The interval between progression and therapy initiation is the key prognostic parameter in relapsing diffuse large B cell lymphoma: analysis from the Czech Lymphoma Study Group database (NIHIL).

Relapsing diffuse large B cell lymphomas (rDLBCL) represent a heterogeneous disease. This heterogeneity should be recognized and reflected, because it can deform the interpretation of clinical trial results. DLBCL patients with the first relapse and without CNS involvement were identified in the Czech Lymphoma Study Group (CLSG) database. Interval-to-therapy (ITT) was defined as the time between the first manifestation of rDLBCL and the start of any treatment. The overall survival (OS) of different ITT cohorts (< 7 vs. 7-21 vs. > 21 days) was compared. In total, 587 rDLBCLs (51.8% males) progressed with a median of 12.8 months (range 1.6 to 152.3) since the initial diagnosis (2000-2017). At the time of relapse, the median age was 67 years (range 22-95). First-line therapy was administered in 99.3% of the patients; CHOP and anti-CD20 were given to 69.2% and 84.7% of the patients, respectively. The salvage immune/chemotherapy was administered in 88.1% of the patients (39.2% platinum-based regimen). The median ITT was 20 days (range 1-851), but 23.2% of patients initiated therapy within 7 days. The 5-year OS was 17.4% (range 10-24.5%) vs. 20.5% (range 13.5-27.4%) vs. 42.2% (range 35.5-48.8%) for ITT < 7 vs. 7-21 vs. > 21 days (p < 0.001). ITT was associated with B symptoms (p 0.004), ECOG (p < 0.001), stage (p 0.002), bulky disease (p 0.005), elevated LDH (p < 0.001), and IPI (p < 0.001). The ITT mirrors the real clinical behavior of rDLBCL. There are patients (ITT < 7 days) with aggressive disease and a poor outcome. Conversely, there are rDLBCLs with ITT ≥ 21 days who survive for a long time.

First-line therapy for T cell lymphomas: a retrospective population-based analysis of 906 T cell lymphoma patients.

Peripheral T cell lymphomas (PTLs) have a globally poor prognosis. The CHOP regimen shows insufficient efficacy; first-line consolidation with autologous stem cell transplantation (auto-SCT) is a promising strategy but has never been confirmed by randomized data. We analyzed retrospectively 906 patients diagnosed with PTL between 1999 and 2015. Chemotherapy was given to 862 patients, and 412 of them were < 60 years. In this subset, we compared induction with CHOP (n = 113) vs. CHOEP (n = 68) and tested auto-SCT (n = 79) vs. no SCT (n = 73) in the intent-to-treat analysis. The median age of the whole cohort at diagnosis was 60 years (range; 18-91); the median follow-up was 4.3 years (range; 0.1-17.8). A shorter overall survival (OS) was associated with the male gender, age ≥ 60 years, stage III/IV, performance status ≥ 2, bulky tumor ≥ 10 cm, and elevated LDH. CHOEP induction showed a better 5-year PFS (25.0% vs. 32.9%; p.001), and 5-year OS (65.6% vs. 47.6%; p.008) than CHOP. Auto-SCT compared to no SCT brought a 5-year OS of 49.2% vs. 59.5% (p.187). Auto-SCT did not influence the OS in low-risk or low-intermediate risk PTLs. The high-intermediate and high-risk IPIs displayed a worse 5-year OS in auto-SCT arm (17.7% vs.46.2%; p.049); however, 73.9% of the patients never received planned auto-SCT. Our population-based analysis showed the superiority of CHOEP over CHOP in first-line treatment. We confirm the 5-year OS of around 50% in PTLs undergoing auto-SCT. However, the intended auto-SCT could not be given in 73.9% of the high-risk PTLs.

The incidence of biopsy-proven transformation in follicular lymphoma in the rituximab era. A retrospective analysis from the Czech Lymphoma Study Group (CLSG) database.

The aim of this study is to assess the incidence, risk factors, and outcome of biopsy-proven transformation in follicular lymphoma (FL) patients in the rituximab era. Transformation was analyzed in 1233 patients with initially diagnosed FL grades 1-3A, identified between 2002 and 2012 in the prospectively maintained Czech Lymphoma Study Group database. Only patients with histologically proven transformation (HT) were included. HT occurred in 58 cases at a median of 3.0 years from the initial FL diagnosis; the HT rate was 4% at 5 years. Transformation occurred most frequently at the first relapse (84% patients). Median OS from the HT was 2.5 years (95% CI 0.4-4.6) and 6-year OS with HT was shorter compared to all FLs (60 vs. 83.9%; 95% CI). A bulky tumor (≥ 10 cm), increased lactate dehydrogenase, age ≥ 60 years, and International Prognostic Index (intermediate/high risk), but not Follicular Lymphoma International Prognostic Index, were associated with transformation (p < 0.05). In the first line, 70% of patients received rituximab (including 36% rituximab maintenance), 57% CHOP-like regimens, and 2.6% of patients were treated with fludarabine-based therapy, whereas 11% of patients were watched only. The patients treated with R-CHOP in the first line (n = 591) showed the transformation rate at 5 years of 4.23% (95% CI 2.52-5.93); subsequent rituximab maintenance (n = 276) vs. observation (n = 153) was associated with a lower transformation rate (p.033; HR 3.29; CI 1.10-9.82). The transformation rate seems to be lower than in previous series, which may be influenced by broad use of rituximab, but prognosis of HT developed during therapy continues to be poor.

Utilization and efficacy of second-line targeted therapy in metastatic renal cell carcinoma: data from a national registry.

BACKGROUND: It is well known that patient characteristics and survival outcomes in randomized trials may not necessarily be similar to those in real-life clinical practice. The aim of the present study was to analyse second line treatment strategies in the real-world practice and to estimate the outcomes of patients treated with second-line targeted therapy for metastatic renal cell carcinoma (mRCC). METHODS: This is a retrospective, registry-based study using data from the national registry of targeted therapies for mRCC. The RENIS registry contains data on 3049 patients who started the therapy with at least one targeted agent before 31 December, 2014. Of these patients, 1029 had a record of at least two different targeted therapies and sufficient data for analysis. Survival analysis was carried out using the Kaplan-Meier method. Statistical significance of differences in survival between subgroups was assessed using the log-rank test. RESULTS: The median overall survival from the start of second-line treatment was 17.0 months (95% confidence interval [CI] 14.5-19.5 months), 17.1 months (95% CI 14.5-19.8), and 15.4 months (95% CI 11.0-19.7) for second-line everolimus, sorafenib, and sunitinib, respectively. Patients receiving second-line everolimus were older at the start of second-line treatment, more likely to have metachronous disease, and less likely to be previously treated with cytokines or to continue to third-line treatment than patients treated with second-line sunitinib or sorafenib. Progression-free survival (PFS) correlated with PFS on first-line treatment only for everolimus. CONCLUSIONS: In this retrospective study, no significant differences in survival were observed between the cohorts treated with different second-line agents including everolimus, sorafenib, and sunitinib.

Weight Concerns Associated With Delay in Quit Date But Not Treatment Outcomes: A Czech Republic Experience.

BACKGROUND: Weight concerns are prevalent in smokers and may reduce the success rate of quitting. This concept has been primarily studied on US populations and it is unknown how weight concerns may differ cross-culturally. This study examined the role of weight concern in European smokers wishing to stop smoking. METHODS: A sample of 593 smokers (299 men and 294 women, mean age 38 years) utilizing the Centre for Tobacco-Dependent in Prague, Czech Republic, between 2010 and 2013 were studied. Weight concerns were assessed at baseline prior to treatment by evidence-based stop smoking methods. Abstinence was evaluated at 12 months post baseline. RESULTS: Approximately 34% of all patients (204/593) were classified as weight concerned (by indicating on the Weight Concern Scale that they would return to smoking after any weight gain) at the time they sought treatment. Among all men, 19.4% (58/299) were weight concerned and among all women, 49.7% (146/294) were weight concerned. Among females, weight-concerned smokers were of similar weight, but younger (p < .001), and had been smoking cigarettes for fewer years (p = .002) compared with those without weight concerns, whereas the male weight-concerned smokers were significantly (p = .030) heavier than those without weight concerns. Although the presence of weight concern was associated with a delay in setting a quit date (log-rank test p = .019), it was not associated with abstinence at one year. CONCLUSION: The quit success rate of weight-concerned smokers in Czech Republic did not differ from those without weight concern when utilizing an individualized smoking cessation treatment program. Individually tailored tobacco dependence treatment could help to prevent weight concern from affecting successful quitting. IMPLICATIONS: This study adds the new cross-cultural aspect of post-cessation weight concern. Weight concern has been studied primarily on US populations and our sample consists of European sample of smokers. Additionally, we have found that the presence of weight concern lead to delay in setting a quit date, but the success rate of those weight concerned did not differ from those without weight concern. Thus, it is possible, that this individualized evidence-based tobacco treatment program was able to prevent weight concern impact towards successful quitting.

Combined Proteomics and Transcriptomics Identifies Carboxypeptidase B1 and Nuclear Factor κB (NF-κB) Associated Proteins as Putative Biomarkers of Metastasis in Low Grade Breast Cancer.

Current prognostic factors are insufficient for precise risk-discrimination in breast cancer patients with low grade breast tumors, which, in disagreement with theoretical prognosis, occasionally form early lymph node metastasis. To identify markers for this group of patients, we employed iTRAQ-2DLC-MS/MS proteomics to 24 lymph node positive and 24 lymph node negative grade 1 luminal A primary breast tumors. Another group of 48 high-grade tumors (luminal B, triple negative, Her-2 subtypes) was also analyzed to investigate marker specificity for grade 1 luminal A tumors. From the total of 4405 proteins identified (FDR < 5%), the top 65 differentially expressed together with 30 previously identified and control markers were analyzed also at transcript level. Increased levels of carboxypeptidase B1 (CPB1), PDZ and LIM domain protein 2 (PDLIM2), and ring finger protein 25 (RNF25) were associated specifically with lymph node positive grade 1 tumors, whereas stathmin 1 (STMN1) and thymosin beta 10 (TMSB10) associated with aggressive tumor phenotype also in high grade tumors at both protein and transcript level. For CPB1, these differences were also observed by immunohistochemical analysis on tissue microarrays. Up-regulation of putative biomarkers in lymph node positive (versus negative) luminal A tumors was validated by gene expression analysis of an independent published data set (n = 343) for CPB1 (p = 0.00155), PDLIM2 (p = 0.02027) and RELA (p = 0.00015). Moreover, statistically significant connections with patient survival were identified in another public data set (n = 1678). Our findings indicate unique pro-metastatic mechanisms in grade 1 tumors that can include up-regulation of CPB1, activation of NF-κB pathway and changes in cell survival and cytoskeleton. These putative biomarkers have potential to identify the specific minor subpopulation of breast cancer patients with low grade tumors who are at higher than expected risk of recurrence and who would benefit from more intensive follow-up and may require more personalized therapy.

PET/CT imaging in polymyalgia rheumatica: praepubic 18F-FDG uptake correlates with pectineus and adductor longus muscles enthesitis and with tenosynovitis.

BACKGROUND: The role of 18F-fluorodeoxyglucose positron emission computed tomography (18F-FDG PET/CT) is increasing in the diagnosis of polymyalgia rheumatica (PMR), one of the most common inflammatory rheumatic diseases. In addition to other locations, increased 18F-FDG accumulation has been detected in the praepubic region in some patients. However, a deeper description and pathophysiological explanation of this increased praepubic accumulation has been lacking. The aim of the presented study is to confirm a decrease in praepubic 18F-FDG accumulation in response to therapy and to describe potential correlations to other 18F-FDG PET/CT scan characteristics during the course of disease. As a secondary objective, we describe the pathological aspects of the observed praepubic 18F-FDG uptake. PATIENTS AND METHODS: A retrospective review of patients with newly suspected PMR undergoing baseline and follow up 18F-FDG PET/CT between February 2010 and March 2016 is given. Those with a visually detected presence of praepubic 18F-FDG accumulation were further analysed. The uptake was assessed visually and also semi-quantitatively in the defined region of interest by calculation of target-to-liver ratios. Other regions typical for PMR were systematically described as well (shoulders, hips, sternoclavicular joints, ischiogluteal bursae, spinous interspaces). RESULTS: Twenty-three out of 89 screened patients (26%) presented with initial praepubic 18F-FDG PET/CT positivity, 15 of whom also underwent follow up 18F-FDG PET/CT examination. Five out of 15 patients presented with increased 18F-FDG accumulation in large arteries as a sign of giant cell arteritis. During follow up examination, decrease in 18F-FDG accumulation caused by therapeutic intervention was observed in all evaluated locations in all analysed patients and no new positivity was indicated, including periarticular, extraarticular tissues or target large vessels. Praepubical accumulation of 18F-FDG was diminished in all patients (15/15, 100%) after treatment with steroids. CONCLUSIONS: Increased praepubic 18F-FDG uptake in patients with PMR is relatively common and this region should be systematically evaluated during differential diagnosis of rheumatic and malignant disease. Praepubic inflammation is probably related to enthesitis and tenosynovitis at the origin of pectineus and adductor longus muscles ventrally from the pubis.

G12V and G12A KRAS mutations are associated with poor outcome in patients with metastatic colorectal cancer treated with bevacizumab.

The v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations are found in 35-45 % of colorectal cancer (CRC) cases. Although the association between the RAS signaling and angiogenesis is well known, the negative predictive value of KRAS mutation has not been established in patients treated with bevacizumab. The aim of this study was to evaluate the association between specific KRAS mutation types and outcome of patients with metastatic CRC treated with bevacizumab. The study included 404 patients with metastatic CRC (mCRC) treated with bevacizumab. Clinical data obtained from the clinical registry CORECT were retrospectively analyzed. The shortest survival was observed in patients with tumors harboring G12V or G12A KRAS mutation (G12V/A). The median progression-free survival (PFS) and overall survival (OS) for patients with tumors harboring G12V/A KRAS mutation was 6.6 and 16.8 compared to 11.6 and 26.3 months for patients with tumors harboring other KRAS mutation type (p < 0.001 and p < 0.001), while the survival of patients harboring other KRAS mutation types was comparable to those with tumors harboring wild-type KRAS gene. In the Cox multivariable analysis, KRAS G12V/A mutation type remains a significant factor predicting both PFS (HR = 2.18, p < 0.001) and OS (HR = 2.58, p < 0.001). In conclusion, the results of the present study indicate that there is a significant difference in biological behavior between tumors harboring G12V/A and other KRAS mutations. Moreover, comparison of the survival of patients with tumors harboring G12V/A KRAS mutations with those harboring wild-type KRAS gene revealed that G12V/A KRAS mutations are prognostic biomarker for inferior PFS and OS in patients with mCRC treated with bevacizumab in univariate as well as multivariable analyses.

Statins augment efficacy of EGFR-TKIs in patients with advanced-stage non-small cell lung cancer harbouring KRAS mutation.

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) represent novel effective agents approved for the treatment of patients with advanced-stage NSCLC. KRAS mutations have been reported as a negative prognostic and predictive factor in patients with NSCLC treated with EGFR-TKIs. Several studies have recently shown that statins can block tumour cell growth, invasion and metastatic potential. We analysed clinical data of 67 patients with locally advanced (IIIB) or metastatic stage (IV) NSCLC harbouring Kirsten rat sarcoma viral oncogene (KRAS) mutation treated with erlotinib or gefitinib. Twelve patients were treated with combination of EGFR-TKI and statin and 55 patients were treated with EGFR-TKI alone. Comparison of patients' survival (progression-free survival (PFS) and overall survival (OS)) according to the treatment used was performed using the Gehan-Wilcoxon test. The median of PFS and OS for patients treated with EGFR-TKI alone was 1.0 and 5.4 months compared to 2.0 and 14.0 months for patients treated with combination of EGFR-TKI and statin (p = 0.025, p = 0.130). In conclusion, the study results suggest significant improvement of PFS for patients treated with combination of statin and EGFR-TKI, and the difference in OS was not significant.

High serum level of C-reactive protein is associated with worse outcome of patients with advanced-stage NSCLC treated with erlotinib.

Erlotinib is a low molecular weight tyrosine kinase inhibitor (TKI) directed at epidermal growth factor receptor (EGFR), widely used in the treatment of locally advanced or metastatic-stage non-small cell lung cancer (NSCLC). Although introduction of EGFR-TKIs have significantly extended survival of advanced-stage NSCLC patients, their efficacy in the entire patient population is relatively low. Aside from activating EGFR mutations, no reliable biochemical or molecular predictors of response to erlotinib have been established. The aim of our retrospective study was to evaluate the association of baseline serum levels of C-reactive protein (CRP) with outcomes in patients with advanced-stage NSCLC treated with erlotinib. We retrospectively analyzed clinical data of 595 patients with advanced-stage NSCLC (IIIB or IV) treated with erlotinib. Serum CRP was measured using an immunoturbidimetric method. High baseline levels of CRP (≥10 mg/l) were measured in 387 (65 %) patients, and normal levels (<10 mg/l) were measured in 208 (35 %) patients. The median progression-free survival (PFS) and overall survival (OS) for patients with high CRP was 1.8 and 7.7 compared to 2.8 and 14.4 months for patients with low CRP (p < 0.001 and p < 0.001). The multivariable Cox proportional hazards model revealed that CRP was significantly associated with PFS and also with OS (hazard ratio (HR) = 1.57, p < 0.001, and HR = 1.63, p < 0.001, respectively). In conclusion, the results of the conducted retrospective study suggest that high baseline level of CRP was independently associated with worse outcome of patients with advanced-stage NSCLC treated with erlotinib. CRP is a commonly used biomarker which is simple and easy to detect, and thus, it is feasible for the use in the routine clinical practice.

Efficacy of bevacizumab and chemotherapy in the first-line treatment of metastatic colorectal cancer: broadening KRAS-focused clinical view.

BACKGROUND: The aim of the present retrospective study was to analyze clinical outcome and risk factors associated with treatment outcomes according to KRAS status in patient with metastatic colorectal cancer (mCRC) treated with bevacizumab (bev) plus chemotherapy in the first-line setting. METHODS: We performed observational study on 1622 patients with mCRC treated with bev plus oxaliplatin- or irinotecan-based chemotherapy, and correlated treatment outcomes with KRAS mutation status. The primary endpoint was progression-free survival (PFS) and additionally overall survival (OS). Adverse events of bevacizumab and risk factors including location of metastases were evaluated. RESULTS: Mutation in KRAS was present in 40.6% of mCRC cases. The median PFS in patients with wild-type KRAS (wtKRAS) vs mutant KRAS was 11.5 vs 11.4 months, respectively. The median OS was 30.7 vs 28.4 months (p = 0.312). Patients with KRAS mutation had lung metastases more frequently than wtKRAS individuals (32.0% vs 23.8%; p = 0.001). We observed no difference in clinical outcome between hepatic and extrahepatic metastatic disease. CONCLUSION: KRAS mutation does not interfere with clinical benefit from first-line treatment with bevacizumab plus chemotherapy in mCRC patients.

Bevacizumab with chemotherapy in patients with KRAS wild-type metastatic colorectal cancer: Czech registry data.

AIM: This retrospective analysis investigated the effectiveness of combination therapy with bevacizumab and chemotherapy in the first-line treatment of patients with KRAS wild-type metastatic colorectal cancer. PATIENTS & METHODS: Patients with KRAS wild-type metastatic colorectal cancer in the CORECT registry who initiated treatment with bevacizumab between 2008 and 2012 were enrolled. Overall survival and progression-free survival were the main effectiveness end points. RESULTS: A total of 981 patients were enrolled. Median progression-free survival was 11.3 months (95% CI: 10.7-11.8) and median overall survival was 28.4 months (95% CI: 26.2-30.6). The most common adverse events were thromboembolic disease (4%) and hypertension (3.5%). CONCLUSION: This retrospective analysis shows the effectiveness of bevacizumab with chemotherapy in patients with KRAS wild-type metastatic colorectal cancer.

[When should empirical antibiotic therapy be indicated in acute community-onset diarrhea of suspected bacterial etiology]. / Kdy indikovat empirickou antibiotickou lécbu u akutní komunitní gastroenyerokolitidy suspektní bakteriální etiologie?

BACKGROUND: The aims of this study were to describe the basic parameters of adult patients with acute community-onset salmonellosis or campylobacteriosis responsible for more than 90 % of all cases of community-onset diarrhea in the Czech Republic, and, according to the results of this analysis, to update the diagnostic and therapeutic algorithms. MATERIALS AND METHODS: The data were collected retrospectively between January 1, 2011 and December 31, 2013. Patients with systemic signs of infection having at least 2 signs of systemic inflammatory response syndrome (SIRS) or with elevated serum procalcitonin levels (more than 0.5 ng/ml) were classified as being at risk for the invasive form of the disease. The remaining patients were classified as having the simple intestinal form of the disease. Patients with community-onset post-antibiotic diarrhea were excluded. The data were statistically processed. RESULTS: The following clinical factors were statistically significantly correlated with the high-risk form of the disease: duration of illness of less than 3 days before admission and any of the following (some of them are part of the SIRS classification), even after being adjusted for age: body temperature above 38 °C, peripheral blood white cell count (WBC) above 12 × 109/l, neutrophil count above 9 × 109/l and CRP level above 150 mg/l. The risk form of the disease occurred in 60 cases (18.7 %). The mean WBC was 9.4 × 109/l (median, 8.4; range, 1.7-89.0). The WBC within the normal range was seen in 194 cases (60.4 %). The mean CRP level was 92.9 mg/l (median, 77.0; range, 1.0-342.0). An elevated procalcitonin level was seen in 21 patients; the marker was not routinely measured. Positive blood culture results were obtained in 2 persons with salmonellosis; the examination was not routinely performed. There were 34 patients (10.6 %) with documented immune system dysfunction; the risk form of salmonellosis or campylobacteriosis was seen in only 11 of them (3.4 %). A total of 306 patients (95.3 %) were treated with antibiotics; the mean duration of antibiotic therapy was 8.7 days (median, 7; range, 2-31). CONCLUSIONS: Antibiotic treatment in salmonellosis/campylobacteriosis should not be indicated only due to elevated CRP levels but rather after comprehensive evaluation of the duration of symptoms, individual risk factors and dynamic changes in markers of inflammation. Blood culture tests should be carried out more frequently.

Bevacizumab with 5-fluorouracil, leucovorin, and oxaliplatin versus bevacizumab with capecitabine and oxaliplatin for metastatic colorectal carcinoma: results of a large registry-based cohort analysis.

BACKGROUND: Data from the Czech national registry were analysed retrospectively to describe treatment outcomes for capecitabine and oxaliplatin (XELOX) regimen with bevacizumab versus 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) regimen with bevacizumab in the first-line therapy for metastatic colorectal cancer (mCRC). METHODS: A national registry containing anonymised individual data on patients treated with targeted therapies was used as a data source. In total, 2,191 mCRC patients who received a first-line therapy with bevacizumab combined with either FOLFOX regimen (n = 1,218, 55.6%) or XELOX regimen (n = 973, 44.4%) were included in the present analysis. RESULTS: No statistically significant difference in survival was observed between the two groups, with median overall survival (OS) of 27.0 months (95% confidence interval [CI] 24.6-29.5 months) and 30.6 months (95% CI 27.8-33.4 months) for FOLFOX/bevacizumab and XELOX/bevacizumab, respectively (p = 0.281). Median progression-free survival (PFS) was 11.4 months (95% CI 10.7-12.1 months) for FOLFOX/bevacizumab and 11.5 months (95% CI 10.8-12.3 months) for XELOX/bevacizumab (p = 0.337). The number of metastatic sites was identified as the most significant predictor of PFS and, together with the presence/absence of metastatic disease at diagnosis, also for OS. CONCLUSIONS: According to this large registry-based analysis, XELOX and FOLFOX regimens have similar effectiveness for use in combination with bevacizumab in the first-line treatment of mCRC. Multiple metastatic sites and the presence of metastatic disease at diagnosis were the strongest negative predictors of OS regardless of backbone chemotherapy regimen.

Efficacy and safety of bevacizumab in elderly patients with metastatic colorectal cancer: results from the Czech population-based registry.

BACKGROUND: Patients aged 65 years and older represent the majority of patients with metastatic colorectal cancer (mCRC). However, this patient population is often underrepresented in clinical trials and probably undertreated in the clinical practice. METHODS: We have analysed the outcomes of 3,187 mCRC patients treated with first-line bevacizumab based on data from the Czech national registry of mCRC patients aiming to compare the treatment efficacy and safety according to the age categories. RESULTS: In total, 2,126 (66.7%), 932 (29.2%), and 129 (4.0%) patients were aged <65 years, 65 to 75 years, and 75+ years, respectively. Median progression-free survival (PFS) was 11.4, 11.3, and 11.8 months for patients aged <65 years, 65 to 75 years, and 75+ years, respectively (p = 0.94). Median overall survival (OS) was 26.9, 27.5, and 25.1 months for patients aged <65 years, 65 to 75 years, and 75+ years, respectively (p = 0.73). Using multivariable Cox model for both PFS and OS, the patient age was not significantly associated with either PFS or OS. No increase in bevacizumab-related toxicity was observed among the elderly mCRC patients with the exception of hypertension, which was observed in 71 (3.3%), 34 (3.6%), and 10 (7.8%) patients aged <65 years, 65 to 75 years, and 75+ years, respectively. CONCLUSIONS: The results of the present study suggest similar outcome in terms of OS and PFS with bevacizumab-containing therapy in elderly mCRC patients fit for chemotherapy combined with targeted therapy compared to younger patients. Thus, chronological age should not be considered to represent a limitation in prescribing bevacizumab-containing therapy in mCRC patients.

[PET-CT documented complete remission of Erdheim-Chester disease, lasting more than 4 years from treatment initiation with cladribine]. / PET-CT dokumentovaná kompletní 4letá remise Erdheimovy-Chesterovy nemoci po lécbe kladribinem.

Erdheim-Chester disease is a very rare histiocytic disease. It represents one form of juvenile xanthogranuloma in WHO classification of blood diseases. The disease often causes B symptoms, skeletal pain and also may cause diabetes insipidus and retroperitoneal fibrosis. Selection of therapy depends on published case reports and small clinical trials. There are no recommendations for treatment based on randomized studies. Interferon α is probably the most commonly used drug for this disease. Some remissions have been described after treatment. However, long-term interferon α application is needed which is associated with numerous side effects. There are limited experiences with clabridine in this indication. In Pubmed Medline database, we have found 3 publications dedicated to description of treatment response after cladribine in Erdheim-Chester disease and other 7 papers evaluating effect of cladribine on juvenile xanthogranuloma forms, mostly with positive outcome. Based on these 10 publications we choose cladribine as first-line treatment in our patient. The treatment started in October 2009 with combination of 2-chlorodeoxyadenosine (Litak) 5 mg/m2 sc. + cyclophosphamide 150 mg/m2 iv. + dexamethasone 24 mg iv., five days consecutively. These cycles were repeated monthly. Mentioned formula was submitted 4 times and 3 times in limited application on day 1 - 3. The reason of that was neutropenia grade 3. All symptoms disappeared after treatment. Only diabetes insipidus persisted because damage of pituitary stalk is irreversible. Therapeutic effect was monitored by PET-CT imaging, initially every 6 months, later in 12-month intervals. PET-CT imaging showed complete remission of disease and 4.5 years duration of remission after treatment. The treatment was well tolerated with no complications implying hospitalization. Only mild thrombocytopenia and neutropenia remains after 4.5 years. Based on case report and publications we consider cladribine as appropriate firs-line drug for Erdheim-Chester disease. Therapeutic failure after 3-4 cycles may suggest other options (interferon α, anakinra, vemurafenib), but only in the case if healthcare provider is willing to cover this new and more expansive treatment than therapy with cladribine.

Tobacco treatment outcomes in patients with and without a history of depression, Czech Republic, 2005-2010.

INTRODUCTION: Higher prevalence of smoking among depressed patients, as well as the risk of depression in smokers, is well documented. The proportion of patients with a history of depression among those seeking intensive treatment of tobacco dependence is also high. In contrast, evidence of treatment success in this subgroup of patients is controversial. The aim of this study was to compare smoking abstinence rates after tobacco treatment in smokers with and without a history of depression. METHODS: We reviewed retrospective data from 1,730 smokers seeking treatment in Prague, Czech Republic. History of depression was defined as past diagnosis of depression or current treatment of depression. After a 1-year, self-reported smoking status was validated by expired-air carbon monoxide. We used logistic regression to analyze associations between abstinence rates, history of depression, and other factors (eg, age, sex, tobacco dependence). RESULTS: Of 1,730 smokers treated, 289 (16.7%) had a history of depression. The smoking abstinence rate at 1 year was 32.5% for smokers with a history of depression and 38.7% for those with no history (P = .048). Among women, abstinence did not differ between groups (35.0% vs 35.7%; P = .86). However, among men, those with a history of depression had lower rates of abstinence (27.4% vs 41.3%; P = .009). After adjustment for baseline covariates, history of depression was not significantly associated with smoking abstinence in men or women. CONCLUSION: Intensive outpatient tobacco treatment programs can achieve abstinence rates among smokers with a history of depression similar to rates among the general population.

The role of a center for tobacco-dependent in cardiovascular prevention. A retrospective study.

OBJECTIVES: Smoking cessation is an essential part of cardiovascular disease (CVD) prevention. At the Center for Tobacco-Dependent (CTD), clients are screened to identify and reduce cardiovascular (CV) risk factors. In our study we have focused on the role of the CTD in reducing global CV risk. METHODS: 1,334 CTD patients aged 25-64 years (52.2% men, mean age 44±12 years, Fagerström Test for Cigarette Dependence 6±2) were included in a retrospective cross-sectional survey. Medical history, blood samples and physical examination were analysed. Blood pressure, weight and exhaled CO were measured at each visit (12-months-follow-up). Patients' CV risk was scored. CO-verified abstinence according to CV risk and prevalence of detected CV risk factors were examined. RESULTS: Among patients who had attended at least their first visit and a visit after one year, 37.9% (506/1,334) had stopped smoking. Among patients with a SCORE of <5%, the success rate was 44.3% (254/574) and 41.2% for patients at high CV risk (105/255, p=0.41). There was a trend towards a lower success rate among patients with CVD, but this difference was not significant. The smoking cessation rate among low and high CV risk patients at the baseline visit was identical (46.2%, resp. 47.3%, p=0.81). 3.1% (42/1,334) of patients were referred to a specialist for hypertension. 62.5% (223/357), without a prior history, were found to have dyslipidemia. CONCLUSIONS: High CV risk patients have the same chance to stop smoking as low risk patients.

Surface-enhanced laser desorption ionization/time-of-flight (SELDI-TOF) mass spectrometry (MS) as a phenotypic method for rapid identification of antibiotic resistance.

Based on experiments with 10 defined strains of Escherichia coli, we present a new method for bacterial phenotyping using SELDI-TOF mass spectrometry. Changes in bacterial protein profiles in the context of the time of cultivation and the antibiotic environment were minimal. Proteom subprofiling may further distinguish between strains with specific susceptibility to antimicrobials. Mass spec-based methods may become common in the future of bacterial pathogen identification in clinical microbiology diagnostics.

Regorafenib in the Real-Life Clinical Practice: Data from the Czech Registry.

OBJECTIVE: To describe the use of regorafenib for the treatment of metastatic colorectal cancer (mCRC) in clinical practice in the Czech Republic, and to describe the clinical outcomes of patients in terms of safety and survival. PATIENTS AND METHODS: The data of patients treated with regorafenib were extracted from the national CORECT registry. The CORECT registry is a non-interventional post-marketing database, gathering information about patients with CRC and treated with targeted agents. Twenty oncology centres in the Czech Republic contributed to this registry. Collected data included patients' characteristics, disease history, cancer treatments, response to treatments and safety. RESULTS: A total of 148 patients treated with regorafenib in clinical practice were analysed. At regorafenib initiation, almost all patients were fully active or slightly restricted in physical activity. Regorafenib was not administered as first-line treatment in any patient. Median progression-free survival was 3.5 months and median overall survival was 9.3 months. One-year survival rate was 44.6 %. Four partial responses were observed and 51 stable diseases. Progression was observed in 66 patients (44.6 %). The main reported adverse events were skin toxicity (5.4 %) and fatigue (2.0 %). CONCLUSIONS: Regorafenib is a well-established treatment for pretreated patients with mCRC, however real-life data are scarce. Our results demonstrated slightly better efficacy of regorafenib and better safety profile in patients with mCRC compared to the randomised trials.