PURPOSE OF REVIEW: This review explores the design and endpoints of perioperative platforms in clinical trials for muscle-invasive bladder cancer (MIBC). RECENT FINDINGS: The choice of clinical trial design in perioperative platforms for MIBC must align with specific research objectives to ensure robust and meaningful outcomes. Novel designs in perioperative platforms for MIBC integrate bladder-sparing approaches. Primary endpoints such as pathological complete response and disease-free survival are highlighted for their role in expediting trial results in perioperative setting. Incorporating patient-reported outcomes is important to inform healthcare decision makers about the outcomes most meaningful to patients. Given the growing body of evidence, potential biomarkers, predictive and prognostic tools should be considered and implemented when designing trials in perioperative platforms for MIBC. SUMMARY: Effective perioperative platforms for MIBC trials are critical in enhancing patient outcomes. The careful selection and standardization of study designs and endpoints in the perioperative platform are essential for the successful implementation of new therapies and the advancement of personalized treatment approaches in MIBC.

• MeSH
• cystektomie metody   škodlivé účinky   MeSH
• invazivní růst nádoru * MeSH
• klinické zkoušky jako téma MeSH
• lidé MeSH
• nádory močového měchýře * chirurgie   patologie   terapie   mortalita   MeSH
• perioperační péče metody   normy   MeSH
• stanovení cílového parametru MeSH
• výsledek terapie MeSH
• výzkumný projekt MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

In this systematic review, we report on the effects of diuretic deprescribing compared to continued diuretic use. We included clinical studies reporting on outcomes such as mortality, heart failure recurrence, tolerability and feasibility. We assessed risk of bias and certainty of the evidence using the GRADE framework. We included 25 publications from 22 primary studies (15 randomized controlled trials; 7 nonrandomized studies). The mean number of participants in the deprescribing groups was 35, and median/mean age 64 years. In patients with heart failure, there was no clear evidence that diuretic deprescribing was associated with increased mortality compared to diuretic continuation (low certainty evidence). The risk of cardiovascular composite outcomes associated with diuretic deprescribing was inconsistent (studies showing lower risk for diuretic deprescribing, or comparable risk with diuretic continuation; very low certainty evidence). The effect on heart failure recurrence after diuretic deprescribing in patients with diuretics for heart failure, and of hypertension in patients with diuretics for hypertension was inconsistent across the included studies (low certainty evidence). In patients with diuretics for hypertension, diuretic deprescribing was well tolerated (moderate certainty evidence), while in patients with diuretics for heart failure, deprescribing diuretics can result in complaints of peripheral oedema (very low certainty evidence). The overall risk of bias was generally high. In summary, this systematic review suggests that diuretic discontinuation could be a safe and feasible treatment option for carefully selected patients. However, there isa lack of high-quality evidence on its feasibility, safety and tolerability of diuretic deprescribing, warranting further research.

• MeSH
• depreskripce * MeSH
• diuretika * škodlivé účinky   aplikace a dávkování   terapeutické užití   MeSH
• dospělí MeSH
• hypertenze farmakoterapie   MeSH
• lidé MeSH
• medicína založená na důkazech MeSH
• randomizované kontrolované studie jako téma MeSH
• směrnice pro lékařskou praxi jako téma MeSH
• srdeční selhání * farmakoterapie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• systematický přehled MeSH

BACKGROUND: Exposure of critically ill patients to antibiotics lead to intestinal dysbiosis, which often manifests as antibiotic-associated diarrhoea. Faecal microbiota transplantation restores gut microbiota and may lead to faster resolution of diarrhoea. METHODS: Into this prospective, multi-centre, randomized controlled trial we will enrol 36 critically ill patients with antibiotic-associated diarrhoea. We will exclude patients with ongoing sepsis, need of systemic antibiotics, or those after recent bowel surgery or any other reason that prevents the FMT. Randomisation will be in 1:1 ratio. Patients in the control group will receive standard treatment based on oral diosmectite. In the intervention group, patients will receive, in addition to the standard of care, faecal microbiota transplantation via rectal tube, in the form of a preparation mixed from 7 thawed aliquots (50 mL) made from fresh stool of 7 healthy unrelated donors and quarantined deep frozen for 3 to 12 months. Primary outcome is treatment failure defined as intervention not delivered or diarrhoea persisting at day 7 after randomisation. Secondary outcomes include safety measures such as systemic inflammatory response, adverse events, and also diarrhoea recurrence within 28 days. Exploratory outcomes focus on gut barrier function and composition of intestinal microbiota. DISCUSSION: Faecal microbiota transplantation has been effective for dysbiosis in non-critically ill patients with recurrent C. difficile infections and it is plausible to hypothesize that it will be equally effective for symptoms of dysbiosis in the critically ill patients. In addition, animal experiments and observational data suggest other benefits such as reduced colonization with multi-drug resistant bacteria and improved gut barrier and immune function. The frozen faeces from unrelated donors are immediately available when needed, unlike those from the relatives, who require lengthy investigation. Using multiple donors maximises graft microbiota diversity. Nonetheless, in vulnerable critically ill patients, Faecal microbiota transplantation might lead to bacterial translocation and unforeseen complications. From growing number of case series it is clear that its off label use in the critically ill patients is increasing and that there is a burning need to objectively assess its efficacy and safety, which this trial aims. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT05430269).

• MeSH
• antibakteriální látky * škodlivé účinky   terapeutické užití   MeSH
• dysbióza terapie   mikrobiologie   MeSH
• feces mikrobiologie   MeSH
• fekální transplantace * metody   škodlivé účinky   MeSH
• klinické zkoušky, fáze II jako téma MeSH
• kritický stav * MeSH
• lidé MeSH
• multicentrické studie jako téma MeSH
• prospektivní studie MeSH
• průjem * terapie   mikrobiologie   MeSH
• randomizované kontrolované studie jako téma MeSH
• střevní mikroflóra * účinky léků   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• protokol klinické studie MeSH

BACKGROUND: Although there is growing evidence of the association between gender and early diagnosis of preclinical Alzheimer's disease, little attention has been given to the enrolment ratio of men and women in clinical trials and data reporting. METHODS: This study aims to analyze gender differences in sociodemographic factors associated with the willingness to participate in clinical trials and undergo specific procedures in the context of an Alzheimer's disease prevention research cohort. 2544 cognitively unimpaired participants from the ALFA parent cohort (age 45-75 years) of the Barcelonaβeta Brain Research Center were contacted through a structured phone call to determine their willingness to participate in Alzheimer's disease clinical trials and undergo trial-related procedures (magnetic resonance imaging, lumbar puncture, positron emission tomography, and cognitive assessment). Sociodemographic data on education, occupational attainment, civil and caregiver status were gathered. Stepwise logistic regression models were performed in order to study the interaction between gender and sociodemographic factors in the willingness to participate in clinical trials and to undergo clinical trial-related procedures. RESULTS: 1,606 out of the 2,544 participants were women (63.1%). Women were significantly younger and had lower educational attainment compared with men. In addition, women were more likely to be caregivers, single and unemployed. Women showed a significantly lower willingness than men to participate in a clinical trial (p = 0.003) and to undergo a lumbar puncture (p < 0.001). Single women were less willing to participate in clinical trials than single men (p = 0.041). Regarding clinical trial-related procedures, women with higher years of education were significantly less willing to undergo a lumbar puncture (p = 0.031). CONCLUSION: We found gender differences regarding the sociodemographic factors that predict the willingness to participate in clinical trials and to undergo clinical trial-related procedures. Our results highlight the urgent need to design recruitment strategies accounting for gender-related factors, particularly those related to marital status and education.

• MeSH
• Alzheimerova nemoc * psychologie   MeSH
• klinické zkoušky jako téma * psychologie   MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• pohlavní dimorfismus MeSH
• senioři MeSH
• sexuální faktory MeSH
• stupeň vzdělání MeSH
• výběr pacientů MeSH
• zapojení pacienta psychologie   statistika a číselné údaje   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

PURPOSE: The AIEOP-BFM ALL 2009 protocol included, at the end of the induction phase, a randomized study of patients with high-risk (HR) ALL to investigate if an intensive exposure to pegylated L-asparaginase (PEG-ASNASE, 2,500 IU/sqm once a week × 4) on top of BFM consolidation phase IB allowed us to decrease minimal residual disease (MRD) and improve outcome. PATIENTS AND METHODS: A total of 1,097 patients presented, from June 2010 to February 2017, with one or more of the following HR criteria: KMT2A::AFF1 rearrangement, hypodiploidy, prednisone poor response, poor bone marrow response at day 15 (Flow MRD ≥10%), or no complete remission (CR) at the end of induction. Of them, 809 (85.1%) were randomly assigned to receive (404) or not receive (405) four weekly doses of PEG-ASNASE. RESULTS: By intention to treat (ITT) analysis, there was no significant difference in the proportion of patients with polimerase chain reaction MRD ≥5 × 10-4 at the end of phase IB in the experimental versus control arm (13.9% v 17.0%, P = .25). The 5-year event-free survival (median follow-up 6.3 years) by ITT in the experimental and control arms was 70.4% (2.3) versus 75.0% (2.2; P = .18), and the 5-year overall survival was 81.5% (2.0) versus 84.0% (1.9; P = .25), respectively. The corresponding 5-year cumulative incidence of death in CR was 9.5% (1.5) versus 5.7% (1.2; P = .08), and that of relapse was 17.7% (1.9) versus 17.2% (1.9), respectively (P = .94). Adverse reactions in phase IB occurred in 22.2% and 8.9% of patients in the experimental and control arm, respectively (P < .001). CONCLUSION: Additional PEG-ASNASE in phase IB did not translate into a benefit for decreasing relapse incidence but was associated with higher toxicity. Further improvements with conventional chemotherapy might be difficult in the context of intensive treatment protocols.

• MeSH
• akutní lymfatická leukemie * MeSH
• asparaginasa * MeSH
• kojenec MeSH
• lidé MeSH
• lokální recidiva nádoru farmakoterapie   MeSH
• polyethylenglykoly MeSH
• prednison škodlivé účinky   MeSH
• přežití po terapii bez příznaků nemoci MeSH
• protokoly antitumorózní kombinované chemoterapie škodlivé účinky   MeSH
• randomizované kontrolované studie jako téma MeSH
• recidiva MeSH
• výsledek terapie MeSH
• Check Tag
• kojenec MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• protokol klinické studie MeSH

Karcinom pankreatu je prognosticky nepříznivé nádorové onemocnění s rostoucí incidencí a mortalitou, které představuje 3. nejčastější příčinu úmrtí na zhoubný nádor ve vyspělých zemích. Pětileté přežití nepřesahuje 11 % a je nejnižší napříč všemi onkologickými diagnózami. Cca 20–30 % pacientů má v době diagnózy resekabilní (resectable pancreatic cancer – RPC) nebo hraničně resekabilní (borderline resectable pancreatic cancer – BRPC) onemocnění. Radikální resekce je v těchto případech zásadní terapeutickou modalitou, která je považována za jediný potenciálně kurativní postup. Neoadjuvantní chemoterapie a/nebo chemoradioterapie je etablována především u BRPC. Role neoadjuvance u RPC se v současnosti zkoumá. Cílem tohoto sdělení je popsat současné možnosti, výhody a nevýhody neoadjuvantní léčby u pacientů BRPC a RPC.

Pancreatic carcinoma is a prognostically unfavorable cancer disease with growing incidence and mortality, which is the 3rd most common cause of cancer-related death in developed countries. The 5-year survival rate does not exceed 11% and is the lowest across all cancer diagnoses. Only about 20–30% of patients have resectable (RPC) or borderline resectable (BRPC) disease at the time of diagnosis. Radical resection is an essential therapeutic modality in these cases and is considered the only potentially curative procedure. Neoadjuvant chemotherapy and/or chemoradiotherapy is established mainly in BRPC. The role of neoadjuvant therapy in RPC is currently under investigation. This review article describes the current options, advantages and disadvantages of neoadjuvant treatment in BRPC and RPC.

• MeSH
• antimetabolity antitumorózní MeSH
• gemcitabin terapeutické užití   MeSH
• klinické zkoušky jako téma MeSH
• lidé MeSH
• lokální recidiva nádoru MeSH
• nádorové biomarkery MeSH
• nádory slinivky břišní * chirurgie   farmakoterapie   MeSH
• neoadjuvantní terapie * MeSH
• protokoly antitumorózní kombinované chemoterapie MeSH
• resekční okraje MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH

BACKGROUND: The fear of taking away hope hinders clinicians' willingness to share serious news with patients with advanced disease. Unrealistic illness expectations, on the other hand, can complicate decision making and end-of-life care outcomes. Exploration of the association between hope and illness expectations can support clinicians in better communication with their patients. AIM: The aim of this study was to explore whether realistic illness expectations are associated with reduced hope in people with advanced cancer. DESIGN: This is a cross-sectional secondary analysis of baseline data from a primary palliative care cluster-randomized trial CONNECT (data collected from July 2016 to October 2020). Hope was measured by Herth Hope Index. Illness expectations were measured by assessing patients' understanding of their treatment goals, life expectancy, and terminal illness acknowledgement. Multivariable regression was performed, adjusting for demographical and clinical confounders. SETTING/PARTICIPANTS: Adult patients with advanced solid cancers recruited across 17 oncology clinics. RESULTS: Data from 672 patients were included in the study, with mean age of 69.3 years (±10.2), 53.6% were female. Proportion of patients indicating realistic expectations varied based on which question was asked from 10% to 46%. Median level of hope was 39 (IQR = 36-43). Multivariate non-inferiority regression did not find any significant differences in hope between patients with more and less realistic illness expectations. CONCLUSIONS: Our results suggest that hope can be sustained while holding both realistic and unrealistic illness expectations. Communication about serious news should focus on clarifying the expectations as well as supporting people's hopes.

• MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• motivace MeSH
• naděje MeSH
• nádory * terapie   MeSH
• paliativní péče metody   MeSH
• péče o umírající * MeSH
• průřezové studie MeSH
• randomizované kontrolované studie jako téma MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Hepatocelulárny karcinóm (HCC) predstavuje najčastejšiu primárnu malignitu pečene, tvorí približne 75–80 % všetkých prípadov rakoviny pečene. Globálny výskyt hepatocelulárneho karcinómu sa zvyšuje v dôsledku rastúceho počtu základných ochorení, čo vytvára významnú rakovinovú záťaž a významnú klinickú výzvu v dôsledku jeho často neskorého prejavu a obmedzených účinných možností liečby. Inhibítory imunitného kontrolného bodu spôsobili revolúciu v prístupe k liečbe rôznych malignít. Pri liečbe pokročilého hepatocelulárneho karcinómu sa imunoterapia ukázala byť účinnejšia ako inhibítory tyrozínkinázy, ktoré boli možnosťou liečby už desaťročie. Klinické štúdie ako HIMALAYA a IMbrave150 preukázali významné prínosy prežitia a preukázali vyššiu účinnosť v porovnaní so sorafenibom. Napriek týmto sľubným výsledkom nie všetci pacienti s HCC reagujú na imunoterapiu rovnako. Je potrebné hľadať spoľahlivé prognostické a prediktívne biomarkery, ktoré môžu pomôcť predpovedať, ktorí pacienti budú s najväčšou pravdepodobnosťou profitovať z imunoterapie, a tým personalizovať liečbu a zlepšiť výsledky. Účelom tohto článku je poskytnúť súhrn klinických štúdií imunoterapie pre rôzne štádiá hepatocelulárneho karcinómu.

Hepatocellular carcinoma (HCC) represents the most common primary liver malignancy, accounting for approximately 75–80% of all liver cancer cases. The global incidence of hepatocellular carcinoma is increasing due to rising rates of underlying diseases, creating a significant cancer burden and a significant clinical challenge due to its often late presentation and limited effective treatment options. Immune checkpoint inhibitors have revolutionized the treatment approach in various malignancies. In the treatment of advanced hepatocellular carcinoma, immunotherapy has proven to be more effective than tyrosine kinase inhibitors, which have been a treatment option for a decade. Clinical trials such as the HIMALAYA and IMbrave150 have demonstrated significant survival benefits, showing superior efficacy compared to sorafenib. Despite these promising results, not all HCC patients respond to immunotherapy equally. There is a need to search for reliable prognostic and predictive biomarkers that can help predict which patients are most likely to benefit from immunotherapy, thereby personalizing treatment and improving outcomes. The purpose of this article is to provide a summary of clinical trials on immunotherapy for various stages of hepatocellular carcinoma.

• MeSH
• hepatocelulární karcinom * farmakoterapie   MeSH
• imunoterapie * MeSH
• inhibitory kontrolních bodů terapeutické užití   MeSH
• klinické zkoušky jako téma MeSH
• lidé MeSH
• monoklonální protilátky terapeutické užití   MeSH
• nádory jater farmakoterapie   MeSH
• protokoly antitumorózní kombinované chemoterapie MeSH
• sorafenib terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

Medikamentózní léčba funkčních trávicích poruch je zpravidla obtížná, vyžaduje komplexní přístup a u řady pacientů také podávání účinných prokinetik. Ta se nově v České republice rozšiřuje o léčivou látku cinitaprid. Předložený text shrnuje jeho základní farmakologické vlastnosti a dostupné relevantní aspekty jeho klinického využití.

Treatment of functional dyspepsia is often medically difficult and requires a comprehensive approach, including the drug group prokinetics. In the Czech Republic, it is now being expanded to include the active substance cinitapride. The presented text summarizes its basic pharmacological properties and summarizes the available relevant aspects of its clinical use.

• Klíčová slova
• Cinitaprid,
• MeSH
• antiemetika farmakologie   terapeutické užití   MeSH
• benzamidy * aplikace a dávkování   farmakologie   terapeutické užití   MeSH
• dyspepsie * farmakoterapie   MeSH
• hodnocení léčiv MeSH
• klinické zkoušky jako téma MeSH
• lidé MeSH
• Check Tag
• lidé MeSH

CONTEXT: The optimal therapeutic agent with respect to metastatic sites is unclear in advanced urothelial carcinoma (UC). OBJECTIVE: To investigate the metastatic organotropism differential treatment response in patients with advanced or metastatic UC. EVIDENCE ACQUISITION: A systematic search and network meta-analysis (NMA) was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. The primary endpoints of interest were the objective response rate, overall survival (OS), and progression-free survival with respect to different metastatic sites. EVIDENCE SYNTHESIS: Twenty-six trials comprising 9082 patients met our eligibility criteria, and a formal NMA was conducted. Durvalumab plus tremelimumab as first-line systemic therapy was significantly associated with better OS than chemotherapy in visceral metastasis (hazard ratio [HR] 0.81, 95% confidence interval [CI] 0.67-0.98). Pembrolizumab as second-line systemic therapy was significantly associated with better OS than chemotherapy in patients with visceral metastasis (HR 0.75, 95% CI 0.60-0.95). Atezolizumab as second-line systemic therapy was significantly associated with better OS than chemotherapy in patients with liver metastasis (in the population of >5% of tumor-infiltrating immune cells) and lymph node metastasis (HR 0.51, 95% CI 0.28-0.96, and HR 0.59, 95% CI 0.37-0.96, respectively). CONCLUSIONS: Administration of immune-oncology treatments with respect to metastatic sites in patients with advanced or metastatic UC might have a positive impact on survival outcomes in both the first- and the second-line setting. Nevertheless, further investigations focusing on metastatic organotropism differential response with reliable oncological outcomes are needed to identify the optimal management strategy for these patients. PATIENT SUMMARY: Although the supporting evidence for oncological benefits of therapeutic systemic agents with respect to metastatic sites is not yet strong enough to provide a recommendation in advanced or metastatic urothelial carcinoma, clinicians may take into account tumor organotropism only in discussion with the patient fully informed on the optimal treatment decision to be taken.

• MeSH
• karcinom z přechodných buněk * farmakoterapie   sekundární   mortalita   patologie   MeSH
• lidé MeSH
• metastázy nádorů MeSH
• randomizované kontrolované studie jako téma * MeSH
• síťová metaanalýza * MeSH
• urologické nádory farmakoterapie   patologie   mortalita   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• přehledy MeSH
• systematický přehled MeSH