OBJECTIVES: Despite increasing interest, prospective data on the use of degradable starch microsphere-transarterial chemoembolization (DSM-TACE) in the management of patients with unresectable HCC are still scarce. The objective of the HepaStar study was to collect prospective safety and effectiveness data in a prospective multicenter observational study. MATERIALS AND METHODS: Between January 2017 and December 2022, consecutive participants with unresectable or recurrent HCC treated with DSM-TACE as standard of care at 6 participating centers in Europe were enrolled. Tumor response was evaluated according to the mRECIST criteria. Overall survival (OS), progression-free survival (PFS), and adverse events (AEs) were assessed by using Kaplan-Meier analysis and Common Terminology Criteria for Adverse Events, version 5. Liver function deterioration was assessed by monitoring changes in liver blood tests during the follow-up. RESULTS: Seventy-nine participants (median age, 69 years (IQR, 51-87 years); 67 men (85%)) were enrolled and treated. The median follow-up time was 18 months (IQR 9.5-38.0 months). The estimated median OS and PFS for the entire cohort was 32 months (CI, 95% 21-NaN) and 9 months (CI, 95% 7-NaN), respectively. Eleven (13.9%) participants experienced at least one grade 3 or 4 AE. The most frequent grade 3-4 AE was elevated bilirubin (2.2%, 5 of 79). Deterioration of bilirubin, AST, ALT, and albumin were observed in 24.1%, 23.7%, 19%, and 24% of participants, respectively. CONCLUSION: DSM-TACE achieves promising survival in patients with unresectable or recurrent HCC. This technique shows a favorable safety profile both in terms of treatment-related AEs and liver function deterioration. KEY POINTS: Question Although degradable starch microspheres transarterial chemoembolization is widely used in clinical practice across Europe, prospective data on its application in hepatocellular carcinoma patients remains limited. Findings Degradable starch microspheres transarterial chemoembolization results in promising survival rates, good tumor response rates, and low rates of treatment-related adverse events. Clinical relevance In patients with unresectable hepatocellular carcinoma, degradable starch microspheres transarterial chemoembolization represents a safe and effective alternative to more well-established chemoembolization techniques like conventional transarterial chemoembolization and drug-eluting beads transarterial chemoembolization.

• MeSH
• chemoembolizace * metody   MeSH
• hepatocelulární karcinom * terapie   mortalita   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mikrosféry MeSH
• nádory jater * terapie   mortalita   MeSH
• prospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• škrob * aplikace a dávkování   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
• multicentrická studie MeSH
• pozorovací studie MeSH

Penile squamous cell carcinoma (pSCC) represents an uncommon malignancy characterized by stagnant mortality, psychosexual distress, and a highly variable prognosis. Currently, the World Health Organization distinguishes between human papillomavirus (HPV)-related and HPV-independent pSCC. Recently, there has been an evolving line of research documenting the enrichment of HPV-independent pSCC with a high tumor mutational burden (TMB) and programmed death ligand-1 expression, as well as clusters of genes associated with HPV status. In this study, we conducted comprehensive next-generation sequencing DNA profiling of 146 pSCC samples using a panel consisting of 355 genes associated with tumors. This profiling was correlated with immunohistochemical markers and prognostic clinical data. A survival analysis of recurrent genomic events (found in ≥10 cases) was performed. TP53, CDKN2A, ATM, EPHA7, POT1, CHEK1, GRIN2A, and EGFR alterations were associated with significantly shortened overall survival in univariate and multivariate analysis. HPV positivity, diagnosed through both p16 immunohistochemistry and HPV DNA analysis, displayed no impact on survival but was associated with high-grade, lymphatic invasion, programmed death ligand-1 negativity/weak expression, and low TMB. FAT1, TP53, CDKN2A, CASP8, and HRAS were more often mutated in HPV-independent pSCC. In contrast, HPV-associated pSCCs were enriched by EPHA7, ATM, GRIN2A, and CHEK1 mutations. PIK3CA, FAT1, FBXW7, and KMT2D mutations were associated with high TMB. NOTCH1, TP53, CDKN2A, POT1, KMT2D, ATM, CHEK1, EPHA3, and EGFR alterations were related to adverse clinicopathologic signs, such as advanced stage, high tumor budding, and lymphovascular invasion. We detected 160 alterations with potential treatment implications, with 21.2% of samples showing alterations in the homologous recombination repair pathway. To the best of our knowledge, this study describes the largest cohort of pSCC with complex molecular pathologic, clinical, and prognostic analysis correlating with prognosis.

• MeSH
• ATM protein genetika   MeSH
• dospělí MeSH
• erbB receptory genetika   MeSH
• infekce papilomavirem MeSH
• inhibitor p16 cyklin-dependentní kinasy genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mutace MeSH
• nádorové biomarkery * genetika   analýza   MeSH
• nádorový supresorový protein p53 genetika   MeSH
• nádory penisu * genetika   mortalita   patologie   virologie   MeSH
• prognóza MeSH
• proteiny vázající telomery MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• shelterinový komplex MeSH
• spinocelulární karcinom * genetika   mortalita   patologie   virologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH

AIM: This study aimed to identify sleep profiles in a representative sample of Slovak adolescents and investigate their associations with adiposity indicators and cardiorespiratory fitness. METHODS: Data from the 2022 Health Behaviour in School-aged Children (HBSC) study conducted in Slovakia were analysed. Survey questions on sleep duration and problems from the entire HBSC sample (n = 8906) were used to identify sleep profiles. Associations with adiposity indicators and cardiorespiratory fitness were investigated in a subsample of 924 adolescents (average age 13.3 ± 1.48; 56.2% boys) who completed the HBSC survey, bioimpedance analysis, and 20-metre shuttle run test. RESULTS: Three sleep profiles were identified-optimal sleepers, optimal sleepers with sporadic sleep problems and poor sleepers. Crude models showed that poor sleepers had significantly higher body fat percentage and fat mass index, along with lower cardiorespiratory fitness, compared to optimal sleepers. After adjustment, only the association between sleep profiles and cardiorespiratory fitness remained significant. CONCLUSION: The observed associations between sleep profiles and cardiorespiratory fitness may help better target future intervention resources towards adolescents with low cardiorespiratory fitness levels.

• MeSH
• adipozita * MeSH
• dítě MeSH
• kardiorespirační zdatnost * fyziologie   MeSH
• lidé MeSH
• mladiství MeSH
• průřezové studie MeSH
• spánek * fyziologie   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Slovenská republika MeSH

The aim of the present study was to assess systemic circulatory and tissue activities of both the classical arm and of the alternative arm of the renin-angiotensin system (RAS) in a new transgenic rat line (TG7371) that expresses angiotensin-(1-7) (ANG 1-7)-producing fusion protein; the results were compared with the activities measured in control transgene-negative Hannover Sprague-Dawley (HanSD) rats. Plasma and tissue concentrations of angiotensin II (ANG II) and ANG 1-7, and kidney mRNA expressions of receptors responsible for biological actions of ANG II and ANG 1-7 [i.e. ANG II type 1 and type 2 (AT1 and AT2) and Mas receptors] were assessed in TG7371 transgene-positive and in HanSD rats. We found that male TG7371 transgene-positive rats exhibited significantly elevated plasma, kidney, heart and lung ANG 1-7 concentrations as compared with control male HanSD rats; by contrast, there was no significant difference in ANG II concentrations and no significant differences in mRNA expression of AT1, AT2 and Mas receptors. In addition, we found that in male TG7371 transgene-positive rats blood pressure was lower than in male HanSD rats. These data indicate that the balance between the classical arm and the alternative arm of the RAS was in male TGR7371 transgene-positive rats markedly shifted in favor of the latter. In conclusion, TG7371 transgene-positive rats represent a new powerful tool to study the long-term role of the alternative arm of the RAS in the pathophysiology and potentially in the treatment of cardio-renal diseases.

• MeSH
• angiotensin I * metabolismus   MeSH
• angiotensin II * MeSH
• kardiovaskulární nemoci metabolismus   genetika   MeSH
• krevní tlak fyziologie   MeSH
• krysa rodu rattus MeSH
• ledviny metabolismus   MeSH
• nemoci ledvin metabolismus   genetika   MeSH
• peptidové fragmenty * metabolismus   MeSH
• potkani Sprague-Dawley * MeSH
• potkani transgenní * MeSH
• protoonkogen Mas MeSH
• receptor angiotensinu typ 1 genetika   metabolismus   MeSH
• receptory spřažené s G-proteiny genetika   metabolismus   MeSH
• rekombinantní fúzní proteiny metabolismus   MeSH
• renin-angiotensin systém * fyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

PURPOSE: While anal cancer is a very rare oncological diagnosis representing less than 2% of lower gastrointestinal tract cancers, the incidence has doubled in the past 20 years. Radical radiochemotherapy with sequential or simultaneous boost is now the standard treatment modality. Interstitial HDR brachytherapy is one of the boost application options. Implementation of new radiotherapy techniques has resulted in improved therapeutic outcomes; however, it is still associated with acute and especially late toxicity. Gastrointestinal disorders and sexual dysfunction are the most frequent factors affecting the long-term quality of cured patients' lives. METHODS: A total of 96 patients consecutively treated between 2000 and 2022 with external beam radio-/chemotherapy and an interstitial brachytherapy boost for histologically verified nonmetastatic anal squamous cell carcinoma were evaluated. The median follow-up time was 15.4 years (range 13.4-17.3 years). The primary objective of the study was to assess local control (LC) and quality of life (QoL). The Czech versions of internationally validated EORTC questionnaires were used to evaluate life quality-the basic EORTC QOL-C30 v.3 and the specific QOL-ANL 27 questionnaire. RESULTS: Local control was 85.5% at 5 years, 83.4% at 10 years, 83.4% at 15 years, and 83.4% at 20 years, and there was no dependence on clinical stage. The most common forms of acute toxicity were cutaneous and hematological but were gastrointestinal for late toxicities. In the evaluation of quality of life, 80.5% of patients alive at the time participated. In the EORTC quality of life questionnaire C30 v.3, patients rated the functional scale score as 86.2 points (standard deviation [SD] = 12.6) and the symptom score as 15.5 points (SD = 12.5). The global health score achieved 68.4 points (SD = 23.6). The most common symptoms were fatigue with 25.6 points (SD = 20.2) and diarrhea with 19.0 points (SD = 27.8). In the QOL-ANL 27 questionnaire, symptom scales assessing bowel symptoms were scored 27.5 points (SD = 19) in non-stoma patients and 11.9 points (SD = 17.2) in stoma patients. In the single-item symptom scales, the highest scores were rated for frequency of urination with 26.4 points (SD = 30.8), need to be close to a toilet with 22.4 points (SD = 27.3), and self-cleaning more often with 25.3 points (SD = 31.8). In the functional scales assessing sex life and interest, men and women reported scores of 45.2 (SD = 23) and 45.5 points (SD = 19), respectively. CONCLUSION: Boost with interstitial HDR brachytherapy is an established safe method of anal cancer treatment, with excellent results and limited late toxicity. Functioning scales were rated relatively highly in QoL questionnaires, and the overall global health score was comparable to published data. Gastrointestinal difficulties, fatigue, and sexual dysfunction dominated the symptom scales in our cohort.

• MeSH
• brachyterapie * metody   MeSH
• celková dávka radioterapie MeSH
• dospělí MeSH
• kvalita života * psychologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory anu * radioterapie   psychologie   patologie   MeSH
• následné studie MeSH
• průzkumy a dotazníky MeSH
• radiační poranění * psychologie   etiologie   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• spinocelulární karcinom * radioterapie   patologie   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Initiation of newborn screening (NBS) programs in Europe dates back to the 1960s. One of the most recent expansions of NBS programs was the addition of severe combined immunodeficiency (SCID) based on detection of T-cell receptor excision circles (TRECs). In this review, we present an overview of the current situation in Europe. To avoid a biased overview based on only published results, a 37-item survey on TREC-based NBS was sent to representatives of 46 European countries. With a response rate of 83%, we collected data of 38 countries. Seventeen of the 38 European countries that have completed the survey have nationally or regionally implemented TREC-based NBS. The survey results emphasize similarities and differences as well as common practices and challenges in TREC-based NBS. Because TRECs are a general surrogate marker for severe T lymphocytopenia, conditions other than SCID are also identified. Therefore, the initial definition of the target disease as "SCID" might need to be reconsidered and extended to "SCID and severe T lymphocytopenia." Even though complete harmonization of TREC-based NBS programs across Europe will remain challenging, collaboration and close partnerships will help in the move toward universal TREC-based screening for all newborns, resulting in more infants with SCID and severe T lymphocytopenia being detected each year.

• MeSH
• lidé MeSH
• lymfopenie * imunologie   diagnóza   MeSH
• novorozenec MeSH
• novorozenecký screening * MeSH
• receptory antigenů T-buněk * genetika   imunologie   MeSH
• těžká kombinovaná imunodeficience * diagnóza   epidemiologie   imunologie   MeSH
• Check Tag
• lidé MeSH
• novorozenec MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Geografické názvy
• Evropa MeSH

INTRODUCTION: Current trends in the addiction field reflect a significant emphasis on the workforce development and education. There are already some data about university-based addiction studies programs, but not much from Australasia. METHODS: The aim is to provide an overview and describe the academic programs for addiction professionals in Australia and Aotearoa NZ. The research was conducted in 2017 and updated in 2023. Firstly, university websites were searched using pre-defined keywords, followed by a content analysis of the identified programs. The data were analysed and interpreted by using descriptive statistics. RESULTS: We found 21 universities in Australia (13) and Aotearoa NZ (8) where 46 single programs are provided. There are three bachelor programs, nine masters, and the majority of degrees include (post)graduate certificates and diplomas. No doctorate programs are identified. The taught courses provide comprehensive coverage of the addiction field topics. Twelve programs state clearly that there is clinical practice/internship included. Application to most programs requires completion of a relevant degree and in some cases possible clinical experience. DISCUSSION AND CONCLUSIONS: In comparison to educational options in other regions, we observe a trend towards preparing university graduates for the workforce, thereby expanding the range of programs at lower levels. Most programs possibly represent clinically oriented education primarily specialising in addictions, and graduate programs in addictions for professionals with other disciplinary bases. Great emphasis is given to the quality standards of education, and also to relationship between education and labour market. Findings help opening opportunities to collaborate globally.

• MeSH
• lidé MeSH
• návykové chování epidemiologie   MeSH
• poruchy spojené s užíváním psychoaktivních látek * epidemiologie   MeSH
• univerzity MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Geografické názvy
• Austrálie MeSH
• Nový Zéland MeSH

While there is substantial research on what people want in their romantic and sexual partners, much of this work focuses on WEIRD, youthful samples, fails to consider the role of undesirable characteristics (i.e., things people do not want in partners) at all, or in conjunction with desirable characteristics (i.e., things people do want in partners), and may be overly reliant on psychometric approaches to pivotal variables in mating psychology like mate value and sociosexuality. In a nationally representative (online) sample of 2280 people from Czechia (aged between 18 and 50 years old), we examined linear and quadratic age, education, and self-perceived mate value (desirability) effects on the desired levels in mate choice of eight undesirable and seven desirable characteristics in men and women in relation to ostensible metrics of mate value. Self-perceived mate value alone explained little variance (men 1%, women 2%), while all mate value and mating strategy indicators together explained little variance of mate preferences and aversions (men 3%, women 5%). Desirable characteristics were better explained by mate value than undesirable ones. Our results are in line with evolutionary predictions suggesting that women are more demanding. Also, more qualities to offer correlate with more expectations in a partner.

• MeSH
• dospělí MeSH
• interpersonální vztahy MeSH
• lidé středního věku MeSH
• lidé MeSH
• manželství psychologie   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• průzkumy a dotazníky MeSH
• sebepojetí MeSH
• sexuální chování psychologie   MeSH
• sexuální partneři * psychologie   MeSH
• výběrové chování MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

INTRODUCTION: The objective of this study was to assess the impact of the Enhanced Recovery After Surgery (ERAS) programme implementation on treatment costs at a university-type centre, using the DRG scheme. MATERIALS AND METHODS: Retrospective analysis of patients' data in a group of 604 individuals enroled in the study. We evaluated three groups of patients according to the ERAS clinical protocol (CP): (1) CP oncogynaecology, (2) CP simple hysterectomy, (3) CP laparoscopy. The study aimed to evaluate the impact on the length of stay (LOS), savings in bed-days, and the reduction in direct treatment costs. Three parameters-antibiotic consumption, blood derivative consumption and laboratory test costs-were chosen to compare direct treatment costs. The statistical significance of the difference in the observed parameters was tested by a two-sample unpaired t test with unequal variances at the 0.05 significance level. RESULTS: We analysed data from 604 patients. In all three groups, the length of stay (LOS) was significantly reduced. The most significant reduction was observed in the CP oncogynaecology group, where the LOS was reduced from 11.1 days to 6.8 days (2022) and 7.6 days (2023) compared to 2019 (p < 0.05). Furthermore, there was a notable reduction in inpatient bed-days, which resulted in the capacity being made available to admit additional patients. A statistically significant reduction in direct costs was observed in the group of CP hysterectomy (antibiotic use) and in the CP laparoscopy (laboratory test costs). CONCLUSIONS: The implementation of the ERAS principles resulted in a number of significant positive economic impacts-reduction in the LOS and a corresponding increase in bed capacity for new patients. Additionally, direct treatment costs, including those related to antibiotic use or laboratory testing were reduced. The Czech Republic's acute healthcare system, like the majority of European healthcare systems, is financed by the DRG system. This flat-rate payment per patient encourages hospital management to seek cost-reduction strategies. The results of our study indicate that fast-track protocols represent a potential viable approach to reducing the cost of treatment while simultaneously meeting the recommendations of evidence-based medicine.

• MeSH
• délka pobytu statistika a číselné údaje   ekonomika   MeSH
• dospělí MeSH
• gynekologické chirurgické výkony * ekonomika   MeSH
• hysterektomie ekonomika   MeSH
• klasifikační systém DRG MeSH
• laparoskopie ekonomika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• náklady na zdravotní péči * statistika a číselné údaje   MeSH
• retrospektivní studie MeSH
• senioři MeSH
• urychlená pooperační rehabilitace * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Around 180 genes have been associated with congenital anomalies of the kidney and urinary tract (CAKUT) in mice, and represent promising novel candidate genes for human CAKUT. In whole-exome sequencing data of two siblings with genetically unresolved multicystic dysplastic kidneys (MCDK), prioritizing variants in murine CAKUT-associated genes yielded a rare variant in the teashirt zinc finger homeobox 3 (TSHZ3) gene. Therefore, the role of TSHZ3 in human CAKUT was assessed. Twelve CAKUT patients from 9/301 (3%) families carried five different rare heterozygous TSHZ3 missense variants predicted to be deleterious. CAKUT patients with versus without TSHZ3 variants were more likely to present with hydronephrosis, hydroureter, ureteropelvic junction obstruction, MCDK, and with genital anomalies, developmental delay, overlapping with the previously described phenotypes in Tshz3-mutant mice and patients with heterozygous 19q12-q13.11 deletions encompassing the TSHZ3 locus. Comparable with Tshz3-mutant mice, the smooth muscle layer was disorganized in the renal pelvis and thinner in the proximal ureter of the nephrectomy specimen of a TSHZ3 variant carrier compared to controls. TSHZ3 was expressed in the human fetal kidney, and strongly at embryonic day 11.5-14.5 in mesenchymal compartments of the murine ureter, kidney, and bladder. TSHZ3 variants in a 5' region were more frequent in CAKUT patients than in gnomAD samples (p < 0.001). Mutant TSHZ3 harboring N-terminal variants showed significantly altered SOX9 and/or myocardin binding, possibly adversely affecting smooth muscle differentiation. Our results provide evidence that heterozygous TSHZ3 variants are associated with human CAKUT, particularly MCDK, hydronephrosis, and hydroureter, and, inconsistently, with specific extrarenal features, including genital anomalies.

• MeSH
• dítě MeSH
• heterozygot * MeSH
• homeodoménové proteiny genetika   MeSH
• kojenec MeSH
• ledviny abnormality   metabolismus   MeSH
• lidé MeSH
• missense mutace MeSH
• močové ústrojí abnormality   metabolismus   MeSH
• multicystické dysplastické ledviny genetika   MeSH
• myši MeSH
• předškolní dítě MeSH
• transkripční faktory genetika   MeSH
• urogenitální abnormality genetika   patologie   MeSH
• vezikoureterální reflux MeSH
• zvířata MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH