[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
KRAS mutation does not interfere with clinical benefit from first-line treatment with bevacizumab plus chemotherapy in mCRC patients.
[Show abstract][Hide abstract] ABSTRACT: Drug addiction is commonly associated with depression and comorbid patients also suffer from higher cravings and increased relapse rate. To address this issue preclinically we combined the olfactory bulbectomy (OBX) model of depression and intravenous methamphetamine self-administration procedure in rats to assess differences in relapse-like behavior. Male Sprague-Dawley rats were divided randomly into two groups; in one group the bilateral olfactory bulbectomy (OBX) was performed while the other group was sham operated. After recovery, intracardiac catheter was implanted. Intravenous self-administration procedure was conducted in operant boxes using nose-poke operandi (Coulbourn Instruments, Inc., USA) under fixed ratio 1 schedule of reinforcement. Methamphetamine was available at dose 0.08 mg/kg/infusion. After stable methamphetamine intake was maintained, a period of forced abstinence was initiated and rats were kept in their home-cages for 14 days. Finally, one reinstatement session was conducted in operant boxes with no drug delivery. In the reinstatement session the mean of 138.4 active nose-pokes was performed by the OBX group, while the sham group displayed 41 responses, i.e. 140 % and 48 % of basal nose-poking during maintenance phase in OBX and sham operated group respectively. OBX group also showed significantly more passive nose-pokes indicating hyperactive behavioral traits in bulbectomized rats. However, the % of active operandum preference was equal in both groups. Olfactory bulbectomy model significantly increased reinstatement of methamphetamine seeking behavior. This paradigm can be used to evaluate potential drugs that are able to suppress the drug-seeking behavior.
Behavioural brain research 10/2015; DOI:10.1016/j.bbr.2015.09.035 · 3.03 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
The role of co-morbidities in the prognosis of patients hospitalized for AHF was examined using the AHEAD (A - atrial fibrillation, H - haemoglobin<130g/l for men and 120g/l for women (anaemia), E - elderly (age>70years), A - abnormal renal parameters (creatinine>130μmol/l), D - diabetes mellitus) scoring system.
AHEAD - multicentre prospective Czech registry of AHF patients; GREAT registry - international cohort of AHF patients. Data from 5846 consecutive patients hospitalized for AHF (AHEAD registry; derivation cohort) were analysed to build the AHEAD score. Each risk factor of the AHEAD score was counted as 1 point. The model was validated externally using an international cohort of similar patients in the GREAT registry (6315).
Main outcome was one year all-cause mortality. The mean age of patients was 72±12years, with 61.6% of patients aged >70years; 43.4% were women. Atrial fibrillation was present in 30.7%, anaemia in 38.2%, creatinine >130mmol/l (abnormal renal parameters) in 30.1%, and diabetes mellitus in 44.0%. The mean AHEAD score was 2.1. In patients with AHEAD scores of 0-5, the one-year mortality rates were 13.6%, 23.4%, 32.0%, 41.1%, 47.7%, and 58.2%, respectively (p<0.001), and the 90month mortality rates were 35.1%, 57.3%, 73.5%, 84.8%, 88.0%, and 91.7%, respectively (p<0.001).
The AHEAD is a simple scoring system based on the analysis of co-morbidities for the estimation of the short and long term prognosis of patients hospitalized for AHF.
International journal of cardiology 09/2015; 202:21-26. DOI:10.1016/j.ijcard.2015.08.187 · 4.04 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: AimsThis paper aims to investigate whether intraepidermal nerve-fibre density (IENFD) may be used as a marker of the course of neuropathy in patients with Type 2 diabetes mellitus.Methods
Skin biopsies from the distal leg were serially evaluated in a group of 30 patients with Type 2 diabetes mellitus (median age 60 years, 17 men) with a short duration of diabetes (< 3 years) and good glucose control, and in 23 age- and sex-matched controls. The time intervals between biopsies were > 2 years (median 33.8 months). Eighteen patients with Type 2 diabetes mellitus had symptoms or signs of distal symmetrical diabetic polyneuropathy, 12 had no neuropathy.ResultsAt first skin biopsy, IENFD was normal in all controls and in patients without neuropathy (mean 9.5 and 7.9 fibres/mm, respectively) compared with abnormal IENFD in 77.8% in patients with polyneuropathy (mean 3.4 fibres/mm). The annual rate of intraepidermal nerve-fibre (IENF) loss expressed as a percentage of the first IENFD value in patients with diabetic polyneuropathy was significantly higher [mean (se), 11.95 (3.82)%] compared with controls [1.92 (1.81)%, P < 0.001] and similar to patients without polyneuropathy [12.16 (4.38)%]. The rate of IENF loss did not correlate with degree of glucose control.Conclusions
The annual rate of IENF loss in patients with Type 2 diabetes mellitus was several times higher than that of healthy participants, irrespective of the presence of signs or symptoms of diabetic polyneuropathy at initial evaluation. The change in IENFD is not linear and should be expressed as a proportion of initial IENFD to serve as a marker of the course of diabetic neuropathy.This article is protected by copyright. All rights reserved.
Diabetic Medicine 08/2015; DOI:10.1111/dme.12890 · 3.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Preventing relapse to drug abuse is one of the struggles faced by clinicians in order to treat patients with substance use disorders (DSM-5). There is a large body of clinical evidence suggesting differential characteristics of the disorder in men and women, which is in line with preclinical findings as well. The aim of this study was to assess differences in relapse-like behavior in methamphetamine (METH) seeking after a period of forced abstinence, which simulates the real clinical situation very well. Findings from such study might add new insights in gender differences in relapse mechanisms to previous studies, which employ a classical drug or cue-induced reinstatement procedure following the extinction training. Adult male and female Sprague-Dawley rats were used in IV self-administration procedure conducted in operant boxes using nose-poke operandi (Coulborn Instruments, USA). Active nose-poke resulted in activation of the infusion pump to deliver one intravenous infusion of METH (0.08 mg/kg). After baseline drug intake was established (maintenance phase), a period of forced abstinence was initiated and rats were kept singly in their home cages for 14 days. Finally, one reinstatement session in operant boxes was conducted. Females were found to self-administer significantly lower dose of METH. The relapse rate was assessed as a number of active nose-pokes during the reinstatement session, expressed as a percentage of active nose-poking during the maintenance phase. Females displayed approximately 300% of active nose-pokes compared to 50% in males. This indicates higher vulnerability to relapse of METH seeking behavior in female rats. This effect was detected in all females, independently of current phase of their estrous cycle. Therefore, this paradigm using operant drug self-administration and reinstatement of drug-seeking after forced abstinence model can be used for preclinical screening for potential new anti-relapse medications specific for women.
Frontiers in Psychiatry 08/2015; 6. DOI:10.3389/fpsyt.2015.00091
[Show abstract][Hide abstract] ABSTRACT: The aim of the study was to evaluate whether the sequential hybrid approach combining surgical CryoMaze followed by the radiofrequency catheter ablation can improve freedom from atrial arrhythmias.
Thirty-five patients with persistent atrial fibrillation underwent a CryoMaze procedure in conjunction with cardiac surgery for structural heart disease. Three months after surgery, all patients underwent a 7-day ECG Holter followed by an electrophysiological study and mapping of the left and right atria. All pulmonary veins were re-isolated and all ablation lines were completed, if necessary, using radiofrequency energy. Patients were followed-up at 3, 6 and 12 months after the catheter ablation.
Before the mapping study and radiofrequency ablation, 9 patients (26%) had ongoing atrial fibrillation or atrial tachycardia, 10 patients (28%) had paroxysmal atrial tachyarrhythmia and 16 patients (46%) had sinus rhythm on the 7-day Holter monitoring. During the electrophysiological procedure, complete cryoablation lines around the left pulmonary veins were found in 29 patients (83%), around the right pulmonary veins in 25 patients (71%), between the superior veins in 20 cases (57%), between the inferior veins in 27 cases (77%), across the mitral isthmus in 12 patients (34%) and across the cavo-tricuspid isthmus in one patient (3%). Arrhythmia-free survival rate off antiarrhythmic drugs after re-isolation of the veins and completion of the lines was 86% at 12 months.
Ablation lines created using surgical CryoMaze are often incomplete. Sequential surgical CryoMaze procedures followed by catheter ablation significantly increase freedom from arrhythmia in patients with persistent atrial fibrillation. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
Pacing and Clinical Electrophysiology 07/2015; DOI:10.1111/pace.12686 · 1.13 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This contribution introduces a new web-based OPTIMED platform for an effective harmonisation of medical and healthcare curriculum. Behind the engineering background stays an original methodology covering planning model based on formal parameterisation of curriculum, which fully support the outcome-based approach to education. With the use of developed system curriculum, designers and senior guarantors can provide a clear and transparent composition of compulsory and optional courses, and easily identify potential duplicities and overlaps across a domain of medical and healthcare education. For students, it means an absolutely new way of how to understand what is really taught during a learning period, including all necessary meta information. All members across the academic community are able to search and consequently display in detail the most important domains related to the particular year, term, course, medical discipline or topic. The presented solution significantly enhances the transparency and continuity of the environment in which the authors of the teaching materials as well as their consumers work daily. Suggestions for future improvements of the OPTIMED platform are discussed.
Studies in health technology and informatics 05/2015; 210(Digital Healthcare Empowering Europeans):511 - 515. DOI:10.3233/978-1-61499-512-8-511
[Show abstract][Hide abstract] ABSTRACT: The study aimed to compare two prognostic models in terms of progression-free survival (PFS), median overall survival (OS), and 1-year survival in patients treated first-line with sunitinib for metastatic renal cell carcinoma (mRCC).
Data from patients who met prognostic model criteria for recording of baseline parameters and outcomes in the Czech Patient Registry RENal Information System (RENIS) were included in the retrospective analysis (n = 495). Performance of the modified Memorial Sloan Kettering Cancer Center (MSKCC) model and International Database Consortium (IDC) model was compared. PFS and OS were estimated using the Kaplan-Meier method. The statistical significance of differences in Kaplan-Meier estimates was assessed using the log-rank test.
Median OS for prognostic groups according to MSKCC and IDC criteria, respectively, was 39.5 months (95 % confidence interval [CI]: 23.9-55.2) versus 44.3 months (95 % CI: 31.6-56.9) for favourable-risk patients (no adverse factors), 28.5 months (95 % CI: 20.1-36.8) versus 24.8 months (95 % CI: 19.8-29.8) for intermediate-risk patients (1-2 adverse factors), and 10.6 months (95 % CI: 6.3-14.8) versus 9.3 months (95 % CI: 5.1-13.5) for poor-risk patients (≥3 adverse factors). The majority of MSKCC poor-risk patients (54.1 %, n = 72) were reclassified as intermediate-risk using IDC criteria, and 20.2 % (n = 61) of MSKCC intermediate-risk patients were reclassified to the IDC favourable-risk group.
Both prognostic models were validated in the present cohort. Use of the IDC model resulted in an upward shift in prognostic assessment compared to the MSKCC model.
[Show abstract][Hide abstract] ABSTRACT: Aim:
To compare the prognostic accuracy of six scoring models for up to three-year mortality and rates of hospitalisation due to acute decompensated heart failure (ADHF) in STEMI patients.
Methods and results:
A total of 593 patients treated with primary PCI were evaluated. Prospective follow-up of patients was ≥3 years. Thirty-day, one-year, two-year, and three-year mortality rates were 4.0%, 7.3%, 8.9%, and 10.6%, respectively. Six risk scores--the TIMI score and derived dynamic TIMI, CADILLAC, PAMI, Zwolle, and GRACE--showed a high predictive accuracy for six- and 12-month mortality with area under the receiver operating characteristic curve (AUC) values of 0.73-0.85. The best predictive values for long-term mortality were obtained by GRACE. The next best-performing scores were CADILLAC, Zwolle, and Dynamic TIMI. All risk scores had a lower prediction accuracy for repeat hospitalisation due to ADHF, except Zwolle with the discriminatory capacity for hospitalisation up to two years (AUC, 0.80-0.83).
All tested models showed a high predictive value for the estimation of one-year mortality, but GRACE appears to be the most suitable for the prediction for a longer follow-up period. The tested models exhibited an ability to predict the risk of ADHF, especially the Zwolle model.
PLoS ONE 04/2015; 10(4):e0123215. DOI:10.1371/journal.pone.0123215 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Obesity is clearly associated with increased morbidity and mortality rates. However, in patients with acute heart failure (AHF), an increased BMI could represent a protective marker. Studies evaluating the "obesity paradox" on a large cohort with long-term follow-up are lacking.
Using the AHEAD database (a Czech multi-centre database of patients hospitalised due to AHF), 5057 patients were evaluated; patients with a BMI <18.5 kg/m2 were excluded. All-cause mortality was compared between groups with a BMI of 18.5-25 kg/m2 and with BMI >25 kg/m2. Data were adjusted by a propensity score for 11 parameters.
In the balanced groups, the difference in 30-day mortality was not significant. The long-term mortality of patients with normal weight was higher than for those who were overweight/obese (HR, 1.36; 95% CI, 1.26-1.48; p<0.001)). In the balanced dataset, the pattern was similar (1.22; 1.09-1.39; p<0.001). A similar result was found in the balanced dataset of a subgroup of patients with de novo AHF (1.30; 1.11-1.52; p = 0.001), but only a trend in a balanced dataset of patients with acute decompensated heart failure.
These data suggest significantly lower long-term mortality in overweight/obese patients with AHF. The results suggest that at present there is no evidence for weight reduction in overweight/obese patients with heart failure, and emphasize the importance of prevention of cardiac cachexia.
PLoS ONE 02/2015; 10(2):e0117142. DOI:10.1371/journal.pone.0117142 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
Cancer burden in the Czech population ranks among the highest worldwide, which introduces a strong need for a prospective modelling of cancer incidence and prevalence rates. Moreover, a prediction of number of cancer patients requiring active antitumor therapy is also an important issue. This paper presents the stage-specific predictions of cancer incidence and prevalence, and the stage- and region-specific patients requiring active antitumor therapy for the most common cancer diagnoses in the Czech Republic for years 2015 and 2020. The stage-specific estimates are also presented with regard to the treatment phase as newly diagnosed patients, patients treated for non-terminal recurrence, and patients treated for terminal recurrence.
Patients and methods:
Data of the Czech National Cancer Registry from 1977 to 2011 has been used for the analysis, omitting the records of patients diagnosed as death certificate only or at autopsy. In total, 1,777,775 incidences have been considered for the estimation using a statistical model utilizing solely the population-based cancer registry data. All estimates have been calculated with respect to the changing demographic structure of the Czech population and the clinical stage at diagnosis.
Considering year 2011 as the baseline, we predict 89%, 15%, 31% and 32% increase in prostate, colorectal, female breast and lung cancer incidence, respectively, in 2020 resulting in 13,153, 9,368, 8,695, and 8,604 newly dia-g--nosed cancer patients in that year, respectively. Regarding cancer prevalence in 2020, the estimated increase is 140%, 40%, 51%, and 17% for prostate, colorectal, female breast and lung cancer, respectively, meaning that more than 100,000 prevalent female breast cancer patients as well as more than 100,000 prevalent prostate cancer patients are expected in the Czech Republic. The estimated numbers of patients requiring active antitumor therapy for prostate, colorectal, female breast and lung cancer in the Czech Republic in 2020 are 23,652, 14,006, 14,759 and 8,272; respectively.
The analysis documents a serious increase in cancer incidence and prevalence in the Czech Republic in years 2015 and 2020 when compared to the situation in 2011. Regarding the estimated numbers of patients requiring active antitumor therapy, the model confirms a continuous increase that must be accounted for in the future planning of health care in the Czech Republic.
Klinická onkologie: casopis Ceské a Slovenské onkologické spolecnosti 02/2015; 28(1):30-43.
[Show abstract][Hide abstract] ABSTRACT: 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).
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.
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.
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.
[Show abstract][Hide abstract] ABSTRACT: Unlabelled:
The aim of our study was to determine the risk factors associated with anal HPV infection in HIV-negative women with high-grade cervical lesion. The study group included 172 "high-risk" women who underwent conization for high-grade cervical intraepithelial lesion or microinvasive cervical cancer (CIN 2+). The control group consisted of 100 "low-risk" women with non-neoplastic gynecologic diseases. All participants completed a questionnaire detailing medical history and sexual risk factors and were subjected to anal and cervical HPV genotyping. Concurrent cervical and anal HPV infections were detected in 42.4% (73/172) women of the study group, and in 8.0% (8/100) of women in the control group, respectively. The subgroup with concurrent HPV infections (n=73) dominated women with CIN 3 and microinvasive cancer and anal HPV 16 infections (n=53). Women with concurrent infections more frequently reported any type of sexual contact with the anus including non-penetrative anal sex (OR 2.62, p=0.008). Reporting >5 lifetime sexual partners (OR 2.43, p=0.041), smoking > 60 cigarettes per week (OR 2.33, p=0.048), and a history of penetrative anal intercourse (OR 3.87, p=0.002) were observed as the significant risk factors in women with multiple concurrent HPV infections. Our data support anal HPV testing and anal Pap smear screening in all women with severe cervical lesions caused by HPV 16 and a history of any sexual contact with the anus, heavy smoking and/or more than 5 lifetime sexual partners.
anal cancer, cervical intraepithelial neoplasia, HPV, risk factor.
[Show abstract][Hide abstract] ABSTRACT: Aims and background:
The aim of the study was to compare the safety margin width using skin marks, pelvic skeleton-based targeting and adaptive protocol combining cone-beam computed tomography and kilovoltage image matching.
A total of 434 consecutive patients were treated by image-guided radiotherapy from November 2008 to April 2012. An adaptive protocol combining cone-beam computed tomography and kilovoltage image matching with individualized safety margin calculation according to the Van Herk method was used in a total of 201 patients. The remaining 233 patients had their setup corrected using cone-beam computed tomography daily.
Analysis of the 3,137 cone-beam computed tomography images (201 patients) revealed that the margins between the clinical target volume and planning target volume with skin marks registration should be 1.24 cm in the anteroposterior, 0.98 cm in the craniocaudal, and 1.03 cm in the laterolateral direction. Considering pelvic skeleton-based setup, values of the clinical target volume and planning target volume margins in the anteroposterior, craniocaudal and laterolateral axis were 0.79 cm, 0.41 cm, and 0.19 cm, respectively. In a group of 8,872 cone-beam computed tomography images (233 patients) using CBCT assessment, the calculated margins between clinical target volume and planning target volume with skin marks were 1.15 cm in anteroposterior, 1.06 in craniocaudal, and 1.19 in laterolateral directions. Considering the pelvic skeleton-based setup, the corresponding values were 0.74 cm, 0.51 cm, and 0.25 cm. With the adaptive technique, the margins of most patients in the anteroposterior, craniocaudal, and laterolateral axes were 6 mm, 6 mm, and 6 mm or 8 mm, 6 mm, and 6 mm, respectively.
The adaptive protocol combining cone-beam computed tomography and kilovoltage image matching or daily cone-beam computed tomography allowed us to substantially reduce the safety margins compared with skin marks targeting.