BACKGROUND: Daratumumab, an anti-CD38 monoclonal antibody, has been approved for the treatment of multiple myeloma. Data are needed regarding the use of daratumumab for high-risk smoldering multiple myeloma, a precursor disease of active multiple myeloma for which no treatments have been approved. METHODS: In this phase 3 trial, we randomly assigned patients with high-risk smoldering multiple myeloma to receive either subcutaneous daratumumab monotherapy or active monitoring. Treatment was continued for 39 cycles, for 36 months, or until confirmation of disease progression, whichever occurred first. The primary end point was progression-free survival; progression to active multiple myeloma was assessed by an independent review committee in accordance with International Myeloma Working Group diagnostic criteria. RESULTS: Among the 390 enrolled patients, 194 were assigned to the daratumumab group and 196 to the active-monitoring group. With a median follow-up of 65.2 months, the risk of disease progression or death was 51% lower with daratumumab than with active monitoring (hazard ratio, 0.49; 95% confidence interval [CI], 0.36 to 0.67; P<0.001). Progression-free survival at 5 years was 63.1% with daratumumab and 40.8% with active monitoring. A total of 15 patients (7.7%) in the daratumumab group and 26 patients (13.3%) in the active-monitoring group died (hazard ratio, 0.52; 95% CI, 0.27 to 0.98). Overall survival at 5 years was 93.0% with daratumumab and 86.9% with active monitoring. The most common grade 3 or 4 adverse event was hypertension, which occurred in 5.7% and 4.6% of the patients in the daratumumab group and the active-monitoring group, respectively. Adverse events led to treatment discontinuation in 5.7% of the patients in the daratumumab group, and no new safety concerns were identified. CONCLUSIONS: Among patients with high-risk smoldering multiple myeloma, subcutaneous daratumumab monotherapy was associated with a significantly lower risk of progression to active multiple myeloma or death and with higher overall survival than active monitoring. No unexpected safety concerns were identified. (Funded by Janssen Research and Development; AQUILA ClinicalTrials.gov number, NCT03301220.).
- MeSH
- Progression-Free Survival MeSH
- Adult MeSH
- Smoldering Multiple Myeloma * diagnosis mortality therapy MeSH
- Injections, Subcutaneous MeSH
- Kaplan-Meier Estimate MeSH
- Middle Aged MeSH
- Humans MeSH
- Multiple Myeloma * diagnosis epidemiology prevention & control MeSH
- Antibodies, Monoclonal * administration & dosage adverse effects MeSH
- Watchful Waiting * statistics & numerical data MeSH
- Disease Progression MeSH
- Antineoplastic Agents * administration & dosage adverse effects MeSH
- Aged, 80 and over MeSH
- Aged 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
- Clinical Trial, Phase III MeSH
- Multicenter Study MeSH
- Randomized Controlled Trial MeSH
- Comparative Study MeSH
Nádory močového měchýře představují celosvětově časté onemocnění. Mnohdy se jedná o recidivující nádory s nutností dlouhodobého sledování, což z nich činí nádory s vysokou prevalencí. Základní diagnostickou metodou je cystoskopie, která je nezbytná i v rámci sledování. V obou případech, v diagnostice i dispenzarizaci, tedy využíváme invazivní metodu s nezanedbatelným rizikem komplikací. Jediným doporučeným neinvazivním vyšetřením je cytologie moči. Limitace cystoskopie a cytologie moči motivují výzkum celé řady neinvazivních biomarkerů detekovaných v moči s cílem nalezení dostatečně senzitivního a specifického vyšetření, které by bylo možné využít nejen v diagnostice a sledování nádorů močového měchýře. Doposud bylo na trh uvedeno několik biomarkerů vyskytujících se v přítomnosti nádorového postižení močového měchýře. V článku jsou představeni hlavní zástupci neinvazivních biomarkerů a jejich možné využití.
Major statement: Non-invasive urinary biomarkers represent a promising alternative to cur- rent diagnostic methods for bladder cancer. This study aims to present the main available biomarkers, evaluate their benefits, and assess their potential use in diagnosis and patient monitoring.Summary: Bladder tumors are a common disease worldwide. They are often recurrent tumors requiring long-term monitoring, making them highly prevalent. The primary diagnostic method is cystoscopy, which is also essential for follow-up. In both cases - diagnosis and surveillance - an invasive method is used, carrying a significant risk of complications. The only recommended non-invasive examination is urine cytology. The limitations of cystoscopy and urine cytology drive research into various non-invasive urinary biomarkers to find a test that is sufficiently sensitive and specific for use not only in diagnosing but also in monitoring bladder tumors. Several biomarkers associated with bladder cancer have already been introduced to the market. This article presents the main representatives of non-invasive biomarkers and their potential applications.
BACKGROUND: Since the incidence of vancomycin-resistant enterococci (VRE) is increasing and treatment options remain limited, we aimed to investigate the epidemiology of vancomycin- and tigecycline-resistant enterococci in a university hospital using whole genome sequencing (WGS). METHODS: Between April and December 2021, 102 VRE isolates were collected from a single tertiary care hospital in the Czech Republic. Forty selected isolates underwent antimicrobial susceptibility testing and WGS (Illumina short reads and long reads with MinION in selected isolates). RESULTS: All Enterococcus faecium isolates were resistant to ampicillin, carrying the PBP5_Met485Ala, PBP5_Glu629Val, and fluoroquinolones carrying the GyrA_Ser83Ile and ParC_Ser80Ile substitutions. The vanA operon was found on pELF2-like plasmids and plasmids carrying rep17 and/or rep18b genes. The novel Tn1546 structural variants were identified in vanA-carrying isolates. The vanB operon was located on the chromosome within a Tn1549 structural variant. Linezolid resistance was detected in one isolate carrying the 23S rDNA_G2576T substitution. Twenty-two isolates were resistant to tigecycline (tet(L), tet(M) and rpsJ_del 155-166 or RpsJ_Lys57Arg). Discrepancies between phenotypic and genotypic resistance profiles were observed for daptomycin (RpoB_Ser491Phe), trimethoprim/sulfamethoxazole (dfrG gene), nitrofurantoin (NmrA_Gln48Lys substitution without the EF0404 and EF0648 genes) and tetracycline (truncated TetM). The two multilocus sequence typing (MLST) schemes identified different numbers of STs: 5 STs, with ST117 as the predominant one (n = 32, 80%), versus 10 STs, with ST138 (27.5%), ST136 (25%), and ST1067 (20%) being the most frequent, respectively. The whole genome MLST revealed clonal clustering (0-7 allele differences) among isolates of the same ST. When comparing ST117 isolates from our study with 2,204 ST117 isolates from 15 countries, only one Czech isolate clustered closely with strains from Germany and the Netherlands, differing by just 16 alleles. CONCLUSIONS: The spread of E. faecium isolates ST117 resistant to vancomycin and tigecycline was identified. The discrepancies between resistance genotypes and phenotypes highlight the importance of combining molecular and phenotypic surveillance in antimicrobial resistance monitoring.
- MeSH
- Anti-Bacterial Agents * pharmacology MeSH
- Bacterial Proteins genetics MeSH
- Enterococcus faecium * genetics drug effects isolation & purification classification MeSH
- Vancomycin-Resistant Enterococci * genetics drug effects isolation & purification MeSH
- Genome, Bacterial MeSH
- Gram-Positive Bacterial Infections * microbiology epidemiology MeSH
- Humans MeSH
- Microbial Sensitivity Tests MeSH
- Drug Resistance, Multiple, Bacterial genetics MeSH
- Multilocus Sequence Typing MeSH
- Vancomycin Resistance genetics MeSH
- Whole Genome Sequencing MeSH
- Tigecycline * pharmacology MeSH
- Vancomycin * pharmacology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Czech Republic MeSH
Molecular surveillance was widely used during the COVID-19 pandemic to detect rapidly emerging variants and monitor the transmission of SARS-CoV-2 within communities. In 2021, the Czech COVID-19 Genomics Consortium (COG-CZ) was set up to coordinate a new SARS-CoV-2 molecular surveillance network. In the Czech Republic, molecular surveillance employed whole genome sequencing (WGS) and variant discrimination polymerase chain reaction (VD-PCR) on samples collected through passive, active and sentinel surveillance. All WGS data was uploaded to GISAID and the PANGO lineages used by GISAID were compared to the main variants determined by VD-PCR. To assess the effectiveness and reliability of the gathered data in adapting pandemic responses, the capabilities and turnaround times of the molecular surveillance methods are evaluated. VD-PCR results were available within 48 h of sample collection for 81.5% of cases during the Delta/Omicron transition. WGS enabled the detection of low-frequency novel variants in infection clusters. WGS surveillance showed there was community spread of AY.20.1, a variant that gained novel mutations within the Czech Republic. Molecular surveillance informed the implementation of public health measures; temporal comparisons of restrictions and outcomes are described. Further areas for improvement have been identified for monitoring and managing future pandemics.
- MeSH
- COVID-19 * epidemiology virology MeSH
- Genome, Viral MeSH
- Humans MeSH
- Pandemics MeSH
- SARS-CoV-2 * genetics isolation & purification MeSH
- Whole Genome Sequencing MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Czech Republic MeSH
Respiratory viruses represent a significant public health threat. There is the need for robust and coordinated surveillance to guide global health responses. Established in 2012, the Global Influenza Hospital Surveillance Network (GIHSN) addresses this need by collecting clinical and virological data on persons with acute respiratory illnesses across a network of hospitals worldwide. GIHSN utilizes a standardized patient enrolment and data collection protocol across its study sites. It leverages pre-existing national infrastructures and expert collaborations to facilitate comprehensive data collection. This includes demographic, clinical, epidemiological, and virologic data, and whole genome sequencing (WGS) for a subset of viruses. Sequencing data are shared in the Global Initiative on Sharing All Influenza Data (GISAID). GIHSN uses financing and governance approaches centered around public-private partnerships. Over time, GIHSN has included more than 100 hospitals across 27 countries and enrolled more than 168,000 hospitalized patients, identifying 27,562 cases of influenza and 44,629 of other respiratory viruses. GIHSN has expanded beyond influenza to include other respiratory viruses, particularly since the COVID-19 pandemic. In November 2023, GIHSN strengthened its global impact through a memorandum of understanding with the World Health Organization, aimed at enhancing collaborative efforts and data sharing for improved health responses. GIHSN exemplifies the value of integrating scientific research with public health initiatives through global collaboration and public-private partnerships governance. Future efforts should enhance the scalability of such models and ensure their sustainability through continued public and private support.
- MeSH
- Global Health * MeSH
- Influenza, Human * epidemiology virology MeSH
- COVID-19 epidemiology MeSH
- Epidemiological Monitoring MeSH
- Humans MeSH
- Hospitals * MeSH
- Whole Genome Sequencing MeSH
- Public Health MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
OBJECTIVES: Illicit drug use presents a significant challenge to global health and public safety, requiring innovative and effective monitoring strategies. This study aimed to evaluate the current landscape of wastewater-based epidemiology (WBE) for monitoring illicit drugs in Europe, focusing on collaboration, current practices, and barriers, while identifying opportunities for improvement. STUDY DESIGN: Cross-sectional survey-based study. METHODS: Coordinated by the Sewage Analysis CORe Group Europe (SCORE) and the European Union Drugs Agency (EUDA), two surveys were conducted in 2023 targeting researchers and stakeholders using WBE for illicit drugs. Data were analysed to identify trends, gaps, and opportunities for improving WBE implementation. RESULTS: The findings indicate a robust research infrastructure and diverse analytical methods among European institutions. Two-thirds of the participating countries reported using WBE data to inform policy. However, challenges persist, particularly in securing funding and coordination, as well as generating national estimates from multiple locations and addressing specific local policy needs. CONCLUSIONS: WBE has proven to be a valuable tool for monitoring illicit drug trends and informing drug policies. To unlock its full potential, sustained funding, methodological standardization, and enhanced cooperation are essential. This study provides critical insights into the European WBE landscape, offering a roadmap for strengthening the integration of actionable WBE data into public health and policy frameworks.
- MeSH
- Wastewater-Based Epidemiological Monitoring MeSH
- Humans MeSH
- Wastewater * MeSH
- Substance-Related Disorders epidemiology MeSH
- Cross-Sectional Studies MeSH
- Surveys and Questionnaires MeSH
- Decision Making MeSH
- Illicit Drugs * MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Europe MeSH
This study investigates the presence of perfluoroalkyl substances (PFAS) in the drinking water supplies in the Czech Republic using a risk-based monitoring approach. Tap water samples (n = 27) from sources close to areas potentially contaminated with PFAS were analysed. A total of 28 PFAS were measured using ultra-performance liquid chromatography with tandem mass spectrometry after solid phase extraction. Total PFAS concentrations (∑PFAS) varied from undetectable to 90.8 ng/L, with perfluoropentanoic acid (PFPeA), perfluorohexanoic acid (PFHxA), perfluoroheptanoic acid (PFHpA) and perfluorobutane sulfonic acid (PFBS) being the most abundant, detected in over 70% of samples. Risk-based monitoring in drinking water showed that commercial wells had higher PFAS levels compared to tap water, particularly C4-C9 perfluorocarboxylic acids (PFCAs), possibly due to proximity to industrial areas. However, the hypothesis that risk-based monitoring is more effective than random monitoring was not confirmed, possibly because specific sources did not produce the target PFAS or because of the wide range and less obvious sources of potential contamination. The study also assessed exposure risks and compliance with regulatory thresholds. Weekly intake estimates for adults and children indicated that regular consumption of most contaminated water sample would exceed the tolerable weekly intake. Compared to EU regulations, none of the tap water samples exceeded the 'Sum of PFAS' parametric value of 100 ng/L, though one sample approached this limit. In addition, surface water samples from the Jizera River (n = 21) showed a wider range of PFAS, with C7-C10 PFCAs, PFBS, and perfluorooctane sulfonic acid (PFOS) in every sample, with higher PFOS concentrations at a median of 2.56 ng/L. ∑PFAS concentrations increased downstream, rising from 1.08 ng/L near the spring to 26 ng/L downstream. This comprehensive analysis highlights the need for detailed/areal monitoring to also address hidden or non-obvious sources of PFAS contamination.
- MeSH
- Water Pollutants, Chemical * analysis MeSH
- Solid Phase Extraction MeSH
- Fluorocarbons * analysis MeSH
- Risk Assessment MeSH
- Humans MeSH
- Environmental Monitoring * methods MeSH
- Drinking Water * chemistry MeSH
- Tandem Mass Spectrometry MeSH
- Environmental Exposure analysis statistics & numerical data MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Czech Republic MeSH
Carbonaceous aerosols (CA), composed of black carbon (BC) and organic matter (OM), significantly impact the climate. Light absorption properties of CA, particularly of BC and brown carbon (BrC), are crucial due to their contribution to global and regional warming. We present the absorption properties of BC (bAbs,BC) and BrC (bAbs,BrC) inferred using Aethalometer data from 44 European sites covering different environments (traffic (TR), urban (UB), suburban (SUB), regional background (RB) and mountain (M)). Absorption coefficients showed a clear relationship with station setting decreasing as follows: TR > UB > SUB > RB > M, with exceptions. The contribution of bAbs,BrC to total absorption (bAbs), i.e. %AbsBrC, was lower at traffic sites (11-20 %), exceeding 30 % at some SUB and RB sites. Low AAE values were observed at TR sites, due to the dominance of internal combustion emissions, and at some remote RB/M sites, likely due to the lack of proximity to BrC sources, insufficient secondary processes generating BrC or the effect of photobleaching during transport. Higher bAbs and AAE were observed in Central/Eastern Europe compared to Western/Northern Europe, due to higher coal and biomass burning emissions in the east. Seasonal analysis showed increased bAbs, bAbs,BC, bAbs,BrC in winter, with stronger %AbsBrC, leading to higher AAE. Diel cycles of bAbs,BC peaked during morning and evening rush hours, whereas bAbs,BrC, %AbsBrC, AAE, and AAEBrC peaked at night when emissions from household activities accumulated. Decade-long trends analyses demonstrated a decrease in bAbs, due to reduction of BC emissions, while bAbs,BrC and AAE increased, suggesting a shift in CA composition, with a relative increase in BrC over BC. This study provides a unique dataset to assess the BrC effects on climate and confirms that BrC can contribute significantly to UV-VIS radiation presenting highly variable absorption properties in Europe.
- MeSH
- Aerosols * analysis MeSH
- Air Pollutants analysis MeSH
- Environmental Monitoring MeSH
- Particulate Matter analysis MeSH
- Light MeSH
- Carbon * analysis MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Europe MeSH
BACKGROUND: The war in Ukraine has led to significant migration to neighboring countries, raising public health concerns. Notable tuberculosis (TB) incidence rates in Ukraine emphasize the immediate requirement to prioritize approaches that interrupt the spread and prevent new infections. METHODS: We conducted a prospective genomic surveillance study to assess migration's impact on TB epidemiology in the Czech Republic and Slovakia. Mycobacterium tuberculosis isolates from Ukrainian war refugees and migrants, collected from September 2021 to December 2022 were analyzed alongside 1574 isolates obtained from Ukraine, the Czech Republic, and Slovakia. RESULTS: Our study revealed alarming results, with historically the highest number of Ukrainian tuberculosis patients detected in the host countries. The increasing number of cases of multidrug-resistant TB, significantly linked with Beijing lineage 2.2.1 (p < 0.0001), also presents substantial obstacles to control endeavors. The genomic analysis identified the three highly related genomic clusters, indicating the recent TB transmission among migrant populations. The largest clusters comprised war refugees diagnosed in the Czech Republic, TB patients from various regions of Ukraine, and incarcerated individuals diagnosed with pulmonary TB specialized facility in the Kharkiv region, Ukraine, pointing to a national transmission sequence that has persisted for over 14 years. CONCLUSIONS: The data showed that most infections were likely the result of reactivation of latent disease or exposure to TB before migration rather than recent transmission occurring within the host country. However, close monitoring, appropriate treatment, careful surveillance, and social support are crucial in mitigating future risks, though there is currently no evidence of local transmission in EU countries.
- MeSH
- Adult MeSH
- Incidence MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Molecular Epidemiology * MeSH
- Tuberculosis, Multidrug-Resistant epidemiology MeSH
- Mycobacterium tuberculosis * genetics isolation & purification MeSH
- Transients and Migrants * statistics & numerical data MeSH
- Armed Conflicts MeSH
- Prospective Studies MeSH
- Tuberculosis * epidemiology transmission MeSH
- Refugees * statistics & numerical data MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Geographicals
- Czech Republic MeSH
- Slovakia MeSH
- Ukraine MeSH
Ciele: Cieľom pilotného projektu bolo zvýšiť testovanie ako aj prepojenie so zdravotnou starostlivosťou o novodiagnostikované osoby s infekciou HIV/HCV/syfilisu a tiež zlepšiť zber a prenos údajov pomocou štandardných nástrojov zberu údajov z komunitných centier poskytujúcich dobrovoľné poradenstvo a testovanie (CBVCT) do národného epidemiologického a monitorovacieho systému. Metódy: Integrované dobrovoľné anonymné testovanie z krvi na HIV, HCV a syfilis bolo realizované pomocou rýchlych testov v období 6 mesiacov (03/2019 až 8/2019). Účastníkom s reaktívnymi výsledkami sa odporučilo, aby navštívili špecialistu za účelom potvrdenia diagnózy a nasadenia terapie. Výsledky: Otestovaných bolo 675 klientov na HIV, 410 na HCV a 457 na syfilis. Medián veku účastníkov sa pohyboval od 24 do 35,6 (IQR:24), 75,3 % z nich bolo mužov, 23,7 % žien a 0,6 % transrodových ľudí. Z hľadiska rizika akvírovania testovaných infekcii 48,9 % zo 675 klientov boli muži majúci styk s mužmi (MSM), 0,3 % osoby pracujúce v sex-biznise (SW), 9,0 % injekční užívatelia drog (PWID), 2,4 % migranti (Mi) a 8,3 % klientov uvádzalo kombináciu týchto rizík. Pilotný projekt odhalil infekciu HIV u 0,4 %, HCV u 2,4 % a T. pallidum u 1,8 % klientov. Len 2 klienti, s potvrdenou HIV infekciou boli prepojení s následnou zdravotnou starostlivosťou. Najvyššia prevalencia HIV bola zistená u MSM/Mi (4,2 %), HCV u PWID (30,8 %) a syfilisu u SW/PWID (7,1 %). Bezkondómový styk so SW, PWID, MSM a HIV pozitívnymi za posledných 12 mesiacov uviedlo 5/92, 41/82, 3/78 a 0/88 odpovedajúcich klientov. Výsledky štúdie boli zahrnuté do ročnej národnej epidemiologickej správy. Záver: Pilotný projekt odhalil potrebu podpory integrovaného testovania v CBVCT, prekonania prekážok pri potvrdzujúcom testovaní a prepojení so zdravotnou starostlivosťou ako aj potrebu integrácie základných údajov v rámci monitorovania a hodnotenia (M&E) testovania v CBVCT do národných systémov surveillance na Slovensku.
Aim: Aim of the pilot was to increase HIV/HCV/syphilis testing and linkage to care of newly diagnosed persons, improve data collection and transfer using standard data collection tools in CBVCT services. Methods: Integrated anonymous voluntary testing from blood for HIV, HCV and syphilis was realised using rapid tests in the period of 6 months (03/2019–08/2019). Participants with reactive results were advised to see a specialist for confirmatory testing and/or treatment. Results: A total of 675 clients were tested for HIV, 410 for HCV, and 457 for syphilis. Participants’ median age ranged from 24 to 35.6 (IQR: 24), 75.3% of them were men, 23.7% were women, and 0.6% identified as transgender. In terms of groups at risk 48.9 % of 675 clients were men who have sex with men (MSM), 0.3 % sex workers (SW), 9.0 % people who inject drugs (PWID), 2.4 % migrants (Mi) and the rest of clients (8.3 %) belonged to groups at combined risk. Pilot revealed HIV, HCV and T. pallidum infections in 0.4 %, 2.4 % and 1.8 % of clients, respectively. Just 2 clients, confirmed HIV-positive, were linked to care. The highest prevalence of HIV (4.2 %), HCV (30.8 %) and syphilis (7.1 %) was found among MSM/Mi, PWID and SW/PWID, respectively. Condomless intercourse with SW, PWID, MSM and HIV-positive person in the last 12 months was reported by 5/92, 41/82, 3/78 and 0/88 of responding clients, respectively. Core indicators were included in the yearly national epidemiological report. Conclusions: Pilot revealed the need to support integrated CBVCT to overcome barriers in confirmatory testing and linkage to care and to integrate core data of monitoring and evaluation (M&E) testing framework at CBVCT services into a national surveillance and M&E systems in Slovakia.
- MeSH
- Anonymous Testing * MeSH
- Hepatitis C diagnosis epidemiology MeSH
- HIV Infections diagnosis epidemiology MeSH
- Delivery of Health Care, Integrated methods MeSH
- Humans MeSH
- Public Health Surveillance methods MeSH
- Sexually Transmitted Diseases * diagnosis epidemiology MeSH
- Sexual and Gender Minorities MeSH
- Preventive Health Services methods MeSH
- Syphilis diagnosis epidemiology MeSH
- Drug Users * MeSH
- Check Tag
- Humans MeSH
- Geographicals
- Slovakia MeSH
