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
- Androgen Receptor Antagonists * adverse effects administration & dosage therapeutic use MeSH
- Benzamides MeSH
- Phenylthiohydantoin adverse effects administration & dosage MeSH
- Humans MeSH
- Prostatic Neoplasms * drug therapy pathology MeSH
- Central Nervous System Diseases chemically induced MeSH
- Nitriles MeSH
- Pyrazoles MeSH
- Randomized Controlled Trials as Topic MeSH
- Network Meta-Analysis as Topic * MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Publication type
- Journal Article MeSH
- Meta-Analysis MeSH
- Review MeSH
- Systematic Review 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
- Androstenes MeSH
- Androgen Receptor Antagonists * adverse effects therapeutic use MeSH
- Benzamides adverse effects MeSH
- Phenylthiohydantoin MeSH
- Cardiovascular Diseases * chemically induced epidemiology MeSH
- Humans MeSH
- Prostatic Neoplasms * drug therapy pathology MeSH
- Nitriles adverse effects MeSH
- Randomized Controlled Trials as Topic MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Publication type
- Journal Article MeSH
- Network Meta-Analysis MeSH
- Systematic Review MeSH
- Keywords
- Gapulsid,
- MeSH
- Benzamides * therapeutic use MeSH
- Depression complications MeSH
- Dyspepsia drug therapy psychology MeSH
- Escitalopram adverse effects therapeutic use MeSH
- Drug Therapy, Combination methods MeSH
- Humans MeSH
- Selective Serotonin Reuptake Inhibitors * therapeutic use MeSH
- Aged MeSH
- Anxiety complications MeSH
- Check Tag
- Humans MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Case Reports MeSH
Stenotrophomonas maltophilia, Achromobacter xylosoxidans, and Burkholderia cenocepacia are considered emerging pathogens classified as a public health problem due to extensive antimicrobial resistance. Therefore, the discovery of new therapeutic strategies has become crucial. This study aimed to evaluate the antimicrobial activity of gallic acid and methyl gallate against non-fermenting bacteria. The study included five clinical isolates of Stenotrophomonas maltophilia, Achromobacter xylosoxidans, and Burkholderia cenocepacia. The minimum inhibitory concentrations of gallic acid and methyl gallate were determined by the broth microdilution method. Growth curves, metabolic activity, and biofilm formation of each bacterial strain in the presence or absence of phenolic compounds were performed. Finally, the therapeutic efficacy of the compounds was evaluated using an in vivo model. Gallic acid and methyl gallate showed antibacterial activity against bacterial strains in a concentration range of 64 to 256 μg/mL, both compounds reduced bacterial growth and metabolic activity of the strains, even at subinhibitory concentrations. Only, methyl gallate exhibited activity to inhibit the formation of bacterial biofilms. Moreover, gallic acid and methyl gallate increased larval survival by up to 60% compared to 30% survival of untreated larvae in a bacterial infection model in Galleria mellonella. Our results highlight the potential of gallic acid and methyl gallate as therapeutic alternatives for infections by emerging non-fermentative bacteria.
BACKGROUND: The optimal first-line therapy for metastatic renal cell carcinoma (mRCC) remains uncertain, despite recent advancements in immune-based combinations. This retrospective study compares the effectiveness of pembrolizumab plus axitinib (PA) and nivolumab plus cabozantinib (NC) as first-line treatments for mRCC in a real-world setting. METHODS: Patient data were collected from 55 centers across 16 countries, encompassing individuals diagnosed with mRCC receiving first-line treatment with PA or NC between January 2016 and October 2023. Clinical and tumor features and treatment responses were recorded. The primary endpoints were overall response rate (ORR), overall survival (OS), progression-free survival (PFS), and time to second progression. Statistical analyses included Kaplan-Meier survival estimates, Cox proportional hazard models, and chi-square tests. RESULTS: A total of 760 patients with a median age of 64 years (range, 29-88) were included. Of them, 607 received PA, and only 153 NC. In the overall study population, ORR was 59% for and 49% for PA. Median OS was 55.7 months and not reached (NR) for PA and NC, respectively (P = .51), while median PFS was longer with NC (27.6 months) than for PA (16.2 months, P = .003). Subgroup analysis suggested a PFS benefits for NC in male, younger patients, intermediate risk group, clear cell histology, and lung involvement, as well as ORR favored NC in good risk patients. Multivariate analysis identified first-line therapy as a significant factor associated with PFS. CONCLUSIONS: In this certainly biased retrospective comparison, NC demonstrated superior ORR and longer PFS compared to PA in mRCC. These findings underscore the importance of considering individual patient characteristics and risk profiles when selecting first-line therapy for mRCC.
- MeSH
- Anilides * therapeutic use pharmacology administration & dosage MeSH
- Axitinib * therapeutic use pharmacology administration & dosage MeSH
- Adult MeSH
- Antibodies, Monoclonal, Humanized * therapeutic use pharmacology administration & dosage MeSH
- Carcinoma, Renal Cell * drug therapy mortality pathology MeSH
- Middle Aged MeSH
- Humans MeSH
- Kidney Neoplasms * drug therapy pathology mortality MeSH
- Nivolumab * therapeutic use pharmacology administration & dosage MeSH
- Antineoplastic Combined Chemotherapy Protocols * therapeutic use MeSH
- Pyridines therapeutic use MeSH
- Retrospective Studies MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Comparative Study MeSH
Prokinetika jsou skupinou léčiv, které díky schopnosti stimulace hladké svaloviny zvyšují motilitu trávicího traktu, a to především v jeho proximální části. V současnosti se prokinetika využívají primárně pro léčbu funkční dyspepsie, ale uplatnění mohou nalézt i u jiných indikací. Pozitivního účinku na motilitu dosahují prostřednictvím mechanismů, které jsou v rámci skupiny prokinetik do značné míry heterogenní. Článek poskytuje čtenářům základní přehled informací vztahujícím se k jednotlivým prokinetikům aktuálně registrovaných na trhu v České republice, blíže popisuje jejich farmakologické účinky a diskutuje užití prokinetik v léčbě funkční dyspepsie a refluxní nemoci jícnu, což jsou nejčastější indikace k užití prokinetik v klinické praxi.
Prokinetics are a group of drugs that, due to their ability to stimulate smooth muscle contraction, enhance the motility of the digestive tract, particularly in its proximal part. Currently, prokinetics are primarily used to treat functional dyspepsia, though they may also be prescribed for other indications. They exert their positive effects on motility through mechanisms that vary within this drug class. This article provides readers with a basic overview of the prokinetic agents currently registered on the market in the Czech Republic, describes their pharmacological effects in more detail, and discusses the use of prokinetics in the treatment of functional dyspepsia and gastroesophageal reflux disease, which are the most common indications for the use of prokinetics in clinical practice.
- Keywords
- prokinetika, cinitaprid, itoprid,
- MeSH
- Benzamides administration & dosage pharmacology MeSH
- Dyspepsia drug therapy MeSH
- Gastroesophageal Reflux drug therapy MeSH
- Gastrointestinal Agents * administration & dosage classification MeSH
- Gastrointestinal Motility * drug effects MeSH
- Gastrointestinal Diseases drug therapy MeSH
- Humans MeSH
- Metoclopramide pharmacology therapeutic use MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
Virové bradavice jsou celosvětově časté onemocnění způsobené lidským papilomavirem, který má řadu genotypů. Mnoho z těchto virů je komenzálních a u imunokompetentních hostitelů nevyvolávají žádné projevy. Za vhodných podmínek některé způsobují klinické změny na kůži nebo na sliznicích v anogenitální či orofaryngeální oblasti. U dětí se nejčastěji setkáváme s verruca vulgaris, verruca plantaris a verruca plana. Řada těchto projevů samovolně vymizí, problémem jsou perzistentní či úporně recidivující bradavice. Léčbou se snažíme nejen zlikvidovat viditelné změny za minimalizace bolesti a bez jizvení, ale také o prevenci recidivy ať již v místě původní bradavice nebo kdekoli jinde na těle.
Viral warts are a common disease worldwide caused by the human papillomavirus, which has a number of genotypes. Many of these viruses are commensal and do not cause any symptoms in immunocompetent hosts. Under appropriate conditions, however, some cause clinical changes on the skin or mucous membranes in the anogenital or oropharyngeal part. Verruca vulgaris, verruca plantaris and verruca plana are most often encountered in children. Many of these manifestations disappear on their own, the problem is persistent or stubbornly recurring warts. With the treatment, we try not only to eliminate visible changes while minimizing pain and without scarring, but also to prevent recurrence, whether at the site of the original wart or anywhere else on the body.
- MeSH
- Warts * drug therapy therapy MeSH
- Child * MeSH
- Fluorouracil pharmacology therapeutic use MeSH
- Papillomavirus Infections transmission therapy MeSH
- Keratinocytes pathology MeSH
- Cryotherapy methods MeSH
- Salicylic Acid therapeutic use MeSH
- Trichloroacetic Acid therapeutic use MeSH
- Lasers MeSH
- Humans MeSH
- Podophyllin pharmacology therapeutic use MeSH
- Check Tag
- Child * MeSH
- Humans MeSH
Histone deacetylases (HDACs) are frequently deregulated in cancer, and several HDAC inhibitors (HDACi) have gained approval for treating peripheral T cell lymphomas. Here, we investigated the effects of pharmacological or genetic HDAC inhibition on NPM::ALK positive anaplastic large cell lymphoma (ALCL) development to assess the potential use of HDACi for the treatment of this disease. Short-term systemic pharmacological inhibition of HDACs using the HDACi Entinostat in a premalignant ALCL mouse model postponed or even abolished lymphoma development, despite high expression of the NPM::ALK fusion oncogene. To further disentangle the effects of systemic HDAC inhibition from thymocyte intrinsic effects, conditional genetic deletions of HDAC1 and HDAC2 enzymes were employed. In sharp contrast, T cell-specific deletion of Hdac1 or Hdac2 in the ALCL mouse model significantly accelerated NPM::ALK-driven lymphomagenesis, with Hdac1 loss having a more pronounced effect. Integration of gene expression and chromatin accessibility data revealed that Hdac1 deletion selectively perturbed cell type-specific transcriptional programs, crucial for T cell differentiation and signaling. Moreover, multiple oncogenic signaling pathways, including PDGFRB signaling, were highly upregulated. Our findings underscore the tumor-suppressive function of HDAC1 and HDAC2 in T cells during ALCL development. Nevertheless, systemic pharmacological inhibition of HDACs could still potentially improve current therapeutic outcomes.
- MeSH
- Anaplastic Lymphoma Kinase * metabolism genetics MeSH
- Lymphoma, Large-Cell, Anaplastic * drug therapy pathology genetics metabolism MeSH
- Benzamides pharmacology MeSH
- Histone Deacetylase 1 * genetics antagonists & inhibitors physiology metabolism MeSH
- Histone Deacetylase 2 genetics MeSH
- Histone Deacetylase Inhibitors * pharmacology therapeutic use MeSH
- Humans MeSH
- Mice MeSH
- Pyridines pharmacology MeSH
- Genes, Tumor Suppressor * MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Gynekomastie je benigní zvětšení prsní žlázy u mužů, které může mít významný psychologický dopad, zejména u dětí a adolescentů. Tento článek se zabývá farmakologicky indukovanou gynekomastií a nejčastějšími léky, které mohou přispět k jejímu vzniku. V rámci naší analýzy jsme identifikovali a přezkoumali relevantní studie a kazuistiky publikované v databázi PubMed, které se zabývají různými aspekty gynekomastie u dětských pacientů. Důležitým krokem v prevenci gynekomastie je informovanost zdravotnického personálu, rodičů a pacientů o potenciálních rizicích spojených s užíváním určitých léků. Je nevyhnutelné, aby při předepisovaní léčby byly zohledněny veškeré možné vedlejší účinky, a aby se provedlo důkladné zhodnocení poměru přínosů a rizik. Mimo jiné se doporučuje provádět pravidelné kontroly a hodnocení pacientů, kteří užívají rizikové léky, aby bylo možné včas identifikovat a řešit případné příznaky gynekomastie. Tento článek zdůrazňuje potřebu zvýšené pozornosti k vybraným lékům, které jsou nejčastěji uváděny v odborné literatuře, a multidisciplinární přístup k léčbě. Informovanost o farmakologických rizicích a podpora ze strany zdravotnických odborníků jsou klíčové pro prevenci a zvládnutí tohoto stavu, ale také pro psychologickou pohodu dětských pacientů trpících touto diagnózou.
Gynecomastia is a benign enlargement of breast tissue in males that can have significant psychological impacts, especially in children and adolescents. This article focuses on pharmacologically induced gynecomastia and the most common medications that may contribute to its development. In our analysis, we identified and examined relevant studies and case reports published in the PubMed database that discuss various aspects of gynecomastia in pediatric patients. An important step in the prevention of gynecomastia is the awareness of healthcare professionals, parents, and patients regarding the potential risks associated with the use of certain medications. It is essential that all possible side effects are considered when prescribing treatment and that a thorough assessment of the benefits and risks is conducted. Additionally, it is recommended to carry out regular check-ups and evaluations of patients who are taking high-risk medications to identify and address any symptoms of gynecomastia in a timely manner. This article emphasizes the need for increased attention to selected medications commonly cited in the scientific literature and a multidisciplinary approach to treatment. Awareness of pharmacological risks and support from healthcare professionals are crucial for the prevention and management of this condition, as well as for the psychological well-being of pediatric patients suffering from this diagnosis.
- MeSH
- Anticonvulsants pharmacology adverse effects MeSH
- Antipsychotic Agents pharmacology adverse effects MeSH
- Child MeSH
- Gynecomastia * etiology MeSH
- Isoniazid pharmacology adverse effects MeSH
- Humans MeSH
- Metoclopramide pharmacology adverse effects MeSH
- Drug-Related Side Effects and Adverse Reactions * drug therapy MeSH
- Omeprazole pharmacology adverse effects MeSH
- Check Tag
- Child MeSH
- Humans MeSH
Virové bradavice jsou celosvětově časté onemocnění způsobené lidským papilomavirem, který má řadu genotypů. Mnoho z těchto virů je komenzálních a u imunokompetentních hostitelů nevyvolávají žádné projevy. Za vhodných podmínek některé způsobují klinické změny na kůži nebo na sliznicích v anogenitální či orofaryngeální oblasti. U dětí se nejčastěji setkáváme s verruca vulgaris, verruca plantaris a verruca plana. Řada těchto projevů samovolně vymizí, problémem jsou perzistentní či úporně recidivující bradavice. Léčbou se snažíme nejen zlikvidovat viditelné změny za minimalizace bolesti a bez jizvení, ale také o prevenci recidivy ať již v místě původní bradavice nebo kdekoli jinde na těle.
Viral warts are a common disease worldwide caused by the human papillomavirus, which has a number of genotypes. Many of these viruses are commensal and do not cause any symptoms in immunocompetent hosts. Under appropriate conditions, however, some cause clinical changes on the skin or mucous membranes in the anogenital or oropharyngeal part. Verruca vulgaris, verruca plantaris and verruca plana are most often encountered in children. Many of these manifestations disappear on their own, the problem is persistent or stubbornly recurring warts. With the treatment, we try not only to eliminate visible changes while minimizing pain and without scarring, but also to prevent recurrence, whether at the site of the original wart or anywhere else on the body.
- MeSH
- Warts * therapy MeSH
- Child * MeSH
- Immunotherapy methods MeSH
- Papillomavirus Infections drug therapy therapy MeSH
- Keratinocytes drug effects MeSH
- Cryotherapy methods MeSH
- Salicylic Acid pharmacology therapeutic use MeSH
- Lasers MeSH
- Humans MeSH
- Retinoids pharmacology therapeutic use MeSH
- Check Tag
- Child * MeSH
- Humans MeSH
