BACKGROUND: Baricitinib has shown efficacy in hospitalized patients with COVID-19, but no placebo-controlled trials have focused specifically on severe/critical COVID, including vaccinated participants. METHODS: Bari-SolidAct is a phase-3, multicentre, randomised, double-blind, placebo-controlled trial, enrolling participants from June 3, 2021 to March 7, 2022, stopped prematurely for external evidence. Patients with severe/critical COVID-19 were randomised to Baricitinib 4 mg once daily or placebo, added to standard of care. The primary endpoint was all-cause mortality within 60 days. Participants were remotely followed to day 90 for safety and patient related outcome measures. RESULTS: Two hundred ninety-nine patients were screened, 284 randomised, and 275 received study drug or placebo and were included in the modified intent-to-treat analyses (139 receiving baricitinib and 136 placebo). Median age was 60 (IQR 49-69) years, 77% were male and 35% had received at least one dose of SARS-CoV2 vaccine. There were 21 deaths at day 60 in each group, 15.1% in the baricitinib group and 15.4% in the placebo group (adjusted absolute difference and 95% CI - 0.1% [- 8·3 to 8·0]). In sensitivity analysis censoring observations after drug discontinuation or rescue therapy (tocilizumab/increased steroid dose), proportions of death were 5.8% versus 8.8% (- 3.2% [- 9.0 to 2.7]), respectively. There were 148 serious adverse events in 46 participants (33.1%) receiving baricitinib and 155 in 51 participants (37.5%) receiving placebo. In subgroup analyses, there was a potential interaction between vaccination status and treatment allocation on 60-day mortality. In a subsequent post hoc analysis there was a significant interaction between vaccination status and treatment allocation on the occurrence of serious adverse events, with more respiratory complications and severe infections in vaccinated participants treated with baricitinib. Vaccinated participants were on average 11 years older, with more comorbidities. CONCLUSION: This clinical trial was prematurely stopped for external evidence and therefore underpowered to conclude on a potential survival benefit of baricitinib in severe/critical COVID-19. We observed a possible safety signal in vaccinated participants, who were older with more comorbidities. Although based on a post-hoc analysis, these findings warrant further investigation in other trials and real-world studies. Trial registration Bari-SolidAct is registered at NCT04891133 (registered May 18, 2021) and EUClinicalTrials.eu ( 2022-500385-99-00 ).

• MeSH
• COVID-19 * MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• farmakoterapie COVID-19 MeSH
• lidé středního věku MeSH
• lidé MeSH
• RNA virová MeSH
• SARS-CoV-2 MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH

A proper soil risk assessment needs to estimate the processes that affect the fate and the behaviour of a contaminant, which are influenced by soil biotic and abiotic components. For this reason, the measurement of biomarkers in soil bioindicator organisms, such as earthworms, has recently received increasing attention. In this study, the earthworm Eisenia andrei was used to assess the pollutant-induced stress syndrome after exposure to sublethal concentrations of Cd (10 or 100 μg g(-1)) in OECD soil, after 14 d of exposure. Cadmium bioaccumulation and potential biomarkers such as catalase (CAT), hydrogen peroxide (H2O2), glutathione-S-transferase (GST), malondialdehyde (MDA), phenoloxidase (PO), metallothioneins (MTs) and genotoxic damage were determined. Results suggested that the exposure to 10 and 100 μg g(-1) Cd significantly increased Cd bioaccumulation, MTs and MDA; 100 μg g(-1) Cd contamination evidenced significantly higher values of H2O2 content and PO activity; CAT activity was inhibited at the higher concentration while GST and Comet assay did not show any significant differences from the control. Rank-based biomarker index showed that both different contaminated soils had an effect on the earthworms and allowed to validate the ecotoxicological relevance of this battery of biomarkers for a promising integrated multi-marker approach in soil monitoring and assessment.

• MeSH
• biologické markery analýza   metabolismus   MeSH
• ekotoxikologie metody   MeSH
• glutathiontransferasa analýza   metabolismus   MeSH
• kadmium metabolismus   toxicita   MeSH
• katalasa analýza   metabolismus   MeSH
• kometový test MeSH
• látky znečišťující půdu metabolismus   toxicita   MeSH
• malondialdehyd analýza   metabolismus   MeSH
• metalothionein analýza   metabolismus   MeSH
• monitorování životního prostředí metody   MeSH
• Oligochaeta účinky léků   genetika   metabolismus   MeSH
• peroxid vodíku analýza   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• Konspekt
• Lékařské vědy. Lékařství
• NLK Obory
• dějiny lékařství

• MeSH
• balónková koronární angioplastika MeSH
• koronární bypass MeSH
• kvalita života MeSH
• lidé MeSH
• výsledek terapie MeSH
• zátěžový test MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• multicentrická studie MeSH
• přehledy MeSH
• srovnávací studie MeSH
• Geografické názvy
• Spojené státy americké MeSH

Due to the aging population, there is an increasing number of fragility fractures of the pelvis (FFP). They are the result of low energy trauma. The bone breaks but the ligaments remain intact. Immobilizing pain at the pubic region or at the sacrum is the main symptom. Conventional radiographs reveal pubic rami fractures, but lesions of the dorsal pelvis are hardly visible and easily overlooked. CT of the pelvis with multiplanar reconstructions show the real extension of the lesion. Most patients have a history of osteoporosis or other fragility fractures. The new classification distinguishes between four categories of different and increasing instability. FFP Type I are anterior lesions only, FFP Type II are non-displaced posterior lesions, FFP Type III are displaced unilateral posterior lesions and FFP Type IV are displaced bilateral posterior lesions. Subgroups discriminate between the localization of the dorsal instability. FFP Type I lesions are treated non-operatively. FFP Type II lesions are fixed in a percutaneous procedure when a trial of conservative treatment was not successful. FFP Type III lesions are treated with open reduction and internal fixation (ORIF). FFP Type IV lesions are treated with bilateral ORIF or with a bridging osteosynthesis. Iliosacral screw osteosynthesis is widely used, but has an elevated risk of screw loosening due to diminished bine mineral density. Transsacral bar osteosynthesis enable interfragmentary compression and does not have this danger of loosening. Bridging plate osteosynthesis is used as an additional fixation to iliosacral screw osteosynthesis. Lumbopelvic fixation is restricted to highly unstable lumbopelvic dissociations. More studies are needed to find the optimal treatment for each type of instability. Key words: pelvis, fragility fracture, diagnosis, classification, treatment.

• MeSH
• inhibitory kostní resorpce terapeutické užití   MeSH
• lidé MeSH
• management bolesti MeSH
• osteoporotické fraktury klasifikace   radiografie   terapie   MeSH
• pánevní kosti zranění   chirurgie   MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• techniky fyzikální terapie MeSH
• vnitřní fixace fraktury metody   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Management of Ras wild-type colorectal cancer (CRC) patients upon disease progression after the successful use of targeted treatment with anti-EGFR monoclonal antibodies and backbone chemotherapy remains a clinical challenge. SUMMARY: Development of treatment resistance with prevalence of preexisting RAS mutated clones, RAS mutation conversion, truncation of extracellular receptor domains as well as HER2 and MET amplification are molecular events that can be difficult to follow without the use of sophisticated laboratory techniques. The clinical hurdle of re-biopsy and tumor heterogeneity can be overcome by the implementation of next-generation sequencing (NGS) to analyze circulating tumor DNA (ctDNA) and identify druggable mutations or recovery of RAS-wildness. In this opinion paper, we summarize with critical thinking the clinical approach to be followed after the failure of first-line treatment in Ras wild-type CRC tumors with the use of NGS. Rechallenge with anti-EGFR inhibitors, in case of persistent or recovery of RAS-wildness, and targeted approach of specific mutations (BRAF inhibitors), amplifications (anti-Her2 treatment), or fusion proteins (NTRK inhibitors) can by guided by the use of NGS. The use of NGS platforms for serial analysis of ctDNA is an important step to better understand the molecular landscape of metastatic CRC and guide clinical decisions. KEY MESSAGES: NGS should be considered a mainstay in clinical practice for the management of CRC patients and health authorities should consider reimbursing its use in the appropriate clinical settings.

• MeSH
• cirkulující nádorová DNA * genetika   MeSH
• kolorektální nádory * farmakoterapie   genetika   patologie   MeSH
• lidé MeSH
• mutace MeSH
• nádory tračníku * genetika   MeSH
• onkogeny MeSH
• vysoce účinné nukleotidové sekvenování MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

BACKGROUND: Covid-19 vaccination has started in the majority of the countries at the global level. Cancer patients are at high risk for infection, serious illness, and death from COVID-19 and need vaccination guidance and support. Guidance availability in the English language only is a major limit for recommendations' delivery and their application in the world's population and generates information inequalities across the different populations. METHODS: Most of the available COVID-19 vaccination guidance for cancer patients was screened and scrutinized by the European Cancer Patients Coalition (ECPC) and an international oncology panel of 52 physicians from 33 countries. RESULTS: A summary guidance was developed and provided in 28 languages in order to reach more than 70 percent of the global population. CONCLUSION: Language barrier and e-guidance availability in the native language are the most important barriers when communicating with patients. E-guidance availability in various native languages should be considered a major priority by international medical and health organizations that are communicating with patients at the global level.

• MeSH
• COVID-19 * epidemiologie   prevence a kontrola   MeSH
• jazyk (prostředek komunikace) MeSH
• lidé MeSH
• nádory * MeSH
• vakcinace MeSH
• vakcíny proti COVID-19 MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Přehled základních přístupů a aplikací V roce 1995 publikoval Daniel Goleman, žurnalista zaměřený na teorii vědy, knihu Emotional Intelligence, v níž je emoční inteligence (EI) popsána jako nejlepší předpoklad úspěchu v životě, je dosažitelná zdánlivě pro kohokoli a blíží se svou obecností charakteru. Jeho kniha vzbudila mimořádná očekávání směrem k EI a velmi uvolněné vymezení pojmu vedlo k výraznému nárůstu zájmu o tuto oblast. Emoční inteligence se nejčastěji definuje jako schopnost vnímat, vyjadřovat, chápat a usměrňovat vlastní emoce i emoce druhých lidí. Předkládaná kniha na rozdíl od mnoha popularizačních titulů, které někdy až nekriticky vyzdvihují roli emoční inteligence, přehledně a střízlivě prezentuje dosavadní výzkum v dané oblasti s ohledem na její silné i slabé stránky. Autorský tým se věnuje vymezení důležitých pojmů, teoretickým přístupům k EI, metodám měření EI, hlavním aplikačním oblastem a v závěrečné syntéze pak hlavním pokrokům v oblasti i dosud nevyřešeným problémům spojeným s pojmem EI.

• MeSH
• emoce MeSH
• empatie MeSH
• inteligence MeSH
• interpersonální vztahy MeSH
• interprofesionální vztahy MeSH
• osobní uspokojení MeSH
• Publikační typ
• příručky MeSH

• Konspekt
• Senzorické a motorické funkce. Emoce. Vůle
• NLK Obory
• psychologie, klinická psychologie
• sociologie

• MeSH
• lékařství MeSH
• Publikační typ
• encyklopedie MeSH

• Konspekt
• Lékařské vědy. Lékařství
• NLK Obory
• lékařství

BACKGROUND: Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial. OBJECTIVE: To bring together a large multidisciplinary group of experts to develop consensus statements on controversial topics in bladder cancer management. DESIGN: A steering committee compiled proposed statements regarding advanced and variant bladder cancer management which were assessed by 113 experts in a Delphi survey. Statements not reaching consensus were reviewed; those prioritised were revised by a panel of 45 experts before voting during a consensus conference. SETTING: Online Delphi survey and consensus conference. PARTICIPANTS: The European Association of Urology (EAU), the European Society for Medical Oncology (ESMO), experts in bladder cancer management. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Statements were ranked by experts according to their level of agreement: 1-3 (disagree), 4-6 (equivocal), 7-9 (agree). A priori (level 1) consensus was defined as ≥70% agreement and ≤15% disagreement, or vice versa. In the Delphi survey, a second analysis was restricted to stakeholder group(s) considered to have adequate expertise relating to each statement (to achieve level 2 consensus). RESULTS AND LIMITATIONS: Overall, 116 statements were included in the Delphi survey. Of these, 33 (28%) statements achieved level 1 consensus and 49 (42%) statements achieved level 1 or 2 consensus. At the consensus conference, 22 of 27 (81%) statements achieved consensus. These consensus statements provide further guidance across a broad range of topics, including the management of variant histologies, the role/limitations of prognostic biomarkers in clinical decision making, bladder preservation strategies, modern radiotherapy techniques, the management of oligometastatic disease and the evolving role of checkpoint inhibitor therapy in metastatic disease. CONCLUSIONS: These consensus statements provide further guidance on controversial topics in advanced and variant bladder cancer management until a time where further evidence is available to guide our approach.

• MeSH
• delfská metoda MeSH
• konsensus * MeSH
• lékařská onkologie metody   normy   MeSH
• lidé MeSH
• mezinárodní spolupráce MeSH
• močový měchýř patologie   MeSH
• nádory močového měchýře patologie   terapie   MeSH
• průzkumy a dotazníky MeSH
• směrnice pro lékařskou praxi jako téma * MeSH
• společnosti lékařské normy   MeSH
• staging nádorů MeSH
• účast zainteresovaných stran MeSH
• urologie metody   normy   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Evropa MeSH