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Circulating tumor cells predict myeloma outcomes in patients treated with daratumumab, bortezomib, lenalidomide, and dexamethasone
No full textCirculating tumor cells (CTC) represent a high-risk biomarker in newly diagnosed multiple myeloma (NDMM); however, their prognostic value among transplant-eligible (TE) patients receiving daratumumab/bortezomib/lenalidomide/dexamethasone (D-VRd) remains unknown. In this study, we analyzed CTC in the phase 3 PERSEUS/EMN017 trial. TE-NDMM patients were randomized (1:1) to D-VRd with daratumumab/lenalidomide maintenance (D-VRd group) or bortezomib/lenalidomide/dexamethasone (VRd) with lenalidomide maintenance (VRd group), both with transplant. A subset of 451 of 709 patients from PERSEUS (D-VRd, 231/355; VRd, 220/354) had screening blood samples collected for CTC analysis by flow cytometry. CTC were detected in 370 patients (82%; median limit of detection, 0.0004%). CTC were prognostic of progression-free survival (PFS), independent of other factors, as a continuous (hazard ratio [HR], 1.36 [95% confidence interval (CI), 1.15-1.60]; P < .001) and categorical variable (≥0.175% CTC-high, optimal threshold). D-VRd improved PFS vs VRd in CTC-low patients (4-year rates: 88% vs 74%; HR, 0.42 [95% CI, 0.25-0.70]; P = .0013). Regardless of study treatment, minimal residual disease (MRD)-negativity rates were lower in CTC-high vs CTC-low patients (10–5: 52.2% vs 66.2%; 10–6: 34.8% vs 52.4%). D-VRd significantly increased MRD-negativity rates vs VRd among CTC-high (10–5: 69.4% vs 33.3%; 10–6: 47.2% vs 21.2%; both P < .05) and CTC-low patients (10–5: 74.4% vs 57.8%; 10–6: 65.6% vs 38.5%; both P < .001), with similar observations for sustained MRD-negativity. CTC levels are an independent prognostic factor in TE-NDMM treated with standard-of-care frontline quadruplet. D-VRd improved and sustained MRD-negativity rates in CTC-high and CTC-low, and improved PFS for CTC-low with a positive trend in CTC-high patients. This trial was registered atwww.clinicaltrials.govas #NCT03710603.</p
Identifying facilitators and barriers to implementing the Feverkidstool, a clinical decision tool, in the emergency department:a qualitative study in the Netherlands
No full textObjectives This study aimed to identify determinants that hinder or facilitate implementation of the Feverkidstool, a clinical decision support tool offering a quantitative, evidence-based approach, to manage children with fever in the emergency department (ED) setting. Design Qualitative study using semistructured interviews, analysed through directed content analysis guided by the Consolidated Framework for Implementation Research (CFIR). Setting Secondary and tertiary paediatric emergency departments in three hospitals in the Netherlands. Participants Eighteen potential end users of the Feverkidstool, including paediatricians and paediatric residents working in the ED and involved in the care of febrile children, participated in the study. Primary outcome measure Determinants of Feverkidstool implementation, categorised by CFIR domains: intervention characteristics, outer setting, inner setting, characteristics of individuals and implementation process. Results Respondents (n=18) perceived the evidence-based guidance by the Feverkidstool and its potential to reduce antibiotic use as valuable. However, concerns were raised about its applicability to critically ill children and those with comorbidities. User-friendliness was seen as a facilitator, whereas the need for C reactive protein testing and lack of integration with electronic health records were mentioned as barriers. The ability to standardise care for febrile children was considered an important benefit of using the Feverkidstool. Conclusion Barriers and facilitators across all CFIR domains are identified. Addressing these will facilitate implementation. When effectively implemented, the Feverkidstool has the potential to improve care for children presenting with fever in the ED. This may potentially lead to a more standardised approach and reduce unnecessary antibiotic prescriptions.</p
Exploring blood transcriptional signatures for thrombosis diagnosis in critically ill patients with COVID-19
No full textCOVID-19 has revealed novel pathological mechanisms, particularly hypercoagulability, which leads to increased thrombotic risk in critically ill patients. This study investigates transcriptional signatures associated with thrombosis development in patients with COVID-19 in the intensive care unit and evaluates their predictive potential. We performed whole-blood transcriptional profiling of 57 mechanically ventilated patients with COVID-19, comparing those with thrombotic complications (TC; n = 36) with those without (non-TC, n = 21) using differential gene expression and machine learning approaches. Patients with TC showed greater transcriptome disruption and 283 differentially expressed genes compared with patients without TC. Key features included enhanced neutrophil activation, inflammatory responses, and monocyte activation alongside suppressed lymphocyte function. An orthogonal partial least squares discriminant analysis model achieved excellent classification performance (area under the curve [AUC] = 0.961; 95% confidence interval, 0.905-0.997). The maltase-glucoamylase (MGAM) gene was the top discriminatory biomarker outperforming traditional clinical markers such as D-dimer and C-reactive protein (AUC, 0.94). TC in critically ill patients with COVID-19 are characterized by distinct transcriptional signatures reflecting heightened neutrophil activation and inflammatory dysregulation. MGAM represents a novel potential biomarker that outperforms traditional clinical markers for identifying patients at high thrombotic risk, offering new opportunities for personalized risk stratification and management in severe COVID-19.</p
Expression of low molecular weight protein tyrosine phosphatase in gastric cancer and its association with clinical outcomes and oncogenic hallmarks
No full textBackground: Low molecular weight protein tyrosine phosphatase (LMWPTP), encoded by the ACP1 gene, has been implicated in tumor progression across multiple malignancies. While its oncogenic functions have been reported in colorectal cancer (CRC), its role in gastric cancer (GC) remains poorly defined. This study investigated the expression patterns, functional relevance, and prognostic impact of LMWPTP in GC, with comparative analyses in CRC. Methods: Gene expression, immune infiltration, and survival analyses were performed using data from The Cancer Genome Altas (TCGA). LMWPTP protein expression was evaluated in a gastric cancer tissue microarray. Functional assays were conducted in GC and CRC cell lines with CRISPR-Cas9-mediated LMWPTP knockout.Results: ACP1 mRNA expression was significantly upregulated in both GC and CRC compared with adjacent normal tissues. In GC, high LMWPTP expression was associated with poor differentiation in intestinal-type tumors and reduced survival in diffuse-type cases. ACP1 overexpression correlated with an elevated tumor mutation burden but a decreased cytotoxic lymphocyte infiltration signature in GC, indicating a potential relationship between ACP1 expression, tumor mutational load, and tumor immune microenvironment. Functional assays in vitro showed that LMWPTP knockout reduced migration in both GC and CRC cells, whereas a decrease in invasion was observed only in CRC cells. These findings indicate context-dependent contributions of LMWPTP to gastrointestinal tumor biology. Conclusion: LMWPTP is consistently upregulated in gastric and colorectal cancers and exhibits tumor-type-specific functional and immune associated features. These findings highlight its distinct oncogenic role and potential as a biomarker and therapeutic target in GC.</p
Type-2 Biomarkers, Asthma Diagnosis and Lung Function Impairment in the General Population
No full textInstruments to measure nurses' intention-to-stay in the profession:A systematic literature review
No full textIntroduction:There is a large and increasing shortage of nursing staff. To alleviate this problem, healthcare systems should prioritize healthcare interventions that improve nurse retention over healthcare interventions that reduce it or leave it unchanged. One way to do so is to evaluate interventions on their anticipated impact on nurse intention-to-stay, which is an important precursor of retention. An overview of available instruments to quantify nurse intention-to-stay is lacking, resulting in researchers re-inventing the wheel. This review aims to fill this gap. Methods:A systematic literature search was performed in the databases Medline ALL via Ovid, Embase.com, Web of Science Core Collection, CINAHL Plus, PsycINFO, the Cochrane Central Register of Controlled Trials via Wiley, and Google Scholar (200 highest-ranked references only). The search string consisted of terms and associated synonyms for 1) nursing staff, 2) personnel intent to stay/leave, and 3) surveys. Articles were included when there was a quantitative method mentioned for measuring the intention of nurses to stay or quit nursing and/or their job/position/organization. Information was extracted on the year of publication, study design, study population, number of participants, instrument used for measuring intention-to-stay, and whether the instrument was focused on leaving the job, organization, or profession. In addition, we checked whether the instrument was used to evaluate the (expected or realized) impact of an intervention and if an association was determined between intention-to-stay (measured through the instrument) and retention. The protocol was not registered.Results:967 articles fulfilled our inclusion criteria, most of which were published in recent years. A total of 485 instruments were found. Nine regularly used instruments were identified, differing in their respective popularity over time, their size, the population for which they were developed and the strength of their link to actual retention. Notably, compared with the large body of literature on nurse intention-to-stay generally, the number of studies specifically measuring the impact of an intervention on nurse intention-to-stay is limited (n=20). Most of these intervention studies focused on changes in nurse training/mentorship or mental health support.Discussion & conclusion:Many different instruments exist to measure nurses' intention-to-stay. To add to our identified instruments, a comparative study is needed to identify which instrument offers the strongest predictive value for nurse retention. The absence of studies specifically evaluating the impact of interventions on nurses' intention-to-stay creates a critical gap in understanding how health interventions influence retention. Funding Dutch Research Council, 406.XS.04.151.</p
Invisible string(s):Exploring conspiratorial participatory practices among Swifties
No full textThis study explores how Taylor Swift fans, so-called “Swifties,” engage in playful, conspiratorial participation by interpreting hidden messages and developing fan theories, especially around Swift’s queer identity (the “Gaylor” discourse). Drawing on interviews with 18 fans, this article presents an in-depth perspective, demonstrating how speculative fandom blurs the line between interpretive play and conspiracist logic. This helps reveal how participatory practices mirror the structures of (political) conspiracies. Fans organize around theory-building, decipher cryptic clues, and negotiate interpretive boundaries, which echoes behaviors found in extremist communities. These findings suggest that conspiratorial thinking and practices are no longer confined to fringe groups but are embedded in everyday cultural participation, including mainstream pop-culture fandoms. By tracing these participatory practices among Swifties, this research contributes to a broader understanding of how conspiratorial play becomes normalized, offering a cultural lens into the mainstreaming of extremism in today’s societies.</p
The “Good Old Days” Bias and Feigning:Examining the Response Patterns in Genuine and Feigned Injury Accounts
No full textIn this simulation study, we investigated whether the “Good Old Days” (GOD) bias, typically associated with genuine symptom accounts, also occurs in fabricated injury accounts. Based on injury pre-screening, students were allocated to Injured (n= 69), Uninjured (n= 46), or Feigning groups (n= 39). Participants (N= 154) completed well-being and symptom scales and response bias tests, for the pre-injury and current period. The GOD bias, as the discrepancy between these scores, was absent in Uninjured, but present among the Injured and Feigning groups, with larger discrepancies among feigners. Thus, GOD bias presence alone cannot differentiate genuine from fabricated accounts, but its magnitude may inform symptom validity assessment.</p
West Nile Virus and Usutu Virus Neutralizing Antibodies Found in Dutch Rodent Species
No full textBackground:In the Netherlands, Usutu virus (USUV) is endemic in birds, and recently West Nile virus (WNV) was also detected in birds, mosquitoes and humans. Here we investigated the possible role of rodents in the viruses' transmission ecology. Materials and Methods: We sampled rodents at six locations including sites where WNV had been previously detected. Brains (n = 668), oral swabs (n = 282), and ticks (n = 91) collected from rodents were tested for arboviruses via Reverse Transcriptase Polymerase Chain Reaction (RT-PCR). Also, sera from 118 rodents were tested for WNV- and USUV-antibodies. Results and Conclusion: Brain samples, swabs, and ticks tested negative for viral RNA. However, 2.5% (3/118; two wood mice, one field vole) of rodents had WNV-neutralizing antibodies (WNV-NAbs). USUV-NAbs were detected in a wood mouse. Two bank voles had NAbs against both viruses. The WNV and USUV antibody-positive rodents were found at locations with previous WNV and USUV circulations, suggesting that rodents may be involved in the ecology of WNV and USUV.</p
Colchicine Alleviates Non-Atherosclerotic Vascular Aging by Targeting Endothelial Dysfunction and Inflammatory Status
No full textBackground: Non-atherosclerotic vascular aging (NAVA) contributes to cardiovascular risk through progressive arterial stiffening and endothelial dysfunction. Colchicine, best known for anti-inflammatory activity, has been proposed to protect vascular structure and function. We evaluated whether chronic colchicine mitigates NAVA in a smooth-muscle–specific ERCC1 knockout (SMC-KO) mouse model of DNA-damage–driven vascular aging.Methods:We performed experiments in the SMC-KO treated with colchicine (0.1mg/kg/day) or vehicle from the age of 10 to 22 weeks. Endothelial function was assessed by acetylcholine-induced vasorelaxation, and vascular structure by pulse-wave velocity (PWV), carotid intima–media thickness (cIMT), and elastin integrity. Results: SMC-KO mice developed increased arterial stiffness and impaired acetylcholine-mediated relaxation. Chronic colchicine significantly (p<0.01) lowered PWV, preserved elastin architecture, and improved endothelium-dependent relaxation, while sodium-nitroprusside responses and systemic cytokine levels remained unchanged.Conclusion: Chronic colchicine treatment preserves endothelial function and vascular elastin structure and reduces arterial stiffness in a DNA-damage–driven model of non-atherosclerotic vascular aging. These findings highlight colchicine’s pleiotropic vascular benefits beyond anti-inflammation, supporting its potential repurposing for primary prevention in vascular aging and cardiovascular health or the development of colchicine-mimicking drugs with greater selectivity and improved safety profiles.</p