BACKGROUND: Clozapine is recommended by national and international guidelines for people with treatment-resistant schizophrenia. However, available meta-analyses of randomised controlled trials have not shown superior efficacy of clozapine when compared with other second-generation antipsychotics, with heterogeneity identified between the original studies. We aimed to use individual patient data (IPD) to account for potential reasons of variability and to synthesise an adjusted estimate for the difference in efficacy between clozapine and other second-generation antipsychotics for treatment-resistant schizophrenia. METHODS: In this systematic review and IPD meta-analysis, we searched the Cochrane Schizophrenia Group's Study-Based Register from inception to Jan 24, 2024, and previous reviews for blinded randomised controlled trials comparing clozapine with other second-generation antipsychotics in participants with treatment-resistant schizophrenia. Trials were eligible if they included patients with treatment-resistant schizophrenia and had a duration of at least 6 weeks. IPD were requested from trial investigators. The primary outcome was change in overall schizophrenia symptoms as measured by the Positive and Negative Syndrome Scale (PANSS) between clozapine and other second-generation antipsychotics after 6-8 weeks of treatment. The effect size measure for the primary outcome was mean difference with 95% credible interval (CrI). We fitted a Bayesian random-effects IPD meta-regression model that included duration of illness, baseline severity, and sex as potential prognostic factors or treatment effect modifiers. Confidence in the evidence was assessed using Grading of Recommendations, Assessment, Development, and Evaluation (GRADE). People with lived experience of mental illness were involved in this study. This study is registered with PROSPERO, CRD42021254986. FINDINGS: We screened 13 876 references and included 19 studies with data for 1599 participants; IPD were available for 12 of 19 trials (n=1052; mean age 37·67 years [SD 11·24; range 10-66]; 348 [33·08%] women and 704 [66·92%] men). Data on ethnicity were not available. The estimated mean difference in change from baseline PANSS total score was -0·64 points (95% CrI -3·97 to 2·63; τ=2·68) in favour of other second-generation antipsychotics. Shorter duration of illness and higher baseline severity were prognostic factors associated with a larger reduction in symptoms, but neither those factors nor sex were found to modify the relative effect between clozapine and other second-generation antipsychotics. The confidence in the evidence was graded as very low. INTERPRETATION: This IPD meta-analysis found a small and uncertain advantage of other second-generation antipsychotics, mainly olanzapine and risperidone, and so did not provide evidence for superior efficacy of clozapine compared with other second-generation antipsychotics in treatment-resistant schizophrenia. It is limited by unavailability of IPD for some studies, uncaptured sources of variance, and uncertainty due to premature study discontinuation. Given the side-effects of clozapine, the observed uncertainty regarding clozapine's superiority warrants prudent use and further research. FUNDING: German Ministry of Education and Research.

• MeSH
• antipsychotika * terapeutické užití   MeSH
• klozapin * terapeutické užití   MeSH
• lidé MeSH
• randomizované kontrolované studie jako téma MeSH
• refrakterní schizofrenie * farmakoterapie   MeSH
• schizofrenie * farmakoterapie   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• systematický přehled MeSH
• Názvy látek
• antipsychotika * MeSH
• klozapin * MeSH

Carcinoma cuniculatum is a very rare subtype of well-differentiated squamous cell carcinoma affecting several anatomical locations, including the penis. In this paper, we describe a case report of penile carcinoma cuniculatum highlighting some unusual clinical features. The patient was 61-year-old with a cauliflower-like tumor of the glans penis of less than 1-year duration. Microscopic examination revealed a p16-negative well-differentiated squamous proliferation characterized by narrow and cystic spaces extending through the lesion. Carcinoma cuniculatum is characterized by a strong tendency to deep penetration, typically presenting in patients in their seventh to eighth decades and with a long duration of the disease. In contrast, the tumor presented herein occurred in a younger patient with a shorter disease duration and showed only shallow growth into the underlying structures. Since penile carcinoma cuniculatum is a local disease without metastatic potential (regardless of tumor size and disease duration), awareness of this entity is important, especially for distinguishing it from other more aggressive subtypes of squamous cell carcinoma, which require different therapeutic approaches.

• Klíčová slova
• age, carcinoma cuniculatum, disease duration, penis, squamous cell carcinoma,
• Publikační typ
• časopisecké články MeSH

BACKGROUND: This is a multicentre, European, prospective trial evaluating the diagnostic accuracy of One Step Nucleic Acid Amplification (OSNA) compared to sentinel lymph nodes histopathological ultrastaging in endometrial cancer patients. METHODS: Centres with expertise in sentinel lymph node mapping in endometrial cancer patients in Europe will be invited to participate in the study. Participating units will be trained on the correct usage of the OSNA RD-210 analyser and nucleic acid amplification reagent kit LYNOAMP CK19 E for rapid detection of metastatic nodal involvement, based on the cytokeratin 19 (CK19) mRNA detection. Endometrial cancer patients ≥ 18 years listed for surgical treatment with sentinel lymph node mapping, with no history of other types of cancer and who provide a valid written consent will be considered potentially eligible for the study. However, they will only be enrolled if a successful sentinel lymph node mapping is retrieved. Each node will be processed according to the study protocol and assessed by both OSNA and ultrastaging. DISCUSSION: The accuracy of OSNA (index test) will be assessed against sentinel lymph node histopathological ultrastaging (reference test). This European study has the potential to be the largest study on the use of OSNA in endometrial cancer to date. OSNA could represent a modern diagnostic alternative to sentinel lymph node ultrastaging with the added benefits of standardisation and fast results. TRIAL REGISTRATION: The study was registered in the German Clinical Trial Register - Nr. DRKS00021520, registration date 25th of May 2020, URL of the trial registry record: https://drks.de/search/en/trial/DRKS00021520 .

• Klíčová slova
• Endometrial cancer, OSNA, Sentinel lymph nodes, Ultrastaging,
• MeSH
• biopsie sentinelové lymfatické uzliny metody   MeSH
• keratin-19 genetika   MeSH
• lidé MeSH
• lymfatické metastázy * diagnóza   patologie   MeSH
• lymfatické uzliny patologie   MeSH
• multicentrické studie jako téma MeSH
• nádory endometria * patologie   genetika   diagnóza   MeSH
• prospektivní studie MeSH
• sentinelová uzlina * patologie   MeSH
• staging nádorů MeSH
• techniky amplifikace nukleových kyselin * metody   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• protokol klinické studie MeSH
• Geografické názvy
• Evropa MeSH
• Názvy látek
• keratin-19 MeSH

Low temporal stability may complicate the interpretation of survey measures of conspiracy theories (CTs). Current study examines the stability of endorsement of CTs on a popular set of items addressing COVID-19-related CTs. An online survey tapping two CTs about COVID-19 was administered to 179 students of general medicine. The same items were presented twice in March 2022 and once in May 2022. The mean endorsement of the CTs did not differ between March and May. The correlation between answers provided in March and May was low (.5 < r < .7). Most of those reporting agreement with CTs in March reported disagreement in May. Conspiracy believers' responses did not change between two measurements in March but were different in May, suggesting that the low temporal stability was due to situational factors rather than erroneous or random answers. Poor temporal stability of responses endorsing CTs may problematize interpretation of survey data. Respondents' endorsement of CTs may be affected by situational factors, inflating agreement with CTs, and correlations with other survey-based measures.

• Klíčová slova
• COVID-19, common method bias, conspiracy theories, survey, temporal stability,
• MeSH
• COVID-19 * epidemiologie   MeSH
• dospělí MeSH
• lidé MeSH
• průzkumy a dotazníky MeSH
• SARS-CoV-2 MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

AIMS: To evaluate the 3-year follow-up results of two children delivered at our institution in 2019 from mothers with a transplanted uterus. METHODS: Observational data on pregnancy outcomes, neonatal course, and growth trajectory in two children born to mothers after uterus transplantation, including 3-year follow-up and neurodevelopmental status assessed using the Bayley Scales of Infant and Toddler Development, third edition (Bayley-III). RESULTS: Both children were born prematurely via uneventful caesarean sections, to mothers with Mayer-Rokitansky-Küster-Hauser syndrome and a transplanted uterus. An acute caesarean section was performed in one mother because of the onset of regular uterine contractions at 34 weeks and 6 days of pregnancy; in the other mother, an elective caesarean section was performed at 36 weeks and 2 days of gestation. The children were born healthy with no congenital malformations. They had an uneventful postnatal course and showed a normal growth trajectory during 3 years of follow-up. The Bayley-III neurodevelopmental scores of both children were within the normal ranges at ages 2 and 3 years. CONCLUSION: Though pregnancy after uterus transplantation is associated with the risk of premature delivery, no abnormalities were observed in the neonatal course and 3-year follow-up results, including the neurodevelopmental status, of two children born prematurely to mothers with a transplanted uterus. This is the first report on neurodevelopmental outcomes in children born after uterus transplantation. More data on children born after this radical procedure of uterine factor infertility treatment are required to support our promising results.

• Klíčová slova
• Bayley-III scales, absolute uterine factor infertility, assisted reproduction, neurodevelopment, uterus transplantation,
• MeSH
• císařský řez * škodlivé účinky   MeSH
• kojenec MeSH
• lidé MeSH
• matky MeSH
• následné studie MeSH
• novorozenec MeSH
• těhotenství MeSH
• uterus transplantace   MeSH
• ženská infertilita * MeSH
• Check Tag
• kojenec MeSH
• lidé MeSH
• novorozenec MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH

OBJECTIVES: The primary aim was to test the hypothesis that physical interpersonal violence is decreased during the lockdown period in comparison with comparable control periods. The secondary aims were to explore the effects of gender and alcohol consumption on the violence during the lockdown. METHODS: Nationwide records of hospitalizations secondary to an assault were analyzed using quasipoisson regression. Assault rates in two lockdown periods, defined as a national emergency state, were compared to baseline data between 2017 and 2020, controlling for seasonal fluctuations and pandemic-related effects other than lockdown. To validate the findings on independent data, differences between lockdown and baseline in Police records of violent criminality between 2017 and 2021 were examined using one-way ANOVA. RESULTS: The rates of hospitalizations secondary to an assault decreased substantially during lockdowns (IRR = .43; P < .001) and the duration of lockdown did not affect assault rates (P = .07). The decrease in assault rates was more pronounced in males than females (IRR = .77; P < .05) and was weakened in patients with history of alcohol abuse (IRR = 1.83; P < .001). Violent crime rate decreased by 19% during the lockdowns compared to prepandemic baseline (P < .001). CONCLUSION: We found that physical interpersonal violence decreased during the COVID-19 lockdown periods. The reduction is significantly greater in males. Emerging evidence suggests an increased risk of alcohol use and intoxication during the lockdowns. Violent crime rate decreased during the lockdown.

• Klíčová slova
• COVID-19, aggression, alcohol, crime, lockdown, violence, women,
• MeSH
• COVID-19 * epidemiologie   prevence a kontrola   MeSH
• dospělí MeSH
• hospitalizace statistika a číselné údaje   MeSH
• karanténa psychologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• násilí * statistika a číselné údaje   MeSH
• pití alkoholu epidemiologie   MeSH
• registrace * statistika a číselné údaje   MeSH
• senioři MeSH
• sexuální faktory MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• bradykinin analogy a deriváty   terapeutické užití   MeSH
• hereditární angioedémy * diagnóza   farmakoterapie   MeSH
• inhibiční protein komplementu C1 genetika   terapeutické užití   MeSH
• lidé MeSH
• registrace MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• dopisy MeSH
• Názvy látek
• bradykinin MeSH
• icatibant MeSH Prohlížeč
• inhibiční protein komplementu C1 MeSH

Mayer-Rokitansky-Küster-Hauser syndrome is a rare female congenital anomaly that presents with an inability to have coital sexual intercourse and absolute uterine factor infertility. Both surgical and nonsurgical approaches have been described for the treatment of vaginal agenesis to allow satisfactory coitus. Transplantation of the uterus has the challenge of achieving pregnancy and delivery of her own genetic and biological children in a woman without a natural uterus. Women of reproductive age with a congenital form of absolute uterine factor infertility are considered appropriate recipients of a uterus in the experimental phase of uterus transplantation trials. A neovagina in the normal anatomic position covered by natural non-keratinized mucosa is one of the main assumptions for surgical and reproductive success in transplant recipients. More than 70 uterine transplants have been performed to date, and more than 25 childbirths have been achieved by several research centers in the recipients of a uterus with uterine agenesis. In women with Mayer-Rokitansky-Küster-Hauser syndrome, skin-graft neovagina, Vecchietti's vaginoplasty, and self-dilation using Frank's and Ingram's methods are appropriate techniques to create a neovagina if transplantation of the uterus is intended in the future.

• Klíčová slova
• Mayer-Rokitansky-Küster-Hauser syndrome, Vecchietti's method, absolute uterine factor infertility, dilation, neovagina, uterus transplantation,
• MeSH
• dítě MeSH
• ductus Mülleri abnormality   chirurgie   MeSH
• infertilita * MeSH
• lidé MeSH
• poruchy sexuálního vývoje s karyotypem 46, XX * chirurgie   MeSH
• uterus transplantace   MeSH
• vrozené vady * chirurgie   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Amyloid plaques are small (~ 50 μm), highly-dense aggregates of amyloid beta (Aβ) protein in brain tissue, supposed to play a key role in pathogenesis of Alzheimer's disease (AD). Plaques´ in vivo detection, spatial distribution and quantitative characterization could be an essential marker in diagnostics and evaluation of AD progress. However, current imaging methods in clinics possess substantial limits in sensitivity towards Aβ plaques to play a considerable role in AD screening. Contrast enhanced X-ray micro computed tomography (micro CT) is an emerging highly sensitive imaging technique capable of high resolution visualization of rodent brain. In this study we show the absorption based contrast enhanced X-ray micro CT imaging is viable method for detection and 3D analysis of Aβ plaques in transgenic rodent models of Alzheimer's disease. Using iodine contrasted brain tissue isolated from the Tg-F344-AD rat model we show the micro CT imaging is capable of precise imaging of Aβ plaques, making possible to further analyze various aspects of their 3D spatial distribution and other properties.

• MeSH
• Alzheimerova nemoc diagnostické zobrazování   metabolismus   patologie   MeSH
• amyloidní beta-protein metabolismus   MeSH
• amyloidní plaky diagnostické zobrazování   metabolismus   patologie   MeSH
• biologické markery MeSH
• kontrastní látky * MeSH
• krysa rodu Rattus MeSH
• modely nemocí na zvířatech MeSH
• mozek diagnostické zobrazování   metabolismus   patologie   MeSH
• počítačové zpracování obrazu MeSH
• rentgenová mikrotomografie * MeSH
• vylepšení rentgenového snímku * MeSH
• zobrazování trojrozměrné MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• amyloidní beta-protein MeSH
• biologické markery MeSH
• kontrastní látky * MeSH

Purpose: Advanced glycation end products (AGEs) are a heterogeneous group of highly oxidant compounds which can potentiate microvascular and macrovascular complications through the formation of irreversible cross-links between molecules in the basal membrane and also by engaging the receptor for AGEs (RAGE). Soluble receptor for AGEs (sRAGE) is suggested to have a protective role neutralizing the toxic action of AGEs. We aimed to investigate differences in plasma levels of sRAGE alongside with classic cardiovascular risk factors between offspring of patients with early onset of coronary heart disease (CHD) and healthy controls.Materials and methods: In a cross-sectional design, we examined 114 adult offspring of patients with premature CHD and 194 controls. Concentrations of soluble RAGE were quantified by ELISA methods. Aortic PWV was measured using Sphygmocor device. Multivariate logistic regressions were used to compare differences between the offspring and controls.Results: In the offspring group there were more men (p = 0.023), both groups had similar age (28.5 vs. 28.9 years; p = 0.51). After adjustment for covariates, we observed significantly higher aPWV (6.17 vs. 5.82 m s-1; p = 0.001) and lower sRAGE (1308.11 vs. 1475.59; p = 0.009) in the offspring group compared to controls. The significant determinants of the intergroup difference were sRAGE (p = 0.0017), aPWV (p = 0.011) and current smoking (p = 0.0053).Conclusion: Offspring of patients with early onset of CHD compared to age-matched healthy controls had significantly lower sRAGE levels suggesting a shift in the oxidative balance between stressors and defence mechanisms that may influence a higher cardiovascular risk in the future. The measurement of sRAGE might be a valuable predictor for more precise stratification of cardiovascular risk.

• Klíčová slova
• aortic pulse wave velocity, cardiovascular risk factors, family history, premature coronary heart disease, sRAGE,
• MeSH
• biologické markery krev   MeSH
• dítě postižených rodičů * MeSH
• dospělé děti * MeSH
• dospělí MeSH
• hodnocení rizik MeSH
• koronární nemoc * MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• průřezové studie MeSH
• receptor pro konečné produkty pokročilé glykace krev   MeSH
• rizikové faktory kardiovaskulárních chorob MeSH
• studie případů a kontrol MeSH
• věk při počátku nemoci MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• AGER protein, human MeSH Prohlížeč
• biologické markery MeSH
• receptor pro konečné produkty pokročilé glykace MeSH