Search Results (7,211)

Rapid hemostasis assessment is essential for managing acute coagulopathy, guiding anticoagulant therapy, and monitoring cardiac surgery patients. Although viscoelastic testing provides valuable guidance for early intervention, its widespread adoption is constrained by large blood usage (~2 mL), prolonged turnaround times (several hours), long assay durations (~25–40 min), and high costs. To overcome these limitations, we developed an innovative, all-in-one magnetoelastic (ME) sensing chip that enables systematic coagulation kinetics monitoring using only 46 μL of whole blood within 15 min. Featuring prepackaged lyophilized reagents and pumpless blood loading, this user-friendly chip is highly cost-effective for disposable use. The experimental results demonstrated good reproducibility for on-chip extrinsic coagulation activation, with clotting parameters maintaining coefficients of variation under 10%. Furthermore, clotting parameters derived from heparin monitoring results exhibited a strong linear correlation that compares favorably with the clinical standard (r = 0.986). Finally, sensitivity evaluation toward various blood components validated the sensor’s dual-mode characterization strategy for identifying coagulation factors and fibrin-related coagulopathies. The proposed ME sensing chip holds promise for bedside testing and flexible, on-demand coagulation monitoring across diverse clinical scenarios. Full article

Background: Tetranectin (TN) is a protein that plays a role in tissue remodeling. In adults with heart failure, TN has a better prognostic value compared to B-type natriuretic peptide (BNP). We aimed to examine changes in TN in neonates following the Norwood operation and explore its prognostic value. Methods: Retrospective observational pilot cohort study in a tertiary pediatric cardiac intensive care unit. Neonates who underwent the Norwood procedure and had stored plasma samples in our biorepository were screened for inclusion. TN and BNP levels were measured by ELISA at five different time points in relation to cardiopulmonary bypass (CPB) in 26 neonates who met the inclusion criteria. The primary outcomes were time to lactate clearance and duration of inotropic support. Results: Univariate analysis showed that higher TN levels at 0 and 4 h were associated with a longer duration of inotropic support. Logistic regression analyses comparing TN levels at different time points with duration of inotropic support showed that TN level at 4 h post-CPB was a significant predictor (p = 0.04) for a longer duration of inotropic support with an AUC of 0.876. Conclusions: In this pilot cohort, higher observed TN concentrations in the early post-operative period were associated with longer duration of inotropic support. TN was not found to be significantly associated with time to lactate clearance. These exploratory findings require validation in larger prospective studies before TN can be considered for clinical prognostication. Full article

Hepatitis B virus (HBV), hepatitis C virus (HCV), and hepatitis D virus (HDV), together with HIV and bacterial sexually transmitted infections (STIs), account for a rising toll of more than one million deaths annually and overlap within shared behavioral and social networks, yet are still diagnosed through separate, pathogen-specific pathways. This narrative review synthesizes contemporary evidence on the convergence between viral hepatitis, HIV, and high-risk STI groups—men who have sex with men, pre-exposure prophylaxis (PrEP) users, people practicing chemsex, people who inject drugs, incarcerated populations, and migrants from endemic regions—and characterizes the diagnostic technologies and linkage-to-care models available to address it. Despite effective antivirals, the diagnostic cascade remains the principal bottleneck: most people with chronic HCV are undiagnosed, and HDV—with a pooled anti-HDV seroprevalence of approximately 4.5% among HBsAg-positive individuals—is its clearest expression, as most carriers are never tested. Reflex algorithms, multiplex panels, point-of-care assays, dried blood spots, and electronic health record alerts are validated but unevenly implemented. We argue that, alongside persistent resource, political, and equity-related constraints, a substantial share of the remaining barriers is operational rather than purely technological, and propose a practical, STI-clinic-centered framework integrating reflex testing, population-specific periodicity, and explicit linkage pathways toward the WHO 2030 elimination targets. Full article

Background/Objectives: The aim of this study was to simulate the impact of different minimum case volume thresholds, introduced under Germany’s Hospital Care Improvement Act, on the geographic accessibility of inpatient neurosurgical care. The Act introduces minimum case volume thresholds per service group, potentially leading to closures of low-volume neurosurgical units and reduced accessibility within 40 min of driving time (A2N40, Accessibility to a Neurosurgical Facility within 40 min). Methods: Inpatient case volumes of neurosurgical facilities were extracted from the Structured Quality Reports for reporting years 2023 and 2024, published by the Federal Joint Committee. Facilities were geocoded, 40-min driving time isochrones were generated, and the population within each isochrone was calculated. Results: At baseline in 2024, 66.6% of Germany’s area and 84.7% of the population were within the A2N40. Each one-percentile-point increase in the case volume threshold reduced A2N40 area coverage by an average of 0.70 percentage points, corresponding to approximately 305,000 additional people losing access, with the largest reductions observed in rural, less densely populated regions of the eastern federal states. Conclusions: Minimum case volume thresholds may substantially reduce the geographic accessibility of neurosurgical facilities, revealing a measurable trade-off between quality assurance through centralisation and geographic access to care, particularly in rural regions. The presented simulation approach can support evidence-based, geographically informed planning of future minimum case volume regulations. Full article

Pushing ahead in materials chemistry means building tiny substances that work hard and take into account clean power, planet care, life science all at once. From this effort comes a new direction: ZIF-8, a metal-linked cage structure, now fused with active components extracted from the common fungus Aspergillus nidulans. Not just mixed, but grown together with fungal extracts tucked neatly into the skeleton of the material while keeping its orderly shape intact. Three versions appeared—loaded at 2%, 4%, and 6 weight percent—and each one was mapped out using X-ray signals, sharp images from electron scans, and element tracing. A light flickered on and off during tests in which electricity flowed through these new composites set between three points, designed to split water and release hydrogen gas. Surprisingly, the ZIF-8@2% nidulans blend showed strong teamwork between electricity- and light-driven biology, creating a sharp spike in temporary current while cutting down reaction delay to just 310 mV/dec—pushing hydrogen release through a faster molecular handshake. In this mix, natural compounds from fungi act like tiny solar collectors, helping electrons move more freely, which is reflected in impedance scans as lower resistance. On top of that, higher doses of the material effectively blocked harmful microbes, thanks to ZIF-8 breaking cell walls and active fungal ingredients punching holes as well. Instead of relying on harsh chemicals, it uses a nature-inspired design in which molds meet synthetic frameworks, creating a single system with potential for sustainable energy generation and antimicrobial applications. Full article

Background/Objectives: Exacerbations of chronic obstructive pulmonary disease (COPD) are a common reason for emergency department (ED) attendance and hospital admission. Acute respiratory worsening is non-specific, and previous spirometric confirmation may be unavailable at presentation. We aimed to translate current recommendations into an ED-specific clinical pathway that standardizes safety-critical steps without replacing individualized clinical judgment. Methods: We performed a targeted synthesis of international and Spanish guidance and key studies relevant to ED diagnosis, severity assessment, pharmacological treatment, respiratory support, antimicrobial stewardship, and disposition. The evidence base was updated in June 2026, and the pathway was reviewed by a multidisciplinary clinical group. Results: The revised pathway comprises four stages: (1) verify previous COPD confirmation, identify an acute exacerbation-like syndrome, and assess alternative or concomitant diagnoses; (2) grade acute severity using point-of-care variables and separately assess patient vulnerability; (3) provide severity-adjusted treatment with early reassessment; and (4) determine disposition and follow-up. It incorporates controlled oxygen, individualized bronchodilator delivery, explicit criteria for systemic corticosteroids and antibiotics, assessment of risk for Pseudomonas aeruginosa, non-invasive ventilation (NIV), and a defined adjunctive role for high-flow nasal cannula (HFNC). Patients without previous post-bronchodilator spirometry are classified as having suspected COPD and require confirmation after recovery. Conclusions: This evidence-informed pathway is a preliminary clinical framework, not a diagnostic rule or validated decision instrument. It is intended to support, rather than replace, professional judgment. Feasibility, acceptability, diagnostic safety, and clinical impact require prospective evaluation, beginning with a pilot implementation study. Full article

Antimicrobial resistance (AMR), largely driven by the inappropriate and excessive use of antibiotics, requires rapid and reliable bacterial detection and antibiotic susceptibility testing (AST), as conventional culture-based methods remain time-intensive. Here, we report a real-time, label-free interdigitated wave electrode array (IWEA) that combines dielectrophoretic (DEP) enrichment with impedance spectroscopy for rapid bacterial detection and AST. The proposed IWEA was designed and optimized via COMSOL Multiphysics to enhance DEP-relevant electric-field strength, thereby improving DEP-assisted bacterial enrichment compared to conventional planar interdigitated electrodes. The platform enabled sensitive detection of both Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) in 0.1× PBS across 10–10⁵ CFU/mL within 30 min using DEP-assisted preconcentration (100 kHz, 10 V_pp), outperforming passive (non-DEP) operation (10²–10⁵ CFU/mL). For AST, bacterial responses to vancomycin, gentamicin, and ampicillin were monitored through impedance variations following DEP-based enrichment. Susceptible bacteria produced concentration-dependent reductions in ΔZ/Z₀, whereas resistant bacteria showed similar responses to untreated controls. Quantitative assessment yielded CC₅₀ values of 2.86 ± 0.22 µg/mL and 3.06 ± 0.20 µg/mL for vancomycin and gentamicin against S. aureus, and 4.59 ± 0.30 µg/mL for gentamicin against E. coli. Resistance profiles of S. aureus to ampicillin and E. coli to vancomycin and ampicillin were clearly distinguished. SEM imaging and disk diffusion assays independently validated the impedance-derived susceptibility results. Collectively, this IWEA platform offers a rapid, label-free, and quantitative approach for bacterial detection and AST, with strong potential for antimicrobial screening and point-of-care diagnostics. Full article

Dengue virus (DENV) remains a major global public health challenge, driven by the expanding distribution of Aedes vectors, rapid urbanization, and increasing climate variability. This review aimed to synthesize current evidence on dengue transmission dynamics, immunopathogenesis, molecular epidemiology, diagnostic and therapeutic advances, vaccine development, and the influence of climatic factors on disease patterns. A comprehensive search of major electronic databases was conducted to identify relevant literature, followed by a qualitative synthesis of the evidence. The evidence highlights complex transmission cycles involving Aedes aegypti and Aedes albopictus, with transmission strongly influenced by temperature, humidity, rainfall, and extreme climate events. Advances in immunopathogenesis research have improved understanding of mechanisms associated with severe disease, including antibody-dependent enhancement and dysregulated inflammatory responses. Diagnostic innovations, such as reverse transcription polymerase chain reaction (RT-PCR), NS1 antigen detection, and point-of-care technologies, have enhanced case identification, while prevention strategies increasingly incorporate integrated vector management, digital surveillance systems, and emerging vaccines. Integrating epidemiological, molecular, and climatic information may strengthen early warning systems, improve outbreak prediction, and support more effective dengue prevention and control strategies. Full article

Background/Objectives: Whether the prognostic contribution of low skeletal muscle mass varies with age in ventilated patients is untested. We assessed whether the association between low computed tomography (CT)-derived thoracic muscle area and ventilator-liberation outcomes differs by age. Methods: This single-center retrospective cohort included 607 adults with pneumonia requiring invasive ventilation in the intensive care unit (ICU) between 2016 and 2021. Thoracic muscle area was quantified by deep-learning segmentation of the whole thoracic musculature (first to twelfth thoracic vertebra) on the chest CT obtained closest to ICU admission and normalized to the length of the thoracic spine (median offset 0 days; 86% within ±7 days, before or after); low thoracic muscle area was the sex-specific lowest quartile. The primary outcome was composite weaning failure (extubation failure, tracheostomy, or ventilation >21 days). Multivariable logistic regression stratified at 75 years tested a muscle-area-by-age interaction. Results: Composite weaning failure occurred in 290 patients (47.8%). In fully adjusted complete-case models (n = 539), low thoracic muscle area was associated with composite weaning failure in younger patients (adjusted odds ratio 3.63; 95% CI 1.67–7.87) but not significantly in older patients (1.68; 0.91–3.13); the age interaction was not significant (p = 0.061) and was removed by height-normalization and by correction for multiple comparisons. A graded association across muscle-area quartiles was present in both strata (lowest vs. highest quartile: younger 4.79, older 2.53). Low thoracic muscle area was not associated with ICU mortality in either stratum, although an exploratory landmark analysis showed higher 7-day mortality in younger patients with low muscle area (20.6% vs. 10.8%). Conclusions: Low CT-derived thoracic muscle area was associated with composite weaning failure in both age strata, with a larger point estimate in patients younger than 75 years, although the age interaction was not significant in the fully adjusted model and was removed by height-normalization and by correction for multiple comparisons. The graded association in both age strata is hypothesis-generating and requires prospective validation. Full article

Acinetobacter baumannii is a critical WHO priority pathogen due to its multidrug resistance and high mortality in carbapenem-resistant infections. Resistance is predominantly mediated by class D carbapenemase genes bla_OXA-23 and bla_OXA-40, which spread rapidly via horizontal gene transfer in healthcare settings. To address the lack of a rapid assay capable of detecting both blaOXA-23 and blaOXA-40 in a single analytical workflow, we developed a multiplex two-step RPA–CRISPR/Cas12a assay. Since infections caused by strains harboring either gene require identical therapeutic management, their co-detection in a single reaction is clinically justified. Although simultaneous use of two crRNAs within a single CRISPR/Cas12a reaction is often considered technically challenging due to potential inter-crRNA competition, here it advantageously enables dual-target coverage without compromising sensitivity. The assay demonstrated high specificity with no cross-reactivity against a panel of clinically relevant bacterial species, including closely related Acinetobacter spp. Evaluation using genomic DNA extracted from 63 cultured clinical A. baumannii isolates revealed bla_OXA-23 in 19 isolates (30.2%), bla_OXA-40 in 28 (44.4%), and co-carriage of both genes in 9 (14.3%), with at least one resistance gene detected in 60.3% of isolates. The complete workflow was accomplished within 45 min without specialized equipment, offering a rapid, sensitive, and cost-effective solution for point-of-care molecular surveillance of carbapenem-resistant A. baumannii in clinical and resource-limited settings. Full article

Background/Objectives: Lactate is a key biomarker of tissue hypoperfusion in severe trauma. While admission lactate is widely used, the prognostic value of delayed lactate clearance remains a subject of ongoing investigation, notably due to the inherent risk of survivorship bias. This study assessed the association between lactate kinetics and in-hospital mortality in a cohort of severely injured patients admitted to the intensive care unit. Methods: We conducted a single-center retrospective cohort study including adult patients (≥18 years) admitted to the ICU for severe trauma between January 2018 and December 2022. Arterial lactate was measured at H0, H4 (±1 h), and H12 (±1 h). Lactate clearance (LC) was calculated using the formula: LC (%/h) = [(Lactate_t1 − Lactate_t2)/Lactate_t1] × (1/Δt) × 100, where positive values indicate decreasing lactate (clearance) and negative values indicate worsening lactatemia. LC was calculated over H0–H4, H0–H12, and H4–H12. Among the 38 patients who died before 12 h and were excluded from the LC H0–H12 analysis, non-survivors were significantly older, had higher severity scores, and presented more frequently with hemorrhagic shock. Predictive performance was evaluated using ROC curves and multivariate logistic regression. The composite prognostic score was assessed using bootstrap internal validation (1000 resamples) to provide an optimism-adjusted AUC estimate. Results: Among 318 patients (median age 36 years; 86.5% male), hyperlactatemia (>2.2 mmol/L) was present in 70.1% at admission and persisted in 39.9% at 12 h. Non-survivors exhibited higher lactate levels and lower LC at all time points. LC H0–H12 demonstrated the best predictive performance for in-hospital mortality (AUC = 0.75; 95% CI [0.69–0.81]; p < 0.001). For early mortality (≤48 h), LC H0–H12 achieved an AUC of 0.80 (95% CI [0.71–0.89]; p < 0.001). A composite prognostic score incorporating age >60 years, GCS ≤ 7, prothrombin time ≤ 55%, pH ≤ 7.29, and LC H0–H12 > −2.93 %/h demonstrated good discrimination (AUC = 0.84; optimism-adjusted AUC = 0.82). Conclusions: Lactate levels and 12 h lactate clearance are valuable prognostic markers in severe trauma. Given the inherent survivorship bias affecting the LC H0–H12 analysis, its prognostic performance should be interpreted with appropriate caution and within a multimodal clinical assessment. The proposed composite score is promising but requires prospective external validation before clinical implementation. Full article

Background/Objective: Perioperative nursing care encompasses a diverse patient population with varying needs, anatomical and physiological characteristics, and differing levels of vulnerability, demanding specialized knowledge and skills. This study aims to identify key research priorities in perioperative nursing across the lifespan. Methods: A two-round e-Delphi study was conducted across three Portuguese hospitals, involving expert perioperative nurses (87 in the first round and 69 in the second). Participants rated the importance of various research topics on a 5-point Likert scale about six dimensions: (1) professional development and non-technical skills, (2) person-centered care, (3) organizational aspects and work environment, (4) patient and team safety, (5) digital innovation, and (6) patient outcomes and quality of care. Data were analyzed using mean scores, Content Validity Ratio (CVR) for initial validation, and the Coefficient of Variation (CV) to determine the level of consensus. The reporting of this study followed the DELPHISTAR (Guideline for Reporting Delphi Studies) recommendations. Results: A high degree of consensus was achieved (all CV < 0.20). The experts established a consensus on 48 components. The highest-rated priority was nurse burnout and professional satisfaction (Mean = 4.74). This was closely followed by patient safety (Mean = 4.68), team safety (Mean = 4.65), disaster response (Mean = 4.62), and emergency management (Mean = 4.58). Acute pain control and interdisciplinary communication also emerged as critical areas. Topics such as digital innovation and artificial intelligence, while valued, received lower priority scores. Conclusions: The identified priorities should direct funding toward research, education, quality improvement, and health policies. Future studies should focus on developing interventions to promote a favorable perioperative environment and optimize clinical responses to individuals’ conditions, catastrophes, and life-threatening situations across the lifespan. Full article

Background: A substantial proportion of patients with chronic migraine (CM) with previous failures among oral standard-of-care migraine medications do not respond to monoclonal antibodies targeting the calcitonine gene related peptide pathway (CGRP-mAbs), leaving limited evidence-based options for subsequent preventive strategies. The present multicentre real-world study evaluated the effectiveness of onabotulinumtoxin-A (BoNT-A) in CM patients with previous CGRP-mAb failure and multiple prior oral preventive failures. Methods: This prospective, observational, non-randomized multicentre study enrolled patients with CM who had failed ≥3 classes of oral preventive treatments and ≥1 CGRP-mAb due to lack of efficacy or intolerance. Participants received BoNT-A according to the PREEMPT “follow-the-pain” paradigm every three months and were followed for 6 months. Co-primary outcomes were change in monthly headache days (MHD) after three and six months and ≥50% MHD responder rates at both time points. Results: Fifty-three patients were analysed (85% female, aged 48.5 ± 15.2 years, range 20–73). Compared to the baseline, at the third month and sixth month, MHD decreased from 22.83 (SD 6.74) to 15.38 (SD 7.91; p < 0.001) and 14.55 (SD 9.35; p < 0.001), respectively. The percentages of participants achieving the response status in MMD at the third month and sixth month were 30% and 45%, respectively. In the third and sixth months, 22 patients (41.5%) and 27 patients (50.9%), respectively, converted from chronic to episodic migraine, while the prevalence of medication-overuse headache decreased from 81.1% of patients at baseline to 45.3% and 43.4%, respectively. Migraine-related impact and disability scores improved over follow-up, alongside improvements in anxiety and depressive symptoms and in migraine-specific quality of life. Conclusions: The present findings support the use of BoNT-A in difficult-to-treat patients with CM following CGRP-mAb failure and provide further evidence that its therapeutic effects may rely on mechanisms that are at least partially distinct from, and potentially complementary to, those of CGRP-targeted therapies. Full article

Virus-specific antibody responses, including binding antibodies and neutralizing antibodies (nAbs), are important indicators of antiviral immune status after infection or immunization. They provide complementary information on antiviral humoral immunity after infection or vaccination. Antigen-binding antibodies indicate previous exposure and the magnitude of the immune response, whereas receptor-blocking and functional neutralization assays assess whether antibodies interfere with viral entry or infection. Conventional neutralization assays, such as plaque reduction neutralization tests and pseudovirus neutralization tests, provide functional information but are labor-intensive, time-consuming, biosafety-restricted, and difficult to deploy for large-scale or decentralized monitoring. Paper-based biosensors, including lateral flow assays (LFAs), microfluidic paper-based analytical devices (μPADs), and paper-based ELISA, have emerged as promising point-of-care tools owing to their low cost, portability, simple operation, and compatibility with visual or digital readouts. This review critically evaluates these platforms according to whether they measure antigen-binding antibodies, receptor-blocking activity, surrogate neutralization, or functional neutralization and summarizes the applications of these three platforms for monitoring antibody responses against SARS-CoV-2, influenza, dengue, Zika, and monkeypox viruses. Unlike previous reviews that mainly focus on general paper-based biosensor design or conventional nAb assays, this review emphasizes the distinction between antigen-binding, receptor-blocking, and surrogate neutralization readouts, and critically discusses how paper-based signals should be interpreted in relation to functional immunity. We further analyze key translational challenges, including quantitative accuracy, antigen cross-reactivity, standardization, clinical validation, regulatory positioning, and real-world implementation. Future development should combine multiplex detection, standardized calibration, digital and AI-assisted interpretation, and clinically validated assay formats. Paper-based biosensors have considerable potential for decentralized antibody monitoring and public health surveillance, but their clinical utility depends on clear assay positioning and validation against appropriate functional or reference methods. Full article

Background and Objective: Glucagon-like peptide-1 (GLP-1) receptor agonist therapy has intensified the policy debate over whether obesity pharmacotherapy increases short-term healthcare expenditures or reduces downstream medical costs (i.e., non-drug, acute-care expenditures). This study estimated same-year associations between GLP-1 use and medical spending among adults with observed obesity. Methods: Analyses used Medical Expenditure Panel Survey (MEPS) person-year files compiled from 2018 to 2022, with body mass index (BMI)-defined analyses restricted to 2019 and 2021. The primary analytic sample included 7144 person-years, of which 275 represented sustained GLP-1 users. Overlap-weighted Poisson pseudo-maximum likelihood models, utilization regressions, two-part decompositions, and a layered diagnostic framework were applied to assess spending patterns and same-year cost implications. Robustness was evaluated through sensitivity analyses across all-obesity, severe-obesity, and diabetes-excluded subsamples, as well as exploratory molecule-specific specifications. Results: Findings showed no evidence of same-year cost savings, but rather a distinct shift in spending composition. In fully adjusted primary models, GLP-1 use was associated with reduced non-drug medical spending (beta = −0.2494; marginal effect = −$2586 per person-year) and lower acute-care spending (beta = −0.5856; marginal effect = −$2019), while total medical spending was higher (beta = 0.3182; marginal effect = +$6483). Point E values of 1.89 (non-drug) and 2.99 (acute-care) indicated moderate-to-strong resilience to unmeasured confounding. Negative control models using dental spending and visits showed significant positive associations. Since this residual confounding operates in the direction opposite to the negative acute-care association, the headline compositional pattern is unlikely to be an artifact of upward health-seeking bias. Utilization models indicated fewer inpatient discharges (IRR = 0.686) and inpatient nights (IRR = 0.524). Two-part models further suggested that the reduction in acute-care spending was concentrated on the intensive margin among individuals with positive expenditures. Conclusions: The use of GLP-1 is not associated with overall short-term cost savings. This usage is related to a shift in the composition of observed medical spending during the same year. This change is leading to a decline in hospital admissions and acute care costs, in parallel with the rise in pharmaceutical spending. Non-drug and acute-care costs were lower among regular users. However, total spending was at a higher level, consistent with a trend in the budget records from that period in which drug costs were the dominant factor. These associations are consistent with a potential reallocation of healthcare resources from inpatient acute care toward pharmacy and ambulatory services, with corresponding planning implications for payers and possible workforce reallocation of nursing capacity from acute to outpatient settings, contingent on replication in post-2022 data. Full article