CONTEXT: High serum cholesterol is adversely associated with clinical and imaging disease progression outcomes in multiple sclerosis (MS) and in clinically isolated syndrome (CIS), the earliest stage of MS. Low vitamin D levels are associated with an increased risk of disease progression. OBJECTIVES: To investigate the mechanisms mediating the adverse effects of cholesterol in CIS and to determine the role of the nexus between the vitamin D3 (D3) and cholesterol pathways. DESIGN: Multi-center, prospective, longitudinal prospective study. SETTING: University hospital multiple sclerosis centers. INTERVENTION: Serum samples were obtained prior to any treatment from study subjects. METHODS: Serum obtained prior to any treatment from 172 CIS patients enrolled in a multi-center, prospective, longitudinal study (119 females: 53 males, age: 28.1 ± SD 8.1 years) were analyzed for high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein AI (ApoAI), ApoAII, ApoB, ApoE, and lipoprotein-a. Levels of 25-hydroxy vitamin D3 (25(OH)D3), 1,25-dihydroxy D3, and 24,25-dihydroxy D3 were measured using liquid chromatography-mass spectrometry. RESULTS: Greater levels of HDL-C biomarkers (e.g., HDL-C itself, ApoAI, ApoAII and paroxonase arylesterase activity) and LDL-C biomarkers (e.g., LDL-C itself, Apo B) were associated with greater 25(OH)D3. The effects of HDL-C biomarkers were stronger than those of LDL-C. Free cholesterol and cholesteryl ester levels were positively associated with higher 25(OH)D3 levels. Cholesterol palmitate was particularly potent. The nexus between the D3 and cholesterol pathways was proximal to, or in linkage disequilibrium with, 7-dehydrocholesterol reductase DHCR7 rs1790349, endothelial lipase LIPG rs4939883 and proprotein convertase subtilisin/kexin type 9 PCSK9 rs11206510. CONCLUSIONS: The associations between cholesterol biomarkers and vitamin D metabolite levels in CIS are consistent with the biochemical inter-dependence between the two pathways. Cholesterol biomarkers should be considered for inclusion as covariates when assessing vitamin D levels in CIS.

• Klíčová slova
• Cholesterol, Clinically isolated syndromes, Environmental factor, Interactions, Lipid, Multiple sclerosis, Vitamin D,
• MeSH
• cholesterol krev   MeSH
• dospělí MeSH
• HDL-cholesterol krev   MeSH
• LDL-cholesterol krev   MeSH
• lidé MeSH
• longitudinální studie MeSH
• následné studie MeSH
• prognóza MeSH
• prospektivní studie MeSH
• roztroušená skleróza metabolismus   patologie   MeSH
• syndrom MeSH
• vitamin D metabolismus   MeSH
• vitaminy metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• pozorovací studie MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cholesterol MeSH
• HDL-cholesterol MeSH
• LDL-cholesterol MeSH
• vitamin D MeSH
• vitaminy MeSH

BACKGROUND: Treatment of bile duct injuries (BDI) during cholecystectomy depends on the severity of injury and the timing of diagnosis. Standard of care for severe BDIs is hepaticojejunostomy. The aim of this retrospective multi-center study was to assess the optimal timing for repair of BDI with hepaticojejunostomy. METHODS: Members of the European-African HepatoPancreatoBiliary Association were invited to report all consecutive patients with hepaticojejunostomy after BDI from January 2000 to June 2016. Patients were stratified according to the timing of biliary reconstruction with hepaticojejunostomy: early (day 0-7), intermediate (1-6 weeks) and late (6 weeks-6 months). Primary endpoint was re-intervention >90 days after the hepaticojejunostomy and secondary endpoints were severe 90-day complications and liver-related mortality. RESULTS: In total 913 patients from 48 centers were included in the analysis. In 401 patients (44%) the bile duct injury was diagnosed intraoperatively, and 126 patients (14%) suffered from concomitant vascular injury. In multivariable analysis the timing of hepaticojejunostomy had no impact on postoperative complications, the need for re-intervention after 90 days nor liver-related mortality. The rate of re-intervention more than 90 days after the hepaticojejunostomy was significantly increased in male patients but decreased in older patients. Severe co-morbidity increased the risk for liver-related mortality (HR 3.439; CI 1.37-8.65; p = 0.009). CONCLUSION: After BDI occurring during cholecystectomy, the timing of biliary reconstruction with hepaticojejunostomy did not have any impact on severe postoperative complications, the need for re-intervention or liver-related mortality. Individualised treatment after iatrogenic bile duct injury is still advisable.

• MeSH
• čas zasáhnout při rozvinutí nemoci * MeSH
• cholecystektomie škodlivé účinky   MeSH
• dospělí MeSH
• ductus hepaticus communis chirurgie   MeSH
• jejunostomie * MeSH
• komorbidita MeSH
• lidé středního věku MeSH
• lidé MeSH
• retrospektivní studie MeSH
• senioři MeSH
• sexuální faktory MeSH
• žlučové cesty zranění   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

OBJECTIVES: To investigate the associations of environmental MS risk factors with clinical and MRI measures of progression in high-risk clinically isolated syndromes (CIS) after the first demyelinating event. METHODS: We analyzed 211 CIS patients (age: 28.9±7.8 years) enrolled in the SET study, a multi-center study of high-risk CIS patients. Pre-treatment samples were analyzed for IgG antibodies against cytomegalovirus (anti-CMV), Epstein Barr virus (EBV) early nuclear antigen-1 (EBNA-1), viral capsid antigen (VCA), early antigen-diffuse (EA-D), 25 hydroxy-vitamin D3 and cotinine levels and HLA DRB1*1501 status. The inclusion criteria required evaluation within 4 months of the initial demyelinating event, 2 or more brain MRI lesions and the presence of two or more oligoclonal bands in cerebrospinal fluid. All patients were treated with interferon-beta. Clinical and MRI assessments were obtained at baseline, 6, 12, and 24 months. RESULTS: The time to first relapse decreased and the number of relapses increased with anti-CMV IgG positivity. Smoking was associated with increased number and volume of contrast-enhancing lesions (CEL) during the 2-year period. The cumulative number of CEL and T2 lesions during the 2-year period was greater for individuals in the highest quartile of anti-EBV VCA IgG antibodies. The percent loss of brain volume was increased for those in the highest quartile of with anti-EBV VCA IgG antibodies. CONCLUSIONS: Relapses in CIS patients were associated with CMV positivity whereas anti-EBV VCA positivity was associated with progression on MRI measures, including accumulation of CEL and T2 lesions and development of brain atrophy.

• MeSH
• Cytomegalovirus imunologie   MeSH
• dospělí MeSH
• HLA-DRB1 řetězec genetika   MeSH
• kohortové studie MeSH
• kouření škodlivé účinky   MeSH
• lidé MeSH
• longitudinální studie MeSH
• mladý dospělý MeSH
• progrese nemoci MeSH
• prospektivní studie MeSH
• protilátky virové krev   MeSH
• rizikové faktory MeSH
• roztroušená skleróza etiologie   imunologie   virologie   MeSH
• virus Epsteinův-Barrové - jaderné antigeny imunologie   MeSH
• životní prostředí MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Názvy látek
• EBV-encoded nuclear antigen 1 MeSH Prohlížeč
• HLA-DRB1 řetězec MeSH
• HLA-DRB1*15:01 antigen MeSH Prohlížeč
• protilátky virové MeSH
• virus Epsteinův-Barrové - jaderné antigeny MeSH

OBJECTIVES: To investigate the associations between antibody responses to herpesviruses and the development of thalamic, total deep gray matter, cortical and central atrophy in high-risk clinically isolated syndromes (CIS) after the first demyelinating event. METHODS: We analyzed volumetric brain outcomes in 193 CIS patients enrolled in a multi-center study of high-risk CIS. All patients had 2 or more MRI brain lesions and two or more oligoclonal bands in cerebrospinal fluid. Serum samples obtained at the screening visit prior to any treatment were analyzed for IgG antibodies against cytomegalovirus (anti-CMV) and Epstein-Barr virus (EBV) viral capsid antigen (VCA). All patients were treated with interferon-beta. Clinical and MRI assessments were obtained at baseline, 6, 12, and 24 months. RESULTS: Anti-EBV VCA highest quartile status was associated with regional atrophy measures for percent decrease in thalamus. Anti-CMV positivity was associated with greater total deep gray matter atrophy and whole brain atrophy. Anti-EBV VCA highest quartile status was associated as trends with greater whole brain, gray matter atrophy and central atrophy. The associations of anti-EBV VCA antibodies with thalamic atrophy were mediated by its associations with T2 lesions whereas the associations of anti-CMV positivity with deep gray matter atrophy were relatively independent of T2 lesions. CONCLUSIONS: Antibody responses to EBV and CMV are associated with global and regional brain atrophy in CIS patients treated with interferon-beta.

• Klíčová slova
• Cytomegalovirus, Deep gray matter atrophy, Environmental factors, Epstein–Barr virus,
• MeSH
• antigeny virové imunologie   MeSH
• antivirové látky terapeutické užití   MeSH
• atrofie farmakoterapie   etiologie   virologie   MeSH
• časové faktory MeSH
• demyelinizační nemoci komplikace   farmakoterapie   MeSH
• dospělí MeSH
• Herpesviridae imunologie   MeSH
• interferon beta terapeutické užití   MeSH
• leukoencefalopatie etiologie   MeSH
• lidé MeSH
• longitudinální studie MeSH
• magnetická rezonanční tomografie MeSH
• mladý dospělý MeSH
• neurodegenerativní nemoci etiologie   MeSH
• pozorování MeSH
• protilátky virové krev   MeSH
• thalamus patologie   MeSH
• virové plášťové proteiny imunologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• Názvy látek
• antigeny virové MeSH
• antivirové látky MeSH
• Epstein-Barr viral capsid antigen MeSH Prohlížeč
• interferon beta MeSH
• protilátky virové MeSH
• virové plášťové proteiny MeSH

BACKGROUND: Hydroxyethyl starch (HES) solutions are used for volume therapy to treat hypovolemia due to acute blood loss and to maintain hemodynamic stability. This study was requested by the European Medicines Agency (EMA) to provide more evidence on the long-term safety and efficacy of HES solutions in the perioperative setting. METHODS: PHOENICS is a randomized, controlled, double-blind, multi-center, multinational phase IV (IIIb) study with two parallel groups to investigate non-inferiority regarding the safety of a 6% HES 130 solution (Volulyte 6%, Fresenius Kabi, Germany) compared with a crystalloid solution (Ionolyte, Fresenius Kabi, Germany) for infusion in patients with acute blood loss during elective abdominal surgery. A total of 2280 eligible patients (male and female patients willing to participate, with expected blood loss ≥ 500 ml, aged > 40 and ≤ 85 years, and ASA Physical status II-III) are randomly assigned to receive either HES or crystalloid solution for the treatment of hypovolemia due to surgery-induced acute blood loss in hospitals in up to 11 European countries. The dosing of investigational products (IP) is individualized to patients' volume needs and guided by a volume algorithm. Patients are treated with IP for maximally 24 h or until the maximum daily dose of 30 ml/kg body weight is reached. The primary endpoint is the treatment group mean difference in the change from the pre-operative baseline value in cystatin-C-based estimated glomerular filtration rate (eGFR), to the eGFR value calculated from the highest cystatin-C level measured during post-operative days 1-3. Further safety and efficacy parameters include, e.g., combined mortality/major post-operative complications until day 90, renal function, coagulation, inflammation, hemodynamic variables, hospital length of stay, major post-operative complications, and 28-day, 90-day, and 1-year mortality. DISCUSSION: The study will provide important information on the long-term safety and efficacy of HES 130/0.4 when administered according to the approved European product information. The results will be relevant for volume therapy of surgical patients. TRIAL REGISTRATION: EudraCT 2016-002162-30 . ClinicalTrials.gov NCT03278548.

• Klíčová slova
• Blood loss, Colloids, Double-blinded, HES, Hydroxyethyl starch, Multi-center, Multinational, Non-inferiority trial, Randomized controlled trial, Safety, Surgery, Volume therapy,
• MeSH
• břicho * chirurgie   MeSH
• deriváty hydroxyethylového škrobu * škodlivé účinky   chemie   MeSH
• dvojitá slepá metoda MeSH
• elektrolyty MeSH
• lidé MeSH
• multicentrické studie jako téma MeSH
• náhražky plazmy škodlivé účinky   MeSH
• prospektivní studie MeSH
• randomizované kontrolované studie jako téma MeSH
• senioři nad 80 let MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• protokol klinické studie MeSH
• Názvy látek
• deriváty hydroxyethylového škrobu * MeSH
• elektrolyty MeSH
• náhražky plazmy MeSH

The application of texture analysis (TA) in magnetic resonance imaging (MRI) requires the availability of texture phantoms for use in the standardization of in vivo measurements. The aims of our study were (a) to develop a new type of phantoms suitable for MRI and TA and test their long-term stability; (b) to optimize the choice of texture parameters describing the phantoms; (c) to compare different MR imagers according to texture parameters in a multi-center study. A long-term study performed at 4.7 T proved that the developed phantom based on polystyrene spheres and an agar gel solution is stable at least 12 months. This phantom, with nodular patterns, was found useful for the modeling of structural differences. The comparison of TA parameters at 4.7 and 7 T proved that the same parameters can be used for the separation of structures. The proposed algorithm of the selection of TA parameters shows that there exists a part of texture parameters which can be measured with high reproducibility (1-3%); on the other hand, their absolute values can differ by more than 30% if the textures differ. Results obtained from the multi-center study of whole body MR imagers show the wide variation in the misclassification rates at the different sites and point out the importance of the set up of MR sequences.

• MeSH
• agar chemie   MeSH
• časové faktory MeSH
• fantomy radiodiagnostické MeSH
• lidé MeSH
• magnetická rezonanční tomografie metody   MeSH
• počítačová rentgenová tomografie MeSH
• polystyreny chemie   MeSH
• vylepšení obrazu MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Názvy látek
• agar MeSH
• polystyreny MeSH

One of the biggest problems in automated diagnosis of psychiatric disorders from medical images is the lack of sufficiently large samples for training. Sample size is especially important in the case of highly heterogeneous disorders such as schizophrenia, where machine learning models built on relatively low numbers of subjects may suffer from poor generalizability. Via multicenter studies and consortium initiatives researchers have tried to solve this problem by combining data sets from multiple sites. The necessary sharing of (raw) data is, however, often hindered by legal and ethical issues. Moreover, in the case of very large samples, the computational complexity might become too large. The solution to this problem could be distributed learning. In this paper we investigated the possibility to create a meta-model by combining support vector machines (SVM) classifiers trained on the local datasets, without the need for sharing medical images or any other personal data. Validation was done in a 4-center setup comprising of 480 first-episode schizophrenia patients and healthy controls in total. We built SVM models to separate patients from controls based on three different kinds of imaging features derived from structural MRI scans, and compared models built on the joint multicenter data to the meta-models. The results showed that the combined meta-model had high similarity to the model built on all data pooled together and comparable classification performance on all three imaging features. Both similarity and performance was superior to that of the local models. We conclude that combining models is thus a viable alternative that facilitates data sharing and creating bigger and more informative models.

• Klíčová slova
• Machine learning, classification, combining models, first-episode schizophrenia, meta-model, multi-center, prediction, support vector machines (SVM),
• MeSH
• datové soubory jako téma * MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• multicentrické studie jako téma * MeSH
• neurozobrazování metody   MeSH
• rozpoznávání automatizované metody   MeSH
• schizofrenie diagnostické zobrazování   MeSH
• support vector machine * MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

INTRODUCTION: Despite national guidelines and use of intrapartum antibiotic prophylaxis (IAP), Streptococcus agalactiae (group B streptococci (GBS)) is still a leading cause of morbidity and mortality in newborns in Europe and the United States. The European DEVANI (Design of a Vaccine Against Neonatal Infections) program assessed the neonatal GBS infection burden in Europe, the clinical characteristics of colonized women and microbiological data of GBS strains in colonized women and their infants with early-onset disease (EOD). METHODS: Overall, 1083 pregnant women with a GBS-positive culture result from eight European countries were included in the study. Clinical obstetrical information was collected by a standardized questionnaire. GBS strains were characterized by serological and molecular methods. RESULTS: Among GBS carriers included in this study after testing positive for GBS by vaginal or recto-vaginal sampling, 13.4% had at least one additional obstetrical risk factor for EOD. The five most common capsular types (i.e., Ia, Ib, II, III and V) comprised ~ 93% of GBS carried. Of the colonized women, 77.8% received any IAP, and in 49.5% the IAP was considered appropriate. In our cohort, nine neonates presented with GBS early-onset disease (EOD) with significant regional heterogeneity. CONCLUSIONS: Screening methods and IAP rates need to be harmonized across Europe in order to reduce the rates of EOD. The epidemiological data from eight different European countries provides important information for the development of a successful GBS vaccine.

• Klíčová slova
• Streptococcus agalactiae, Early-onset disease, GBS vaccine, Group B streptococcus, Intrapartum prophylaxis, Maternal colonization, Neonatal sepsis, Vertical transmission,
• MeSH
• dospělí MeSH
• infekční komplikace v těhotenství * epidemiologie   mikrobiologie   MeSH
• lidé MeSH
• mladý dospělý MeSH
• novorozenec MeSH
• přenašečství * epidemiologie   mikrobiologie   MeSH
• rizikové faktory MeSH
• Streptococcus agalactiae * izolace a purifikace   klasifikace   MeSH
• streptokokové infekce * epidemiologie   mikrobiologie   prevence a kontrola   MeSH
• těhotenství MeSH
• vagina mikrobiologie   MeSH
• vertikální přenos infekce prevence a kontrola   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• novorozenec MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• Geografické názvy
• Evropa epidemiologie   MeSH

PURPOSE: Group B streptococcus (GBS) remains a leading cause of invasive disease, mainly sepsis and meningitis, in infants < 3 months of age and of mortality among neonates. This study, a major component of the European DEVANI project (Design of a Vaccine Against Neonatal Infections) describes clinical and important microbiological characteristics of neonatal GBS diseases. It quantifies the rate of antenatal screening and intrapartum antibiotic prophylaxis among cases and identifies risk factors associated with an adverse outcome. METHODS: Clinical and microbiological data from 153 invasive neonatal cases (82 early-onset [EOD], 71 late-onset disease [LOD] cases) were collected in eight European countries from mid-2008 to end-2010. RESULTS: Respiratory distress was the most frequent clinical sign at onset of EOD, while meningitis is found in > 30% of LOD. The study revealed that 59% of mothers of EOD cases had not received antenatal screening, whilst GBS was detected in 48.5% of screened cases. Meningitis was associated with an adverse outcome in LOD cases, while prematurity and the presence of cardiocirculatory symptoms were associated with an adverse outcome in EOD cases. Capsular-polysaccharide type III was the most frequent in both EOD and LOD cases with regional differences in the clonal complex distribution. CONCLUSIONS: Standardizing recommendations related to neonatal GBS disease and increasing compliance might improve clinical care and the prevention of GBS EOD. But even full adherence to antenatal screening would miss a relevant number of EOD cases, thus, the most promising prophylactic approach against GBS EOD and LOD would be a vaccine for maternal immunization.

• Klíčová slova
• Early-onset disease, Group B streptococcal vaccine, Group B streptococcus, Late-onset disease, Neonatal infection, Streptococcus agalactiae,
• MeSH
• antibiotická profylaxe škodlivé účinky   MeSH
• infekční komplikace v těhotenství * diagnóza   epidemiologie   MeSH
• kojenec MeSH
• lidé MeSH
• novorozenec MeSH
• Streptococcus agalactiae MeSH
• streptokokové infekce * diagnóza   epidemiologie   prevence a kontrola   MeSH
• těhotenství MeSH
• Check Tag
• kojenec MeSH
• lidé MeSH
• novorozenec MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• Geografické názvy
• Evropa epidemiologie   MeSH

BACKGROUND: Thrombosis and pulmonary embolism appear to be major causes of mortality in hospitalized coronavirus disease 2019 (COVID-19) patients. However, few studies have focused on the incidence of venous thromboembolism (VTE) after hospitalization for COVID-19. METHODS: In this multi-center study, we followed 1529 COVID-19 patients for at least 45 days after hospital discharge, who underwent routine telephone follow-up. In case of signs or symptoms of pulmonary embolism (PE) or deep vein thrombosis (DVT), they were invited for an in-hospital visit with a pulmonologist. The primary outcome was symptomatic VTE within 45 days of hospital discharge. RESULTS: Of 1529 COVID-19 patients discharged from hospital, a total of 228 (14.9%) reported potential signs or symptoms of PE or DVT and were seen for an in-hospital visit. Of these, 13 and 12 received Doppler ultrasounds or pulmonary CT angiography, respectively, of whom only one patient was diagnosed with symptomatic PE. Of 51 (3.3%) patients who died after discharge, two deaths were attributed to VTE corresponding to a 45-day cumulative rate of symptomatic VTE of 0.2% (95%CI 0.1%-0.6%; n = 3). There was no evidence of acute respiratory distress syndrome (ARDS) in these patients. Other deaths after hospital discharge included myocardial infarction (n = 13), heart failure (n = 9), and stroke (n = 9). CONCLUSIONS: We did not observe a high rate of symptomatic VTE in COVID-19 patients after hospital discharge. Routine extended thromboprophylaxis after hospitalization for COVID-19 may not have a net clinical benefit. Randomized trials may be warranted.

• Klíčová slova
• COVID-19, Cohort study, Hospitalization, Thromboprophylaxis, Venous thromboembolism,
• MeSH
• časové faktory MeSH
• COVID-19 diagnóza   epidemiologie   mortalita   terapie   MeSH
• dospělí MeSH
• incidence MeSH
• lidé středního věku MeSH
• lidé MeSH
• plicní embolie diagnóza   epidemiologie   mortalita   MeSH
• propuštění pacienta * MeSH
• prospektivní studie MeSH
• rizikové faktory MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• žilní tromboembolie diagnóza   epidemiologie   mortalita   MeSH
• žilní trombóza diagnóza   epidemiologie   mortalita   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
• multicentrická studie MeSH
• Geografické názvy
• Írán epidemiologie   MeSH