临床与实验医学研究所

This study aimed to obtain data describing the epidemiology and antifungal susceptibility of yeasts isolated from bloodstream infections (BSI) in the Czech Republic (CR). This study presents data from the first year of a national, long-term surveillance program. All microbiologically confirmed candidemia cases in patients hospitalized at 30 Czech centers in 2023 were evaluated. This study assessed BSI incidence per 100,000 inhabitants, species distribution, and antifungal susceptibilities (EUCAST E.Def 7.4 protocol) of strains.aff Whole-genome sequencing was performed on selected isolates with acquired resistance or non-wild-type phenotypes to determine the molecular mechanisms of resistance. In total, 433 isolates from 408 unique BSI episodes in 398 patients were recorded in 2023. Candida albicans was the most frequent species (40.6%), followed by Candida glabrata (24.5%), Candida parapsilosis (14.5%), and Candida tropicalis (5.5%). In pediatric patients, C. albicans (58.8%) was the most common, followed by C. parapsilosis (17.6%). Candida auris BSI was not detected in 2023. The highest rates of acquired fluconazole resistance were detected in C. parapsilosis (16.9%) and C. glabrata (15.4%). Most fluconazole-resistant (FLC-R) C. parapsilosis isolates carried Y132F mutation in ERG11 gene (14/15; 93.3%). One isolate of C. glabrata was resistant to echinocandins (1.3%), but remained susceptible to azoles, mutations in FKS1 (G14S) and FKS2 (S663P, T926P) were identified. This nationwide survey provides the first comprehensive yeast BSI surveillance data from the Czech Republic, which spans the entire country. CR follows trends observed in developed countries, with a decline in C. albicans and a rise in C. glabrata infections. To our knowledge, this is the first report describing FLC-R C. parapsilosis isolates carrying the Y132F ERG11 mutation in CR. These findings highlight several emerging challenges that reflect global trends: a shifting spectrum of Candida species from C. albicans to non-albicans species, and rising levels of acquired azole resistance. Therefore, continuous national monitoring is essential.

Deep learning methods in medical imaging often suffer from the limited availability of high-quality annotated data, especially for rare conditions. This data scarcity is largely due to the need for domain expertise and the time-consuming process of data collection and annotation. Recent advances in generative neural networks offer a promising solution by producing realistic synthetic images that can supplement or partially replace scarce real data. In this work, we propose a framework for synthesizing realistic microscopy images together with their corresponding structural annotations. The proposed method combines a procedural generator that encodes expert-defined diagnostic rules with a diffusion-based refinement that enhances visual realism while preserving the prescribed structure. We further introduce a multi-stage diffusion-based refinement process that utilizes a segmentation mask to guide refinement and ensure a predefined structure. We demonstrate the ability of the proposed framework on the use case of synthesizing microscopic images of motile cilia cross-sections, which are important for the diagnosis of Primary Ciliary Dyskinesia (PCD). Our results show that data created by the proposed approach can serve as both a complement to and a substitute for real training data in a downstream segmentation task.

STUDY QUESTION:What have been the activities, characteristics, and outcomes of uterus transplantation (UTx) performed worldwide from 2000 through 2024? SUMMARY ANSWER:In 91 UTx cases, 67 involved live donors and 80 of the recipients had Mayer-Rokitansky-Küster-Hauser syndrome, with 12-month graft survival of 74%, enabling pregnancy attempts that yielded 44 healthy singleton deliveries with a live birth rate per embryo transfer of 30.3%. WHAT IS KNOWN ALREADY:UTx is the only treatment for women with absolute uterine factor infertility who wish to carry a pregnancy. According to a comprehensive report including data up to 2020 on 45 UTx cases, 19 live births occurred (35.8% per embryo transfer) at a mean of 35.3 weeks gestation. STUDY DESIGN, SIZE, DURATION:Data were extracted from the web-based registry of the International Society of Uterus Transplantation (ISUTx). This registry captures information on donor and recipient characteristics, transplantation procedures, postoperative complications, immunosuppression, complications including rejections, and reproductive outcome. Analyses were undertaken of the 91 transplants performed between 6 April 2000 and 31 December 2024, that were recorded in the registry. PARTICIPANTS/MATERIALS, SETTING, METHODS:Twenty-four medical centers in five continents registered their uterus transplants by entering data from the day of transplantation until 3 months after graft removal. The following variables were assessed: the demographic and laboratory characteristics of donors and recipients, the source of graft (live versus deceased donor), surgical specifics including technique, duration, ischemic times, and post-op complications, immunosuppression, rejection data, pregnancy with live birth(s), and hysterectomy. MAIN RESULTS AND THE ROLE OF CHANCE:In 91 uterus transplantations (67 from live donors, 24 from deceased donors), the overall surgical success rate, defined as graft viability by 12 months, was 75%. Most recipients (88%) had Mayer-Rokitansky-Küster-Hauser syndrome, with mothers being the most frequent (64%) live donors. Live donor hysterectomies were performed by laparotomy (54%), robotics (28%), or laparoscopy (18%). Total ischemic time was shorter in live- versus deceased-donor UTx procedures. Rejection episodes that were treated with escalations of immunosuppression were more frequent during months 1-5 (44%) than during months 6-10 (28%) post-UTx. Graft survival during the first 12 months was superior when grafts from premenopausal donors were used as compared to from postmenopausal donors. Forty-four singleton live births (mean gestational length of 34.5 weeks), including eight second births, were reported, with a live birth rate per embryo transfer of 30%. Preeclampsia was the most common pregnancy complication, occurring in 23% of live-birth pregnancies. Major postnatal complications occurred in 11 infants, 9 with respiratory distress syndrome; no major malformations were observed. LIMITATIONS, REASONS FOR CAUTION:Data in the registry are self-reported and not subjected to validation. Although the ISUTx registry represents the most comprehensive quality registry of UTx activity in the world, cases from at least four centers are excluded as they were not entered into the registry. Birth outcomes from some registry cases are as yet unknown as these ongoing cases have not yet reached the endpoint of hysterectomy. WIDER IMPLICATIONS OF THE FINDINGS:This study presents the most comprehensive analysis to date of UTx, the only fertility treatment for absolute uterine factor infertility. The registry serves as the prime source for quality assessment and process improvement in UTx. STUDY FUNDING/COMPETING INTEREST(S):The establishment and operation of the registry were funded by the Swedish Research Council (2024-03487 to M.B.) and Jane and Dan Olsson Foundation (2024-11 to M.B.). There was no competing interest. TRIAL REGISTRATION NUMBER:Not applicable.

BACKGROUND:No large registries of patients with acute eosinophilic myocarditis (EM) are available. However, EM is perceived as a cardiac disease with high mortality, affecting mainly young and middle-aged adults according to small series and case reports. Awareness of the clinical presentation, associated systemic conditions, treatments, and outcomes of this uncommon condition is an unmet need. METHODS:In this international, multicenter, retrospective cohort study, 53 centers screened 193 patients with histologically proven acute EM between 1992 and 2023. After the exclusion of patients with insufficient data (n=10), symptoms lasting >30 days (n=19), or histological diagnosis not confirmed after review (n=8), 156 patients were included. RESULTS:Median age at presentation was 48 years (first to third quartile, 34-59 years) with male predominance (67.3%), and only 2 were pediatric cases (≤16 years of age; 1.3%). The main signs and symptoms at presentation were dyspnea (75.6%), fever (61.3%), and chest pain (53.2%). Unexpectedly, peripheral eosinophilia was reported in only 57.4% of cases, with a median cell count of 630 eosinophils/μL. The median left ventricular ejection fraction at presentation was 32% (first to third quartile, 25%-48%). The disorders most frequently associated with EM were eosinophilic granulomatosis with polyangiitis (22.4% of cases) and hypersensitivity forms (14.1%). Idiopathic/undefined forms accounted for 44.9% of cases, and miscellaneous causes accounted for 18.6%. In-hospital death or need for heart transplantation (HTx) occurred in 23 patients (14.7%; 22 deaths and 1 HTx), despite 43.6% being treated with temporary mechanical circulatory support and 92.9% being treated with immunosuppressive agents. Estimated rates of death or HTx at 1 and 3 years were 19.0% and 23.8%. Increased age, decreased left ventricular ejection fraction on admission, and no immunosuppressive therapy during hospitalization were independent predictors of death or HTx. A nonsignificant higher occurrence of deaths or HTx was observed in the hypersensitivity form (46.1%) compared with the eosinophilic granulomatosis with polyangiitis-associated form (13.1%) at 3 years (P=0.15). CONCLUSIONS:Acute EM can often present without peripheral eosinophilia, and rates of in-hospital and midterm mortality or HTx are high. Endomyocardial biopsy is required to reach the final diagnosis of EM because relying on peripheral eosinophilia can lead to missing diagnosis. In-hospital immunosuppression is associated with HTx-free survival, although tailored immunosuppressive therapies are needed to improve outcomes. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT06447935.

BackgroundRecent studies suggest that the development of prediabetes and its associated comorbidities may depend on sex and reproductive status. While the exact mechanism is unclear, differences in insulin sensitivity, body fat distribution, and glucose and lipid metabolism may play a role. In this study, we investigated how sex differences in metabolic and inflammatory parameters affect the development of prediabetic conditions in a non-obese rat model with severe dyslipidaemia.MethodsWistar Kyoto (WKY) rats served as the control group, while age-matched Hereditary Hypertriglyceridaemic (HHTg) rats were used as a non-obese, prediabetic model with genetically determined hypertriglyceridaemia, insulin resistance and impaired glucose tolerance.ResultsCompared to WKY controls, the HHTg strain exhibited increased serum triacylglyceroles (TAG) as well as ectopic TAG accumulation in the liver, heart and skeletal muscle which was more pronounced in HHTg females. However, this higher ectopic TAG accumulation in HHTg females was not associated with increased lipotoxic diacylglyceroles. The HHTg strain showed increased visceral adiposity, which was distributed differently: HHTg females had increased perimetrial adipose tissue, while HHTg males had increased perirenal adipose tissue. Impaired insulin sensitivity was observed in both sexes of the HHTg strain in skeletal muscle and adipose tissue. Insulin resistance in the HHTg strain may be due to elevated leptin and NEFA levels, as well as decreased GLUT4 in skeletal muscle. In addition, the HHTg strain showed impaired glucose tolerance, as well as hyperinsulinaemia, which was more pronounced in HHTg males. Increased lipogenesis (mRNA Scd1), oxidative stress (decreased SOD activity) and inflammation (mRNA Tnfα) in the liver may contribute to the development of hepatic steatosis and hepatic lipid accumulation. In visceral adipose tissue, increased mRNA Hif1 may contribute to adipose tissue hypoxia and impair insulin sensitivity, particularly in males.ConclusionsDespite having more pronounced dyslipidaemia, ectopic lipid accumulation, and visceral adiposity, prediabetic females have better glucose tolerance and insulin sensitivity markers than prediabetic males. These sex differences may be due to variations in fat distribution, lipid metabolism and chronic inflammation. Our findings suggest that males are more susceptible to developing early prediabetic damage, such as insulin resistance and fatty liver, regardless of obesity.