OBJECTIVE: To investigate the influence of statins on the survival outcomes of patients with non-muscle-invasive bladder cancer (NMIBC) treated with adjuvant intravesical bacille Calmette-Guérin (BCG) immunotherapy. PATIENTS AND METHODS: A retrospective cohort of consecutive patients with NMIBC who received intravesical BCG therapy from 2001 to 2020 and statins prescription were identified. Overall survival (OS), cancer-specific survival (CSS), recurrence-free survival (RFS), and progression-free survival (PFS) were analysed between the Statins Group vs No-Statins Group using Kaplan-Meier method and multivariable Cox regression. RESULTS: A total of 2602 patients with NMIBC who received intravesical BCG were identified. The median follow-up was 11.0 years. On Kaplan-Meier analysis, the Statins Group had significant better OS (P < 0.001), CSS (P < 0.001), and PFS (P < 0.001). Subgroup analysis indicated statins treatment started before BCG treatment had better CSS (P = 0.02) and PFS (P < 0.01). Upon multivariable Cox regression analysis, the 'statins before BCG' group was an independent protective factor for OS (hazard ratio [HR] 0.607, 95% confidence interval [CI] 0.514-0.716), and CSS (HR 0.571, 95% CI 0.376-0.868), but not RFS (HR 0.885, 95% CI 0.736-1.065), and PFS (HR 0.689, 95% CI 0.469-1.013). CONCLUSIONS: Statins treatment appears to offer protective effects on OS and CSS for patients with NMIBC receiving adjuvant intravesical BCG.
- MeSH
- adjuvancia imunologická terapeutické užití MeSH
- aplikace intravezikální MeSH
- BCG vakcína * terapeutické užití MeSH
- invazivní růst nádoru MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory močového měchýře neinvadující svalovinu MeSH
- nádory močového měchýře * farmakoterapie patologie mortalita MeSH
- retrospektivní studie MeSH
- senioři MeSH
- statiny * terapeutické užití 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
The utilization of 3D printing- digital light processing (DLP) technique, for the direct fabrication of microneedles encounters the problem of drug solubility in printing resin, especially if it is predominantly composed of water. The possible solution how to ensure ideal belonging of drug and water-based printing resin is its pre-formulation in nanosuspension such as nanocrystals. This study investigates the feasibility of this approach on a resin containing nanocrystals of imiquimod (IMQ), an active used in (pre)cancerous skin conditions, well known for its problematic solubility and bioavailability. The resin blend of polyethylene glycol diacrylate and N-vinylpyrrolidone, and lithium phenyl-2,4,6-trimethylbenzoylphosphinate as a photoinitiator, was used, mixed with IMQ nanocrystals in water. The final microneedle-patches had 36 cylindrical microneedles arranged in a square grid, measuring approximately 600 μm in height and 500 μm in diameter. They contained 5wt% IMQ, which is equivalent to a commercially available cream. The homogeneity of IMQ distribution in the matrix was higher for nanocrystals compared to usual crystalline form. The release of IMQ from the patches was determined ex vivo in natural skin and revealed a 48% increase in efficacy for nanocrystal formulations compared to the crystalline form of IMQ.
- MeSH
- 3D tisk * MeSH
- aplikace kožní MeSH
- imichimod * chemie aplikace a dávkování MeSH
- jehly * MeSH
- kožní absorpce MeSH
- kůže metabolismus MeSH
- mikroinjekce přístrojové vybavení MeSH
- nanočástice * chemie aplikace a dávkování MeSH
- polyethylenglykoly chemie aplikace a dávkování MeSH
- povidon chemie MeSH
- rozpustnost * MeSH
- systémy cílené aplikace léků přístrojové vybavení MeSH
- uvolňování léčiv MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The use of nanoparticles as a delivery system for a specific antigen could solve many limitations of mucosal vaccine applications, such as low immunogenicity, or antigen protection and stabilization. In this study, we tested the ability of nasally administered chitosan nanoparticles loaded with glycoprotein B of murine cytomegalovirus to induce an immune response in an animal model. The choice of chitosan nanoparticle type was made by in vitro evaluation of sorption efficiency and antigen release. Three types of chitosan nanoparticles were prepared: crosslinked with tripolyphosphate, coated with hyaluronic acid, and in complex with polycaprolactone. The hydrodynamic size of the nanoparticles by dynamic light scattering, zeta potential, Fourier transform infrared spectroscopy, scanning electron microscopy, stability, loading efficiency, and release kinetics with ovalbumin were evaluated. Balb/c mice were immunized intranasally using the three-dose protocol with nanoparticles, gB, and adjuvants Poly(I:C) and CpG ODN. Subsequently, the humoral and cell-mediated antigen-specific immune response was determined. On the basis of the properties of the tested nanoparticles, the cross-linked nanoparticles were considered optimal for further investigation. The results show that nanoparticles with Poly(I:C) and with gB alone raised IgG antibody levels above the negative control. In the case of mucosal IgA, only gB alone weakly induced the production of IgA antibodies compared to saline-immunized mice. The number of activated cells increased slightly in mice immunized with nanoparticles and gB compared to those immunized with gB alone or to negative control. The results demonstrated that chitosan nanoparticles could have potential in the development of mucosal vaccines.
- MeSH
- adjuvancia imunologická MeSH
- aplikace intranazální MeSH
- chitosan * chemie MeSH
- glykoproteiny MeSH
- imunizace MeSH
- imunoglobulin A MeSH
- Muromegalovirus * MeSH
- myši inbrední BALB C MeSH
- myši MeSH
- nanočástice * chemie MeSH
- slizniční imunita MeSH
- vakcíny * MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: The tumoricidal complex alpha1-oleate targets bladder cancer cells, triggering rapid, apoptosis-like tumor cell death. Clinical effects of alpha1-oleate were recently observed in patients with non-muscle invasive bladder cancer (NMIBC), using a randomized, placebo-controlled study protocol. AIMS: To investigate if there are dose-dependent effects of alpha1-oleate. MATERIALS AND METHODS: Here, patients with NMIBC were treated by intravesical instillation of increasing concentrations of alpha1-oleate (1.7, 8.5, or 17 mM) and the treatment response was defined relative to a placebo group. RESULTS: Strong, dose-dependent anti-tumor effects were detected in alpha1-oleate treated patients for a combination of molecular and clinical indicators; a complete or partial response was detected in 88% of tumors treated with 8.5 mM compared to 47% of tumors treated with 1.7 mM of alpha1-oleate. Uptake of alpha1-oleate by the tumor triggered rapid shedding of tumor cells into the urine and cell death by an apoptosis-like mechanism. RNA sequencing of tissue biopsies confirmed the activation of apoptotic cell death and strong inhibition of cancer gene networks, including bladder cancer related genes. Drug-related side effects were not recorded, except for local irritation at the site of instillation. DISCUSSION AND CONCLUSIONS: These dose-dependent anti-tumor effects of alpha1-oleate are promising and support the potential of alpha1-oleate treatment in patients with NMIBC.
- MeSH
- antitumorózní látky terapeutické užití MeSH
- aplikace intravezikální MeSH
- apoptóza účinky léků MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory močového měchýře * farmakoterapie patologie genetika MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- výsledek terapie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie MeSH
BACKGROUND: Current European Association of Urology (EAU) guidelines support adjuvant intravesical Bacillus Calmette-Guérin (BCG) treatment after Transurethral Resection of Bladder Tumor (TURB) for intermediate- or high-risk Non-Muscle-Invasive Bladder Cancer (NMIBC) patients, aiming to reduce the risk of tumor recurrence. The quality of data, however, does not allow definitive conclusions on whether different strains and dosages of BCG have different efficacies on long-term survival outcomes. OBJECTIVE: To evaluate the long-term survival outcomes of different strains and dosages of BCG in patients with NMIBC. DESIGN, SETTING, AND PARTICIPANTS: All NMIBC patients treated with intravesical BCG therapy from 2001 to 2020 were identified using a territory-wide database in Hong Kong. INTERVENTION: BCG strains and dosages (Connaught strain 81 mg, Connaught strain 27 mg, Tokyo strain 80 mg, and Danish strain 30 mg) were retrieved from medical records. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Overall Survival (OS), Cancer-Specific Survival (CSS), Recurrence-Free Survival (RFS), and Progression-Free Survival (PFS) were analyzed using the Kaplan-Meier method. A multivariable Cox regression analysis was used to adjust potential confounding factors, and to estimate Hazard Ratio (HR) and 95% confidence interval (CI) of different BCG strains. A further subgroup analysis on adequate versus inadequate BCG treatment was performed. RESULTS AND LIMITATIONS: A total of 2602 NMIBC patients treated with intravesical BCG were identified. Among them, 1291 (49.6%) received Connaught strain 81 mg, 199 (7.6%) received Connaught strain 27 mg, 1014 (39.0%) received Tokyo strain, and 98 (3.8%) received Danish strain. The median follow-up was 11.0 years. No statistically significant differences in OS, CSS, RFS, and PFS were detected among the different groups. At the multivariable analysis, the Connaught strain 27 mg group was inferior to the Connaught strain 81 mg group in terms of OS (HR: 1.26, 95% CI: 1.05-1.51), CSS (HR: 1.69, 95% CI: 1.08-2.66), and PFS (HR: 1.86, 95% CI: 1.20-2.88). Adequate BCG treatment was associated with improved OS (HR: 0.82, 95% CI: 0.73-0.92), CSS (HR: 0.64, 95% CI: 0.47-0.86), RFS (HR: 0.80, 95% CI: 0.70-0.92), and PFS (HR: 0.52, 95% CI: 0.39-0.68). Among patients treated with adequate BCG, at the multivariable analysis the Connaught strain 27 mg group showed worse results than the Connaught strain 81 mg group in terms of CSS (HR: 1.93, 95% CI: 1.07-3.51). Compared with the Connaught strain 81 mg group, both Tokyo and Danish strains had similar survival outcomes in the whole cohort and the adequate BCG treatment subgroup. CONCLUSIONS: Our findings suggest that adequate BCG remains the most important factor in optimizing survival outcomes in patients with intermediate- and high-risk NMIBC. No significant differences in survival outcomes were observed between full-dose Connaught, Tokyo, and Danish strains. Reduced-dose Connaught strain was associated with the worst survival outcomes. PATIENT SUMMARY: We evaluated the efficacy of different strains and dosages of bacillus Calmette-Guérin (BCG) in patients with intermediate- or high-risk non-muscle-invasive bladder cancer in the past two decades in Hong Kong. We conclude no significant differences in long-term survival outcomes in terms of full-dose Connaught, Tokyo, and Danish strains, while reduced-dose Connaught strain was inferior to the full-dose group. Adequate BCG treatment benefits long-term survival.
- MeSH
- adjuvancia imunologická terapeutické užití aplikace a dávkování MeSH
- aplikace intravezikální MeSH
- BCG vakcína * terapeutické užití aplikace a dávkování MeSH
- invazivní růst nádoru MeSH
- lidé středního věku MeSH
- lidé MeSH
- míra přežití MeSH
- nádory močového měchýře neinvadující svalovinu * mortalita terapie MeSH
- nádory močového měchýře * mortalita terapie MeSH
- retrospektivní 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
- Geografické názvy
- Hongkong MeSH
Na akutní urologickou ambulanci se dostavil 93letý pacient stěžující si na obtékající permanentní močový katétr a bolesti podbřišku. Mezi pro případ relevantní pacientovy diagnózy patřily velmi vysoce rizikový uroteliální karcinom močového měchýře po opakovaných transuretrálních resekcích a recentně také výplaších intravezikální chemoterapií, diabetes mellitus druhého typu na dvojkombinaci perorálních antidiabetik a recidivující močové infekce. Pro suspekci na perforaci močového měchýře či komunikaci močového měchýře se střevem, při sterkorálně zapáchající moči, bylo doplněno kontrastní CT s vylučovací fází a CT cystogram. Perforaci či píštěl jsme neprokázali, avšak na základě zobrazovacích vyšetření jsme stanovili diagnózu emfyzematózní cystitidy. Tato kazuistika má za cíl upozornit na tuto vzácnou, mnohdy nenápadně se projevující, avšak potenciálně život ohrožující urologickou nosologickou jednotku.
A 93-year-old male presented to the urology outpatient clinic with complaints of a leaking indwelling urinary catheter and suprapubic pain. Our patient had a history of urothelial carcinoma of the bladder, for which he has undergone multiple transurethral resections and recent intravesical chemotherapy instillations. He also has type 2 diabetes mellitus, which is managed with a combination of oral antidiabetic medications and has a history of recurrent urinary tract infections. A CT scan with contrast and an excretory phase and CT cystogram were performed to rule out bladder perforation or a bladder-bowel fistula in the presence of foul-smelling urine. The CT scan did not show any evidence of colo-vesicalor fistula, but it did show evidence of emphysematous cystitis. This case report aims to highlight this rare, often presenting in a subtle manner, but life-threatening urological disease.
- Klíčová slova
- emfyzematózní cystitida,
- MeSH
- antibakteriální látky farmakologie terapeutické užití MeSH
- aplikace intravezikální MeSH
- cystitida * diagnóza farmakoterapie terapie MeSH
- diabetes mellitus 2. typu farmakoterapie komplikace MeSH
- diagnostické zobrazování metody MeSH
- Escherichia coli patogenita MeSH
- hypoglykemika farmakologie terapeutické užití MeSH
- karcinom z přechodných buněk chirurgie farmakoterapie MeSH
- lidé MeSH
- nádory močového měchýře * chirurgie farmakoterapie MeSH
- senioři nad 80 let MeSH
- Check Tag
- lidé MeSH
- senioři nad 80 let MeSH
- Publikační typ
- kazuistiky MeSH
- práce podpořená grantem MeSH
OBJECTIVE: To investigate the impact of ageing on survival outcomes in Bacillus Calmette-Guérin (BCG) treated non-muscle invasive bladder cancer (NMIBC) patients and its synergy with adequate BCG treatment. METHOD: Patients with NMIBC who received BCG treatment from 2001 to 2020 were divided into group 1 (< = 70 years) and group 2 (> 70 years). Overall Survival (OS), Cancer-Specific Survival (CSS), Recurrence-Free Survival (RFS), and Progression-Free Survival (PFS) were analyzed using the Kaplan-Meier method. Multivariable Cox regression analysis was used to adjust potential confounding factors and to estimate Hazard Ratio (HR) and 95% Confidence Interval (CI). Subgroup analysis was performed according to adequate versus inadequate BCG treatment. RESULTS: Overall, 2602 NMIBC patients were included: 1051 (40.4%) and 1551 (59.6%) in groups 1 and 2, respectively. At median follow-up of 11.0 years, group 1 (< = 70 years) was associated with better OS, CSS, and RFS, but not PFS as compared to group 2 (> 70 years). At subgroup analysis, patients in group 1 treated with adequate BCG showed better OS, CSS, RFS, and PFS as compared with inadequate BCG treatment in group 2, while patients in group 2 receiving adequate BCG treatment had 41% less progression than those treated with inadequate BCG from the same group. CONCLUSIONS: Being younger (< = 70 years) was associated with better OS, CSS, and RFS, but not PFS. Older patients (> 70 years) who received adequate BCG treatment had similar PFS as those younger with adequate BCG treatment.
- MeSH
- adjuvancia imunologická * terapeutické užití MeSH
- aplikace intravezikální MeSH
- BCG vakcína * terapeutické užití MeSH
- invazivní růst nádoru * MeSH
- lidé středního věku MeSH
- lidé MeSH
- míra přežití MeSH
- nádory močového měchýře neinvadující svalovinu MeSH
- nádory močového měchýře * farmakoterapie patologie terapie mortalita MeSH
- retrospektivní studie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- věkové faktory MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Sildenafil citrate has low oral bioavailability, systemic adverse effects, and a relatively delayed action. These issues may be addressed through direct transdermal delivery to the penis. This study aims to investigate the microemulsion formulation of the drug for effective transdermal delivery. Sildenafil citrate was formulated as a microemulsion using clove oil, dimethyl sulphoxide, phosphate buffer (pH 7), propylene glycol, Tween®80, and distilled water. Different proportions of these components were used to create six formulations of the microemulsion (F1-F6), which were then characterised by their physical appearance and clarity, pH, viscosity, conductivity, percent transmission, and droplet size. Furthermore, the stability, content analysis, in-vitro drug release, and transdermal permeation of sildenafil citrate from the generated drug-loaded microemulsions were studied. All prepared formulas contained nano-sized oil droplets (less than 20 nm), and the pH values were within the range of skin pH; however, two formulas were not transparent. Additionally, all formulations were thermodynamically stable, passing freeze-thaw, heating-cooling, and centrifugation tests. Next, the formulas demonstrated zero-order release kinetics, indicating that they can provide a sustained release profile for sildenafil citrate. Finally, the microemulsion formulation exhibited a 2.8-fold enhancement in skin permeation compared with that of the sildenafil citrate suspension. The prepared microemulsions demonstrated beneficial physical properties and skin permeation profiles that are promising for the local administration of sildenafil citrate.
- Klíčová slova
- mikroemulze,
- MeSH
- aplikace kožní * MeSH
- emulze MeSH
- hřebíčkový olej MeSH
- krysa rodu rattus MeSH
- lékové formy MeSH
- modely u zvířat MeSH
- permeabilita MeSH
- příprava léků metody MeSH
- sildenafil citrát * aplikace a dávkování farmakokinetika farmakologie MeSH
- stabilita léku MeSH
- suspenze MeSH
- uvolňování léčiv MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- klinická studie MeSH
Na pracovišti ambulance bolesti v Českých Budějovicích se v posledních dvou letech věnujeme ošetřování akutní progrese chronických bolestí hlavy intranazální aplikací lidokainu. Jedná se o ambulantní, minimálně invazivní a pacienty dobře snášenou metodu. V poloze vleže podáváme malé množství 4% lidokainového gelu opakovaně po 3–5 minutách celkem 3–5krát nosní dírkou na postižené bolestivé polovině hlavy. Aplikátor zavádíme po znecitlivění vstupu do nosu šetrně až do kontaktu se zadní stěnou nosohltanu, pod jehož sliznicí se nachází trigeminální ganglion. Cílem ošetření je ovlivnit lokálním anestetikem ganglion sphenopalatinum a snížit vedení bolesti v povodí trigeminálního nervu z postižené poloviny hlavy a obličeje. Zákrok provádíme opakovaně třikrát týdně. Výkon často kombinujeme s podáním antineuropatické infuze. Metodu jsme vyzkoušeli u pacientů s postherpetickými bolestmi obličeje, při atakách bolestí hlavy u pacientů s roztroušenou sklerózou, u pacientů čekajících na intervenční zákrok při neuralgiích trigeminu na podkladě neurovaskulárního konfliktu. Dobrý efekt byl pozorován i u akutních postpunkčních bolestí hlavy a u migrény. Úlevu od bolesti lze pozorovat po 1–2 hodinách a trvání efektu léčby je velmi individuální: 2 dny až 4 týdny. Opakování zákroku obden a současná aplikace antineuropatické infuze nebo myorelaxační infuze potencují analgetický účinek. Ošetření bývá pacienty dobře snášeno. Při zavádění aplikátoru může dojít k poranění nosní sliznice, během aplikace je patrné slzení, necitlivost a pocit chladu pod okem a v okolí jařmového oblouku ošetřované strany. Občas se vyskytne pálení v oblasti nosohltanu ze zatékajícího lidokainového gelu, což se dá ovlivnit množstvím aplikované látky. Ze zájmu pacientů o opakování aplikace lze usuzovat na pozitivní efekt metody.
At the pain clinic in Budweis, we have been treating the acute progression of chronic headaches using intranasal lidocaine for the past two years. It is an outpatient, minimally invasive method that is well tolerated by patients. In the supine position, we administer a small amount of 4 % lidocaine gel repeatedly after 3-5 minutes a total of 3-5 times through the nostril on the affected painful half of the head. After anesthetizing the entrance to the nose, the applicator is gently inserted until it comes into contact with the back wall of the nasopharynx, under the mucosa of which the trigeminal ganglion is located. The aim of the treatment is to affect the sphenopalatine ganglion with a local anesthetic and to reduce the conduction of pain in the basin of the trigeminal nerve from the affected half of the head and face. We perform the procedure repeatedly 3 times a week. We often combine the procedure with the administration of an antineuropathic infusion. We tried the method in patients with post-herpetic facial pain, in headache attacks in patients with multiple sclerosis, in patients waiting for intervention for trigeminal neuralgia based on neurovascular conflict. A good effect was also observed in acute postpuncture headaches and migraines. The effect can be observed after 1-2 hours and the duration is very individual from 2 days to 4 weeks. Repeating the procedure every other day and simultaneous application of antineuropathic infusion or myorelaxant infusion potentiate the analgesic effect. Treatment is usually well tolerated by patients. When inserting the applicator, the nasal mucosa may be injured, during the application there is steamy lacrimation, numbness and a feeling of coldness under the eye and around the zygomatic arch of the treated side. Sometimes there is a burning sensation in the nasopharynx area from leaking lidocaine gel, which can be influenced by the amount of applied substance. The positive effect of the method can be inferred from the patients‘ interest in repeating the application.
- MeSH
- aplikace intranazální * metody škodlivé účinky MeSH
- bolesti hlavy * etiologie farmakoterapie klasifikace MeSH
- dospělí MeSH
- extrakce zubů škodlivé účinky MeSH
- ganglia parasympatická účinky léků MeSH
- lidé středního věku MeSH
- lidé MeSH
- lidokain * aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- nervus trigeminus fyziologie MeSH
- neuralgie trigeminu etiologie farmakoterapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
- přehledy MeSH
