OBJECTIVE: Epilepsy surgery in the operculoinsular cortex is challenging due to the difficult delineation of the epileptogenic zone and the high risk of postoperative deficits. METHODS: Pre- and postsurgical data from 30 pediatric patients who underwent operculoinsular cortex surgery at the Motol Epilepsy Center Prague from 2010 to 2022 were analyzed. RESULTS: Focal cortical dysplasia (FCD; n = 15, 50%) was the predominant cause of epilepsy, followed by epilepsy-associated tumors (n = 5, 17%) and tuberous sclerosis complex (n = 2, 7%). In eight patients where FCD was the most likely etiology, the histology was negative. Seven patients (23%) displayed normal magnetic resonance imaging results. Seizures exhibited diverse semiology and propagation patterns (frontal, perisylvian, and temporal). The ictal and interictal electroencephalographic (EEG) findings were mostly extensive. Multimodal imaging and advanced postprocessing were frequently used. Stereo-EEG was used for localizing the epileptogenic zone and eloquent cortex in 23 patients (77%). Oblique electrodes were used as guides for better neurosurgeon orientation. The epileptogenic zone was in the dominant hemisphere in 16 patients. At the 2-year follow-up, 22 patients (73%) were completely seizure-free, and eight (27%) experienced a seizure frequency reduction of >50% (International League Against Epilepsy class 3 and 4). Fourteen patients (47%) underwent antiseizure medication tapering; treatment was completely withdrawn in two (7%). Nineteen patients (63%) remained seizure-free following the definitive outcome assessment (median = 6 years 5 months, range = 2 years to 13 years 5 months postsurgery). Six patients (20%) experienced corona radiata or basal ganglia ischemia; four (13%) improved to mild and one (3%) to moderate hemiparesis. Two patients (7%) operated on in the anterior insula along with frontotemporal resection experienced major complications: pontine ischemia and postoperative brain edema. SIGNIFICANCE: Epilepsy surgery in the operculoinsular cortex can lead to excellent patient outcomes. A comprehensive diagnostic approach is crucial for surgical success. Rehabilitation brings a great chance for significant recovery of postoperative deficits.

• MeSH
• dítě MeSH
• elektroencefalografie * MeSH
• epilepsie chirurgie   diagnostické zobrazování   MeSH
• kohortové studie MeSH
• kojenec MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• malformace mozkové kůry chirurgie   komplikace   diagnostické zobrazování   MeSH
• mladiství MeSH
• mozková kůra diagnostické zobrazování   chirurgie   MeSH
• neurochirurgické výkony metody   MeSH
• předškolní dítě MeSH
• retrospektivní studie MeSH
• výsledek terapie MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

INTRODUCTION: Currently, limited data are available on long-term use of dupilumab to treat atopic dermatitis (AD) in a multinational real-world setting. The aim of this analysis was to report the interim 1-year data for patients with AD enrolled in the GLOBOSTAD registry, including treatment patterns, dupilumab effectiveness and safety, and healthcare burden. METHODS: GLOBOSTAD is an ongoing, 5-year, multinational, prospective, observational study of adult/adolescent (aged ≥ 12 years at baseline) patients with AD who initiated dupilumab in real-world settings according to their local country-specific prescribing guidelines. Outcomes were evaluated at baseline and at 3, 6 and 12 months and included Eczema Area and Severity Index (EASI) total score, SCORing Atopic Dermatitis (SCORAD) total score, percent body surface area (BSA) affected, Patient-Oriented Eczema Measure (POEM), Dermatology Life Quality Index (DLQI) total score for adults or Children's Dermatology Life Quality Index (CDLQI) total score for adolescents and pruritus Numeric Rating Scale (NRS) total score. RESULTS: At the interim 1-year cut-off (March 2023), 955 patients were enrolled in GLOBOSTAD, and follow-up data were obtained from 903 patients. After dupilumab initiation, mean improvements in effectiveness outcome measures from baseline to month 3 were EASI from 25.1 to 6.1, SCORAD 59.3 to 25.3, POEM 19.7 to 8.7, DLQI 13.7 to 5.3, CDLQI 12.2 to 2.7 and pruritus NRS 6.3 to 2.5, with each measure exceeding the minimal clinically important difference. These positive changes in effectiveness outcomes were maintained or further improved through 12 months since treatment initiation. AD-related hospitalizations and emergency room or urgent care facility visits decreased from 11.1% to 1.7% from baseline to month 12. CONCLUSIONS: In a multinational real-world setting, dupilumab demonstrated rapid, robust and sustained effectiveness in patients with moderate-to-severe AD across multiple disease domains, including AD signs, symptoms, quality of life and emergency/urgent care visits. Safety was consistent with the known dupilumab safety profile. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT03992417.

• MeSH
• atopická dermatitida * farmakoterapie   MeSH
• dítě MeSH
• dospělí MeSH
• humanizované monoklonální protilátky * terapeutické užití   MeSH
• kvalita života * MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• prospektivní studie MeSH
• registrace MeSH
• stupeň závažnosti nemoci * MeSH
• výsledek terapie MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• pozorovací studie MeSH

PURPOSE: MRI-only adaptive brachytherapy (MRI-ABT) is the state-of-the-art for treating locally advanced cervical cancer (LACC) in combination with concurrent chemoradiotherapy. We aimed to evaluate the pattern of pelvic recurrence after the treatment. MATERIAL AND METHODS: A total of one hundred LACC patients were treated between January 2017 and December 2023 with concurrent chemoradiotherapy of 45 Gy in 25 fractions ± boost to lymphadenopathy (up to a maximum dose of 60 Gy in 25 fractions) with concurrent weekly cisplatin chemotherapy at the dose of 40 mg/m2/week, and MR-ABT. RESULTS: At a median follow-up of 30.2 months, there were 2 local recurrences (2%) and 9 regional pelvic recurrences (9%). The median time to local/regional recurrence was 11 months (range 6-21). For all stages, the 3-year local control was 97.66%, and the 3-year pelvic control was 89.45%. Twenty-four patients died during follow-up; the 3-year overall survival was 75.11%, and the 3-year disease-free survival was 70.97%. CONCLUSION: MRI-ABT combined with external beam radiotherapy and concurrent chemotherapy for LACC demonstrates excellent local and regional pelvic control. Most local/regional recurrences occur inside or at the edge of the external-beam irradiated field. Recurrences inside the field of brachytherapy are rare. Distant recurrences are the predominant cause of death in LACC patients treated with definitive CRT and MRI-ABT.

• MeSH
• brachyterapie * metody   MeSH
• chemoradioterapie * MeSH
• cisplatina terapeutické užití   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• lokální recidiva nádoru * radioterapie   MeSH
• magnetická rezonanční tomografie * MeSH
• nádory děložního čípku * radioterapie   diagnostické zobrazování   patologie   MeSH
• retrospektivní studie MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: The knowledge and proficiency of primary care practitioners (PCPs) in diagnosing and managing irritable bowel syndrome (IBS) remain generally low and variable internationally. This variability is partly due to a lack of familiarity with the Rome Foundation diagnostic criteria and treatment guidelines for this condition. METHODS: We conducted an electronic survey of PCPs in the United States and nine European countries to assess their understanding of IBS pathophysiology; the use of Rome IV criteria in diagnosis, knowledge of and frequency in prescribing various recommended treatments; and the likelihood of referring patients with suspected IBS to subspecialists. RESULTS: Most PCPs in the United States and Europe perceive IBS as a diagnosis of exclusion rather than a definitive diagnosis. They also believe IBS is underdiagnosed in primary care and challenging to diagnose confidently. The majority of PCPs consider diet as a crucial component of IBS management. Notably, US PCPs reported greater confidence than their European counterparts in recommending dietary interventions such as increased dietary fiber, a low FODMAP diet, and gluten restriction. Conversely, both groups exhibited moderate to high confidence in recommending over-the-counter treatments. European PCPs showed greater confidence in treating IBS with antispasmodics and secretagogues, while US PCPs expressed greater confidence in prescribing neuromodulators. Additionally, US PCPs were more likely to refer patients with suspected IBS to a gastroenterologist, whereas both US and European PCPs showed similar referral patterns to dietitians and referred very few patients to mental health providers. Both US and European PCPs reported that IBS is moderately to extremely difficult to treat effectively and emphasized the importance of a strong and longitudinal doctor-patient relationship in managing the condition. CONCLUSION: Despite the Rome Foundation recommendations and criteria to support a positive diagnosis of IBS, most PCPs still rely on exclusionary investigations such as endoscopy and a serologic workup, while a significant percentage suggest referring patients to gastroenterologists.

• MeSH
• lékaři primární péče MeSH
• lékařská praxe - způsoby provádění * statistika a číselné údaje   MeSH
• lidé MeSH
• postoj zdravotnického personálu MeSH
• primární zdravotní péče MeSH
• průzkumy a dotazníky MeSH
• syndrom dráždivého tračníku * diagnóza   terapie   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Evropa MeSH
• Spojené státy americké MeSH

During development, tooth germs undergo various morphological changes resulting from interactions between the oral epithelium and ectomesenchyme. These processes are influenced by the extracellular matrix, the composition of which, along with cell adhesion and signaling, is regulated by metalloproteinases. Notably, these include matrix metalloproteinases (MMPs), a disintegrin and metalloproteinases (ADAMs), and a disintegrin and metalloproteinases with thrombospondin motifs (ADAMTSs). Our analysis of previously published scRNAseq datasets highlight that these metalloproteinases show dynamic expression patterns during tooth development, with expression in a wide range of cell types, suggesting multiple roles in tooth morphogenesis. To investigate this, Marimastat, a broad-spectrum inhibitor of MMPs, ADAMs, and ADAMTSs, was applied to ex vivo cultures of mouse molar tooth germs. The treated samples exhibited significant changes in tooth germ size and morphology, including an overall reduction in size and an inversion of the typical bell shape. The cervical loop failed to extend, and the central area of the inner enamel epithelium protruded. Marimastat treatment also disrupted proliferation, cell polarization, and organization compared with control tooth germs. In addition, a decrease in laminin expression was observed, leading to a disruption in continuity of the basement membrane at the epithelial-mesenchymal junction. Elevated hypoxia-inducible factor 1-alpha gene (Hif-1α) expression correlated with a disruption to blood vessel development around the tooth germs. These results reveal the crucial role of metalloproteinases in tooth growth, shape, cervical loop elongation, and the regulation of blood vessel formation during prenatal tooth development.NEW & NOTEWORTHY Inhibition of metalloproteinases during tooth development had a wide-ranging impact on molar growth affecting proliferation, cell migration, and vascularization, highlighting the diverse role of these proteins in controlling development.

• MeSH
• faktor 1 indukovatelný hypoxií - podjednotka alfa metabolismus   genetika   MeSH
• inhibitory matrixových metaloproteinas farmakologie   MeSH
• kyseliny hydroxamové farmakologie   MeSH
• metaloproteasy metabolismus   genetika   MeSH
• moláry embryologie   růst a vývoj   metabolismus   enzymologie   MeSH
• morfogeneze MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• odontogeneze * MeSH
• proliferace buněk * MeSH
• vývojová regulace genové exprese MeSH
• zubní zárodek embryologie   metabolismus   enzymologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

PURPOSE OF REVIEW: A critical evaluation of contemporary literature regarding the role of big data, artificial intelligence, and digital technologies in precision cardio-oncology care and survivorship, emphasizing innovative and groundbreaking endeavors. RECENT FINDINGS: Artificial intelligence (AI) algorithm models can automate the risk assessment process and augment current subjective clinical decision tools. AI, particularly machine learning (ML), can identify medically significant patterns in large data sets. Machine learning in cardio-oncology care has great potential in screening, diagnosis, monitoring, and managing cancer therapy-related cardiovascular complications. To this end, large-scale imaging data and clinical information are being leveraged in training efficient AI algorithms that may lead to effective clinical tools for caring for this vulnerable population. Telemedicine may benefit cardio-oncology patients by enhancing healthcare delivery through lowering costs, improving quality, and personalizing care. Similarly, the utilization of wearable biosensors and mobile health technology for remote monitoring holds the potential to improve cardio-oncology outcomes through early intervention and deeper clinical insight. Investigations are ongoing regarding the application of digital health tools such as telemedicine and remote monitoring devices in enhancing the functional status and recovery of cancer patients, particularly those with limited access to centralized services, by increasing physical activity levels and providing access to rehabilitation services. SUMMARY: In recent years, advances in cancer survival have increased the prevalence of patients experiencing cancer therapy-related cardiovascular complications. Traditional cardio-oncology risk categorization largely relies on basic clinical features and physician assessment, necessitating advancements in machine learning to create objective prediction models using diverse data sources. Healthcare disparities may be perpetuated through AI algorithms in digital health technologies. In turn, this may have a detrimental effect on minority populations by limiting resource allocation. Several AI-powered innovative health tools could be leveraged to bridge the digital divide and improve access to equitable care.

• Publikační typ
• časopisecké články MeSH

BACKGROUND: The medication used to treat benign prostate hyperplasia (BPH), a common condition in men over 50 years of age, can alter the levels of biomarkers used in prostate cancer detection. Commonly used medications for BPH include alpha-blockers, 5-alpha reductase inhibitors (5-ARIs), and muscarinic antagonists. We studied the impact of these drugs on total prostate-specific antigen (tPSA), free PSA (fPSA), [-2]proPSA, fPSA/tPSA ratio, and the Prostate Health Index (PHI), as well as novel potential biomarkers in the form of glycan composition of fPSA. PATIENTS AND METHODS: Serum samples were collected from 564 males with BPH, with a mean age of 68.5 years. The samples were used to measure levels of tPSA, fPSA, and [-2]proPSA. The fPSA/tPSA and PHI were then calculated. The glycan composition of fPSA was analyzed using lectin-based glycoprofiling. Pharmacotherapy data was collected from the patients' medical records. RESULTS: Alpha-blocker monotherapy was associated with higher fPSA and fPSA/tPSA ratio, and decreased PHI. Levels of tPSA were not impacted. Alpha-blocker and 5-ARI dual therapy was associated with reduced levels of fPSA, [-2]proPSA, and PHI. Therapy combining alpha-blockers and antimuscarinic agents did not significantly influence biomarker levels apart from an increase in a Maackia amurensis lectin-recognized glycan originating in fPSA. CONCLUSION: BPH pharmacotherapy notably affects prostate cancer biomarkers. Recognizing the impact of pharmacotherapy is crucial for achieving an accurate diagnosis of prostate cancer and for planning treatment.

• MeSH
• alfa blokátory terapeutické užití   MeSH
• antagonisté muskarinových receptorů * terapeutické užití   MeSH
• glykosylace MeSH
• hyperplazie prostaty * krev   farmakoterapie   MeSH
• inhibitory 5-alfa-reduktasy terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory prostaty krev   farmakoterapie   MeSH
• prostata patologie   metabolismus   MeSH
• prostatický specifický antigen * krev   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH

The forskolin-induced swelling assay (FIS) in patient-derived intestinal organoids (PDIOs), used to determine in vitro responsiveness to elexacaftor/tezacaftor/ivacaftor (ETI), showed variability in swelling among PDIOs obtained from people with CF (pwCF) carrying the same F508del/F508del CFTR genotype. We aimed to characterise the effect of ETI on the transcriptional activity of PDIOs-derived cells to understand the intracellular processes triggered by ETI and the differences in treatment response. Six high- and six low-responding PDIOs to ETI, derived from F508del/F508del pwCF, were incubated with or without ETI for 2 to 6 h. Gene expression was assessed using 3'-mRNA sequencing and modelled using negative binomial models. Incubation with ETI resulted in a significant upregulation of several biological processes: mostly related to chemokines and signalling, chemotaxis, and tissue development processes. No changes were observed in abundance of the CFTR transcripts or in CFTR-related gene sets and pathways. The genes and pathways associated with ETI did not overlap with those whose expression changed with time only. PDIOs with a high FIS response did not significantly differ in any interpretable gene from the FIS-low organoids. The changes in the PDIOs gene expression upon the exposure to ETI cannot explain differences in the magnitude of PDIOs FIS-measured response to ETI. In conclusion, on incubation with ETI, genes of the CFTR-related pathways do not change their transcriptional activity; instead, overexpression was observed in genes of inflammatory-like cytokine response and receptor activation pathways.

• MeSH
• aktivátory chloridových kanálů terapeutické užití   farmakologie   MeSH
• aminofenoly * terapeutické užití   farmakologie   MeSH
• benzodioxoly * terapeutické užití   farmakologie   MeSH
• chinolony * farmakologie   terapeutické užití   MeSH
• cystická fibróza * genetika   farmakoterapie   MeSH
• fixní kombinace léků MeSH
• indoly * farmakologie   MeSH
• lidé MeSH
• organoidy * metabolismus   MeSH
• protein CFTR genetika   MeSH
• pyrazoly * farmakologie   MeSH
• pyridiny farmakologie   MeSH
• pyrrolidiny farmakologie   MeSH
• pyrroly farmakologie   MeSH
• stanovení celkové genové exprese metody   MeSH
• střeva účinky léků   MeSH
• transkriptom MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Clear-cell renal cell carcinoma (ccRCC) is a common urological malignancy with an increasing incidence. The development of molecular biomarkers that can predict the response to treatment and guide personalized therapy selection would substantially improve patient outcomes. Dysregulation of non-coding RNA (ncRNA) has been shown to have a role in the pathogenesis of ccRCC. Thus, an increasing number of studies are being carried out with a focus on the identification of ncRNA biomarkers in ccRCC tissue samples and the connection of these markers with patients' prognosis, pathological stage and grade (including metastatic potential), and therapy outcome. RNA sequencing analysis led to the identification of several ncRNA biomarkers that are dysregulated in ccRCC and might have a role in ccRCC development. These ncRNAs have the potential to be prognostic and predictive biomarkers for ccRCC, with prospective applications in personalized treatment selection. Research on ncRNA biomarkers in ccRCC is advancing, but clinical implementation remains preliminary owing to challenges in validation, standardization and reproducibility. Comprehensive studies and integration of ncRNAs into clinical trials are essential to accelerate the clinical use of these biomarkers.

• MeSH
• karcinom z renálních buněk * genetika   diagnóza   MeSH
• lidé MeSH
• nádorové biomarkery * genetika   MeSH
• nádory ledvin * genetika   diagnóza   MeSH
• nekódující RNA * genetika   MeSH
• prognóza MeSH
• regulace genové exprese u nádorů MeSH
• stanovení celkové genové exprese MeSH
• transkriptom * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

BACKGROUND: Treatment of simple goiter (SG) growing over time with thyroid hormone (TH) therapy is discouraged by international guidelines. PURPOSE: To ascertain views of European thyroid specialists about TH treatment for euthyroid patients with growing SG and explore associations with management choice. METHODS: Online survey on the use of TH for growing SG among thyroid experts from 28 European countries. RESULTS: The response rate was 31.5% (5430/17,247). Most respondents were endocrinologists. Twenty-eight percent asserted that TH therapy may be indicated in euthyroid patients with a growing SG. National and regional differences were noted, from 7% of positive responses in The Netherlands to 78% in Czech Republic (p < 0.0001). TH was more frequently prescribed by respondents over 40 years old (OR 1.77, 2.13, 2.41 if 41-50, 51-60, >60, respectively), and working in areas of former iodine insufficiency (OR 1.24, 95% CI 1.03-1.50). TH was less frequently prescribed by endocrinologists (OR 0.77, 95% CI 0.62-0.94) and respondents working in Southern Europe (OR 0.40, 95% CI 0.33-0.48), Northern Europe (OR 0.28, 95% CI 0.22-0.36) and Western Asia (OR 0.16, 95% CI 0.11-0.24) compared to Western Europe. Associations with respondents' sex, country, availability of national thyroid guidelines, and gross national income per capita were absent or weak. CONCLUSIONS: Almost a third of European thyroid specialists support treating SG with TH, contrary to current guidelines and recommendations. This calls for urgent attention.

• MeSH
• dospělí MeSH
• endokrinologové statistika a číselné údaje   MeSH
• hormony štítné žlázy * terapeutické užití   MeSH
• lékařská praxe - způsoby provádění statistika a číselné údaje   MeSH
• lidé středního věku MeSH
• lidé MeSH
• průzkumy a dotazníky MeSH
• struma * epidemiologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Evropa MeSH