Bortlik M.,Charles University |
Duricova D.,Charles University |
Machkova N.,Charles University |
Kozeluhova J.,University Hospital Plzen |
And 10 more authors.
Inflammatory Bowel Diseases | Year: 2014
Background: Prenatal exposure to anti-tumor necrosis factor α (TNF-α) antibodies seems to be safe for fetal development. Data on long-term outcome of exposed children are missing. Our aim was to assess long-term postnatal development of children exposed to anti-TNF-α during pregnancy. Methods: Consecutive children aged ≥12 months exposed to anti-TNFs prenatally for maternal inflammatory bowel disease in 3 centers in the Czech Republic were enrolled. Data on psychomotor development, infections, antibiotics, vaccination, and allergy were retrospectively obtained from mothers, treating pediatricians, and children's vaccination cards. Furthermore, standardized laboratory tests on humoral and cellular immunity were performed. Results: Twenty-five children exposed to biologicals were included (median age, 34 mo; range, 14-70 mo). All children had normal growth, and all but 1 had normal psychomotor development. Majority (80%) experienced at least 1 infection (mainly respiratory), and 60% of infants received antibiotics, 32% of those within the first year of life. Vaccination was undertaken according to vaccination protocol to 23 infants (92%). Fifteen children also had tuberculosis vaccination without serious complication. Immunological investigation was performed with 17 children (68%). Cellular immunity was normal in all infants, and 7 children had mild decrease in IgA and/or IgG immunoglobulins without clinical significance. All children had a detectable serologic response to vaccination. Conclusions: Exposure to anti-TNF-α antibodies seems to be safe for growth and psychomotor development of children, although clinical significance of relatively high frequency of infections and antibiotic use among infants remains questionable because of the lack of a control group. Continuous follow-up of exposed children is absolutely warranted. Copyright © 2014 Crohn's & Colitis Foundation of America, Inc.
Kholova I.,University of Tampere |
Ludvikova M.,Charles University |
Ludvikova M.,General University Hospital in Prague
Acta Cytologica | Year: 2014
Objective: The Bethesda System for Reporting Thyroid Cytopathology (BSRTC) was introduced in thyroid cytology in 2007 and is now generally accepted. BSRTC categories include a morphologic description and risk of malignancy as well as follow-up suggestions in each group. However, the category entitled 'atypia of undetermined significance or follicular lesion of undetermined significance' (AUS/FLUS) is problematic. This category is heterogeneous and has been overused so far. Study Design: Twenty-six studies were included in a meta-analysis. In addition to AUS/FLUS percentage, we analysed repeated AUS/FLUS percentage, cytological and histological correlations, and risk of malignancy and neoplasm for AUS/FLUS. Furthermore, stratification, interand intra-observer variability, and the possibility of a switch to another category and its clinical consequences were reviewed. Results: Out of a total of 81,833 cases, AUS/FLUS accounted for 10.9%, with a 34% risk of malignancy. Persistent AUS/FLUS was found in 21.6% in repeated cytology. Cytohistological correlation was analysed from 16 studies (4,964 cases), revealing 10.4% as AUS/FLUS and a 21.5% risk of malignancy. Conclusions: An AUS/FLUS category seems to be currently reasonable with clearly defined cytomorphological criteria which do not correspond unequivocally with those of the other categories. An AUS/FLUS category is justified and possible means of its improvement with immunohistochemistry, molecular analysis and imaging are discussed. © 2014 S. Karger AG, Basel.
Kudlova E.,General University Hospital in Prague
Journal of Pediatric Gastroenterology and Nutrition | Year: 2010
Objectives: The aim of the study was to investigate home management of childhood acute diarrhoea. Methods: A cross-sectional questionnaire study was conducted in Prague, Czech Republic. The caregivers of 210 children ages 6 to 59 months were approached in public places and interviewed about the knowledge and use of oral rehydration solution (ORS) and about management of the childs last episode of diarrhoea. Results: Maternal knowledge of ORS (27.6%) and ORS use (1.9% during the child's last episode of diarrhoea) were low. They were positively associated with education level but not with the source of advice. Small volumes of ORS given and its refusal were issues. Increased amounts of fluid offered to 60% of children were significantly associated with higher maternal education and relatives/friends (76%) as a source of advice rather than a paediatrician (57.9%), the most frequent source of advice (78.1%). Black tea was the most common fluid given (86.2%) followed by plain or mineral water (41.9%). Breast-feeding of all breast-fed children was continued; low-lactose formula was given in 1 case only. Withholding food was rare (5.2%), but the diet of 75.2% cases was modified. Drugs were given to 52.4% children, most frequently smectite and/or probiotics, and antimicrobials were given to 6.4% cases. © Copyright 2010 by European Society for Pediatric Gastroenterology.
Stewart A.K.,Mayo Medical School |
Rajkumar S.V.,Mayo Medical School |
Dimopoulos M.A.,Alexandra Hospital |
Masszi T.,Semmelweis University |
And 26 more authors.
New England Journal of Medicine | Year: 2015
Background Lenalidomide plus dexamethasone is a reference treatment for relapsed multiple myeloma. The combination of the proteasome inhibitor carfilzomib with lenalidomide and dexamethasone has shown efficacy in a phase 1 and 2 study in relapsed multiple myeloma. Methods We randomly assigned 792 patients with relapsed multiple myeloma to carfilzomib with lenalidomide and dexamethasone (carfilzomib group) or lenalidomide and dexamethasone alone (control group). The primary end point was progression-free survival. Results Progression-free survival was significantly improved with carfilzomib (median, 26.3 months, vs. 17.6 months in the control group; hazard ratio for progression or death, 0.69; 95% confidence interval [CI], 0.57 to 0.83; P = 0.0001). The median overall survival was not reached in either group at the interim analysis. The Kaplan-Meier 24-month overall survival rates were 73.3% and 65.0% in the carfilzomib and control groups, respectively (hazard ratio for death, 0.79; 95% CI, 0.63 to 0.99; P = 0.04). The rates of overall response (partial response or better) were 87.1% and 66.7% in the carfilzomib and control groups, respectively (P<0.001; 31.8% and 9.3% of patients in the respective groups had a complete response or better; 14.1% and 4.3% had a stringent complete response). Adverse events of grade 3 or higher were reported in 83.7% and 80.7% of patients in the carfilzomib and control groups, respectively; 15.3% and 17.7% of patients discontinued treatment owing to adverse events. Patients in the carfilzomib group reported superior health-related quality of life. Conclusions In patients with relapsed multiple myeloma, the addition of carfilzomib to lenalidomide and dexamethasone resulted in significantly improved progression-free survival at the interim analysis and had a favorable risk-benefit profile. (Funded by Onyx Pharmaceuticals; ClinicalTrials.gov number, NCT01080391.) Copyright © 2015 Massachusetts Medical Society. All rights reserved.
Nielsen N.,Helsingborg Hospital |
Nielsen N.,Lund University |
Wetterslev J.,Copenhagen University |
Cronberg T.,Lund University |
And 32 more authors.
New England Journal of Medicine | Year: 2013
BACKGROUND: Unconscious survivors of out-of-hospital cardiac arrest have a high risk of death or poor neurologic function. Therapeutic hypothermia is recommended by international guidelines, but the supporting evidence is limited, and the target temperature associated with the best outcome is unknown. Our objective was to compare two target temperatures, both intended to prevent fever. METHODS: In an international trial, we randomly assigned 950 unconscious adults after out-ofhospital cardiac arrest of presumed cardiac cause to targeted temperature management at either 33°C or 36°C. The primary outcome was all-cause mortality through the end of the trial. Secondary outcomes included a composite of poor neurologic function or death at 180 days, as evaluated with the Cerebral Performance Category (CPC) scale and the modified Rankin scale. RESULTS: In total, 939 patients were included in the primary analysis. At the end of the trial, 50% of the patients in the 33°C group (235 of 473 patients) had died, as compared with 48% of the patients in the 36°C group (225 of 466 patients) (hazard ratio with a temperature of 33°C, 1.06; 95% confidence interval [CI], 0.89 to 1.28; P=0.51). At the 180-day follow-up, 54% of the patients in the 33°C group had died or had poor neurologic function according to the CPC, as compared with 52% of patients in the 36°C group (risk ratio, 1.02; 95% CI, 0.88 to 1.16; P=0.78). In the analysis using the modified Rankin scale, the comparable rate was 52% in both groups (risk ratio, 1.01; 95% CI, 0.89 to 1.14; P=0.87). The results of analyses adjusted for known prognostic factors were similar. Conclusions In unconscious survivors of out-of-hospital cardiac arrest of presumed cardiac cause, hypothermia at a targeted temperature of 33°C did not confer a benefit as compared with a targeted temperature of 36°C. Copyright © 2013 Massachusetts Medical Society.
Hnizda A.,General University Hospital in Prague |
Spiwok V.,Institute of Chemical Technology Prague |
Jurga V.,Institute of Chemical Technology Prague |
Kozich V.,General University Hospital in Prague |
And 2 more authors.
Biochemistry | Year: 2010
Cystathionine β-synthase (CBS) is a modular enzyme which catalyzes condensation of serine with homocysteine. Cross-talk between the catalytic core and the C-terminal regulatory domain modulates the enzyme activity. The regulatory domain imposes an autoinhibition action that is alleviated by S-adenosyl-l-methionine (AdoMet) binding, by deletion of the C-terminal regulatory module, or by thermal activation. The atomic mechanisms of the CBS allostery have not yet been sufficiently explained. Using pulse proteolysis in urea gradient and proteolytic kinetics with thermolysin under native conditions, we demonstrated that autoinhibition is associated with changes in conformational stability and with sterical hindrance of the catalytic core. To determine the contact area between the catalytic core and the autoinhibitory module of the CBS protein, we compared side-chain reactivity of the truncated CBS lacking the regulatory domain (45CBS) and of the full-length enzyme (wtCBS) using covalent labeling by six different modification agents and subsequent mass spectrometry. Fifty modification sites were identified in 45CBS, and four of them were not labeled in wtCBS. One differentially reactive site (cluster W408/W409/W410) is a part of the linker between the domains. The other three residues (K172 and/or K177, R336, and K384) are located in the same region of the 45CBS crystal structure; computational modeling showed that these amino acid side chains potentially form a regulatory interface in CBS protein. Subtle differences at CBS surface indicate that enzyme activity is not regulated by conformational conversions but more likely by different allosteric mechanisms. © 2010 American Chemical Society.
Basaran D.,Hacettepe University |
Dusek L.,Masaryk University |
Majek O.,Masaryk University |
Cibula D.,General University Hospital in Prague
Annals of Surgical Oncology | Year: 2015
Background: This study aimed to review the oncologic outcomes of nerve-sparing radical hysterectomy (NSRH) in cervical cancer and to compare them with those of standard conventional radical hysterectomy (CRH). Methods: A search of the MEDLINE (Ovid), EMBASE (Ovid), and Cochrane Central Register of Controlled Trials (CENTRAL) databases for studies published to March 3, 2014 was performed using the search term “nerve sparing or radical hysterectomy and cervical cancer.” The main outcome measure was the recurrence rate after NSRH. The hazard ratio for recurrence was used to compare NSRH and CRH. Results: A total of 21 studies reported data on oncologic outcomes of NSRH. The recurrence rate after NSRH was reported to be 0 to 19.6 %. Of the 21 studies, 10 comparing outcomes between NSRH and CRH were assessed for their eligibility to be included in a meta-analysis. However, the scarcity and heterogeneity of effect estimates in these comparison trials precluded performance of a meta-analysis. Conclusions: The results showed that the evidence addressing the oncologic safety of NSRH over that of CRH in cervical cancer is neither adequate nor statistically relevant. A properly designed, prospective randomized noninferiority trial is needed to assess the oncologic outcomes of NSRH before this surgical approach is adopted as the standard of care for patients with tumors that have unfavorable prognostic features. Until then, NSRH should be considered primarily for patients with small tumors due to the very low risk of parametrial and lymph node involvement, with maximum benefit conferred to the patient from autonomic nerve preservation without any requirement for adjuvant treatment. © 2015, Society of Surgical Oncology.
Zidkova A.,General University Hospital in Prague |
Zidkova A.,Charles University |
Coufalova P.,Institute of Criminalistics Prague |
Capek P.,Institute of Criminalistics Prague
International Journal of Legal Medicine | Year: 2014
Sample containing 234 unrelated males and 197 unrelated females from Czech Republic was genotyped using an X-STR decaplex system in the following loci: DXS6789, DXS6809, DXS7132, DXS7133, DXS7423, DXS8378, DXS9898, DXS9902, GATA172D05, and GATA31E08. The linkage disequilibrium was observed between DXS6789 and DXS6809. The combined power of discrimination was 0.9999999998 (females) and 0.999998 (males). The mean exclusion chance was 0.999995 (trios) and 0.9998 (duos). This work presents the first population data for X-STR decaplex in Central Europe. © 2013 Springer-Verlag Berlin Heidelberg.
Poupetova H.,General University Hospital in Prague |
Ledvinova J.,General University Hospital in Prague |
Berna L.,General University Hospital in Prague |
Dvorakova L.,General University Hospital in Prague |
And 2 more authors.
Journal of Inherited Metabolic Disease | Year: 2010
The aim of this retrospective study was to determine the prevalence of lysosomal storage disorders (LSDs) in the Czech Republic. The data on cases diagnosed between 1975 and 2008 were collected and analyzed. The overall prevalence of LSDs in the Czech population (12.25 per 100,000) is comparable to that reported for the countries with well-established and advanced diagnostics of LSDs such as the Netherlands (14 per 100,000), Australia (12.9 per 100,000) and Italy (12.1 per 100,000). Relatively higher prevalence of LSDs was reported in the north of Portugal (25 per 100,000). Thirty-four different LSDs were diagnosed in a total of 478 individuals. Gaucher disease was the most frequent LSD with a birth prevalence of 1.13 per 100,000 births. The most frequent LSD groups were lipidoses, mucopolysaccharidoses, and neuronal ceroid lipofuscinoses, with combined prevalences of 5.0, 3.72, and 2.29 per 100,000 live births, respectively. Glycoproteinoses (0.57 per 100,000 live births), glycogenosis type II (0.37), and mucolipidoses (0.31) rarely occur in the Czech population, and a range of other LSDs have not been detected at all over the past three decades. Knowledge of the birth prevalence and carrier frequency of particular disorders is important in genetic counselling for calculation of the risk for the disorder in the other members of affected families. Earlier diagnosis of these disorders will permit timely intervention and may also result in lowering of the number of newborns with LSDs. © 2010 The Author(s).
PubMed | General University Hospital in Prague and Charles University
Type: Journal Article | Journal: Central European journal of public health | Year: 2017
The problem of family care for people dependent on another person has only recently become a focus of research. As demand for health and social services has not been adequately met by public service providers, growing attention has been given to informal care and the integration of families within systems of health and social care at the community level. This paper presents the results of a survey on informal carers views and opinions under the current conditions of social support in the Czech Republic. The survey was based on theoretical concepts of caring societies, deinstitutionalization, refamilization, and integrated community care, and aimed to shed light on caring families experiences and needs in the Czech Republic.Family lay carers completed an original self-administered questionnaire. A convenient sample of 200 family carers was selected.The survey collected information about the most influential factors in determining whether the families continue to provide care for their relatives in the household. More than 50% of the caregivers provide care from moral and emotional reasons. Financial problems, risk of losing their jobs, and further deterioration of health of the person they care for emerged as key risk factors, but overall, determination among carers to continue providing care at any cost was high (53%).Involving local communities and services, e.g. general practitioners (GPs) to a greater extent in the coordination of various social and health services, and in support mechanisms at the juncture between informal and formal care would make it easier for family carers to continue providing long-term care.