Dexamethasone doses in patients with COVID-19 and hypoxia: A systematic review and meta-analysis.

BACKGROUND: The optimal dose of dexamethasone for severe/critical COVID-19 is uncertain. We compared higher versus standard doses of dexamethasone in adults with COVID-19 and hypoxia. METHODS: We searched PubMed and trial registers until 23 June 2023 for randomised clinical trials comparing higher (>6 mg) versus standard doses (6 mg) of dexamethasone in adults with COVID-19 and hypoxia. The primary outcome was mortality at 1 month. Secondary outcomes were mortality closest to 90 days; days alive without life support; and the occurrence of serious adverse events/reactions (SAEs/SARs) closest to 1 month. We assessed the risk of bias using the Cochrane RoB2 tool, risk of random errors using trial sequential analysis, and certainty of evidence using Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTS: We included eight trials (2478 participants), of which four (1293 participants) had low risk of bias. Higher doses of dexamethasone probably resulted in little to no difference in mortality at 1 month (relative risk [RR] 0.97, 95% CI: 0.79-1.19), mortality closest to Day 90 (RR 1.01, 95% CI: 0.86-1.20), and SAEs/SARs (RR 1.00, 95% CI: 0.97-1.02). Higher doses of dexamethasone probably increased the number of days alive without invasive mechanical ventilation and circulatory support but had no effect on days alive without renal replacement therapy. CONCLUSIONS: Based on low to moderate certainty evidence, higher versus standard doses of dexamethasone probably result in little to no difference in mortality, SAEs/SARs, and days alive without renal replacement therapy, but probably increase the number of days alive without invasive mechanical ventilation and circulatory support.

Palliative care practice and moral distress during COVID-19 pandemic (PEOpLE-C19 study): a national, cross-sectional study in intensive care units in the Czech Republic.

BACKGROUND: Providing palliative care at the end of life (EOL) in intensive care units (ICUs) seems to be modified during the COVID-19 pandemic with potential burden of moral distress to health care providers (HCPs). We seek to assess the practice of EOL care during the COVID-19 pandemic in ICUs in the Czech Republic focusing on the level of moral distress and its possible modifiable factors. METHODS: Between 16 June 2021 and 16 September 2021, a national, cross-sectional study in intensive care units (ICUs) in Czech Republic was performed. All physicians and nurses working in ICUs during the COVID-19 pandemic were included in the study. For questionnaire development ACADEMY and CHERRIES guide and checklist were used. A multivariate logistic regression model was used to analyse possible modifiable factors of moral distress. RESULTS: In total, 313 HCPs (14.5% out of all HCPs who opened the questionnaire) fully completed the survey. Results showed that 51.8% (n = 162) of respondents were exposed to moral distress during the COVID-19 pandemic. 63.1% (n = 113) of nurses and 71.6% of (n = 96) physicians had experience with the perception of inappropriate care. If inappropriate care was perceived, a higher chance for the occurrence of moral distress for HCPs (OR, 1.854; CI, 1.057-3.252; p = 0.0312) was found. When patients died with dignity, the chance for moral distress was lower (OR, 0.235; CI, 0.128-0.430; p < 0.001). The three most often reported differences in palliative care practice during pandemic were health system congestion, personnel factors, and characteristics of COVID-19 infection. CONCLUSIONS: HCPs working at ICUs experienced significant moral distress during the COVID-19 pandemic in the Czech Republic. The major sources were perceiving inappropriate care and dying of patients without dignity. Improvement of the decision-making process and communication at the end of life could lead to a better ethical and safety climate. TRIAL REGISTRATION: NCT04910243 .

The prognostic effect of different types of cardiac rehabilitation in patients with coronary artery disease.

AIM: The purpose of this study was to access and compare the prognostic effects of different types of cardiac rehabilitation (CR) in patients with chronic coronary artery disease. METHODS: One hundred fifty-two patients were retrospectively divided into 4 groups according to their adherence to physical activity recommendations. Patients in groups 1 and 2 participated in the guided 3-month exercise programme. Patients in group 1 then continued with individual exercise training, while patients in the group 2 stopped exercising after finishing the guide exercise programme. Patients in group 3 participated only in individual exercise training throughout the whole follow-up period, and patients in group 4 declined all exercise recommendations and did not exercise. The prognostic outcome of different types of cardiac rehabilitation was compared among the groups. In addition, patients who participated in individual exercise training according to recommendations (cohort IT+) were compared with patients who declined these activities (cohort IT-). RESULTS: During a median follow-up of 94 months, 33 deaths occurred: 17 cardiovascular and 16 non-cardiac deaths. A Kaplan-Meier survival analysis demonstrated significantly better survival rates for patients who followed a long-term aerobic exercise training (IT+) than for those who did not participate or who had only a short-term exercise programme (IT-) (P = 0.009). CONCLUSION: In our study, long-term exercise training had a higher impact on patient survival than short-term guided CR.

Orally Administered Probiotics in the Prevention of Chemotherapy (± Radiotherapy)-Induced Gastrointestinal Toxicity: A Systematic Review With Meta-Analysis of Randomized Trials.

BACKGROUND: Chemoradiotherapy-induced gastrointestinal toxicity may lead to a significant impairment of the oncological patient's quality of life, as well as to reduced adherence to the treatment, which may have a negative impact on survival and mortality rates. OBJECTIVE: The aim of this review was to investigate whether oral probiotic administration prevents chemotherapy (± radiotherapy)-induced gastrointestinal toxicity, particularly diarrhea. METHODS: We searched the MEDLINE, Web of Science, and SCOPUS databases for randomized controlled trials in English published between 1990 and 2020. We conducted statistical data analyses expressing the treatment effect size as a risk ratio (RR) together with a 95% confidence interval (CI). Implications are based on trials rated as having a low risk of bias (RoB). RESULTS: We included 8 trials (n = 697 participants), from which 3 studies rated as low RoB contained primary endpoint data; the risk of developing grade 3/4 diarrhea in patients receiving probiotics was reduced by 78% compared to the control group (RR = 0.22 [95% CI 0.05-1.08]; P = .06; n = 114 participants). Probiotics showed preventive effects in patients treated with chemotherapy alone (RR = 0.34 [0.12-0.94]; P = .04, n = 121 participants) and in patients with colorectal cancer (RR = 0.56 [0.34-0.92]; P = .02; n = 208 participants). The reduction in the incidence of overall diarrhea was not significant. CONCLUSIONS: Probiotics failed to prove a preventive effect of statistical significance against the development of severe and overall diarrhea in cancer patients treated with chemotherapy (± radiotherapy). However, we cannot rule out that the effects of probiotics are clinically relevant, especially in certain subgroups of patients. This needs to be clarified in further well-performed studies.

Effect of dexamethasone in patients with ARDS and COVID-19 (REMED trial)-study protocol for a prospective, multi-centre, open-label, parallel-group, randomized controlled trial.

BACKGROUND: Since December 2019, SARS-CoV-2 virus has infected millions of people worldwide. In patients with COVID-19 pneumonia in need of oxygen therapy or mechanical ventilation, dexamethasone 6 mg per day is currently recommended. However, the dose of 6 mg of dexamethasone is currently being reappraised and may miss important therapeutic potential or may prevent potential deleterious effects of higher doses of corticosteroids. METHODS: REMED is a prospective, open-label, randomised controlled trial testing the superiority of dexamethasone 20 mg (dexamethasone 20 mg on days 1-5, followed by dexamethasone 10 mg on days 6-10) vs 6 mg administered once daily intravenously for 10 days in adult patients with moderate or severe ARDS due to confirmed COVID-19. Three hundred participants will be enrolled and followed up for 360 days after randomization. Patients will be randomised in a 1:1 ratio into one of the two treatment arms. The following stratification factors will be applied: age, Charlson Comorbidity Index, CRP levels and trial centre. The primary endpoint is the number of ventilator-free days (VFDs) at 28 days after randomisation. The secondary endpoints are mortality from any cause at 60 days after randomisation; dynamics of the inflammatory marker, change in WHO Clinical Progression Scale at day 14; and adverse events related to corticosteroids and independence at 90 days after randomisation assessed by the Barthel Index. The long-term outcomes of this study are to assess long-term consequences on mortality and quality of life at 180 and 360 days. The study will be conducted in the intensive care units (ICUs) of ten university hospitals in the Czech Republic. DISCUSSION: We aim to compare two different doses of dexamethasone in patients with moderate to severe ARDS undergoing mechanical ventilation regarding efficacy and safety. TRIAL REGISTRATION: EudraCT No. 2020-005887-70. ClinicalTrials.gov NCT04663555. Registered on December 11, 2020.

N-of-1 Trials in Pediatric Oncology: From a Population-Based Approach to Personalized Medicine-A Review.

Pediatric oncology is a critical area where the more efficient development of new treatments is urgently needed. The speed of approval of new drugs is still limited by regulatory requirements and a lack of innovative designs appropriate for trials in children. Childhood cancers meet the criteria of rare diseases. Personalized medicine brings it even closer to the horizon of individual cases. Thus, not all the traditional research tools, such as large-scale RCTs, are always suitable or even applicable, mainly due to limited sample sizes. Small samples and traditional versus subject-specific evidence are both distinctive issues in personalized pediatric oncology. Modern analytical approaches and adaptations of the paradigms of evidence are warranted. We have reviewed innovative trial designs and analytical methods developed for small populations, together with individualized approaches, given their applicability to pediatric oncology. We discuss traditional population-based and individualized perspectives of inferences and evidence, and explain the possibilities of using various methods in pediatric personalized oncology. We find that specific derivatives of the original N-of-1 trial design adapted for pediatric personalized oncology may represent an optimal analytical tool for this area of medicine. We conclude that no particular N-of-1 strategy can provide a solution. Rather, a whole range of approaches is needed to satisfy the new inferential and analytical paradigms of modern medicine. We reveal a new view of cancer as continuum model and discuss the "evidence puzzle".

Effect of dexamethasone in patients with ARDS and COVID-19 - prospective, multi-centre, open-label, parallel-group, randomised controlled trial (REMED trial): A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: The primary objective of this study is to test the hypothesis that administration of dexamethasone 20 mg is superior to a 6 mg dose in adult patients with moderate or severe ARDS due to confirmed COVID-19. The secondary objective is to investigate the efficacy and safety of dexamethasone 20 mg versus dexamethasone 6 mg. The exploratory objective of this study is to assess long-term consequences on mortality and quality of life at 180 and 360 days. TRIAL DESIGN: REMED is a prospective, phase II, open-label, randomised controlled trial testing superiority of dexamethasone 20 mg vs 6 mg. The trial aims to be pragmatic, i.e. designed to evaluate the effectiveness of the intervention in conditions that are close to real-life routine clinical practice. PARTICIPANTS: The study is multi-centre and will be conducted in the intensive care units (ICUs) of ten university hospitals in the Czech Republic. INCLUSION CRITERIA: Subjects will be eligible for the trial if they meet all of the following criteria: 1. Adult (≥18 years of age) at time of enrolment; 2. Present COVID-19 (infection confirmed by RT-PCR or antigen testing); 3. Intubation/mechanical ventilation or ongoing high-flow nasal cannula (HFNC) oxygen therapy; 4. Moderate or severe ARDS according to Berlin criteria: • Moderate - PaO2/FiO2 100-200 mmHg; • Severe - PaO2/FiO2 < 100 mmHg; 5. Admission to ICU in the last 24 hours. EXCLUSION CRITERIA: Subjects will not be eligible for the trial if they meet any of the following criteria: 1. Known allergy/hypersensitivity to dexamethasone or excipients of the investigational medicinal product (e.g. parabens, benzyl alcohol); 2. Fulfilled criteria for ARDS for ≥14 days at enrolment; 3. Pregnancy or breastfeeding; 4. Unwillingness to comply with contraception measurements from enrolment until at least 1 week after the last dose of dexamethasone (sexual abstinence is considered an adequate contraception method); 5. End-of-life decision or patient is expected to die within next 24 hours; 6. Decision not to intubate or ceilings of care in place; 7. Immunosuppression and/or immunosuppressive drugs in medical history: a) Systemic immunosuppressive drugs or chemotherapy in the past 30 days; b) Systemic corticosteroid use before hospitalization; c) Any dose of dexamethasone during the present hospital stay for COVID-19 for ≥5 days before enrolment; d) Systemic corticosteroids during present hospital stay for conditions other than COVID-19 (e.g. septic shock); 8. Current haematological or generalized solid malignancy; 9. Any contraindication for corticosteroid administration, e.g. • intractable hyperglycaemia; • active gastrointestinal bleeding; • adrenal gland disorders; • presence of superinfection diagnosed with locally established clinical and laboratory criteria without adequate antimicrobial treatment; 10. Cardiac arrest before ICU admission; 11. Participation in another interventional trial in the last 30 days. INTERVENTION AND COMPARATOR: Dexamethasone solution for injection/infusion is the investigational medicinal product as well as the comparator. The trial will assess two doses, 20 mg (investigational) vs 6 mg (comparator). Patients in the intervention group will receive dexamethasone 20 mg intravenously once daily on day 1-5, followed by dexamethasone 10 mg intravenously once daily on day 6-10. Patients in the control group will receive dexamethasone 6 mg day 1-10. All authorized medicinal products containing dexamethasone in the form of solution for i.v. injection/infusion can be used. MAIN OUTCOMES: Primary endpoint: Number of ventilator-free days (VFDs) at 28 days after randomisation, defined as being alive and free from mechanical ventilation. SECONDARY ENDPOINTS: a) Mortality from any cause at 60 days after randomisation; b) Dynamics of inflammatory marker (C-Reactive Protein, CRP) change from Day 1 to Day 14; c) WHO Clinical Progression Scale at Day 14; d) Adverse events related to corticosteroids (new infections, new thrombotic complications) until Day 28 or hospital discharge; e) Independence at 90 days after randomisation assessed by Barthel Index. The long-term outcomes of this study are to assess long-term consequences on mortality and quality of life at 180 and 360 days through telephone structured interviews using the Barthel Index. RANDOMISATION: Randomisation will be carried out within the electronic case report form (eCRF) by the stratified permuted block randomisation method. Allocation sequences will be prepared by a statistician independent of the study team. Allocation to the treatment arm of an individual patient will not be available to the investigators before completion of the whole randomisation process. The following stratification factors will be applied: • Age <65 and ≥ 65; • Charlson Comorbidity index (CCI) <3 and ≥3; • CRP <150 mg/L and ≥150 mg/L • Trial centre. Patients will be randomised in a 1 : 1 ratio into one of the two treatment arms. Randomisation through the eCRF will be available 24 hours every day. BLINDING (MASKING): This is an open-label trial in which the participants and the study staff will be aware of the allocated intervention. Blinded pre-planned statistical analysis will be performed. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The sample size is calculated to detect the difference of 3 VFDs at 28 days (primary efficacy endpoint) between the two treatment arms with a two-sided type I error of 0.05 and power of 80%. Based on data from a multi-centre randomised controlled trial in COVID-19 ARDS patients in Brazil and a multi-centre observational study from French and Belgian ICUs regarding moderate to severe ARDS related to COVID-19, investigators assumed a standard deviation of VFD at 28 days as 9. Using these assumptions, a total of 142 patients per treatment arm would be needed. After adjustment for a drop-out rate, 150 per treatment arm (300 patients per study) will be enrolled. TRIAL STATUS: This is protocol version 1.1, 15.01.2021. The trial is due to start on 2 February 2021 and recruitment is expected to be completed by December 2021. TRIAL REGISTRATION: The study protocol was registered on EudraCT No.:2020-005887-70, and on December 11, 2020 on ClinicalTrials.gov (Title: Effect of Two Different Doses of Dexamethasone in Patients With ARDS and COVID-19 (REMED)) Identifier: NCT04663555 with a last update posted on February 1, 2021. FULL PROTOCOL: The full protocol (version 1.1) is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, the standard formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

An Investigation into the Prevalence of Migraine and Its Prophylactic Treatment Patterns in the Czech Republic: An Observational Study.

PURPOSE: A national primary and secondary healthcare-level study in the Czech Republic has not yet been conducted to evaluate the prevalence of migraine. We analyzed the current treatment patterns (acute and prophylactic) in migraine patients and the number of migraine patients potentially eligible for treatment with recent calcitonin gene-related peptide (CGRP) pathway-targeted therapies. METHODS: This retrospective study utilized the Ministry of the Interior Health Insurance Fund claims database of the Czech Republic wherein every citizen is insured. Migraine patients with or without aura, and potentially on triptan therapy were included in this study (index years 2012-2016). The prevalence approach included all patients (new and old) present in each index year. Prophylactic therapies were followed f0or three and seven years prior to the index year, including the index year, until 2010. The incidence approach included all patients first diagnosed in each index year. Prophylactic therapies were followed for the next three years, including the index year, until 2017 following incidence approach. The primary endpoint of this study was to determine the rate of migraine prevalence and diagnosis for each index year during the period 2012-2016. The study also evaluated prophylactic and acute treatment patterns and comorbidities among patients in 2016. RESULTS: The rate of migraine prevalence was 1% and the rate of diagnosis was 0.2-0.4%. By prevalence approach, approximately 39% of the patients were on prophylactics, and 11.2% and 21.6% of the patient population had two prior treatment failures (three- and seven-year recall period, respectively). Antiepileptics (26%) and beta blockers (15.8%) were the most prescribed prophylactics, and sumatriptan was the predominant triptan used (12%) for acute treatment. CONCLUSION: Taking into account the number of inhabitants in the Czech Republic (10.7 million), there could be up to 23,000 adult patients eligible for novel CGRP therapies.

[Efficacy of pegylated interferon alpha-2a and ribavirin treatment in chronic hepatitis C patients depends on various baseline parameters and early viral kinetics]. / Závislost úcinnosti lécby chronické hepatitidy C pegylovaným interferonem alfa-2a a ribavirinem na v stupních parametrech a virové kinetice v pocátcích lécby.

OBJECTIVE: The aim of the study was to compare efficacy and viral kinetics during antiviral treatment in different chronic hepatitis C patients--naïve, relapsers and non-responders to previous pegylated interferon alpha (PEG-IFN) and ribavirin treatment, with different genotypes, baseline viremia, body weight, age and gender--and to find some baseline parameters which can predict Sustained Virological Response (SVR; negative serum HCV RNA 24 weeks after treatment). MATERIAL AND METHODS: 216 chronic hepatitis C patients were treated with PEG-IFN alpha-2a 180 mg/wk and ribavirin 1 000 or 1 200 mg/day. There were 140 men and 76 women, mean age 40, range 19-70 years; 142 (66 %) naïve, 37 (17 %) relapsers after previous PEG-IFN and ribavirin treatment, and 37 (17 %) non-responders to this treatment. 172 (79,6%) has genotype 1 infection, 4 (1,9 %) genotype 2, 34 (15,6 %) genotype 3, 1 (0,5 %) genotype 4 or 6 infection, and 4 (1,9 %) were infected by unknown viral genotype. Quantitative detection of HCV RNA was done at baseline (216 pts.), 24 hours (83 pts.), 14 days (85 pts.), 28 days (88 pts.), and 84 days (211 pts.) after the first dose of PEG-IFN. RESULTS: 195 patients have completed the treatment period and 179 patients the 24-week follow-up period. The probability of SVR was significantly higher (P < 0,001) in naïve patients (74/114, 64,9 %) and relapsers (22/30, 73,3 %) than in non-responders (9/35, 25,7 %) and in genotype 3 patients (23/28, 82,1%) than genotype 1 patient (77/143, 53,8 %) (P = 0,002). The patients with SVR comparing those without SVR have significantly lower weight (mean 72,8 kg vs. 79,1, P = 0,008(, were younger (mean 36,2, vs. 45,5, P > 0,001), and had lower baseline viremia (mean 1,014 3 106 IU/mL vs. 2,415 3 106 IU/mL, P > 0,001). SVR was more frequent in women than in men (43/63, 62,8 % vs. 62/116, 53,4 %) but difference was not significant (P = 0,059). Undetectable serum HCV RNA at week 12 was more predictive of SVR than early viral response (minimum 2 log decrease of serum HCV RNA during the first 12 weeks of treatment)--98/122 (80,3 %) versus 104/141 (73,1 %) of SVR. CONCLUSIONS: 1) The monitoring of viral kinetics during first 12 weeks of antiviral therapy in hepatitis C patients was an important predictive value for SVR. 2) Negative serum HCV RNA at week 12 was more predictive of SVR than early viral response. 3) The probability of SVR was significantly higher in patients with lower baseline viremia, body weight and younger adults. 4) Gender was not significant for the efficacy of treatment.

Outcome of patients with multiple myeloma and hypertension treated with angiotensin-I-converting enzyme inhibitors during high-dose chemotherapy.

In a retrospective study we have sought to determine whether the administration of angiotensin-I-converting enzyme inhibitors (ACEI) influences the outcome of patients with multiple myeloma (MM). Patients with MM who underwent autologous peripheral blood stem cell transplantation (PBSCT) (n=168) were studied. Patients taking ACEI alone or in combination with other antihypertensive agents during the hospital admission for PBSCT were allocated to the ACEI group (n=25; 15%). Patients from the non-ACEI group (n=143; 85%) were taking other or no antihypertensive medication. Patients taking ACEI had worse overall survival (OS) compared to patients not taking ACEI (38.7 versus 73.3 months after diagnosis; P=0.025). Among patients with hypertension, both OS and progression-free survival were significantly shorter in patients taking ACEI. There were no significant differences between the studied groups in standard prognostic parameters for MM (age, albumin, beta 2-microglobulin, IPI and Durie-Salmon stage, LDH, CRP, performance status) or in engraftment. The mortality in our study has been mostly myeloma related. In conclusion, according to our findings, ACEI administered during PBSCT have adverse effect on survival of patients with MM.

Quality of life in 650 lung cancer survivors 6 months to 4 years after diagnosis.

OBJECTIVE: To present the results of a quality-of-life (QOL) assessment performed with the current version of the Lung Cancer Symptom Scale (LCSS) questionnaire in a large single-institutional data set of 650 patients with lung cancer. PATIENTS AND METHODS: The study group included 650 patients with pathologically confirmed primary lung cancer whose conditions were diagnosed and/or treated at the Mayo Clinic in Rochester, Minn, between January 1, 1997, and December 31, 2001. The QOL assessment was performed using the self-administered LCSS questionnaire (version 2) 6 months to 4 years after the diagnosis of lung cancer. RESULTS: The item response rate for all 9 LCSS questions was 94.2% with a minimum of 92.9%. Significant differences in overall QOL by sex (P=.04), Karnofsky scale (P<.001), weight loss (P<.001), disease stage (P<.001), and histology (P=.001) were found, but no significant differences in overall QOL by age (P=.17) or marital status (P=.06) were observed. CONCLUSION: Our data suggest that QOL in patients with lung cancer at varying times after diagnosis highly correlates with baseline prognostic factors (disease stage, histology, Karnofsky scale, weight loss, and sex).

Effects of low-power laser irradiation on cell locomotion in protozoa.

Low-power lasers are commonly used in human medicine for treatment of various pathological conditions, but mechanisms of their healing effects are still poorly understood. The results of this study provide information related to these effects at the cellular level. Two different protozoan species, Euglena gracilis and Tetrahymena thermophila, were used to study changes in locomotion behavior in response to low-power lasers. The cells were irradiated at 830 and 650 nm generated by a semiconductor laser (99 J/cm2, 360 mW) and a laser pointer (0.75 J/cm2, 5 mW), respectively, and their locomotion was recorded by a TV camera and analyzed using computer software. Exposure to laser light, regardless of the wavelength, resulted in increased cell velocity in both species (P <0.001). Exposure to 650 nm produced an equal increase in median cell velocity in both E. gracilis (19.0%) and T. thermophila (18.2%), and some increase persisted in the postirradiation 30 s period. Irradiation by the 830 nm laser resulted in a markedly higher response in Tetrahymena (29.4%) than in Euglena (15.2%), and the two median values remained increased after irradiation was discontinued. Different reactions found in the species studied and some mechanisms underlying the response of cells to radiation are discussed.

Prevalence of perfusion defects detected by stress 99mtechnetium sestamibi myocardial perfusion single-photon emission computed tomography in asymptomatic patients with breast cancer.

AIM: The aim of the present study was to investigate myocardial perfusion in relation to disease history and laboratory parameters of atherosclerosis risk in asymptomatic patients with breast carcinoma. PATIENTS AND METHODS: One-hundred and eighty-one patients with breast carcinoma were studied. Myocardial perfusion was assessed using single-photon emission computed tomography (SPECT) with 99mtechnetium sestamibi. RESULTS: Perfusion defects were detected in 12 patients (7%). Higher body-mass index, increased concentrations of D-dimers, C-reactive protein, fibrinogen, glucose, triglycerides, and urinary albumin, a history of hypertension and of radiotherapy to the left chest wall were all associated with increased risk of perfusion defects. In a multivariate stepwise selection logistic regression model, body mass index, albuminuria and radiotherapy to the left hemithorax were significantly associated with the presence of perfusion defects. CONCLUSION: In addition to other factors, treatment history may be associated with the presence of perfusion defects in patients with breast cancer.

Urinary neopterin concentration and toxicity of radiotherapy in patients with head and neck carcinoma during external beam radiation.

AIM: Increased serum or urinary concentrations of neopterin are predictive of poor prognosis in patients with tumors across a spectrum of primary locations. Less information is available about the significance of changes of urinary neopterin concentrations during therapy. The aim of the present study was to examine the association between urinary neopterin and toxicity of radiotherapy. PATIENTS AND METHODS: We analyzed changes of urinary neopterin and toxicity of therapy in 12 patients with head and neck carcinoma during external-beam radiation. Urinary neopterin was determined daily by high-performance liquid chromatography. RESULTS: In addition to a trend for increased neopterin concentrations during radiation therapy, a significant association between changes of neopterin and toxicity and vice versa was observed with a rise of neopterin predicting a later manifestation of toxicity as well as manifestion of toxicity predicting a later rise of neopterin. CONCLUSION: Urinary neopterin is predictive of toxicity in patients with head and neck carcinoma. An association between toxicity and subsequent rise of urinary neopterin concentrations was also observed.

Carotid intima-media thickness and laboratory parameters of atherosclerosis risk in patients with breast cancer.

AIM: To investigate the relation between intima-media thickness (IMT) and laboratory parameters of atherosclerosis risk in patients with breast carcinoma. PATIENTS AND METHODS: IMT and a panel of laboratory parameters associated with the risk of atherosclerosis were studied in 192 patients with histologically-verified breast carcinoma. RESULTS: Patients with metastatic disease had significantly higher fibrinogen, C-reactive protein (CRP), urinary neopterin and mean IMT, and significantly lower serum albumin and hemoglobin concentrations. Significant correlations were observed between CRP, urinary neopterin, mean IMT and other parameters of cardiovascular risk. Age was an independent predictor of the presence of sonographic signs of atherosclerosis using logistic regression, and age, glucose, time from start of chemotherapy, high-density lipoprotein cholesterol, D-dimers were independently associated with IMT in stepwise regression models. CONCLUSION: In addition to the associations between IMT and laboratory or clinical parameters of the risk of atherosclerosis, IMT may also be associated with the time from chemotherapy.

Breast cancer risk assessment in the Czech female population--an adjustment of the original Gail model.

BACKGROUND: Several mathematical models have been developed for predicting individual breast cancer risk. Such models can help clinicians to choose appropriate preventive and therapeutic interventions for each patient. Unfortunately, the validity of these models has not been tested outside the USA. METHODS: The authors describe a case-control study in the Czech Republic with a similar design to that of the US Breast Cancer Detection and Demonstration Project (BCDDP). The main objective of the study was to evaluate the validity of the Gail model in the Czech female population, and to develop a local model using the same statistical approach as the Gail model. Between November 2000 and May 2004, 14,566 questionnaires containing case history data from both healthy women (control group) and women with breast cancer were collected. Case-control age-matched pairs (n = 4598) have subsequently been matched and analyzed. RESULTS: Our results show that the original Gail model was not able to properly distinguish between controls and breast cancer cases in the Czech female population. Based on paired data, the mean 5-year and life-time breast cancer risk was 1.379 +/- 0.668 and 7.990 +/- 3.184 in the control group and 1.375 +/- 0.692 and 8.028 +/- 3.506 in the patients with breast cancer group. The original Gail model was also not able to properly describe age-specific baseline risk of breast cancer development in the Czech population. In response the authors developed two variants of modified/locally adjusted models. CONCLUSION: The original Gail model is not an accurate breast cancer risk assessment tool for the Czech female population.

Treatment of arrhythmic storm in implantable defibrillator patients.

BACKGROUND: A common ICD therapy-related complication is arrhythmic storm (AS). The objective of our study was to define the impact of AS on patients' prognoses in order to compare the total mortality of AS patients with the rest of the group. MATERIAL/METHODS: We studied 138 patients who received ICDs between 1994 and 2001. Patients who experienced one or more arrhythmic storms were statistically compared with patients who had no accumulation of malignant arrhythmia or no episodes. RESULTS: One thousand four hundred ninety episodes of arrhythmia were analyzed. Arrhythmia recurrence was present in 71% of the patients. The majority of episodes (78%) were ventricular tachycardias and only 3% of episodes were ventricular fibrillation. Seventy percent of all arrhythmic episodes were asymptomatic. The ICD therapy sensitivity was 99.7%. Thirty-eight arrhythmic storms in 19 patients (14%) were observed during follow-up. The occurrence of AS was twice as high among patients with LVEF <35% than the rest of the group (18% vs. 8%). The total survival of patients with AS was significantly lower than that of the ICD patients who did not experience an AS (36.8% vs. 16.8%, p=0.042). All episodes of arrhythmic clusters during the AS were ventricular tachycardias. CONCLUSIONS: Arrhythmic storm is a serious risk marker for cardiac death. Ventricular tachycardia is a basic rhythm disorder of AS episodes and occurs significantly more often than ventricular fibrillation. Arrhythmic storm is responsible for a 4.6 times more frequent re-admission to hospital.

Autologous versus allogenic bone grafts in instrumented anterior cervical discectomy and fusion: a prospective study with respect to bone union pattern.

BACKGROUND: The purpose of this prospective semi-randomised comparative study was to compare fusion rates, course of fusion, and occurrence of collapse and subsidence of autologous and allogenic bone grafts in instrumented anterior cervical fusion. The number of fused levels and the smoking status were investigated as potential factors influencing the bone-healing process. No similar prospective study on instrumented anterior cervical discectomy and fusion was found in the literature. METHODS: Seventy-nine consecutive patients were operated on using the Smith-Robinson technique with a single instrumentation system at one or two levels. Seventy-six cadaverous fibular bone grafts and 37 autologous iliac-crest bone grafts were inserted. All patients were followed up for at least 2 years. RESULTS: The radiographs obtained during the follow-up were analysed, and showed no statistical difference in fusion and collapse rate between autografts and allografts. Allografts showed significantly longer time to union. No case of graft migration was observed. No difference was found between fusion and collapse rate with respect to the number of fused levels in general, but greater time to union was seen in two-level fusions. When one- and two-level subgroups were compared, there was no evidence of any significant difference in fusion or collapse rates between autografts and allografts, and the healing process took longer in allogenic grafts. Smoking status did not alter any of the fusion or collapse rates, or the course of bone fusion. CONCLUSIONS: This study demonstrates that allografts are suitable substitutes for autografts in instrumented ACDF. Prolonged time to union observed in allogenic bone grafts does not seem to be an important factor in instrumented procedures. Two-level grafting does not imply a significantly lower fusion rate, but longer time to union can be expected than with single-level instrumented procedures in both allograft and autograft subgroups. Our relatively small number of patients may not have been sufficient to decipher significant differences between smokers and non-smokers in the rate or course of fusion as previously reported.

Generation of antigen-loaded dendritic cells in a serum-free medium using different cytokine combinations.

Dendritic cells (DCs) are antigen-presenting cells that play a critical role in the induction of cytotoxic T-lymphocytes. An optimal method for the generation of DC for clinical use remains to be established. The aim of our study was to find an optimal cytokine combination for DC generation from peripheral blood stem cells (PBSC) and peripheral blood mononuclear cells (PBMC) in serum-free conditions. Serial immunophenotyping enabled us to observe changes in DC content during the culture as well as the development of maturation and activation markers. As a source for DC culture, we used PBSC from patients with multiple myeloma after stem cell mobilization using cyclophosphamide and G-CSF, or PBMC from healthy donors without mobilization. The cells were cultured in a serum-free medium with different cytokine combinations including GM-CSF, TNF-alpha, Flt-3, CD40L, IFN-gamma, IL-1alpha, IL-6, PGE1, and IL-4. The cell cultures were evaluated by immunophenotyping. For PBMC, interleukin-12 assay was performed. For PBSC, the yield of DC as determined by CD83+ cell count ranged from 0. 6 x 10(5) to 30.1 x 10(4) (mean: 9.4 x 10(4)) of DC generated per 1 x 10(6) of initially plated nucleated cells from apheresis. This yield corresponded to (0.3-19.1) x 10(5) (mean: 4.3 x 10(5)) per 1 x 10(6) of CD34+ cells in the apheresis products. For PBMC, the yield was (0.4-24.8) x 10(4) (mean: 2.4 x 10(4)) of DC generated per 1 x 10(6) of initially plated mononuclear cells from venous blood. The cultured cells expressed the mature immunophenotype. No significant differences in cell yield or immunophenotype were detected when comparing different cytokine combinations.