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
• doba přežití bez progrese choroby MeSH
• dospělí MeSH
• doutnající mnohočetný myelom * diagnóza   mortalita   terapie   MeSH
• injekce subkutánní MeSH
• Kaplanův-Meierův odhad MeSH
• lidé středního věku MeSH
• lidé MeSH
• mnohočetný myelom * diagnóza   epidemiologie   prevence a kontrola   MeSH
• monoklonální protilátky * aplikace a dávkování   škodlivé účinky   MeSH
• pozorné vyčkávání * statistika a číselné údaje   MeSH
• progrese nemoci MeSH
• protinádorové látky * aplikace a dávkování   škodlivé účinky   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH
• srovnávací studie MeSH

x

x

• MeSH
• Enterovirus * izolace a purifikace   MeSH
• lidé MeSH
• monitorování životního prostředí MeSH
• odpadní vody * analýza   MeSH
• Poliovirus * izolace a purifikace   MeSH
• SARS-CoV-2 izolace a purifikace   MeSH
• Check Tag
• lidé MeSH
• Geografické názvy
• Česká republika MeSH

Palindromický revmatismus (PR) je klinický syndrom charakterizovaný opětovnými epizodami vzplanutí bolesti, otoku a zarudnutí kloubu/ů a přilehlých tkání s kompletní remisí bez zbytkového poškození. Ultrasonografickým zobrazováním se zjistilo, že u těchto epizod jde hlavně o extrakapsulární zánět. Epizodická vzplanutí jsou u PR zpravidla monoartikulární a postihují nejčastěji tytéž klouby jako revmatoidní artritida (RA), tj. hlavně proximální interfalangeální, metakarpofalangeální a zápěstní klouby. Klinická zkušenost nabízí hodnotit PR jako neobvyklou vstupní formu RA. Genotypové studie, recentně zvláště sekvenování kompletního exomu, však ukázaly rozdíly mezi PR a RA; u části PR byla zjištěna také mutace MEFV genu. Nejčastější prognózou PR je vyústění do RA; platí to hlavně pro PR s protilátkami proti citrulinovaným peptidům. Konečnou diagnózou u PR ale může být i jiné systémové autoimunitní revmatické onemocnění, např. systémový lupus erythematodes. Rekurentní zánětlivá vzplanutí mohou přetrvávat beze změny i po léta, nebo naopak dojde k dlouhodobé remisi, ale opětovné vzplanutí se nedá vyloučit. Terapie PR napodobuje léčbu RA; úspěšnou blokaci rekurencí extrakapsulárního zánětu u PR je možné hodnotit obdobně jako léčebné „okno příležitosti“ u RA.

Palindromic rheumatism (PR) is a clinical syndrome characterized by recurrent, transient episodes of joint pain, erythema, and swelling, typically without resulting in permanent joint damage. Ultrasonographic studies have shown that extra-capsular inflammation is a distinctive feature of this condition. PR flares are frequently monoarticular and commonly involve joints also affected in rheumatoid arthritis (RA), particularly the proximal interphalangeal, metacarpophalangeal, and wrist joints. Although clinical experience has long suggested that PR may represent an atypical form or precursor of RA, recent genetic analyses, particularly whole-exome sequencing, have revealed notable distinctions between the two diseases. In some patients with PR, mutations in the MEFV gene have been identified, further supporting its heterogeneous nature. RA remains the most frequent definitive diagnosis in patients with PR, especially in those positive for anti-citrullinated peptide antibodies. However, a subset of PR cases may evolve into other systemic autoimmune rheumatic diseases, such as systemic lupus erythematosus. In many patients, PR persists for years with recurrent flares or may enter remission, which may be prolonged but not necessarily permanent. Lifelong monitoring is essential, as flares can recur unpredictably. Management strategies for PR often mirror those of RA. Early and effective suppression of extra-capsular inflammation during PR flares may be as crucial as the "window of opportunity" concept in RA, potentially influencing long-term outcomes

• Klíčová slova
• palindromický revmatismus,
• MeSH
• genotyp MeSH
• lidé MeSH
• prognóza MeSH
• progrese nemoci MeSH
• prospektivní studie MeSH
• revmatické nemoci * diagnóza   farmakoterapie   patologie   MeSH
• revmatoidní artritida MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy 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.

• MeSH
• časná detekce nádoru MeSH
• cystoskopie MeSH
• cytodiagnostika MeSH
• lidé MeSH
• moč cytologie   MeSH
• nádorové biomarkery analýza   MeSH
• nádorové proteiny MeSH
• nádory močového měchýře * chirurgie   diagnóza   patologie   MeSH
• Check Tag
• lidé MeSH

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
• antibakteriální látky * farmakologie   MeSH
• bakteriální proteiny genetika   MeSH
• Enterococcus faecium * genetika   účinky léků   izolace a purifikace   klasifikace   MeSH
• enterokoky rezistentní vůči vankomycinu * genetika   účinky léků   izolace a purifikace   MeSH
• genom bakteriální MeSH
• grampozitivní bakteriální infekce * mikrobiologie   epidemiologie   MeSH
• lidé MeSH
• mikrobiální testy citlivosti MeSH
• mnohočetná bakteriální léková rezistence genetika   MeSH
• multilokusová sekvenční typizace MeSH
• rezistence na vankomycin genetika   MeSH
• sekvenování celého genomu MeSH
• tigecyklin * farmakologie   MeSH
• vankomycin * farmakologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika 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 * epidemiologie   virologie   MeSH
• genom virový MeSH
• lidé MeSH
• pandemie MeSH
• SARS-CoV-2 * genetika   izolace a purifikace   MeSH
• sekvenování celého genomu MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika 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
• celosvětové zdraví * MeSH
• chřipka lidská * epidemiologie   virologie   MeSH
• COVID-19 epidemiologie   MeSH
• epidemiologické monitorování MeSH
• lidé MeSH
• nemocnice * MeSH
• sekvenování celého genomu MeSH
• veřejné zdravotnictví MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články 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
• epidemiologie odpadních vod MeSH
• lidé MeSH
• odpadní voda * MeSH
• poruchy spojené s užíváním psychoaktivních látek epidemiologie   MeSH
• průřezové studie MeSH
• průzkumy a dotazníky MeSH
• rozhodování MeSH
• zakázané drogy * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Evropa 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
• chemické látky znečišťující vodu * analýza   MeSH
• extrakce na pevné fázi MeSH
• fluorokarbony * analýza   MeSH
• hodnocení rizik MeSH
• lidé MeSH
• monitorování životního prostředí * metody   MeSH
• pitná voda * chemie   MeSH
• tandemová hmotnostní spektrometrie MeSH
• vystavení vlivu životního prostředí analýza   statistika a číselné údaje   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika 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
• aerosoly * analýza   MeSH
• látky znečišťující vzduch analýza   MeSH
• monitorování životního prostředí MeSH
• pevné částice analýza   MeSH
• světlo MeSH
• uhlík * analýza   MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Evropa MeSH