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PURPOSE: TACE induces variable systemic effects by producing factors that promote inflammation, oncogenesis, and angiogenesis. Here we compare concentrations of microRNAs (miR-21, miR-210 and miR-34a) and vascular endothelial growth factor (VEGF) in hepatocellular carcinoma (HCC) patients undergoing TACE with degradable (DSM) and nondegradable (DEB) particles and potential use of these biomarker changes for prediction of patient outcomes. MATERIALS AND METHODS: Overall, 52 patients with HCC treated with DSM TACE (24 patients) and DEB TACE (28 patients) were included in this prospective study. Concentrations of studied biomarkers were measured from blood plasma preprocedurally, immediately (< 90 min) postprocedurally, and 24-h after TACE. Levels were compared between DSM and DEB TACE and correlated with treatment response six and 12 months after the first TACE. RESULTS: Both DSM and DEB TACE elevated plasma levels of miR-21, miR-34a, and miR-210 at 24 h post-procedure compared to baseline levels (FC 1.25-4.0). MiR-34a elevation immediately after TACE was significantly associated with nonprogressive disease compared to those with progressive disease at both six months (FCa: p = 0.014) and 12 months (FCa: p = 0.029) post-TACE. No significant biomarker changes were found between the embolization particle groups. However, VEGF levels showed a decrease only in the DSM TACE group (FC24: p = < 0.001). CONCLUSION: Embolization particle type did not significantly impact miRNA or VEGF changes post-TACE. However, miR-34a elevation immediately after the procedure predicts better patient outcome and may prove useful as a biomarkers for the monitoring of clinical outcomes. LEVEL OF EVIDENCE: Level 3 Prospective cohort study.
- MeSH
- biologické markery krev MeSH
- chemoembolizace * metody MeSH
- hepatocelulární karcinom * terapie krev genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikro RNA * krev MeSH
- nádorové biomarkery * krev MeSH
- nádory jater * terapie genetika krev MeSH
- prospektivní studie MeSH
- senioři MeSH
- vaskulární endoteliální růstový faktor A * krev 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
INTRODUCTION: This study was performed to compare the efficacy and safety of PreserFlo MicroShunt (PMS) implantation with mitomycin C (MMC) applied by sub-tenon injection versus conventional application by MMC-soaked sponges. METHODS: This retrospective, 1-year cohort study included 100 eyes of 100 patients with glaucoma who underwent PMS implantation with MMC (0.4 mg/ml) delivered either by sub-tenon injection (50 eyes) or via soaked sponges (50 eyes). The primary outcome measure at 1 year was intraocular pressure (IOP) reduction, with complete success defined as an IOP reduction of ≥ 20% and achieving a target IOP of ≤ 21 or 18 mmHg without the use of medication. Secondary outcomes, including corneal endothelial cell density (CECD) loss, the number of medications, and complications, were assessed and compared between the groups. RESULTS: Sustained reductions in mean IOP were observed in both groups over the 1-year follow-up, with no significant differences between the groups. The complete success rate, with a target IOP of ≤ 21 mmHg after 1 year, was 19.3% in the sponge group and 26.4% in the injection group. The qualified success rate was 59.0% and 87.4% in the sponge and injection groups, respectively. A longer survival rate was observed in the injection group than in the sponge group when IOP was below 21 mmHg. The mean CECD significantly decreased (P < 0.01) from baseline to each postoperative follow-up time point in both groups. At 1 year postoperatively, the percentage of total CECD loss was 8.1% in the sponge group and 8.0% in the injection group. However, no significant differences in mean CECD values, the number of medications, or adverse events were found between the groups. CONCLUSIONS: PMS implantation with sub-tenon injection of MMC was comparable in terms of efficacy and safety to traditional MMC delivery via soaked sponges. However, the injection group demonstrated a significantly higher success rate than the sponge group.
- Publikační typ
- časopisecké články MeSH
Syphilis, known as "the great mimicker," is caused by the spirochete Treponema pallidum and is characterized by a diverse array of clinical and histopathologic presentations. In secondary cutaneous syphilis, the most consistent morphological features include a superficial and deep perivascular infiltrate containing plasma cells, varying degrees of endothelial swelling, irregular acanthosis, elongation of rete ridges, a vacuolated pattern, and the presence of plasma cells. Although serologic tests are essential for definitive diagnosis, spirochetes can sometimes be directly identified in silver-stained tissue slides or through immunohistochemistry. Granuloma annulare is a relatively common, benign, self-limiting condition with 3 main variants: conventional, subcutaneous, and interstitial, each with distinct characteristics. In this study, we report 2 cases of cutaneous secondary syphilis with a striking granulomatous reaction pattern that closely mimics the interstitial variant of granuloma annulare. Owing to the severity of the tertiary stage of syphilis, distinguishing between these 2 entities is crucial.
- MeSH
- anulární granulom * patologie diagnóza mikrobiologie MeSH
- diferenciální diagnóza MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- syfilis kožní patologie diagnóza mikrobiologie MeSH
- syfilis * diagnóza patologie mikrobiologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
INTRODUCTION: The objective of this study was to assess the relationship between longitudinal changes in the uterine Doppler velocimetry and the maternal profile of angiogenic factors in the third trimester and to assess their ability to predict term preeclampsia (PE). METHODS: A cohort of low-risk pregnant women was scheduled for a uterine Doppler evaluation and measurement of the circulating levels of angiogenic factors at ∼30 and ∼36 weeks. The performance of both parameters and their change over time in predicting term PE was evaluated. RESULTS: A total of 1,191 women were analyzed, of which 28 (2.4%) women developed term PE. At ∼30 weeks, a model including the sFlt-1/PlGF (fms-like tyrosine kinase-1/placental growth factor) ratio and the uterine Doppler explained 16.2% of the uncertainty of developing term PE, while at ∼36 weeks, the same variables explained 25.2% [p < 0.001]. The longitudinal changes of both predictors had an R2 of 26.8%, which was not different from that of the ∼36 weeks evaluation [p = 0.45]. The area under the curve (AUC) of the ∼36 weeks ratio was significantly higher than at ∼30 weeks (0.86 [0.77-0.94] vs. 0.81 [0.73-0.9]; p = 0.043). The AUC of the longitudinal change of the ratio (0.85 [0.77-0.94]) did not differ from that of at ∼36 weeks (p = 0.82). At ∼36 weeks, for a 10% of false positives, the ratio had a detection rate of 71.4%. CONCLUSION: A cross-sectional measurement of the sFlt-1/PlGF ratio outperforms uterine Doppler in predicting term PE. The combination of both markers does not improve such prediction, nor the evaluation of the longitudinal changes between weeks.
- MeSH
- dospělí MeSH
- lidé MeSH
- placentární oběh fyziologie MeSH
- placentární růstový faktor * krev MeSH
- plocha pod křivkou MeSH
- prediktivní hodnota testů MeSH
- preeklampsie * krev diagnostické zobrazování MeSH
- receptor 1 pro vaskulární endoteliální růstový faktor * krev MeSH
- reologie * metody statistika a číselné údaje MeSH
- reprodukovatelnost výsledků MeSH
- rychlost toku krve fyziologie MeSH
- těhotenství MeSH
- třetí trimestr těhotenství * krev fyziologie MeSH
- ultrasonografie dopplerovská metody statistika a číselné údaje MeSH
- ultrasonografie prenatální * metody statistika a číselné údaje MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
- srovnávací studie MeSH
The alveolar-capillary interface is the key functional element of gas exchange in the human lung, and disruptions to this interface can lead to significant medical complications. However, it is currently challenging to adequately model this interface in vitro, as it requires not only the co-culture of human alveolar epithelial and endothelial cells but mainly the preparation of a biocompatible scaffold that mimics the basement membrane. This scaffold should support cell seeding from both sides, and maintain optimal cell adhesion, growth, and differentiation conditions. Our study investigates the use of polycaprolactone (PCL) nanofibers as a versatile substrate for such cell cultures, aiming to model the alveolar-capillary interface more accurately. We optimized nanofiber production parameters, utilized polyamide mesh UHELON as a mechanical support for scaffold handling, and created 3D-printed inserts for specialized co-cultures. Our findings confirm that PCL nanofibrous scaffolds are manageable and support the co-culture of diverse cell types, effectively enabling cell attachment, proliferation, and differentiation. Our research establishes a proof-of-concept model for the alveolar-capillary interface, offering significant potential for enhancing cell-based testing and advancing tissue-engineering applications that require specific nanofibrous matrices.
Cervical cancer (CC) is the fourth most common malignant tumor in women worldwide. Detecting different biomarkers together on single cells by novel method mass cytometry could contribute to more precise screening. Liquid-based cytology (LBC) cervical samples were collected (N = 53) from women categorized as normal and precancerous lesions. Human papillomavirus was genotyped by polymerase chain reaction, while simultaneous examination of the expression of 29 proteins was done by mass cytometry (CyTOF). Differences in cluster abundances were assessed with Spearman's rank correlation as well as high dimensional data analysis (t-SNE, FlowSOM). Cytokeratin (ITGA6, Ck5, Ck10/13, Ck14, Ck7) expression patterns allowed determining the presence of different cells in the cervical epithelium. FlowSOM analysis enabled to phenotype cervical cells in five different metaclusters and find new markers that could be important in CC screening. The markers Ck18, Ck18, and CD63 (Metacluster 3) showed significantly increasing associated with severity of the precancerous lesions (Spearman rank correlation rho 0.304, p = 0.0271), while CD71, KLF4, LRIG1, E-cadherin, Nanog and p53 (Metacluster 1) decreased with severity of the precancerous lesions (Spearman rank correlation rho -0.401, p = 0.0029). Other metaclusters did not show significant correlation, but metacluster 2 (Ck17, MCM, MMP7, CD29, E-cadherin, Nanog, p53) showed higher abundance in low- and high-grade intraepithelial lesion cases. CyTOF appears feasible and should be considered when examining novel biomarkers on cervical LBC samples. This study enabled us to characterize different cells in the cervical epithelium and find markers and populations that could distinguish precancerous lesions.
- MeSH
- cervix uteri patologie metabolismus MeSH
- dospělí MeSH
- dysplazie děložního hrdla diagnóza patologie MeSH
- infekce papilomavirem patologie diagnóza virologie MeSH
- Krüppel-like faktor 4 * MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádorové biomarkery * genetika metabolismus MeSH
- nádory děložního čípku * diagnóza patologie genetika MeSH
- prekancerózy * patologie diagnóza MeSH
- průtoková cytometrie * metody MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
OBJECTIVE: This study aimed to demonstrate the clinical equivalence of biosimilar QL1205 and reference ranibizumab, Lucentis, in patients with neovascular age-related macular degeneration (nAMD). DESIGN: This was a multicenter, double-masked, randomized, controlled phase III trial. PARTICIPANTS: Treatment-naive patients with active nAMD were randomly assigned to receive QL1205 or reference ranibizumab. METHODS: Patients received intravitreal injection of QL1205 or reference ranibizumab at a dose of 0.5 mg in the study eye once every 4 weeks for 48 weeks. MAIN OUTCOME MEASURES: The primary end point was change in best-corrected visual acuity (BCVA) by ETDRS letters at week 8 compared with baseline level. Biosimilarity of QL1205 to reference ranibizumab was assessed with an equivalence range for the difference in BCVA letters between -3.49 and +3.49. RESULTS: Between June 27, 2019 and June 8, 2021, 616 patients were randomized to the QL1205 group (n = 308) and the reference ranibizumab group (n = 308). The mean improvement of BCVA was +6.3 ± 9.13 ETDRS letters in the QL1205 group and +7.3 ± 8.82 ETDRS letters in the reference ranibizumab group at week 8. Both the 90% confidence interval (CI, -2.23 to 0.13) and 95% CI (-2.46 to 0.36) of the difference between the 2 treatment groups (P = 0.1434) were within the predefined equivalence range. Safety profiles were manageable in both groups. CONCLUSIONS: QL1205 was biosimilar to reference ranibizumab regarding clinical efficacy, ocular and systemic safety, as well as immunogenicity and pharmacokinetics profiles in the treatment of patients with nAMD. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
- MeSH
- biosimilární léčivé přípravky * aplikace a dávkování škodlivé účinky MeSH
- dvojitá slepá metoda MeSH
- inhibitory angiogeneze aplikace a dávkování škodlivé účinky MeSH
- injekce intravitreální MeSH
- lidé středního věku MeSH
- lidé MeSH
- následné studie MeSH
- optická koherentní tomografie MeSH
- ranibizumab * aplikace a dávkování škodlivé účinky MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- vaskulární endoteliální růstový faktor A antagonisté a inhibitory MeSH
- vlhká makulární degenerace * farmakoterapie diagnóza MeSH
- výsledek terapie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zraková ostrost * 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
- klinické zkoušky, fáze III MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
Nebivolol spadá do skupiny selektivních β-blokátorů s nejvyšší selektivitou k receptorům β1 mezi běžně užívanými betablokátory. Je indikovaný k léčbě chronického srdečního selhání a arteriální hypertenze, zejména u pacientů s komorbiditami, jakými jsou ischemická choroba srdeční či tachyarytmie. Indukcí produkce oxidu dusnatého v arteriální stěně zprostředkuje endotel-dependentní vazodilataci, nezávisle na β-adrenergní stimulaci. Kazuistika demonstruje jeho využití u pacienta s arteriální hypertenzí a známkami endoteliální dysfunkce.
Nebivolol is classified as a β-selective blocker, known for having the highest β-selectivity among commonly used beta-blockers. It is indicated for the treatment of chronic heart failure and arterial hypertension, especially in patients with comorbidities such as coronary artery disease or tachyarrhythmias. By promoting the production of nitric oxide in the arterial wall, it facilitates endothelium-dependent vasodilation, independent of β-adrenergic stimulation. A case report illustrates its application in a patient with arterial hypertension and evidence of endothelial dysfunction.
Cíl: Porovnat četnost výskytu pooperačních komplikací po operaci katarakty u současných typů akrylátových nitroočních čoček (NOČ) v souvislosti s materiálem, který je použit k výrobě implantátu, publikovanou v odborné literatuře. Metodika: Vyhledání publikací v databázi Pubmed, zveřejněných v letech 2015–2024 (včetně), bez jazykového omezení, s klíčovými slovy Hydrophobic, Hydrophilic, Intraocular lens. Projití všech abstrakt a vyloučení publikací, která neodpovídají zadanému tématu. Výsledky: Celkem bylo v období posledních 10 let publikováno 220 prací splňující zadaná klíčová slova. Z toho 92 publikací se věnovalo porovnání obou typů nitroočních čoček. Jednalo se o 4 metaanalýzy, 10 review a 47 klinických studií, 21 laboratorních a experimentální prací a 10 prací jiného charakteru (editorialy, úvahy, kapitoly v učebnicích). Závěr: Současné typy měkkých akrylátových nitroočních čoček dosahují vynikajících refrakčních výsledků i vysoké subjektivní spokojenosti pacientů. To se týká čoček vyrobených jak z hydrofilního, tak hydrofobního materiálu. Hlavní nevýhodou hydrofilních implantátů je vyšší riziko opacifikace zadního pouzdra čočky, a také riziko kalení samotného implantátu. Především u pacientů, kde je předpoklad následné operace (dystrofie endotelu rohovky, sítnicové patologie), a také u pacientů s vyšším rizikem komplikací po Nd:YAG laserové kapsulotomii (myopové, pacienti s chronickými uveitidami, pacienti s glaukomem) by mělo být zvažováno přednostně použití hydrofobního materiálu.
Objective: To compare the incidence of postoperative complications after cataract surgery in current types of acrylic intraocular lenses (IOLs) in relation to the material used to manufacture the implant, published in the scientific literature. Methodology: Search for publications in the Pubmed database, published in 2015–2024 (inclusive), without language restrictions, featuring the keywords Hydrophobic, Hydrophilic, Intraocular lens. Reviewing all abstracts and excluding publications that do not match the specified topic. Results: A total of 220 works were published in the last 10 years that met the specified keywords. Of these, 92 publications were dedicated to the comparison of both types of IOLs. These were 4 meta-analyses, 10 reviews and 47 clinical studies, 21 laboratory and experimental studies and 10 studies of a different nature (editorials, considerations, chapters in textbooks). Conclusion: Current types of soft acrylic intraocular lenses achieve excellent refractive results and high subjective patient satisfaction. This applies to lenses made of both hydrophilic and hydrophobic materials. The main disadvantage of hydrophilic implants is the higher risk of opacification of the posterior capsule of the lens, as well as the risk of opacification of the implant itself. Especially in patients who are expected to undergo subsequent surgery (corneal endothelial dystrophy, retinal pathology), as well as in patients with a higher risk of complications after Nd:YAG laser capsulotomy (patients with myopia, chronic uveitis or glaucoma), the use of hydrophobic material should be considered as a priority.
Doporučená léčba první a druhé linie metastazujícího kolorektálního karcinomu (metastatic coiorectai cancer, mCRC) zahrnuje chemoterapii na bázi fluorouracilu, oxaliplatiny, irinotekanu; terapii založenou na antiangiogenní léčbě bevacizumabem s účinkem na vaskulární endoteliální růstový faktor (vascular endothelial growth factor, VEGF) a terapii cílenou na receptor epidermálního růstového faktoru (epidermal growth factor receptor, EGFR) podle mutační stavu RAS a BRAF. Studie SUNLIGHT prokázala ve třetí linii léčby mCRC, že podání trifluridin/tipiracilu v kombinaci s bevacizumabem má významný přínos pro přežití a je nyní doporučeným režimem třetí linie u pacientů s refrakterním mCRC, bez ohledu na mutační stav RAS a předchozí léčbu anti-VEGF. Zvláště u mladších pacientů dlouhodobě v dobrém celkovém stavu je vhodné indikovat třetí nebo i vyšší linii léčby, možnosti systémové léčby jsou však velmi omezené.
The recommended firstand second-line treatment of metastatic coiorectai cancer (mCRC) includes fluorouracii, oxaiipiatin, and irinotecan-based chemotherapy; antiangiogenic therapy based on bevacizumab with an effect on vascular endothelial growth factor (VEGF) receptor and therapy targeting epidermal growth factor receptor (EGFR) according to RAS and BRAF mutational status. The SUNLIGHT study demonstrated in third-iine mCRC that administration of trifluridine/tipiracii in combination with bevacizumab has a significant survival benefit and is now the recommended third-iine regimen for patients with refractory mCRC, regardless of RAS mutational status and prior anti-VEGF therapy. Particularly in younger patients in long-term good general condition, third-line or even higher-line therapy is indicated, but systemic treatment options are very limited.