Robak T.,Medical University of Lódz |
Huang H.,Sun Yat Sen University |
Jin J.,Zhejiang University |
Zhu J.,Beijing Cancer Hospital |
And 15 more authors.
New England Journal of Medicine | Year: 2015
Background The proteasome inhibitor bortezomib was initially approved for the treatment of relapsed mantle-cell lymphoma. We investigated whether substituting bortezomib for vincristine in frontline therapy with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) could improve outcomes in patients with newly diagnosed mantle-cell lymphoma. Methods In this phase 3 trial, we randomly assigned 487 adults with newly diagnosed mantlecell lymphoma who were ineligible or not considered for stem-cell transplantation to receive six to eight 21-day cycles of R-CHOP intravenously on day 1 (with prednisone administered orally on days 1 to 5) or VR-CAP (R-CHOP regimen, but replacing vincristine with bortezomib at a dose of 1.3 mg per square meter of body-surface area on days 1, 4, 8, and 11). The primary end point was progression-free survival. Results After a median follow-up of 40 months, median progression-free survival (according to independent radiologic review) was 14.4 months in the R-CHOP group versus 24.7 months in the VR-CAP group (hazard ratio favoring the VR-CAP group, 0.63; P<0.001), a relative improvement of 59%. On the basis of investigator assessment, the median durations of progression-free survival were 16.1 months and 30.7 months, respectively (hazard ratio, 0.51; P<0.001), a relative improvement of 96%. Secondary end points were consistently improved in the VR-CAP group, including the complete response rate (42% vs. 53%), the median duration of complete response (18.0 months vs. 42.1 months), the median treatment-free interval (20.5 months vs. 40.6 months), and the 4-year overall survival rate (54% vs. 64%). Rates of neutropenia and thrombocytopenia were higher in the VR-CAP group. Conclusions VR-CAP was more effective than R-CHOP in patients with newly diagnosed mantlecell lymphoma but at the cost of increased hematologic toxicity. Copyright © 2015 Massachusetts Medical Society.
Kaevska M.,Veterinary Research Institute |
Sterba J.,Faculty Hospital Brno |
Svobodova J.,Regional Institute of Public Health |
Pavlik I.,Veterinary Research Institute
Epidemiology and Infection | Year: 2014
Non-tuberculous mycobacteria are increasingly described as infectious agents in immunocompromised patients. A 17-year-old male patient suffering from secondary non-Hodgkin's lymphoma and treated with chemotherapeutic agents was admitted to hospital due to pleuropneumonia. Mycobacterium neoaurum was cultured repeatedly from his sputum and, Mycobacterium avium subsp. avium (M. a. avium) was detected by IS901 qPCR from detached fragments of his intestinal mucosa. We attempted to determine the possible sources of infection by analysing environmental samples from the closed oncology unit and conventional unit in the hospital, and from the patient's home residence and places which he frequented. The environment of the patient harboured mycobacteria (41 isolates in total); however, M. neoaurum was not recovered. M. a. avium was detected by qPCR in the environmental samples from a small flock of hens kept by his neighbour. Although it was not confirmed by DNA fingerprinting methods, the M. a. avium infection could have been acquired through the eating of incompletely cooked eggs. © 2013 Cambridge University Press.
Trc T.,Charles University |
Bohmova J.,Faculty Hospital Brno
International Orthopaedics | Year: 2011
This was a 13-week, multicentre, randomised, parallel, double-blind study. One hundred men and women volunteers aged ≥40 years with knee osteoarthritis (KOA) were randomised to once daily enzymatic hydrolysed collagen (EHC) 10 g or glucosamine sulphate (GS) 1.5 g for 90 consecutive days. Follow-up took place after two weeks and after one, two and three months. Primary [visual analogue scale (VAS), Western Ontario and McMaster Universities (WOMAC Index)] and secondary outcomes variables, assessed at weeks two, four, eight and 12, were KOA pain intensity measured by quadruple visual analogue scales in the target knee, the WOMAC total score index, patient's and investigator's global assessments of disease activity, joint assessment, use of rescue medication (ibuprofen 400 mg tablets) and assessment of Quality of Life index (SF-36 Questionnaire). Safety and tolerability were also evaluated. Clear improvement was observed in both joint pain and symptoms in patients with KOA treated with EHC (Colatech ®) and significant differences were observed. Mean reductions from baseline for EHC 10 g daily and GS 1.5 g, respectively, were KOA pain intensity reduction in the target knee for Colatech® (p<0.05): WOMAC index decrease ≤ 15 points at the last visit (day 90) for Colatech® in 16 patients (34.04%) (p<0.05) and for glucosamine in six patients (13.04%); total score index for painful joints: Colatech® 1.6 (p<0.05) and glucosamine 1.8; total score index for swollen joints: Colatech® 0.5 (p<0.05) and glucosamine 0.7; patient's global assessment of efficacy as the sum of improvement good + ideal: 80.8% for Colatech® and 46.6% for glucosamine (p<0.05). EHC (Colatech®) showed superior improvement over GS in the SF-36 Questionnaire in the Physical Health Index (42.0 for Colatech and 40.0 for glucosamine). The incidence of adverse events was similar in both groups. Both EHC and GS were well tolerated. © Springer-Verlag 2010.
Wierda W.G.,University of Texas M. D. Anderson Cancer Center |
Kipps T.J.,University of California at San Diego |
Durig J.,University of Duisburg - Essen |
Griskevicius L.,Vilnius University |
And 13 more authors.
Blood | Year: 2011
We conducted an international phase 2 trial to evaluate 2 dose levels of ofatumumab, a human CD20 mAb, combined with fludarabine and cyclophosphamide (O-FC) as frontline therapy for chronic lymphocytic leukemia (CLL). Patients with active CLL were randomized to ofatumumab 500 mg (n = 31) or 1000 mg (n = 30) day 1, with fludarabine 25 mg/m2 and cyclophosphamide 250 mg/m2 days 2-4, course 1; days 1-3, courses 2-6; every 4 weeks for 6 courses. The first ofatumumab dose was 300 mg for both cohorts. The median age was 56 years; 13% of patients had a 17p deletion; 64% had β2-microglobulin > 3.5 mg/L. Based on the 1996 National Cancer Institute Working Group (NCI-WG) guidelines, the complete response (CR) rate as assessed by an independent review committee was 32% for the 500-mg and 50% for the 1000-mg cohort; the overall response (OR) rate was 77% and 73%, respectively. Based on univariable regression analyses, β2-microglobulin and the number of O-FC courses were significantly correlated (P < .05) with CR and OR rates and progression-free survival (PFS). The most frequent Common Terminology Criteria (CTC) grade 3-4 investigator-reported adverse events were neutropenia (48%), thrombocytopenia (15%), anemia (13%), and infection (8%). O-FC is active and safe in treatment-naive patients with CLL, including high-risk patients. This trial was registered at www.clinicaltrials.gov as NCT00410163. © 2011 by The American Society of Hematology.
Flasarova M.,Masaryk University |
Pospisilova P.,Masaryk University |
Mikalova L.,Masaryk University |
Valisova Z.,Masaryk University |
And 6 more authors.
Acta Dermato-Venereologica | Year: 2012
A set of 415 clinical samples isolated from 294 patients suspected of having syphilis collected in the Czech Republic between 2004 and 2010 was tested for the presence of treponemal DNA. Standard serological tests showed that 197 patients were syphilis-seropositive and 97 patients were syphilis-seronegative. In each sample, PCR tests for polA (TP0105), tmpC (TP0319), TP0136, TP0548 and 23S rRNA genes were performed. Samples taken from 91 patients were PCR-positive. Molecular typing of treponemal DNA was based on the sequencing of TP0136, TP0548 and 23S rRNA genes. Treponemal DNA was typeable in samples taken from 64 PCR-positive patients and 9 different genotypes were found. The proportion of treponemal strains resistant to macrolide antibiotics was 37.3%. In the DNA samples taken from 39 patients, a parallel treponemal typing approved by Centers for Disease Control and Prevention was performed. The variants of arp and tpr genes appear to combine independently with sequence variants of TP0136, TP0548 and 23S rRNA genes. © 2012 The Authors.
Raja K.R.M.,Masaryk University |
Kovarova L.,Masaryk University |
Kovarova L.,Faculty Hospital Brno |
Hajek R.,Masaryk University |
Hajek R.,Faculty Hospital Brno
British Journal of Haematology | Year: 2010
Flow cytometric immunophenotyping is considered an indispensable tool for the diagnosis, classification and monitoring of disease in monoclonal gammopathies. The clinical sensitivity of flow cytometry is comparable with advanced molecular methods. Clinical application of flow cytometry in monoclonal gammopathies has various dimensions, such as differential diagnosis of malignant plasma cell disorder from reactive plasmacytosis, identifying the progression risk in monoclonal gammopathy of undetermined significance (MGUS) and asymptomatic multiple myeloma (MM), and minimal residual disease detection. Flow cytometry-based clonality assessment with immunophenotyping encourages and enables the most stringent method of diagnosis and follow-up. The objective of this review is to update the malignant plasma cells phenotypic profile of MGUS and MM. The most comprehensive antigens, such as CD19, CD27, CD28, CD45, CD56 and CD117, play a significant role in the characterization of normal and malignant plasma cells. Several research groups described the putative phenotype of myeloma cell progenitors, but no remarkable suggestion could be made because of disparity. This review also focuses on the association of malignant phenotypic markers and chromosomal aberrations that identify the specific prognostic features in monoclonal gammopathies. © 2010 Blackwell Publishing Ltd.
Pohanka M.,University of Hradec Kralove |
Snopkova S.,Masaryk University |
Snopkova S.,Faculty Hospital Brno |
Havlickova K.,Masaryk University |
And 6 more authors.
Current Medicinal Chemistry | Year: 2011
Macrophages play an important role in the immune system. They also participate in multiple processes including angiogenesis and triggering of inflammation. The present study summarizes pieces of knowledge on the importance of macrophages in disease, especially the inflammation. Special attention is paid to the cholinergic anti-inflammatory pathway (CAP) associated with the nicotinic acetylcholine receptor (nAChR) and the parasympathetic nervous system. The current pharmacological effectiveness in suppressing the inflammation in general and the septic shock in particular, is limited. CAP was discovered recently and it seems to be a suitable target for the development of new drugs. Moreover, available drugs binding to either nAChR or acetylcholinesterase (AChE) are candidates for either an inhibition or enhancement of CAP. Though the current scientific databases do not include all necessary data on the association of CAP with body functions and the research is quite intensive, the objective of the present review is to introduce the current trends and to critically evaluate CAP and macrophage-associated pathways. © 2011 Bentham Science Publishers Ltd.
SSmajs D.,Masaryk University |
Micenkova L.,Masaryk University |
SSmarda J.,Masaryk University |
Vrba M.,Faculty Hospital Brno |
And 3 more authors.
BMC Microbiology | Year: 2010
Background. Bacteriocin production is an important characteristic of E. coli strains of human origin. To date, 26 colicin and 9 microcin types have been analyzed on a molecular level allowing molecular detection of the corresponding genes. The production incidence of 29 bacteriocin types and E. coli phylogroups were tested in a set of 361 E. coli strains isolated from human urinary tract infections (UTI) and in 411 control strains isolated from feces of patients without bacterial gut infection. Results. Production of 17 and 20 individual bacteriocin types was found in the UTI and control strains, respectively. Microcin H47 encoding determinants were found more often among UTI strains compared to controls (37.9% and 27.0% respectively, p = 0.02) and strains producing microcin H47 belonged predominantly to phylogroup B2 when compared to other bacteriocin producers (67.4% and 36.7%, respectively; p < 0.0001). Producers of 3 or more identified bacteriocin types were more common in the UTI group (20.0% compared to 12.4% in controls, p = 0.03). In the UTI strains, there was a markedly higher number of those producing colicin E1 compared to controls (22.1% to 10.2%, respectively, p = 0.0008). Moreover, colicin E1 production was more common in the UTI bacteriocinogenic strains with multi-producer capabilities. As shown by Southern blotting, pColE1 DNA was not recognized by the ColIa probe and vice versa suggesting that pColE1 was independently associated with pColIa in UTI strains. Conclusion. E. coli strains isolated from human urinary tract infections showed increased incidence of microcin H47 and colicin E1 production, respectively. Moreover, colicin E1 itself appears to be a potentially important virulence factor of certain uropathogenic E. coli strains. © 2010 Šmajs et al; licensee BioMed Central Ltd.
Kianicka B.,St Annes University Hospital Brno |
Dite P.,Faculty Hospital Brno |
Piskac P.,St Annes University Hospital Brno
Hepato-Gastroenterology | Year: 2012
Background/Aims: The aim of this retrospective study is the analysis of the success rate of diagnostic and therapeutic endoscopic retrograde cholangiopancreatography (ERCP) in our group of patients with Billroth 11 gastrectomy. Methodology: The study of the group was carried out during 14 years, i.e. from November 1994 to December 2008. It retrospectively evaluates 120 patients with Billroth II gastrectomy. Results: A cannulation success rate of 90.8% (109 of 120 patients) was reached in performing ERCP in 120 patients with Billroth II gastrectomy. There were normal ERCP results in 4 patients. ERCP results in the remaining 105 patients were pathological. Endoscopic treatment was started in all of these 105 patients immediately after diagnostic ERCP. Overall, therapeutic ERCP was completely successful in 91 of 105 patients (86.66%) who were originally treated with endoscopy. Conclusions: ERCP in patients with Billroth II gastrectomy is much more demanding in contrast with standard procedure due to different postoperative anatomy. ERCP success is determined mainly by great personal experience and skillfulness of the endoscopist. ERCP performed lege artis in patients with Billroth II gastrectomy is a highly effective and safe method where the success rate reached can be almost the same as in a normal anatomical situation. © H.G.E. Update Medical Publishing S.A.
Joeris A.,University of Bern |
Ondrus S.,Faculty Hospital Brno |
Planka L.,Faculty Hospital Brno |
Gal P.,Faculty Hospital Brno |
Slongo T.,University of Bern
European Journal of Pediatric Surgery | Year: 2010
Objective: Benign bone lesions in children although rare, can result in a pathological fracture. Although their etiology and pathogenesis are not yet entirely clear, the phenomenon of spontaneous healing is well known. Nevertheless, some benign bone lesions are unlikely to heal spontaneously due to the patient's age or high risk of fracture and deformity due to the lesion's location or size. The following study presents our results after treatment of these bone cysts with chronOS Inject. Methods: From June 2004 to May 2007 23 patients with 24 benign bone cysts were treated with chronOS Inject, an injectable tricalcium phosphate, using a minimally invasive technique at two pediatric surgery departments. Postoperative follow-up examined bone healing, remodeling, chronOS Inject resorption and adverse effects. Results: 15 males and 9 females, mean age 11 years at time of diagnosis, were treated with chronOS Inject. The humerus was affected 13 times, the femur 7 times, the tibia twice and the radius, the fibula and talus once each. Except for one case, all pathological fractures healed within five weeks post-injection. Two children had cystic residues. No severe adverse effects were seen. Conclusions: These preliminary results indicate that chronOS Inject could provide an alternative treatment for benign bone cysts that are unlikely to heal spontaneously due to the patient's age, high risk of instability or pathological fracture due to the lesion's size or location, or lesions that have already been treated several times using other methods without success. © Georg Thieme Verlag KG Stuttgart - New York.