OP and three non-osteoporotic controls. qPCR and WB were used to analyze the whole bone homogenate, IHC was used to detect decalcified bone sections, and mediation analysis was used to explore potential regulatory associations.

RESULTS: Among the proteins of the SERPIN family, only SERPING1 had an obvious positive correlation with the risk of osteoporosis (OR = 1.06, P = 0.0012). qPCR, WB, and IHC analyses demonstrated increased SERPING1 mRNA and protein expression in bone tissue from OP patients. Mediation analyses suggested that cg15918732 DNA methylation may serve as an upstream regulatory factor for SERPING1 expression. In addition, the downstream associations also consist of the alteration of immune cell conditions, like the decrease in the quantity of natural killer cells and T cells, and the rise in the level of mononuclear cells, and so forth.

DISCUSSION: These findings provide genetic evidence for the possible role of SERPING1 in OP, which may be achieved through epigenetic regulation and immune pathways. Due to the corresponding characteristics of genetic inference and the small sample size, these results are hypothetical and generative.

CONCLUSION: This study shows that DNA methylation of cg15918732 may be associated with SERPING1 expression in osteoporosis and immune-related traits. These findings provide new insights into potential epigenetic and immunological pathways in osteoporosis, which may contribute to future mechanistic and translational research.

PMID:41832983 | DOI:10.2174/0118715303462423260125161230

Int J Qual Health Care. 2026 Mar 14:mzag038. doi: 10.1093/intqhc/mzag038. Online ahead of print.

ABSTRACT

INTRODUCTION: Diagnostic errors in laboratory processes can compromise the accuracy of final diagnoses. Such errors represent a significant patient safety concern and are linked to adverse clinical outcomes. This study aimed to determine the frequency, types, and impacts of laboratory-related diagnostic errors on the final clinical diagnosis, patient harm, and organizational reputation in a large private hospital network in Thailand.

METHODS: A retrospective study analyzed diagnostic errors in clinical laboratory testing processes at Bangkok Hospital Headquarters (BHQ), Thailand, over a three-year period (January 1, 2021-December 31, 2023). Data were retrieved from a voluntary incident reporting system covering domains such as clinical hematology, clinical chemistry, metabolic diagnostics, genetics, microbiology, hormonology, serology, and coagulation. Descriptive statistics were employed to classify errors by laboratory process, sub-process, and subtype, identify causal factors, and evaluated the clinical impacts.

RESULTS: Out of 5,951,783 samples processed, 34,395 incidents were reported, of which 1,031 (2.9%) related to diagnostic errors. Errors predominantly occurred in the pre-analytical process (89.2%), followed by post-analytical (10.7%) and analytical process (0.1%). The most common error subtypes were incorrect test ordering (48.2%) and specimen collection (34.6%). Human factors accounted for 91.1% of errors, with technical and organizational factors contributing minimally. 90.6% of errors had no impact on final clinical diagnosis; 7.8% resulted in delayed diagnosis, 0.9% in missed diagnosis, and 0.7% in wrong diagnoses. Most errors (98%) caused no patient harm, 1.9% led to temporary harm, and one error affected organizational reputation. No sentinel events were reported.

DISCUSSION AND CONCLUSION: To strengthen diagnostic safety across healthcare systems, organizations should adopt comprehensive, system-level strategies that effectively address human-factor vulnerabilities and streamline laboratory workflows. Implementing evidence-based strategies could contribute to achieving higher diagnostic accuracy and advancing patient safety within clinical laboratory processes.

PMID:41832967 | DOI:10.1093/intqhc/mzag038

JNCI Cancer Spectr. 2026 Mar 14:pkag024. doi: 10.1093/jncics/pkag024. Online ahead of print.

ABSTRACT

BACKGROUND: S0221 investigated weekly vs (vs) every 2 weeks (Q2W) dosing of doxorubicin(A)/cyclophosphamide (C) followed by paclitaxel (P) in patients with high-risk early breast cancer. After an interim analysis, randomization to the two AC arms was stopped for futility and the trial was modified to study only the P schedules.

PATIENTS AND METHODS: Between December 2003 and November 2010, 2716 patients were randomized in a 2 x 2 factorial design to: 15 weeks of weekly A and daily C vs 6 cycles of Q2W AC; and weekly P for 12 weeks vs 6 cycles of Q2W P. Between January 2011 and January 2012, an additional 578 patients were assigned to 4 cycles of Q2W AC x 4 and randomized to weekly vs Q2W P. Updated survival was assessed using log-rank tests and Cox regression models. We compared outcomes by breast cancer subtype as well.

RESULTS: At a median follow-up of 12.1 years, there were no significant differences among the four treatment arms in disease free survival [DFS] (p = 0.91) or overall survival [OS] (p = 0.34) in the original protocol. Among the 578 patients assigned AC for 4 cycles and randomized to P weekly vs Q2W P, there were no overall differences in DFS (p = 0.32) or OS (p = 0.42).

CONCLUSION: As there were no significant outcome differences in DFS or OS between the studied schedules of AC and P with extended follow-up in the original or revised protocol, either paclitaxel schedule may be recommended, with selection based on toxicity, cost, or patient preference.

PMID:41832961 | DOI:10.1093/jncics/pkag024