Zobrazovací metoda pozitronové tomografie s výpočetní tomografií (positron emission tomography / computed tomography, PET/CT) s využitím prostatického specifického membránového antigenu (prostate-specific membrane antigen, PSMA), PSMA PET/CT, představuje zásadní pokrok v diagnostice a léčbě karcinomu prostaty. V oblasti diagnostiky nabízí výrazně vyšší senzitivitu a specificitu oproti konvenčním metodám, zejména při primárním stagingu, perzistenci prostatického specifického antigenu (PSA) po radikální prostatektomii a biochemickém relapsu po radikální léčbě. Stále častěji se uplatňuje i v rámci teranostiky, tedy propojení diagnostiky a cílené radionuklidové terapie u pacientů s metastazujícím kastračně rezistentním karcinomem prostaty. Klinické studie fáze III (např. VISION, TheraP, PSMAfore) prokázaly významný přínos PSMA značeného luteciem-177 (177Lu-PSMA-617) z hlediska přežití i kvality života ve srovnání s jinými léčebnými možnostmi. Využití PSMA PET/CT tak výrazně přispívá k personalizovanému přístupu k pacientům a mění zavedené algoritmy diagnostiky a léčby karcinomu prostaty.
The imaging modality prostate specific membrane antigen positron emission tomography / computed tomography (PSMA PET/CT) represents a major advancement in the diagnosis and treatment of prostate cancer. In diagnostics, it offers significantly higher sensitivity and specificity compared to conventional methods, particularly in primary staging, persistent prostate specific antigen (PSA) following radical prostatectomy, and biochemical recurrence after radical treatment. It is increasingly utilized in theranostics, which combines diagnostic imaging with targeted radionuclide therapy in patients with metastatic castration-resistant prostate cancer. Phase III clinical trials (e.g. VISION, TheraP, PSMAfore) have demonstrated a significant benefit of 177Lu-PSMA-617 in terms of survival and quality of life compared to other treatment options. The use of PSMA PET/CT thus contributes substantially to personalized patient care and is reshaping established diagnostic and therapeutic algorithms in prostate cancer management.
Radioligandová terapie, někdy označovaná i radiofarmaceutická terapie pomocí značeného prostatického specifického membránového antigenu (prostate specific membrane antigen, PSMA) u karcinomu prostaty, je používána zhruba deset let v západní Evropě u pacientů s pokročilým, kastračně rezistentním, metastazujícím onemocněním. V krátkém přehledovém článku jsou uvedeny současné indikace přípravku Pluvicto (177Lu značené PSMA), způsob a možnosti aplikace, nežádoucí účinky a očekávaný účinek léčby. Naznačen je i další směr vývoje radioligandové terapie do budoucna v léčbě časnějších stadií onemocnění karcinomu prostaty.
Summary Radioligand therapy (RLT) using labeled prostate specific membrane antigen (PSMA) in prostate cancer has been used for about ten years in Western Europe in patients with advanced, castration-resistant, metastatic disease. In this short review article, the current indications of Pluvicto (177Lu labeled PSMA), the method and possibilities of application, side effects and the expected effect of treatment are presented. Further direction of the development of RLT in the future in the treatment of earlier stages of prostate cancer disease is also indicated.
BACKGROUND AND AIMS: Anti-tumor necrosis factor-α inhibitors (anti-TNFs) are the established treatment for perianal Crohn's disease (pCD), but relapse and non-response are common. Data on second- and third-line biologics are limited. We present the first direct comparison of second- and third-line biologics in pCD patients with active perianal disease previously treated with first-line anti-TNFs. METHODS: A multicenter retrospective cohort study included adult patients with pCD who failed first-line anti-TNF. The primary outcome was clinical perianal response, with secondary outcomes of radiological response (magnetic resonance imaging or transrectal ultrasound) and healing, and clinical remission. Propensity score matching (PSM) was used to adjust for baseline differences. RESULTS: A total of 486 pCD patients from 23 IBD centers were included, with 333/486 (68.5%) and 216/263 (82.1%) matched by PSM in the second and third-line treatment groups, respectively. In the second-line group, 62/78 (79.5%) of ustekinumab (UST)-treated patients achieved clinical perianal response, compared to 46/78 (58.9%) with vedolizumab (VDZ) (OR 4.47, 95% CI, 1.94-10.28, P < .001) and 38/78 (48.7%) with anti-TNFs (OR 5.29, 95% CI, 2.39-11.71, P < .001). In the third-line group, 38/49 (77.6%) of UST-treated patients achieved clinical perianal response, compared to 29/49 (59.2%) with VDZ (OR 9.96, 95% CI, 2.6-38.4, P < .001) and 27/49 (55.1%) with anti-TNFs (OR 12.03, 95% CI, 2.99-48.47, P < .001). UST-treated patients also had higher radiological response rates than VDZ (OR 3.28, 95% CI, 1.07-10.07, P = .038). CONCLUSION: In pCD patients failing anti-TNFs as first-line treatment, ustekinumab may be more effective than vedolizumab or another anti-TNF as second or third-line therapy.
- MeSH
- Biological Products * therapeutic use MeSH
- Crohn Disease * drug therapy diagnostic imaging MeSH
- Adult MeSH
- Gastrointestinal Agents * therapeutic use MeSH
- Antibodies, Monoclonal, Humanized therapeutic use MeSH
- Remission Induction MeSH
- Tumor Necrosis Factor Inhibitors therapeutic use MeSH
- Middle Aged MeSH
- Humans MeSH
- Magnetic Resonance Imaging MeSH
- Anus Diseases * drug therapy MeSH
- Retrospective Studies MeSH
- Propensity Score MeSH
- Ustekinumab * therapeutic use MeSH
- Treatment Outcome MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
The influence of surgical volume on partial nephrectomy (PN) outcomes is a subject of debate. The European Association of Urology (EAU) renal cell carcinoma (RCC) guideline panel performed a protocol-driven systematic review of the association between hospital volume (HV) and oncological, functional, and complication outcomes following PN for RCC. The intervention was PN performed in a higher-volume hospital (defined according to the number of procedures per unit time) and the comparator was PN performed in a lower-volume hospital. Ten studies involving a total of 106 569 patients were included in the review. Higher HV was associated with lower complication rates, shorter length of stay, lower positive surgical margin rates, and lower transfusion rates. For six studies, multivariable analyses showed that low HV was an independent risk factor for inpatient complications, PSM presence, longer LOS, and failure to achieve a trifecta of no complications, warm ischemia time <25 min, and negative surgical margins. Most studies were judged to have high risk of bias. The available evidence suggests a potential association between higher HV and better PN outcomes in RCC. The EAU RCC guidelines panel encourages the development and rigorous evaluation of indicators of surgery quality in RCC to better inform the designation of high-quality centers within models of centralized care.
- MeSH
- Hospitals, Low-Volume * statistics & numerical data MeSH
- Length of Stay MeSH
- Carcinoma, Renal Cell * surgery MeSH
- Humans MeSH
- Kidney Neoplasms * surgery MeSH
- Nephrectomy * methods standards adverse effects MeSH
- Postoperative Complications epidemiology MeSH
- Practice Guidelines as Topic MeSH
- Hospitals, High-Volume * statistics & numerical data MeSH
- Urology standards MeSH
- Treatment Outcome MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Systematic Review MeSH
- Geographicals
- Europe MeSH
Karcinom prostaty je nejčastěji diagnostikovaným maligním nádorem v české mužské populaci. Důležitá je jeho včasná a správná detekce. Pozitronovou emisní tomografii s prostatickým specifickým membránovým antigenem (prostate specific membrane antigen positron emission tomography, PSMA PET) využíváme jako diagnostický indikátor. PSMA terapeutické radiofarmakum podporované nejspolehlivějšími daty je 177Lu-PSMA-617.
Prostate cancer is the most frequently diagnosed malignant tumor in the Czech male population. Its early and correct detection is important. We use prostate specific membrane antigen positron emission tomography (PSMA PET) as a diagnostic indicator. The PSMA therapeutic radiopharmaceutical supported by the most reliable data is 177Lu-PSMA-617.
... Kyslík v tabletě 202 -- II/21 Příběh olomoucinu aneb Z Hané do celého světa 211 -- II/22 Lutecium PSMA ...
Vydání první 354 stran : ilustrace ; 25 cm
Publikace obsahuje příběhy spojené s vývojem léčivých přípravků zejména ve 20. století. Určeno odborné i široké veřejnosti.; V roce 2023 vyšla kniha s názvem Příběhy spojené s objevy nových léčiv. Na rozdíl od mnoha jiných děl popisujících výzkum a vývoj léčiv striktně z odborného nebo převážně historického zaměření byla tato kniha pojata jako soubor příběhů zahrnujících jak historická fakta, tak někdy až detektivní zápletky. Zvolený formát se osvědčil, o čemž svědčí opravdu nečekaný zájem čtenářů. Proto se autor pustil do pokračování s názvem Příběhy spojené s objevy nových léčiv II. Volné pokračování. Nově předkládaná kniha si jistě opět najde své čtenáře. Kniha je vhodná pro každého se zájmem o problematiku léčiv, ať už je jeho znalost chemie nebo farmacie na jakékoli úrovni.
- MeSH
- History, 20th Century MeSH
- History of Pharmacy MeSH
- Pharmacists history MeSH
- Pharmaceutical Research history MeSH
- Pharmaceutical Preparations history MeSH
- Drug Development history MeSH
- Check Tag
- History, 20th Century MeSH
- Publication type
- Personal Narrative MeSH
- Popular Work MeSH
- Conspectus
- Farmacie. Farmakologie
- NML Fields
- farmacie a farmakologie
- dějiny lékařství
- NML Publication type
- literatura faktu
OBJECTIVE: To assess the oncological outcomes of patients with high-risk (HR) and very high-risk (VHR) non-muscle-invasive bladder cancer (NMIBC) treated with upfront radical cystectomy (RC) vs Bacillus Calmette-Guérin (BCG) instillations from a contemporary European multicentre cohort. PATIENTS AND METHODS: We conducted a retrospective analysis of 1491 patients diagnosed with HR- or VHR-NMIBC from a European multicentre database between 2015 and 2024. Patients were included if they received either upfront RC or at least five doses of BCG. A 1:1 propensity score matching (PSM) according to clinically relevant variables was applied. Progression was defined as muscle-invasive or metastatic disease. Cumulative incidence plots and multivariable competing risk regression models addressing cancer-specific mortality (CSM) were fitted. RESULTS: Among the 1221 patients with HR- (n = 1221 [90%]) or VHR-NMIBC (n = 121 [10%]), 87 (7.1%) underwent upfront RC. The median follow-up was 2.6 years. After PSM (87 vs 87 patients), the 5-year CSM rate was similar in patients treated with BCG (13%) vs their upfront RC counterparts (16%) (hazard ratio: 1.77, 95% confidence interval [CI] 0.66-4.73; P = 0.3). Of the 1134 patients who initially received BCG, 73 (6.6%) eventually required delayed RC, with 34 (47%) progressing to muscle-invasive bladder cancer before delayed RC. The 3-year CSM rate was comparable in upfront RC (13%) vs delayed RC (11%) among non-progressing patients (P = 0.3). However, patients who progressed before delayed RC had worse 3-year CSM relative to those who did not (13% vs 31%, hazard ratio: 0.32, 95% CI 0.13-0.83; P = 0.018). CONCLUSION: Within a European cohort of patients with HR- and VHR-NMIBC, upfront RC was rarely performed. Patients treated with BCG did not exhibit a CSM disadvantage relative to their upfront RC counterparts. After matching, long-term CSM was similar between BCG therapy and upfront RC. Delayed RC, led to worse outcomes if performed after progression, but matched upfront RC when performed before progression, underscoring importance of timely surgery.
- MeSH
- Adjuvants, Immunologic * therapeutic use MeSH
- BCG Vaccine * therapeutic use MeSH
- Cystectomy * methods MeSH
- Neoplasm Invasiveness MeSH
- Middle Aged MeSH
- Humans MeSH
- Non-Muscle Invasive Bladder Neoplasms MeSH
- Urinary Bladder Neoplasms * pathology mortality surgery therapy drug therapy MeSH
- Retrospective Studies MeSH
- Aged MeSH
- Treatment Outcome MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Comparative Study MeSH
BACKGROUND AND AIMS: Myocardial infarction (MI) in multivessel disease (MVD) and chronic total occlusion (CTO) is associated with high mortality. However, all-cause mortality of matched cohort without a CTO is unclear. Our aim was to analyse clinical characteristics, presenting symptoms, and survival of patients with MI in MVD and the possible impact of CTO on 1-year mortality. METHODS: All MI patients with MVD (two or three vessel disease) hospitalized in our center from January 2020 to September 2022 (1309 patients) were selected. We conducted a propensity score matching (PSM) analysis based on age, gender, type of MI, and compared patients with CTO (CTO group, n = 90) and without CTO (Control group, n = 90). RESULTS: We observed no difference in presenting clinical symptoms and initial heart rhythm between the groups. 1-year follow-up shows all-cause mortality rate of 23.3 % (n = 21) in the CTO group (Mean survival [MS] = 292.1 days, 95 % CI = 263.8 to 320.4) and 18.9 % (n = 17) in the Control group (MS = 310.2 days, 95 % CI = 285.3 to 335.2), p = 0.44. PCI alone was performed in 64.4 % (n = 58) in both groups, CABG in 18.8 % (n = 17) and 24.4 % (n = 22) (CTO vs. Control group respectively). Combination of PCI and CABG occurred in 8.8 % (n = 8) in both groups. Conservative treatment was chosen for 7 CTO and 2 Control group patients. CONCLUSION: We observed no 1-year mortality difference in patients with MI, MVD and a CTO compared to a matched cohort of patients with MI, MVD without CTO. Excellent 1-year survival was observed in patients treated by CABG, irrespective of CTO presence.
- MeSH
- Chronic Disease MeSH
- Myocardial Infarction * mortality diagnosis MeSH
- Cohort Studies MeSH
- Percutaneous Coronary Intervention methods MeSH
- Coronary Occlusion * diagnosis mortality surgery MeSH
- Middle Aged MeSH
- Humans MeSH
- Survival Rate trends MeSH
- Follow-Up Studies MeSH
- Coronary Artery Disease mortality diagnosis surgery MeSH
- Retrospective Studies MeSH
- Aged MeSH
- Propensity Score MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Fast Photochemical Oxidation of Proteins (FPOP) is a promising technique for studying protein structure and dynamics. The quality of insight provided by FPOP depends on the reliability of the determination of the modification site. This study investigates the performance of two search engines, Mascot and PEAKS, for the data processing of FPOP analyses. Comparison of Mascot and PEAKS of the hemoglobin--haptoglobin Bruker timsTOF data set (PXD021621) revealed greater consistency in the Mascot identification of modified peptides, with around 26% of the IDs being mutual for all three replicates, compared to approximately 22% for PEAKS. The intersection between Mascot and PEAKS results revealed a limited number (31%) of shared modified peptides. Principal Component Analysis (PCA) using the peptide-spectrum match (PSM) score, site probability, and peptide intensity was applied to evaluate the results, and the analyses revealed distinct clusters of modified peptides. Mascot showed the ability to assess confident site determination, even with lower PSM scores. However, high PSM scores from PEAKS did not guarantee a reliable determination of the modification site. Fragmentation coverage of the modification position played a crucial role in Mascot assignments, while the AScore localizations from PEAKS often become ambiguous because the software employs MS/MS merging.
Renal cell carcinoma (RCC) represents 2% of all diagnosed malignancies worldwide, with disease recurrence affecting 20% to 40% of patients. Existing prognostic recurrence models based on clinicopathological features continue to be a subject of controversy. In this meta-analysis, we summarized research findings that explored the correlation between clinicopathological characteristics and post-surgery survival outcomes in non-metastatic RCC patients. Our analysis incorporates 99 publications spanning 140 568 patients. The study's main findings indicate that the following clinicopathological characteristics were associated with unfavorable survival outcomes: T stage, tumor grade, tumor size, lymph node involvement, tumor necrosis, sarcomatoid features, positive surgical margins (PSM), lymphovascular invasion (LVI), early recurrence, constitutional symptoms, poor performance status (PS), low hemoglobin level, high body-mass index (BMI), diabetes mellitus (DM) and hypertension. All of which emerged as predictors for poor recurrence-free survival (RFS) and cancer-specific survival. Clear cell (CC) subtype, urinary collecting system invasion (UCSI), capsular penetration, perinephric fat invasion, renal vein invasion (RVI) and increased C-reactive protein (CRP) were all associated with poor RFS. In contrast, age, sex, tumor laterality, nephrectomy type and approach had no impact on survival outcomes. As part of an additional analysis, we attempted to assess the association between these characteristics and late recurrences (relapses occurring more than 5 years after surgery). Nevertheless, we did not find any prediction capabilities for late disease recurrences among any of the features examined. Our findings highlight the prognostic significance of various clinicopathological characteristics potentially aiding in the identification of high-risk RCC patients and enhancing the development of more precise prediction models.
