BACKGROUND: Androgen-receptor signaling inhibitors (ARSIs) significantly improve survival in systemic therapy for advanced/metastatic prostate cancer (PCa) patients; however possible central nervous system (CNS) toxicity is an unaddressed concern. We aimed to assess and compare the incidence of CNS-related adverse events (AEs) secondary to the treatment of PCa patients with different ARSIs. MATERIALS: In August 2023, a comprehensive seach was conducted in three databases for randomized controlled trials (RCTs) of PCa patients receiving ARSIs plus ADT. The primary endpoints included mental impairment, cognitive impairment, seizure, fatigue, and falls. RESULTS: Twenty-six RCTs, comprising 20,328 patients, were included in meta-analyses and network meta-analyses (NMAs). ARSIs increased the risk of mental impairment (RR: 1.72; 95% CI, 1.09-2.71), cognitive impairment (RR: 2.25; 95% CI, 1.78-2.86), seizure (RR: 2.20, 95% CI, 1.09-4.45), fatigue (RR: 1.31, 95% CI, 1.20-1.43), and falls (RR: 2.07, 95% CI, 1.60-2.67) compared to standard of care (SOC). Based on NMAs, Enzalutamide showed a significant increase in risk for all assessed CNS-related AEs, while Abiraterone demonstrated significant risk increases in cognitive impairment, fatigue, and falls. Conversely, Darolutamide did not exhibit significant increases in risk for any CNS-related AEs, except for fatigue. CONCLUSIONS: The addition of ARSIs to ADT increased all examined CNS-related AEs compared to SOC. Each ARSI is associated with a distinct profile of CNS-related AEs. Careful patient selection and monitoring for CNS sequelae is necessary to achieve the best quality of life in patients on ARSI + ADT for PCa.

• MeSH
• antagonisté androgenních receptorů * škodlivé účinky   aplikace a dávkování   terapeutické užití   MeSH
• benzamidy MeSH
• fenylthiohydantoin škodlivé účinky   aplikace a dávkování   MeSH
• lidé MeSH
• nádory prostaty * farmakoterapie   patologie   MeSH
• nemoci centrálního nervového systému chemicky indukované   MeSH
• nitrily MeSH
• pyrazoly MeSH
• randomizované kontrolované studie jako téma MeSH
• síťová metaanalýza * MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• přehledy MeSH
• systematický přehled MeSH

BACKGROUND: Androgen-receptor pathway inhibitors (ARPIs) have dramatically changed the management of advanced/metastatic prostate cancer (PCa). However, their cardiovascular toxicity remains to be clarified. OBJECTIVE: To analyze and compare the risks of cardiovascular events secondary to treatment of PCa patients with different ARPIs. METHODS: In August 2023, we queried PubMed, Scopus, and Web of Science databases to identify randomized controlled studies (RCTs) that analyze PCa patients treated with abiraterone, apalutamide, darolutamide, and enzalutamide. The primary outcomes of interest were the incidence of cardiac disorder, heart failure, ischemic heart disease (IHD), atrial fibrillation (AF), and hypertension. Network meta-analyses (NMAs) were conducted to compare the differential outcomes of each ARPI plus androgen deprivation therapy (ADT) compared to standard of care (SOC). RESULTS: Overall, 26 RCTs were included. ARPIs were associated with an increased risk of cardiac disorders (RR: 1.74, 95% CI: 1.13-2.68, p = 0.01), heart failure (RR: 2.49, 95% CI: 1.05-5.91, p = 0.04), AF (RR: 2.15, 95% CI: 1.14-4.07, p = 0.02), and hypertension (RR: 2.06, 95% CI: 1.67-2.54, p < 0.01) at grade ≥3. Based on NMAs, abiraterone increased the risk of grade ≥3 cardiac disorder (RR:2.40, 95% CI: 1.42-4.06) and hypertension (RR:2.19, 95% CI: 1.77-2.70). Enzalutamide was associated with the increase of grade ≥3 AF(RR: 3.17, 95% CI: 1.05-9.58) and hypertension (RR:2.30, 95% CI: 1.82-2.92). CONCLUSIONS: The addition of ARPIs to ADT increases the risk of cardiac disorders, including IHD and AF, as well as hypertension. Each ARPI exhibits a distinct cardiovascular event profile. Selecting patients carefully and vigilant monitoring for cardiovascular issues is imperative for those undergoing ARPI + ADT treatment.

• MeSH
• androsteny MeSH
• antagonisté androgenních receptorů * škodlivé účinky   terapeutické užití   MeSH
• benzamidy škodlivé účinky   MeSH
• fenylthiohydantoin MeSH
• kardiovaskulární nemoci * chemicky indukované   epidemiologie   MeSH
• lidé MeSH
• nádory prostaty * farmakoterapie   patologie   MeSH
• nitrily škodlivé účinky   MeSH
• randomizované kontrolované studie jako téma MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• síťová metaanalýza MeSH
• systematický přehled MeSH

BACKGROUND: Prostate Imaging Reporting and Data System (PI-RADS) 3 lesions, identified through multiparametric magnetic resonance imaging (mpMRI), present a clinical challenge due to their equivocal nature in predicting clinically significant prostate cancer (csPCa). Aim of the study is to improve risk stratification of patients with PI-RADS 3 lesions and candidates for prostate biopsy. METHODS: A cohort of 4841 consecutive patients who underwent MRI and subsequent MRI-targeted and systematic biopsies between January 2016 and April 2023 were retrospectively identified from independent prospectively maintained database. Only patients who have PI-RADS 3 lesions were included in the final analysis. A multivariable logistic regression analysis was performed to identify covariables associated with csPCa defined as International Society of Urological Pathology (ISUP) grade group ≥2. Performance of the model was evaluated using the area under the receiver operating characteristic curve (AUC), calibration, and net benefit. Significant predictors were then selected for further exploration using a Chi-squared Automatic Interaction Detection (CHAID) analysis. RESULTS: Overall, 790 patients had PI-RADS 3 lesions and 151 (19%) had csPCa. Significant associations were observed for age (OR: 1.1 [1.0-1.1]; p = 0.01) and PSA density (OR: 1643 [2717-41,997]; p < 0.01). The CHAID analysis identified PSAd as the sole significant factor influencing the decision tree. Cut-offs for PSAd were 0.13 ng/ml/cc (csPCa detection rate of 1% vs. 18%) for the two-nodes model and 0.09 ng/ml/cc and 0.16 ng/ml/cc for the three-nodes model (csPCa detection rate of 0.5% vs. 2% vs. 17%). CONCLUSIONS: For individuals with PI-RADS 3 lesions on prostate mpMRI and a PSAd below 0.13, especially below 0.09, prostate biopsy can be omitted, in order to avoid unnecessary biopsy and overdiagnosis of non-csPCa.

• MeSH
• hodnocení rizik metody   MeSH
• lidé středního věku MeSH
• lidé MeSH
• multiparametrická magnetická rezonance * metody   MeSH
• nádory prostaty * patologie   diagnostické zobrazování   diagnóza   krev   MeSH
• prostata patologie   diagnostické zobrazování   MeSH
• prostatický specifický antigen * krev   MeSH
• retrospektivní studie MeSH
• ROC křivka MeSH
• senioři MeSH
• stupeň nádoru MeSH
• ultrazvukem navigovaná biopsie metody   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH

Deficit alfa-1 antitrypsinu (AATD) je jednou z nejčastějších dědičných genetických poruch dospělých na světě postihující kromě funkce plic i jaterní tkáň a zřídka kůži. Stále se jedná o diagnózu, která je výrazně poddiagnostikovaná (1, 2). Poprvé byla popsána před více než 60 lety vědci ve švédské univerzitě Lund a je způsobena poruchou genu pro inhibitory serinových proteáz skupiny A1 (SERPINA1, chromozom 14q32.13, wild type M), který kóduje vznik alfa-1 antitrypsinu (AAT), nejdůležitější antiproteázy v plicích (3). Při AATD dochází k vytváření menšího množství AAT, k vytváření neplnohodnotného AAT nebo k produkci AAT nedochází. Nedostatečná/nesprávná tvorba AAT v játrech vedoucí k nižší sérové hladině, logicky vede ke snížení jeho koncentrace v plicích, což způsobuje časnější vznik panacinárního emfyzému, bronchiektázií (BE) a následně i vznik chronické obstrukční plicní nemoci (CHOPN, COPD). Případné hromadění defektních proteinů v játrech vede v dětství k cholestáze, v pozdějším věku ke zvýšení rizika jaterní cirhózy či dokonce karcinomu (CA) jater. Výše uvedená plicní postižení jsou způsobena převahou proteáz nad účinkem inhibitorů serinových proteáz, jejichž tvorba je u nosičů defektních alel nedostatečná (4–6). Kouření vede k zásadnímu urychlení patologických procesů v plíci, které probíhají také u nekouřící populace s AATD, avšak výrazně pomaleji než u kuřáků. Hlavně u nositelů homozygotní varianty PiZZ a Pi00 (Pi – proteinázový inhibitor) vede kouření poměrně záhy k těžkému snížení hladiny AAT v séru. Cílem současného přístupu k pacientům s AATD je časná diagnostika onemocnění, sledování v čase a správné načasovaní terapie včetně augmentační (4, 7, 8).

Alpha-1 antitrypsin deficiency (AATD) is one of the most common inherited genetic disorders in adults worldwide, affecting not only lung function but also liver tissue and, rarely, the skin. It is still a significantly underdiagnosed diagnosis (1, 2). First described more than 60 years ago by scientists at Lund University in Sweden, it is caused by a defect in the serine protease inhibitor group A1 gene (SERPINA1, chromosome 14q32.13, wild-type M), which codes for the production of alpha-1 antitrypsin (AAT), the major antiprotease in the lungs (3). In AATD, less AAT is produced, insufficient AAT is produced, or no AAT is produced. Inadequate/faulty AAT production in the liver leading to lower serum levels, logically leads to lower AAT concentrations in the lungs, causing earlier onset of panacinar emphysema, bronchiectasis (BE) and subsequently chronic obstructive pulmonary disease (COPD). The eventual accumulation of defective proteins in the liver leads to cholestasis in childhood and to an increased risk of cirrhosis or even carcinoma (CA) of the liver later in life. The abovementioned lung diseases are caused by the predominance of proteases over the effect of serine protease inhibitors, the production of which is deficient in carriers of defective alleles (4-6). Smoking significantly accelerates the pathological processes in the lungs, which also occur in the non-smoking population with AATD, but at a much slower rate than in smokers. Particularly in carriers of the homozygous PiZZ and Pi00 (Pi - proteinase inhibitor) variants, smoking leads to a relatively early and severe reduction in serum AAT levels. The current approach to patients with AATD is to diagnose the disease at an early stage, monitor the disease over time and determine the correct timing of therapy, including augmentation therapy (4, 7, 8).

• MeSH
• chronická obstrukční plicní nemoc etiologie   genetika   terapie   MeSH
• deficit alfa1-antitrypsinu * epidemiologie   genetika   komplikace   MeSH
• kouření škodlivé účinky   MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

IMPORTANCE: The successful implementation of artificial intelligence (AI) in health care depends on its acceptance by key stakeholders, particularly patients, who are the primary beneficiaries of AI-driven outcomes. OBJECTIVES: To survey hospital patients to investigate their trust, concerns, and preferences toward the use of AI in health care and diagnostics and to assess the sociodemographic factors associated with patient attitudes. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study developed and implemented an anonymous quantitative survey between February 1 and November 1, 2023, using a nonprobability sample at 74 hospitals in 43 countries. Participants included hospital patients 18 years of age or older who agreed with voluntary participation in the survey presented in 1 of 26 languages. EXPOSURE: Information sheets and paper surveys handed out by hospital staff and posted in conspicuous hospital locations. MAIN OUTCOMES AND MEASURES: The primary outcome was participant responses to a 26-item instrument containing a general data section (8 items) and 3 dimensions (trust in AI, AI and diagnosis, preferences and concerns toward AI) with 6 items each. Subgroup analyses used cumulative link mixed and binary mixed-effects models. RESULTS: In total, 13 806 patients participated, including 8951 (64.8%) in the Global North and 4855 (35.2%) in the Global South. Their median (IQR) age was 48 (34-62) years, and 6973 (50.5%) were male. The survey results indicated a predominantly favorable general view of AI in health care, with 57.6% of respondents (7775 of 13 502) expressing a positive attitude. However, attitudes exhibited notable variation based on demographic characteristics, health status, and technological literacy. Female respondents (3511 of 6318 [55.6%]) exhibited fewer positive attitudes toward AI use in medicine than male respondents (4057 of 6864 [59.1%]), and participants with poorer health status exhibited fewer positive attitudes toward AI use in medicine (eg, 58 of 199 [29.2%] with rather negative views) than patients with very good health (eg, 134 of 2538 [5.3%] with rather negative views). Conversely, higher levels of AI knowledge and frequent use of technology devices were associated with more positive attitudes. Notably, fewer than half of the participants expressed positive attitudes regarding all items pertaining to trust in AI. The lowest level of trust was observed for the accuracy of AI in providing information regarding treatment responses (5637 of 13 480 respondents [41.8%] trusted AI). Patients preferred explainable AI (8816 of 12 563 [70.2%]) and physician-led decision-making (9222 of 12 652 [72.9%]), even if it meant slightly compromised accuracy. CONCLUSIONS AND RELEVANCE: In this cross-sectional study of patient attitudes toward AI use in health care across 6 continents, findings indicated that tailored AI implementation strategies should take patient demographics, health status, and preferences for explainable AI and physician oversight into account.

• MeSH
• dospělí MeSH
• důvěra MeSH
• internacionalita MeSH
• lidé středního věku MeSH
• lidé MeSH
• nemocnice MeSH
• poskytování zdravotní péče * MeSH
• průřezové studie MeSH
• průzkumy a dotazníky MeSH
• senioři MeSH
• umělá inteligence * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Pokrok v léčbě mnohočetného myelomu (MM) je mimořádný. Kombinované režimy, které se u nové diagnózy dostávají do standardně používané terapie, dosahují doby do progrese více než sedm let. V České republice očekáváme v roce 2025 schválení čtyřkombinace anti-CD38 monoklonální protilátky (mAb) spolu s proteasomovým inhibitorem (PI), imunomodulační látkou (IMiD) a dexametazonem. Není zatím jasné, zda konsolidace autologní transplantaci při této čtyřkombinaci bude přínosem stran prodloužení doby do progrese. Doslova exploze nastala ve vývoji imunoterapie. Autologní T-lymfocyty s chiméricky upraveným receptorem (CAR T-lymfocyty) cíleným na BCMA antigen se v USA již dostaly do druhé linie léčby. Vývoj je ještě rychlejší u bispecifických protilátek (bsAb). V pozdním relapsu máme k dispozici bsAb, které cílí na BCMA a GPRC5D antigen. V rámci klinických studií se zkouší další terapeutické cíle (např. FcRH5) i kombinované režimy (např. bsAb, PI, IMiD). Účinnost těchto kombinací v první linii je 90–100 %, přičemž vysoké procento pacientů dosahuje negativní minimální reziduální nemoci (MRD). Vyhodnocování MRD v klinických studiích bylo v roce 2024 schváleno jako primární výsledkový cíl a je pravděpodobné, že směřujeme do období MRD řízené terapie.

Progress in multiple myeloma (MM) treatment is remarkable. Combined regimens for newly diagnosed MM patients achieve progression-free survival of more than seven years. In the Czech Republic, the approval of a four-drug combination of anti-CD38 monoclonal antibody (mAb) with a proteasome inhibitor (PI), immunomodulatory agent (IMiD) and dexamethasone is expecting in 2025. It is not yet clear whether consolidation with autologous transplantation will be beneficial in terms of extending the time to progression. The development of immunotherapy has literally exploded. Autologous chimeric antigen receptor T-cell therapy (CAR T-cells) targeting the BCMA antigen have already been approved for second-line therapy in the USA. The development of bispecific antibodies (bsAb) is even faster. Bispecific antibodies targeting BCMA and GPRC5D antigens are available in late relapse. Clinical trials are testing additional therapeutic targets (e.g., FcRH5) and combination regimens (e.g., bsAb, PI, IMiD). Response rates to these combinations in the first line treatment are 90-100 %, with a high percentage of patients achieving minimal residual disease (MRD) negativity. In 2024, assessment of MRD was approved as a primary outcome in clinical trials and it is likely that we are now moving to wals an era of MRD-driven therapy.

• MeSH
• chimerické antigenní receptory terapeutické užití   MeSH
• imunoterapie metody   MeSH
• lidé MeSH
• mnohočetný myelom * farmakoterapie   MeSH
• protilátky bispecifické farmakologie   terapeutické užití   MeSH
• reziduální nádor MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

BACKGROUND: Immune checkpoint inhibitors (ICI) and chemotherapy, including antibody-drug conjugates, are widely used for the treatment of patients with advanced unresectable or metastatic urothelial carcinoma (UC). The majority of elderly patients receive concomitant medications to address various comorbidities. We aimed to evaluate the impact of concomitant medications on oncological outcomes in patients with advanced unresectable or metastatic UC treated with systemic therapy. MATERIAL & METHODS: In August 2024, three datasets were queried for studies evaluating concomitant medications in patients with advanced unresectable or metastatic UC. The review protocol was registered in PROSPERO (CRD42024547335). The primary outcome was overall survival (OS). A fixed- or random-effects model was used for meta-analysis depending on the heterogeneity. RESULTS: We identified 16 eligible studies (3 prospective and 13 retrospective) comprising 4,816 patients. Most reported concomitant medications included proton pump inhibitors (PPIs), antibiotics, steroids, and opioids. The use of concomitant PPIs, antibiotics, steroids or opioids during ICI therapy was associated with worsened OS (PPIs: HR: 1.43, 95% CI: 1.31-1.57, p < 0.001; antibiotics: HR: 1.2, 95% CI: 1.04-1.38, p = 0.01; steroids: HR: 1.45, 95% CI: 1.25-1.67, p < 0.001; and opioids: HR: 1.74, 95% CI: 1.46-2.07, p < 0.001). Concomitant use of antibiotics during chemotherapy did not impact OS (HR: 1.01, 95% CI: 0.67-1.51). CONCLUSIONS: When treating advanced unresectable or metastatic UC with ICI therapy, we need to pay attention to concomitant medications, such as PPIs and antibiotics to avoid reducing the efficacy of ICI therapy. The mechanism of action of these drugs on ICI efficacy requires further examination.

• MeSH
• inhibitory kontrolních bodů * terapeutické užití   MeSH
• karcinom z přechodných buněk * diagnóza   farmakoterapie   mortalita   sekundární   MeSH
• lidé MeSH
• metastázy nádorů MeSH
• protinádorové látky * terapeutické užití   MeSH
• urologické nádory * diagnóza   farmakoterapie   mortalita   patologie   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• systematický přehled MeSH

PI3K signaling pathway is crucial for a plethora of cellular processes and is extensively linked with tumorigenesis and chemo-/radioresistance. Although a number of small molecule inhibitors have been synthesized to control PI3K-mediated signaling, only a limited clinical success has been reached. Thus, the search for novel promising candidates is still ongoing. Herein, we present a novel series of N-(5-(2-morpholino-4-oxo-3,4-dihydroquinazolin-8-yl)pyridin-2-yl)acylamides designed to simultaneously inhibit PI3K and DNA-PK activity. Compared to a commercial DNA-PK/PI3K inhibitor AZD7648, synthesized compounds generally exhibited markedly lower baseline cytotoxicity in all tested cell lines (MC38, B16F10, 4T1, CT26 and HEK-239). Through an array of biological experiments, we selected two most promising compounds, 2 and 6. While in cell-free conditions, 6 acted as a very efficient pan-PI3K and DNA-PK inhibitor, in physiological conditions, 2 performed better and acted as a potent chemosensitizer able to increase the amount of DNA double strand breaks induced by doxorubicin. This was plausibly due to its improved ability to accumulate in nuclei as evidenced by confocal analyses. Importantly, using P-gp overexpressing CT26 cells, we found that 2 is an efficient inhibitor of multidrug resistance (MDR) able to down-regulate expression of mRNA encoding MDR-driving proteins ABCB1A, ABCB1B and ABCC1. We also demonstrate that 2 can be simply loaded into lipid nanoparticles that retain its chemosensitizing properties. Taken together, the presented study provides a solid basis for a subsequent rational structure optimization towards new generation of multitarget inhibitors able to control crucial signaling pathways involved in tumorigenesis and drug resistance.

• MeSH
• chemorezistence * účinky léků   MeSH
• fosfatidylinositol-3-kinasy metabolismus   MeSH
• inhibitory fosfoinositid-3-kinasy * farmakologie   MeSH
• inhibitory proteinkinas * farmakologie   chemie   chemická syntéza   MeSH
• lidé MeSH
• mnohočetná léková rezistence * účinky léků   MeSH
• molekulární struktura MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• P-glykoprotein * antagonisté a inhibitory   metabolismus   MeSH
• proliferace buněk účinky léků   MeSH
• proteinkinasa aktivovaná DNA * antagonisté a inhibitory   metabolismus   MeSH
• protinádorové látky * farmakologie   chemie   chemická syntéza   MeSH
• screeningové testy protinádorových léčiv MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• vztahy mezi strukturou a aktivitou MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Fibroblast growth factor 21 (FGF21), a metabolic hormone with pleiotropic effects, is beneficial for various cardiac disorders. However, FGF21's role in heart failure with preserved ejection fraction (HFpEF) remains unclear. Here, we show that elevated circulating FGF21 levels are negatively associated with cardiac diastolic function in patients with HFpEF. Global or adipose FGF21 deficiency exacerbates cardiac diastolic dysfunction and damage in high-fat diet (HFD) plus N[w]-nitro-L-arginine methyl ester (L-NAME)-induced HFpEF mice, whereas these effects are notably reversed by FGF21 replenishment. Mechanistically, FGF21 enhances the production of adiponectin (APN), which in turn indirectly acts on cardiomyocytes, or FGF21 directly targets cardiomyocytes, to negatively regulate pyruvate dehydrogenase kinase 4 (PDK4) production by activating PI3K/AKT signals, then promoting mitochondrial bioenergetics. Additionally, APN deletion strikingly abrogates FGF21's protective effects against HFpEF, while genetic PDK4 inactivation markedly mitigates HFpEF in mice. Thus, FGF21 protects against HFpEF via fine-tuning the multiorgan crosstalk among the adipose, liver, and heart.

• MeSH
• adiponektin * metabolismus   genetika   MeSH
• dieta s vysokým obsahem tuků * škodlivé účinky   MeSH
• energetický metabolismus * účinky léků   MeSH
• fibroblastové růstové faktory * metabolismus   genetika   MeSH
• fosfatidylinositol-3-kinasy metabolismus   MeSH
• kardiomyocyty * metabolismus   účinky léků   MeSH
• lidé MeSH
• myši inbrední C57BL MeSH
• myši knockoutované MeSH
• myši MeSH
• PDH-kinasa * metabolismus   genetika   MeSH
• protoonkogenní proteiny c-akt metabolismus   MeSH
• signální transdukce MeSH
• srdeční mitochondrie * metabolismus   účinky léků   MeSH
• srdeční selhání * metabolismus   prevence a kontrola   genetika   MeSH
• tepový objem účinky léků   MeSH
• tuková tkáň metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Despite currently used intravesical therapies in non-muscle-invasive bladder cancer (NMIBC), the rate of intravesical recurrence remains very high. We aimed to evaluate the effectiveness of adding nonintravesical interventions to standard intravesical therapies to prevent intravesical recurrence. In April 2024, 3 databases were queried for prospective studies evaluating nonintravesical interventions in addition to standard intravesical therapies for NMIBC (CRD42024490988). The primary outcome was intravesical recurrence-free survival (iRFS). Standard pairwise meta-analyses were performed using hazard ratios (HR) and 95% confidence intervals (95% CI) with a random-effects model. We identified 18 eligible studies (14 RCTs and 4 prospective trials) comprising 4,593 NMIBC patients, which investigated pharmacological interventions (eg, selenium, vitamins, Lactobacillus casei, celecoxib, metformin, mistletoe lectin) and lifestyle modifications (diet). The addition of Lactobacillus casei significantly improved iRFS (HR: 0.50; 95% CI: 0.34-0.73; P < .001). A high western diet pattern significantly worsened iRFS (HR:1.48, 95%CI:1.06-2.06, P = .03). The other nonintravesical interventions were not associated with iRFS. Our comprehensive review of the published literature highlights the need for further research into the efficacy of nonvesical interventions for NMIBC. While Lactobacillus was shown to improve iRFS in 2 RCTs, additional high-quality randomized studies are required to evaluate the effectiveness of other interventions.

• MeSH
• aplikace intravezikální MeSH
• celekoxib aplikace a dávkování   terapeutické užití   MeSH
• Lactobacillus casei MeSH
• lidé MeSH
• lokální recidiva nádoru * prevence a kontrola   MeSH
• metformin terapeutické užití   aplikace a dávkování   MeSH
• nádory močového měchýře * patologie   farmakoterapie   MeSH
• probiotika aplikace a dávkování   terapeutické užití   MeSH
• randomizované kontrolované studie jako téma MeSH
• selen aplikace a dávkování   terapeutické užití   MeSH
• vitaminy aplikace a dávkování   terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• přehledy MeSH
• systematický přehled MeSH