We estimated the effectiveness of the adapted monovalent XBB.1.5 COVID-19 vaccines against PCR-confirmed SARS-CoV-2 hospitalisation during the BA.2.86/JN.1 lineage-predominant period using a multicentre test-negative case-control study in Europe. We included older adults (≥ 65 years) hospitalised with severe acute respiratory infection from November 2023 to May 2024. Vaccine effectiveness was 46% at 14-59 days and 34% at 60-119 days, with no effect thereafter. The XBB.1.5 COVID-19 vaccines conferred protection against BA.2.86 lineage hospitalisation in the first 4 months post-vaccination.
- MeSH
- COVID-19 * prevention & control epidemiology immunology MeSH
- Hospitalization * statistics & numerical data MeSH
- Humans MeSH
- SARS-CoV-2 * immunology MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Case-Control Studies MeSH
- Vaccine Efficacy * MeSH
- Vaccination statistics & numerical data MeSH
- COVID-19 Vaccines * immunology administration & dosage MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Research Support, Non-U.S. Gov't MeSH
- Geographicals
- Europe MeSH
Current European/US guidelines recommend that molecular testing in advanced non-small cell lung cancer (aNSCLC) be performed using next-generation sequencing (NGS). However, the global uptake of NGS is limited, largely owing to reimbursement constraints. We compared real-world costs of NGS and single-gene testing (SGT) in nonsquamous aNSCLC. This observational study was conducted across 10 pathology centers in 10 different countries worldwide. Biomarker data collected via structured questionnaires (1 January-31 December 2021) were used to feed micro-costing analyses for three scenarios ['Starting Point' (SP; 2021-2022), 'Current Practice' (CP; 2023-2024), and 'Future Horizons' (FH; 2025-2028)] in both a real-world model, comprising all biomarkers tested by each center, and a standardized model, comprising the same sets of biomarkers across centers. Testing costs (including retesting) encompassed personnel costs, consumables, equipment, and overheads. Overall, 4,491 patients with aNSCLC were evaluated. Mean per-patient costs decreased for NGS relative to SGT over time, with real-world model costs 18% lower for NGS than for SGT in the SP scenario, and 26% lower for NGS than for SGT in the CP scenario. Mean per-biomarker costs also decreased over time for NGS relative to SGT. In the standardized model, the tipping point for the minimum number of biomarkers required for NGS to result in cost savings (per patient) was 10 and 12 in the SP and CP scenarios, respectively. Retesting had a negligible impact on cost analyses, and results were robust to variation in cost parameters. This study provides robust real-world global evidence for cost savings with NGS-based panels over SGT to evaluate predictive biomarkers in nonsquamous aNSCLC when the number of biomarkers to be tested exceeds 10. Widespread adoption of NGS may enable more efficient use of limited healthcare resources.
- MeSH
- Cost-Benefit Analysis MeSH
- Genetic Testing economics methods MeSH
- Middle Aged MeSH
- Humans MeSH
- Biomarkers, Tumor * genetics MeSH
- Lung Neoplasms * genetics pathology diagnosis MeSH
- Health Care Costs MeSH
- Carcinoma, Non-Small-Cell Lung * genetics diagnosis pathology MeSH
- Aged MeSH
- High-Throughput Nucleotide Sequencing * economics MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Observational Study MeSH
- Comparative Study MeSH
BACKGROUND: Influenza is a relatively serious infection that causes considerable morbidity and mortality. Epidemics of influenza are reported almost every year. METHODS: Based on the Czech national all-cause mortality and acute respiratory infection/influenza-like illness surveillance data for the 1999/2000 to 2019/2020 influenza seasons, excess deaths attributable to influenza were estimated using the threshold derived as 90th percentile of death counts during nonepidemic periods. Daily death counts broken by the 5-year age intervals were modelled via Poisson generalised additive model. RESULTS: The estimated total number of excess deaths from influenza during study period was 22,306. Thus, the mean total of excess deaths related to influenza per season was 1062 for the age group 40-94 years. The total number of excess deaths increased steadily with age from the 40-44 age group to the 85-89 age group, which accounted for the highest percentage of excess deaths (17%), followed closely by the 80-84 age group (16%). The age groups 40-44 years and 45-49 years contributed the least (3% each). More than three quarters of excess deaths occurred at age 65 and over (17,027 cases; 76%). Relative numbers of excess deaths per 100,000 population peaked in the oldest age groups of 85-89 and 90-94 years. CONCLUSIONS: We estimate that at least 0.98% of all-cause mortality throughout the study period was attributable to influenza in the Czech Republic. This excess is not negligible, and public health actions in the field of influenza prevention are vitally needed.
- MeSH
- Influenza, Human * mortality epidemiology MeSH
- Child MeSH
- Adult MeSH
- Infant MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Infant, Newborn MeSH
- Child, Preschool MeSH
- Seasons * MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Check Tag
- Child MeSH
- Adult MeSH
- Infant MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Infant, Newborn MeSH
- Child, Preschool MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Geographicals
- Czech Republic MeSH
The serotonergic psychedelics psilocybin, LSD and DMT hold great promise for the development of new treatments for psychiatric conditions such as major depressive disorder, addiction and end-of-life anxiety. Previous studies in both animals and humans have confirmed the effects of these drugs on neuronal activity and plasticity. However, the understanding of the mechanisms of action of these substances is limited. Here we show rapid effects of psychedelics on presynaptic properties, using live cell imaging at the level of single synapses in primary rat cortical neurons. Using the genetically encoded reporter of synaptic vesicle fusion synaptopHluorin, we detected a reduced fraction of synaptic vesicles that fused in response to mild or strong electrical stimulation 3-30 min after application of serotonergic psychedelics. These effects were transient and no longer present 24 h after treatment. While DMT only reduced the total recycling pool, LSD and psilocin also reduced the size of the readily releasable vesicle pool. Imaging with the sensors for glutamate, iGluSnFR, and presynaptic calcium, synGCaMP6, showed that while psilocin and DMT increased evoked glutamate release, LSD and psilocin reduced evoked presynaptic calcium levels. Interestingly, psilocin also affected short-term plasticity leading to a depression of responses to paired stimuli. The rapid and drug-specific modulation of glutamatergic neurotransmission described in this study may contribute to distinct anxiolytic and antidepressant properties of serotonergic psychedelics.
- MeSH
- Hallucinogens * pharmacology MeSH
- Rats MeSH
- Cells, Cultured MeSH
- Glutamic Acid * metabolism MeSH
- Lysergic Acid Diethylamide pharmacology MeSH
- Cerebral Cortex * drug effects metabolism cytology MeSH
- Neurons * drug effects metabolism MeSH
- Rats, Sprague-Dawley MeSH
- Psilocybin pharmacology MeSH
- Serotonin Agents pharmacology MeSH
- Synaptic Vesicles drug effects metabolism MeSH
- Tryptamines pharmacology MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Proteomics is nowadays increasingly becoming part of the routine clinical practice of diagnostic laboratories, especially due to the advent of advanced mass spectrometry techniques. This review focuses on the application of proteomic analysis in the identification of pathological conditions in a hospital setting, with a particular focus on the analysis of protein biomarkers. In particular, the main purpose of the review is to highlight the challenges associated with the identification of specific disease-causing proteins, given their complex nature and the variety of posttranslational modifications (PTMs) they can undergo. PTMs, such as phosphorylation and glycosylation, play critical roles in protein function but can also lead to diseases if dysregulated. Proteomics plays an important role especially in various medical fields ranging from cardiology, internal medicine to hemato-oncology emphasizing the interdisciplinary nature of this field. Traditional methods such as electrophoretic or immunochemical methods have been mainstay in protein detection; however, these techniques are limited in terms of specificity and sensitivity. Examples include the diagnosis of multiple myeloma and the detection of its specific protein or amyloidosis, which relies heavily on these conventional methods, which sometimes lead to false positives or inadequate disease monitoring. Mass spectrometry in this respect emerges as a superior alternative, providing high sensitivity and specificity in the detection and quantification of specific protein sequences. This technique is particularly beneficial for monitoring minimal residual disease (MRD) in the diagnosis of multiple myeloma where traditional methods fall short. Furthermore mass spectrometry can provide precise typing of amyloid proteins, which is crucial for the appropriate treatment of amyloidosis. This review summarizes the opportunities for proteomic determination using mass spectrometry between 2012 and 2024, highlighting the transformative potential of mass spectrometry in clinical proteomics and encouraging its wider use in diagnostic laboratories.
- MeSH
- Amyloidosis * diagnosis MeSH
- Biomarkers analysis MeSH
- Mass Spectrometry * methods MeSH
- Humans MeSH
- Multiple Myeloma * diagnosis MeSH
- Protein Processing, Post-Translational MeSH
- Proteomics * methods MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
Considering the growing role of ultrasound-guided procedures in musculoskeletal medicine, training as regards these interventions is pivotal. While hands-on training on cadavers can be considered optimal, it has several drawbacks, e.g., high cost, poor availability, and technical challenges regarding preservation. Apart from cadavers, different approaches to practicing needle guidance are taught in ultrasound workshops whereby phantoms from meat (e.g., chicken breast), cheese or gelatin are used. Likewise, this article aims to provide a detailed description as to how different gelatin-based phantoms can be prepared. In line with the EURO-MUSCULUS/USPRM (European Musculoskeletal Ultrasound Study Group/Ultrasound Study Group of the International Society of Physical and Rehabilitation Medicine) protocols/background, the authors describe particular basic and advanced phantoms to be used for practicing different technical/manual skills pertaining to common ultrasound-guided procedures. The present manuscript can be considered a practical and ready-to-use "recipe book" for readers who are interested in the wide spectrum of interventional ultrasound.
- MeSH
- Phantoms, Imaging * MeSH
- Ultrasonography, Interventional * MeSH
- Clinical Competence MeSH
- Humans MeSH
- Musculoskeletal Diseases diagnostic imaging rehabilitation MeSH
- Physical and Rehabilitation Medicine * education MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Europe MeSH
Background Randomized clinical trials have demonstrated that endovascular thrombectomy reduces functional disability in patients with large ischemic stroke; arterial collateral status might be used to select these patients for endovascular thrombectomy. Purpose To investigate whether arterial collateral status modifies the treatment effect of endovascular thrombectomy in patients with large ischemic stroke. Materials and Methods The Efficacy and Safety of Thrombectomy in Stroke with Extended Lesion and Extended Time Window (TENSION) trial was a prospective, multicenter, randomized study investigating participants with acute large ischemic stroke due to anterior circulation large-vessel occlusion. Participants with an Alberta Stroke Program Early CT Score of 3-5 were enrolled at 41 participating centers between July 2018 and February 2023. Participants were randomly assigned to undergo either endovascular thrombectomy with best medical treatment or best medical treatment alone within 12 hours from stroke onset. Collateral status was graded on pretreatment single-phase CT angiography (CTA) images using the Tan score and dichotomized into poor (grade, 0-1) or good (grade, 2-3) based on the extent of collateral supply filling the affected middle cerebral artery territory. The primary outcome was the shift on the 90-day modified Rankin Scale (mRS). Results Of 253 randomized patients, 201 with pretreatment CTA were included (median age, 74 years; IQR, 66-80 years; 103 [51.2%] female patients; 103 [51.2%] patients underwent endovascular thrombectomy). Endovascular thrombectomy compared with best medical treatment (adjusted common odds ratio [OR], 3.69; 95% CI: 2.12, 6.54; P < .001) and good collaterals compared with poor collaterals (adjusted common OR, 2.88; 95% CI: 1.63, 5.11; P < .001) were independently associated with a shift in the 90-day mRS scores toward better functional outcomes. The treatment effect of endovascular thrombectomy over best medical treatment was not modified by collateral status (interaction, P = .88). The treatment effect of endovascular thrombectomy versus best medical treatment was found in patients with good collaterals (adjusted common OR, 3.93; 95% CI: 1.65, 9.69; P = .002) and poor collaterals (adjusted common OR, 3.92; 95% CI: 1.86, 8.52; P < .001). Conclusion In this secondary analysis of data from the TENSION trial, endovascular thrombectomy reduced 90-day functional disability compared with best medical treatment in patients with good and poor collaterals. These findings suggest that patients with large ischemic stroke manifesting within 12 hours after onset should undergo endovascular thrombectomy irrespective of single-phase CTA collateral status. ClinicalTrials.gov Identifier: NCT03094715 © RSNA, 2025 Supplemental material is available for this article. See also the editorial by Benomar and Raymond in this issue.
- MeSH
- Computed Tomography Angiography methods MeSH
- Endovascular Procedures * methods MeSH
- Ischemic Stroke * diagnostic imaging surgery therapy MeSH
- Collateral Circulation * MeSH
- Middle Aged MeSH
- Humans MeSH
- Prospective Studies MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Thrombectomy * methods MeSH
- Treatment Outcome MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Randomized Controlled Trial MeSH
BACKGROUND: Recently, a plethora of novel systemic agents have been incorporated into the therapeutic armamentarium of advanced urothelial carcinoma (aUC). The antibody-drug conjugate (ADC), enfortumab vedotin (EV), has demonstrated relevant clinical benefit in patients with aUC refractory to platinum and immune-checkpoint inhibitor (ICI) therapy. Our study provides a retrospective, international, real-world analysis comparing the effectiveness of EV to chemotherapy in this setting. METHODS: The data were extracted from the medical records of patients treated with EV or chemotherapy following pembrolizumab for recurrent or progressive aUC after platinum-based chemotherapy. Patients were assessed for overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and duration of response (DoR). RESULTS: Our analysis included 247 patients treated with EV (88, 36%) or chemotherapy (159, 64%). Median OS was 9.1 months (95%CI 7.2-10.7) in the overall study population, 13.6 months (95%CI 10.0-31.0) in patients receiving EV and 6.8 months (95%CI 6.0-8.9) in patients receiving chemotherapy (p < 0.001). The OS benefit of EV was not affected by primary tumour site and histology, metastatic sites, type of first platinum-based chemotherapy or response to pembrolizumab. In the EV cohort, the median PFS was significantly longer (8.8 months [95%CI 6.5-17.0] vs. 3.0 months [95%CI 2.6-3.7]) and the ORR was significantly higher (56% vs. 23%) than in the chemotherapy cohort. CONCLUSIONS: The results of our international analysis of real-world data confirm the effectiveness of EV in the sequential strategy of aUC patients who have received prior platinum-based chemotherapy and anti-PD-1 pembrolizumab, regardless of commonly considered prognostic factors. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05290038.
- MeSH
- Progression-Free Survival MeSH
- Adult MeSH
- Antibodies, Monoclonal, Humanized * therapeutic use administration & dosage MeSH
- Immune Checkpoint Inhibitors therapeutic use MeSH
- Carcinoma, Transitional Cell drug therapy mortality pathology MeSH
- Middle Aged MeSH
- Humans MeSH
- Antibodies, Monoclonal therapeutic use administration & dosage MeSH
- Antineoplastic Combined Chemotherapy Protocols * therapeutic use MeSH
- Retrospective Studies MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Urologic Neoplasms drug therapy pathology mortality MeSH
- Treatment Outcome MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
The establishment of the first JBI Affiliated group in Poland at Wroclaw Medical University marks a significant advancement in evidence-based healthcare (EBHC) nationally. This editorial explores the evolution of EBHC and the critical role of JBI in driving its progress. Founded in 1996 as a research institute at the Royal Adelaide Hospital in South Australia and now based at the University of Adelaide, JBI has emerged as an international leader in evidence synthesis, transfer and implementation. Its Feasibility, Appropriateness, Meaningfulness, and Effectiveness (FAME) framework highlights the feasibility, appropriateness, meaningfulness, and effectiveness of healthcare practices, ensuring that decisions are patient-centered and contextually relevant. JBI's global collaboration network encompasses over 85 entities, with 23 located in Europe, emphasizing the importance of cultural inclusivity and international partnerships. Recent initiatives include translating the JBI Model of into Polish, German and Czech, linking global knowledge to local contexts, and enhancing understanding for professionals and students alike. This editorial also underscores the collaborative achievements of JBI entities in Wroclaw, Brandenburg an der Havel, Prague, and Olomouc. These partnerships have propelled regional implementation, research and education, fostering a shared vision for elevating healthcare quality. Launching a new EBHC section in the Advances in Clinical and Experimental Medicine journal is a significant step forward, inviting global contributions and stimulating innovation and knowledge sharing in EBHC. The presence of a JBI Affiliated group at Wroclaw Medical University symbolizes a transformative commitment to excellence and collaboration. It sets new benchmarks for healthcare in Poland and beyond while reinforcing the global mission of evidence-based practice.
Multidimensional chromatography coupled to tandem mass spectrometry (MS/MS), including simple sample preparation with protein precipitation, anion conversion with ammonium hydroxide, and solid-phase extraction using mixed-mode anion exchange in a 96-well plate format, has been validated for rapid simultaneous analysis of human insulin and its six analogs (lispro, glulisine, glargine, degludec, detemir, and aspart) in human plasma. This method is critical for clinical diagnostics, forensic investigations, and anti-doping efforts due to the widespread use of these substances. In the present study, improved chromatographic resolution was achieved using a first-dimension trap-and-elute configuration with an XBridge C18 (2.1 × 20 mm, 3.5 μm) trap column combined with second dimension separation on a Cortecs Ultra-High-Performance Liquid Chromatography (UHPLC) C18+ (2.1 × 100 mm, 1.6 μm) analytical column implemented within a two-dimensional-LC-MS/MS system. The total chromatographic run time was 11 min. This setup increases both the resolution and sensitivity of the method. A mobile phase consisting of 0.8% formic acid (FA) in water and 0.7% FA in acetonitrile was used for gradient elution. Bovine insulin was used as the internal standard. MS detection was performed in positive electrospray ionization mode, and the ion suppression due to matrix effects was evaluated. Validation criteria included linearity, precision, accuracy, recovery, lower limit of quantitation, matrix effect, and stability tests with and without protease inhibitor cocktail under different conditions (short-term stability, long-term stability, and freeze-thaw stability). The concentration range for all insulins was 50-15 000 pg/mL, with limits of quantification below the therapeutic reference range for all analytes. Intra-run precision ranged from 1.1% to 5.7%, inter-run precision from 0.7% to 5.9%, and overall recovery from 96.9% to 114.3%. The validated method has been implemented successfully by the Department of Forensic Medicine at our hospital for the investigation of unexplained deaths.
