Předmětem studie HOPE-3 bylo zjištění významu polypillu a mini-polypillu v široké klinické praxi zahrnující osoby různého pohlaví bez kardiovaskulárních chorob s intermediárním rizikem kardiovaskulárních onemocnění. Autory studie zajímala otázka, zda osoby z různých antropologických skupin zahrnujících nejen bělochy, ale také osoby dalších antropologických skupin – černochy, asiaty, osoby jihoamerického původu a další celkem z 6 kontinentů, budou reagovat obdobně. Studie se zabývala zejména významem mini-polypillu sestávajícího z použití antihypertenzní léčby (16 mg candesartanu denně + 12,5 mg hydrochlorothiazidu), dále léčby statiny (10 mg rosuvastatinu denně) a použití jejich kombinace. Studie představuje novou cestu v prevenci kardiovaskulárních chorob, ale má také svá úskalí, spočívající v nízké četnosti lékařských kontrol včetně laboratorních vyšetření. Koncepce mini-polypillu je z uvedených důvodů přijímána zdrženlivě. Přináší však úspory v nákladech na zdravotnictví.

The HOPE-3 study focused on identifying the significance of the polypill and mini-polypill in broad clinical practice, including individuals of different gender without cardiovascular diseases with an intermediate risk of cardiovascular diseases. The authors were interested in the question whether people from various antropologhy groups including not only white people but also other antropologhy groups – the blacks, people of Asian and South American origin and more covering 6 continents, would respond in a similar way. The study mainly examined the significance of the mini-polypill, comprising the use of antihypertensive treatment (16 mg candesartan per day + 12.5 mg hydrochlorothiazide), treatment with statins (10 mg rosuvastatin per day), and their combination. The study presents a new way forward in the prevention of cardiovascular diseases, but it also entails some weaknesses which consist in rather rare medical checkups including laboratory tests. Owing to that the concept of mini-polypill has met with some reservation. But it also brings with it reduction of healthcare costs.

• MeSH
• antihypertenziva farmakologie   MeSH
• dvojitá slepá metoda MeSH
• kardiovaskulární nemoci * prevence a kontrola   MeSH
• kombinovaná farmakoterapie MeSH
• lidé středního věku MeSH
• lidé MeSH
• randomizované kontrolované studie jako téma MeSH
• statiny * farmakologie   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• přehledy MeSH

BACKGROUND AND OBJECTIVE: Intravesical mitomycin C (MMC) instillations are recommended to prevent recurrence of intermediate-risk non-muscle-invasive bladder cancer (IR-NMIBC); however, the optimal regimen and dose are uncertain. Our aim was to assess the effectiveness of adjuvant MMC and compare different MMC regimens in preventing recurrence. METHODS: We performed a comprehensive search in PubMed, Scopus, and Web of Science in November 2023 for studies investigating recurrence-free survival (RFS) among patients with IR-NMIBC who received adjuvant MMC. Prospective trials with different MMC regimens or other intravesical drugs as comparators were considered eligible. KEY FINDINGS AND LIMITATIONS: Overall, 14 studies were eligible for systematic review and 11 for meta-analysis of RFS. Estimates of 1-yr, 2-yr, and 5-yr RFS rates were 84% (95% confidence interval [CI] 79-89%), 75% (95% CI 68-82%), and 51% (95% CI 40-63%) for patients treated with MMC induction plus maintenance, and 88% (95% CI 83-94%), 78% (95% CI 67-89%), and 66% (95% CI 57-75%) for patients treated with bacillus Calmette-Guérin (BCG) maintenance, respectively. Estimates of 2-yr RFS rates for MMC maintenance regimens were 76% (95% CI 69-84%) for 40 mg MMC (2 studies) and 66% (95% CI 60-72%) for 30 mg MMC (4 studies). Among the studies included, BCG maintenance provided comparable 2-yr RFS to 40 mg MMC with maintenance (78% vs 76%). RFS did not differ by MMC maintenance duration (>1 yr vs 1 yr vs <1 yr). CONCLUSIONS AND CLINICAL IMPLICATIONS: MMC induction and maintenance regimens seem to provide short-term RFS rates equivalent to those for BCG maintenance in IR-NMIBC. For adjuvant induction and maintenance, 40 mg of MMC appears to be more effective in preventing recurrence than 30 mg. We did not observe an RFS benefit for longer maintenance regimens. PATIENT SUMMARY: For patients with intermediate-risk non-muscle-invasive bladder cancer, bladder treatments with a solution of a drug called mitomycin C (MMC) seem to be as effective as BCG (bacillus Calmette-Guérin) in preventing recurrence after tumor removal. Further trials are needed for stronger evidence on the best MMC dose and treatment time.

• MeSH
• adjuvantní chemoterapie metody   MeSH
• aplikace intravezikální MeSH
• hodnocení rizik MeSH
• invazivní růst nádoru * MeSH
• lidé MeSH
• lokální recidiva nádoru prevence a kontrola   MeSH
• mitomycin * terapeutické užití   aplikace a dávkování   MeSH
• nádory močového měchýře neinvadující svalovinu MeSH
• nádory močového měchýře * farmakoterapie   patologie   MeSH
• protinádorová antibiotika * terapeutické užití   aplikace a dávkování   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• přehledy MeSH
• systematický přehled MeSH

PURPOSE: We hypothesized that differences in active treatment rates may exist according to race/ethnicity in favorable as well as unfavorable intermediate risk prostate cancer. MATERIALS AND METHODS: We relied on the Surveillance, Epidemiology, and End Results 18 database 2010-2015. We stratified according to 3 racial/ethnic groups (White vs Black vs Hispanic) and prostate cancer baseline characteristics (prostate specific antigen, clinical T stage, Gleason group grading, percentage of biopsy cores). We tabulated active treatment rates (radical prostatectomy, external beam radiotherapy) without and with adjustment for baseline age and prostate cancer characteristics. RESULTS: Baseline prostate specific antigen, clinical T stage, Gleason grade and percentage of positive biopsy cores differed according to racial/ethnic groups in both favorable and unfavorable intermediate risk prostate cancer patients (all p <0.05). Similarly, radical prostatectomy and external beam radiotherapy rates differed according to race/ethnicity in both favorable and unfavorable intermediate risk prostate cancer patients. Radical prostatectomy and external beam radiotherapy rates respectively ranged from 31.7%-41.8% and 26.3%-31.0% in favorable intermediate risk cases and from 33.4%-43.9% and 30.9%-35.5% in unfavorable intermediate risk prostate cancer, across the 3 race/ethnicity groups (both p <0.05). The above heterogeneity in active treatment rates disappeared and marginal differences remained after adjustment for baseline age and prostate cancer characteristics. CONCLUSIONS: Interpretation of active treatment rates in favorable and unfavorable intermediate risk prostate cancer may be severely biased, unless detailed and systematic consideration or adjustment for baseline age and prostate cancer characteristic is enforced.

• MeSH
• běloši statistika a číselné údaje   MeSH
• černoši nebo Afroameričané statistika a číselné údaje   MeSH
• disparity zdravotní péče statistika a číselné údaje   MeSH
• Hispánci a Latinoameričané statistika a číselné údaje   MeSH
• hodnocení rizik MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory prostaty krev   patologie   terapie   MeSH
• prostatický specifický antigen krev   MeSH
• retrospektivní studie MeSH
• senioři MeSH
• staging nádorů MeSH
• stupeň nádoru MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH

BACKGROUND: There is an urgent need to provide a risk-stratification tool for intermediate-risk non-muscle-invasive bladder cancer (NMIBC), especially at the time of bacillus Calmette-Guerin (BCG) shortage. OBJECTIVE: To assess whether patients with intermediate-risk NMIBC can be stratified into different risk groups, thereby providing a practical tool for the selection of the optimal adjuvant therapy, based on the individualized risk of disease progression. DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective analysis of 636 patients with intermediate-risk NMIBC. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: A multivariable Cox-regression model was built to evaluate the impact of each variable on recurrence and progression to muscle-invasive disease. A Cox-based nomogram to predict patient-specific probability of disease progression was performed, and the decision curve analysis (DCA) was used to evaluate its clinical benefit. RESULTS AND LIMITATIONS: Within a median follow-up of 92 mo (interquartile range 56-118), disease recurrence and progression occurred in 346 (54%) and 91 (14%) patients, respectively. On multivariable analysis, age, early recurrence (<12 mo), and tumor size≥3cm were found to be independent predictors of progression. The Harrell C-index of the model for the prediction of progression was 0.75 and exceeded that of the model proposed by the International Bladder Consultation Group. DCA showed superior net benefits for the nomogram compared with the strategies of treating all/none and previous predictive models. Limitations are inherent to the retrospective design. CONCLUSIONS: We provided a risk-stratification tool that helps identify individual risk of disease progression in patients with intermediate-risk NMIBC. This tool outperforms standard strategies in the threshold probability range of interest and could help select the optimal intravesical therapy regimen based on the individual risk of disease progression. PATIENT SUMMARY: In this study, we provided a practical tool for risk stratification in patients with intermediate-risk non-muscle-invasive bladder cancer. This tool may help select the most appropriate adjuvant therapy (either bacillus Calmette-Guerin [BCG] or chemotherapy) based on patient and tumor characteristics, thus making a step forward toward the era of personalized medicine.

• MeSH
• adjuvancia imunologická terapeutické užití   MeSH
• BCG vakcína * terapeutické užití   MeSH
• lidé MeSH
• lokální recidiva nádoru farmakoterapie   epidemiologie   MeSH
• nádory močového měchýře * farmakoterapie   patologie   MeSH
• progrese nemoci MeSH
• retrospektivní studie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• chemoradioterapie MeSH
• lidé MeSH
• nádory děložního čípku * farmakoterapie   MeSH
• rizikové faktory MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• komentáře MeSH
• úvodníky MeSH

PURPOSE: The European Organisation for Research and Treatment of Cancer (EORTC) trial 22991 (NCT00021450) showed that 6 months of concomitant and adjuvant androgen suppression (AS) improves event- (EFS, Phoenix) and clinical disease-free survival (DFS) of intermediate- and high-risk localized prostatic carcinoma, treated by external-beam radiotherapy (EBRT) at 70-78 Gy. We report the long-term results in intermediate-risk patients treated with 74 or 78 Gy EBRT, as per current guidelines. PATIENT AND METHODS: Of 819 patients randomly assigned between EBRT or EBRT plus AS started on day 1 of EBRT, 481 entered with intermediate risk (International Union Against Cancer TNM 1997 cT1b-c or T2a with prostate-specific antigen (PSA) ≥ 10 ng/mL or Gleason ≤ 7 and PSA ≤ 20 ng/mL, N0M0) and had EBRT planned at 74 (342 patients, 71.1%) or 78 Gy (139 patients, 28.9%). We report the trial primary end point EFS, DFS, distant metastasis-free survival (DMFS), and overall survival (OS) by intention-to-treat stratified by EBRT dose at two-sided α = 5%. RESULTS: At a median follow-up of 12.2 years, 92 of 245 patients and 132 of 236 had EFS events in the EBRT plus AS and EBRT arm, respectively, mostly PSA relapse (48.7%) or death (45.1%). EBRT plus AS improved EFS and DFS (hazard ratio [HR] = 0.53; CI, 0.41 to 0.70; P < .001 and HR = 0.67; CI, 0.49 to 0.90; P = .008). At 10 years, DMFS was 79.3% (CI, 73.4 to 84.0) with EBRT plus AS and 72.7% (CI, 66.2 to 78.2) with EBRT (HR = 0.74; CI, 0.53 to 1.02; P = .065). With 140 deaths (EBRT plus AS: 64; EBRT: 76), 10-year OS was 80.0% (CI, 74.1 to 84.7) with EBRT plus AS and 74.3% (CI, 67.8 to 79.7) with EBRT, but not statistically significantly different (HR = 0.74; CI, 0.53 to 1.04; P = .082). CONCLUSION: Six months of concomitant and adjuvant AS statistically significantly improves EFS and DFS in intermediate-risk prostatic carcinoma, treated by irradiation at 74 or 78 Gy. The effects on OS and DMFS did not reach statistical significance.

• MeSH
• antagonisté androgenů farmakologie   terapeutické užití   MeSH
• časové faktory MeSH
• dávka záření MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory prostaty farmakoterapie   radioterapie   MeSH
• rizikové faktory 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
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

INTRODUCTION: Focal therapy (FT) for localized prostate cancer (PCa) is a promising treatment strategy. Although, according to guidelines, it should be regarded as an experimental option, its introduction into clinical practice has occurred at an accelerated speed. It is, thus, crucial for Urologists to understand FT limitations and potential drawbacks that may derive from its use. METHODS: We performed a literature search of peer-reviewed English language articles using Pubmed and the words "focal therapy" AND "prostate cancer" to identify relevant articles. Web search was complemented by manual search. RESULTS: From a biological perspective, in contrast with the index lesion theory, which still needs to be better supported, PCa is a multifocal and multiclonal entity. Also, the effects of FT on PCa microenvironment are unclear. From a clinical perspective, patient selection is still not precisely defined. Even when all variables potentially decreasing mpMRI and biopsy accuracy are optimized, up to one out of two men may be incorrectly selected for FT, leaving a significant proportion of clinically significant PCa (csPCa) untreated. Underestimation of PCa volume and variant histologies are other additional mpMRI potential limitations. No RCTs have been performed against the standard of care to support FT. There is absence of long-term results and FT series reaching medium-term follow-up have non-optimal oncological control with significant re-treatment needs. When PCa recurs/persists after FT, little is known about the appropriate management strategies and their outcomes. Finally, the optimal follow-up scheme post-FT remains unclear. CONCLUSIONS: Several arguments are present against the use of FT for localized PCa. Studies are needed to overcome current limitations and support FT before it can be included as part of the standard management of prostate cancer.

• MeSH
• ablace * škodlivé účinky   metody   MeSH
• hodnocení rizik MeSH
• léčba šetřící orgány MeSH
• lidé MeSH
• nádory prostaty chirurgie   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

CONTEXT: Patients with intermediate-risk non-muscle-invasive bladder cancer (NMIBC) may pose a clinical dilemma without an agreed evidence-based decision tree for personalized treatment. OBJECTIVE: To perform a systematic review and network meta-analysis (NMA) to summarize available evidence on the oncologic outcomes of intravesical therapy in patients with intermediate-risk NMIBC. EVIDENCE ACQUISITION: The MEDLINE, EMBASE, and ClinicalTrials.gov databases were searched in October 2020 according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. Studies were deemed eligible if they reported on oncologic outcomes in patients with intermediate-risk NMIBC treated with transurethral resection of bladder tumor with and without intravesical chemotherapy or bacillus Calmette-Guérin (BCG) immunotherapy. EVIDENCE SYNTHESIS: Twelve studies were included in a qualitative synthesis (systematic review); three were deemed eligible for a quantitative synthesis (NMA). An NMA of five different regimens was conducted for the association of treatment with the 5-yr recurrence risk. Chemotherapy with maintenance was associated with a lower likelihood of 5-yr recurrence than chemotherapy without maintenance (odds ratio [OR] 0.51, 95% credible interval [CI] 0.26-1.03). Immunotherapy, regardless of whether a full- or reduced-dose regimen, was not associated with a significantly lower likelihood of 5-yr recurrence when compared with chemotherapy without maintenance (OR 0.90, 95% CI 0.39-2.11 vs OR 0.93, 95% CI 0.40-2.19). Analysis of the treatment ranking revealed that chemotherapy with maintenance had the lowest 5-yr recurrence risk (P score 0.9666). CONCLUSIONS: Our analysis indicates that chemotherapy with a maintenance regimen confers a superior oncologic benefit in terms of 5-yr recurrence risk compared to chemotherapy without maintenance in patients with intermediate-risk NMIBC. Regardless of the dose regimen, immunotherapy with BCG does not appear to be superior to chemotherapy in patients with intermediate-risk NMIBC in term of disease recurrence. However, owing to the lack of comparative studies, there is an unmet need for well-designed, large-scale trials to validate our findings and generate robust evidence on disease recurrence and progression. PATIENT SUMMARY: A maintenance schedule of chemotherapy reduces the rate of long-term recurrence of bladder cancer that has not invaded the bladder muscle. Chemotherapy inserted directly into the bladder and immunotherapy without maintenance schedules seem to have limited benefit in preventing cancer recurrence.

• MeSH
• aplikace intravezikální MeSH
• BCG vakcína terapeutické užití   MeSH
• lidé MeSH
• lokální recidiva nádoru prevence a kontrola   MeSH
• nádory močového měchýře * farmakoterapie   patologie   MeSH
• síťová metaanalýza MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• přehledy MeSH
• systematický přehled MeSH

CONTEXT: Intermediate-risk (IR) non-muscle-invasive bladder cancer (NMIBC) is a heterogeneous disease. OBJECTIVE: To update the International Bladder Cancer Group (IBCG) guidance and provide practical recommendations on IR NMIBC management. EVIDENCE ACQUISITION: A collaborative review of published randomized clinical trials, meta-analyses, systematic reviews, and clinical practice guidance on IR NMIBC published before January 2022 was undertaken using PubMed/Medline. EVIDENCE SYNTHESIS: Variation exists between guidelines in defining IR NMIBC. The IBCG recommends defining IR NMIBC as any TaLG tumor that is either recurrent or multifocal or has size ≥3 cm, OR any T1LG tumor. If the 3 tier grading system is used, than any TaG2 tumor would also be considered IR diease regardless of whether new diagnosis or recurrent. Accurate grading and staging of tumor, particularly in ruling out HG/G3 disease and/or carcinoma in situ, are crucial. The IBCG recommends that management of IR NMIBC should be further based on the following risk factors: multifocal tumor (more than one), early recurrence (<1 yr), frequent recurrence (>1/yr), tumor size (≥3 cm), and failure of prior intravesical treatment. Patients with no risk factors are best managed by one dose of postoperative intravesical chemotherapy. Patients with one to two risk factors should be offered additional adjuvant induction intravesical chemotherapy (or bacillus Calmette-Guérin (BCG) if prior chemotherapy has been used). Patients with three or more risk factors should be offered induction plus 1-yr maintenance BCG. Where BCG is not available or recurrent disease following BCG is present, alternative intravesical treatments such as chemotherapy (single agent, combination, or chemohyperthermia) or a clinical trial are recommended. CONCLUSIONS: Standardizing the definition of IR NMIBC is critical for appropriate management of patients and for allowing a comparison of outcomes across clinical trials. The IBCG recommends defining IR NMIBC as any TaLG tumor that is either recurrent or multifocal or ≥3 cm, OR any T1LG tumor. If the 3 tier grading system is used, than any TaG2 tumor would also be considered IR disease regardless of whether new diagnosis or recurrent. Adjunctive management should then be based on established risk factors. PATIENT SUMMARY: Standardizing the definition of intermediate-risk (IR) non-muscle-invasive bladder cancer (NMIBC), which is a heterogeneous disease, is critical for appropriate management of patients. The International Bladder Cancer Group recommends classification of IR NMIBC tumors and personalized management based on the following risk factors: multifocal tumor (more than one), early recurrence (<1 yr), frequent recurrence (>1/yr), tumor size (≥3 cm), and previous intravesical treatment.

• MeSH
• adjuvancia imunologická terapeutické užití   MeSH
• aplikace intravezikální MeSH
• BCG vakcína terapeutické užití   MeSH
• konsensus MeSH
• lidé MeSH
• nádory močového měchýře * farmakoterapie   terapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

BACKGROUND: Perioperative goal directed therapy (pGDT) using flow monitoring has been associated with improved outcomes. However, its protocols are often based on stroke volume only: as a target for fluid loading, inotropic support and vasopressors (via mathematical coupling of systemic vascular resistance). In this trial, we have tested the multi-parametric pGDT protocol based on esophageal Doppler variables (corrected flow time, peak velocity) in intermediate-to-high risk patients undergoing gastrointestinal surgery. METHODS: Intermediate-to-high risk patients undergoing gastrointestinal surgery were randomized to standard care (control) or multi-parametric pGDT (intervention). Postoperative complications and death rate as well as hospital length of stay were assessed as primary and secondary outcomes. RESULTS: Overall, 140 patients (intervention, N.=71, and control, N.=69) were included and randomized out of 197 eligible. Higher vasoactive/inotropic drug use and lower fluid balance were observed in the intervention group leading to favorable hemodynamic profile. The pGDT intervention was associated with improved primary outcome (28 days mortality and morbidity defined as occurrence of any defined complication) - 20 patients (28.2%) versus 32 (46.4%) in the control group (P=0.036); RR 0.61 (95% CI: 0.39-0.95), P=0.03. No differences in mortality and hospital length of stay were observed between groups. CONCLUSIONS: In this monocentric trial the multi-parametric pGDT protocol based on domain specific functional hemodynamic parameters was associated with lower rate of postoperative complications in intermediate-to-high risk patients undergoing scheduled gastrointestinal procedures.

• MeSH
• chirurgie trávicího traktu metody   MeSH
• EGDT MeSH
• hemodynamika * MeSH
• hodnocení rizik MeSH
• lidé středního věku MeSH
• lidé MeSH
• pooperační komplikace prevence a kontrola   MeSH
• prospektivní studie MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH