[Cost analysis of radiotherapy provided in inpatient setting -  testing potential predictors for a new prospective payment system]. / Analýza nákladu na radioterapii v luzkové péci - hledání vhodných prediktoru pro potreby nového prospektivního úhradového modelu.

BACKGROUND: As a part of the development of a new prospective payment model for radiotherapy we analyzed data on costs of care provided by three comprehensive cancer centers in the Czech Republic. Our aim was to find a combination of variables (predictors) which could be used to sort hospitalization cases into groups according to their costs, with each group having the same reimbursement rate. We tested four variables as possible predictors -  number of fractions, stage of disease, radiotherapy technique and diagnostic group. METHODS: We analyzed 7,440 hospitalization cases treated in three comprehensive cancer centers from 2007 to 2011. We acquired data from the I COP database developed by Institute of Biostatistics and Analyses of Masaryk University in cooperation with oncology centers that contains records from the National Oncological Registry along with data supplied by healthcare providers to insurance companies for the purpose of retrospective reimbursement. RESULTS: When comparing the four variables mentioned above we found that number of fractions and radiotherapy technique were much stronger predictors than the other two variables. Stage of disease did not prove to be a relevant indicator of cost distinction. There were significant differences in costs among diagnostic groups but these were mostly driven by the technique of radiotherapy and the number of fractions. Within the diagnostic groups, the distribution of costs was too heterogeneous for the purpose of the new payment model. CONCLUSION: The combination of number of fractions and radiotherapy technique appears to be the most appropriate cost predictors to be involved in the prospective payment model proposal. Further analysis is planned to test the predictive value of intention of radiotherapy in order to determine differences in costs between palliative and curative treatment.

[Continuing progress in withdrawal of axillary dissection in early stage breast cancer]. / Dalsí postupný ústup od axilární disekce u casného karcinomu prsu.

For a long period of time, axillary dissection represented a standard approach for axillary node management in the case of sentinel node biopsy positivity during early stage breast cancer treatment. In recent years, there has been a trend to highlight the morbidity of such an axillary procedure considering longterm survival of early stage breast cancer patients. Two big trials, AMAROS and Z0011, were initiated to answer the question whether axillary dissection should be performed in the case of positivity of axillary sentinel node considering the fact that more than 70% of these patients will have no metastasis found during the axillary dissection and such a procedure only increases the morbidity of the surgery. Considering the results of the above mentioned trials, axillary dissection may be avoided in the case of fulfilling of inclusion criteria of these trials without any impact on the patient survival. IBCSG 23- 01 study brought similar conclusion in the case of micrometastasis in axillary sentinel node.

Impaired bioavailability and antiplatelet effect of high-dose clopidogrel in patients after cardiopulmonary resuscitation (CPR).

PURPOSE: Bioavailability of clopidogrel in the form of crushed tablets administered via nasogastric tube (NGT) has not been established in patients after cardiopulmonary resuscitation. Therefore, we performed a study comparing pharmacokinetic and pharmacodynamic response to high loading dose of clopidogrel in critically ill patients after cardiopulmonary resuscitation (CPR) with patients scheduled for elective coronary angiography with stent implantation. METHODS: In the NGT group (nine patients, after cardiopulmonary resuscitation, mechanically ventilated, therapeutic hypothermia), clopidogrel was administered in the form of crushed tablets via NGT. Ten patients undergoing elective coronary artery stenting took clopidogrel per os (po) in the form of intact tablets. Pharmacokinetics of clopidogrel was measured with high-performance liquid chromatography (HPLC) before and at 0.5, 1, 6, 12, 24 h after administration of a loading dose of 600 mg. In five patients in each group, antiplatelet effect was measured with thrombelastography (TEG; Platelet Mapping) before and 24 h after administration. RESULTS: The carboxylic acid metabolite of clopidogrel was detected in all patients in the po group. In eight patients, the maximum concentration was measured in the range of 0.5-1 h after the initial dose. In four patients in the of NGT group, the carboxylic acid metabolite of clopidogrel was undetectable and in the remaining patients was significantly delayed (peak values at 12 h). All patients in the po group reached clinically relevant (>50 %) inhibition of thrombocyte adenosine diphosphate (ADP) receptor after 24 h compared with only two in the NGT group (p = 0.012). There was a close correlation between peak of inactive clopidogrel metabolite plasmatic concentration and inhibition of the ADP receptor (r = 0.79; p < 0.001). CONCLUSION: The bioavailability of clopidogrel in critically ill patients after cardiopulmonary resuscitation is significantly impaired compared with stable patients. Therefore, other drugs, preferentially administered intravenously, should be considered.

Porcine model of ruptured abdominal aortic aneurysm repair.

OBJECTIVES: To validate a porcine model of ruptured abdominal aortic aneurysm (rAAA) repair. DESIGN: Experimental study. METHODS: Ten experimental and five sham-operated pigs were studied. Instrumentation for cardiac output (CO) measurement, regional blood flow (renal-REN and portal-PORT) and blood sampling (inferior vena cava (IVC), renal and portal vein) was done. Microcirculation was visualised sublingually and in ileostoma. PROTOCOL: simulation of rAAA with bleeding (mean arterial pressure (MAP) 45 mmHg) and increased abdominal pressure (25 mmHg) for 4 h; 2 h of infrarenal clamp with shed blood retransfusion; 11 h of post-surgery care. RESULTS: Six experimental pigs completed the protocol and are presented. Bleeding decreased CO to 95%, PORT to 80% and REN to 10% of baseline. From clamping on CO and PORT increased above baseline whereas REN (47%) with creatinine clearance remained compromised till the end. Microcirculation was affected more in ileum than sublingually. Approximately threefold increase in cytokines (tumour necrosis factor-α (TNF-alpha), interleukin (IL)-6 and IL-10) and oxidative stress markers (thiobarbituric acid-reactive substances (TBARs) and 4-hydroxy-2-trans-nonenal (HNE) was observed. Only mild increase in IL-6 and TBARs was observed in sham-operated animals. Organ histology did not reveal differences between groups. CONCLUSIONS: This near-lethal model of rAAA induced expected severe deterioration of haemodynamics and metabolism accompanied with a moderate inflammatory and oxidative stress response.

Repeated chemosensitivity testing in patients with epithelial ovarian carcinoma.

Epithelial ovarian carcinoma (EOC) is a highly chemosensitive tumor, but most patients with advanced EOC initially responding to first-line chemotherapy will eventually relapse. Chemosensitivity testing may offer an opportunity for the optimal selection of chemotherapeutic agents for individual patients. In the present retrospective analysis we have examined the changes in chemosensitivity profiles during the course of the disease. Chemosensitivity was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) test. Two or more samples at least 14 days apart were obtained from 34 patients with ovarian cancer. Chemoresistance increased significantly at the second measurement only for paclitaxel and carboplatin, the most frequently used cytotoxic drugs. No significant difference compared to baseline was observed at subsequent measurements for any other cytotoxic agent studied, although a non-significant trend for increased chemoresistance was observed. In conclusion, in the present cohort only paclitaxel and carboplatin chemosensitivity changed significantly, although to a limited extent, during the course of the disease. In contrast to a limited increase of paclitaxel and carboplatin chemoresistance, no significant changes were observed for other cytotoxic agents examined. The present data indicate that chemoresistance increases, to a modest extent, against the drug most frequently used, but remains relatively stable during the course of disease, especially for agents that are not used in the therapeutic regimen.

[Immodin in the treatment of immunoparalysis in intensive care patients]. / Immodin v lécbe imunoparalýzy nemocných v intenzivní péci.

OBJECTIVE: The objective of the study was to evaluate the effect of administration of the immunoregulating preparation Immodin (Sevapharma, CZ) to influence immunoparalysis in intensive care unit patients. METHOD: A double blind, randomised clinical study was designed for the above purpose. The patients in whom immunoparalysis was detected during monitoring (CD14+ HLA-DR+ < or = 40 %) were randomised for the administration of Immodin (IM) or placebo (PL); the treatment lasted for 5 days. 45 (25% of all monitored) patients - the men/women ratio being 29/16, 60 (54; 65) years of age - were enrolled in the study (of which 25 IM and 20 PL). RESULTS: The patients did not show differences in ICU mortality - 23 IM patients survived, 2 IM patients died; 15 PL patients survived and 5 PL patients died (p = 0.214). The time of ICU hospitalisation did not differ, either - 11.6 days for IM patients (8.2; 14.9), 12.6 days for PL patients (9.1; 16.1) (P = 0.659) - nor did the number of nosocomial infections - 4 out of 25 IM patients and 4 out of 20 PL patients (p = 0.776). No difference was observed between the patient groups during a 5 day intervention period in terms of SOFA score development (p = 0.954), SIRS days (p = 0.614), sepsis or severe sepsis (respectively p = 0.451 and p = 0.250). No difference was recorded in the trends of basic immunologic parameters, either (CD14+ HLA-DR+ - p = 0.460, production of TNFalpha - p = 0.802, IL-6 - p = 0.335 , IL-10 - p = 0.226). The trend of inflammation parameters was also identical (CRP - p = 0.673, PCT - p = 0.711 ). CONCLUSION: The effect of 5 day administration of Immodin to ICU patients with symptoms of immunoparalysis does not differ from that of placebo.

Effects of ultrafiltration, dialysis, and temperature on gas exchange during hemodiafiltration: a laboratory experiment.

To study gas exchange in the filter during continuous venovenous hemodiafiltration (CVVHDF), an air-tight heated mixing chamber with adjustable CO2 supply was constructed and connected to a CVVHDF monitor. Bicarbonate-free crystalloid (Part 1) and packed red blood cell (Part 2) solutions were circulated at 150 ml x min(-1). Gas exchange expressed as pre-postfilter difference in CO2 and O2 contents was measured at different CVVHDF settings and temperatures of circulating and dialysis solutions. Ultrafiltration was most efficacious for CO2 removal (at 1,000 ml x h(-1) ultrafiltration CO2 losses reached 13% of prefilter CO2 content). Addition of dialysis (1,000 ml x h(-1)) increased CO2 loss to 17% and at maximal parameters (filtration 3,000 ml x h(-1), dialysis 2,500 ml x h(-1)), the loss of CO2 amounted to 35% of prefilter content. Temperature changes of circulating and/or dialysis fluids had no significant impact on CO2 losses. The O2 exchange during CVVHDF was negligible. Currently used CVVHDF is only marginally effective in CO2 removal. Higher volume ultrafiltration combined with dialysis can be expected to reach clinical significance.

Effect of dopexamine on outcome after major abdominal surgery: a prospective, randomized, controlled multicenter study. European Multicenter Study Group on Dopexamine in Major Abdominal Surgery.

OBJECTIVE: To test the hypothesis that dopexamine reduces postoperative mortality and morbidity in high-risk, major abdominal surgery patients, when given to fluid-resuscitated patients starting before the operation and continued for 24 hrs after surgery. DESIGN: Prospective, randomized, controlled, double-blind multicenter trial. SETTING: Intensive care units in 13 hospitals from six European countries. PATIENTS: A total of 412 patients with predefined high-risk criteria, undergoing major abdominal surgery with an expected duration of at least 1.5 hrs. INTERVENTIONS: The patients received placebo (n = 140), dopexamine at 0.5 microg/kg/min (n = 135), or dopexamine at 2.0 microg/kg/ min (n = 137) starting after preoperative hemodynamic stabilization and continued for 24 hrs after surgery. MEASUREMENTS AND MAIN RESULTS: The primary outcome variable was mortality at 28 days. Analysis was by intention to treat. Dopexamine had no effect on mortality (at 28 days, 13%, 7%, and 15%, for the groups receiving placebo, dopexamine at 0.5 microg/kg/ min, and dopexamine at 2.0 microg/kg/min, respectively), despite the expected dose-dependent hemodynamic responses. No effect was observed on the occurrence of organ dysfunction, duration of intensive care unit stay, or length of hospital stay. CONCLUSION: We conclude that dopexamine in doses that result in increased cardiac output and oxygen delivery after preoperative stabilization with fluids does not improve outcome after major abdominal surgery compared with fluids alone. Based on post hoc subgroup analysis and stratification according to the number of risk factors, we suggest that the concept should be further tested in patients at higher risk of complications or undergoing emergency surgery.

Continuous venovenous hemodiafiltration (CVVHDF) with citrate anticoagulation in the treatment of a patient with acute renal failure, hypercalcemia, and thrombocytopenia.

A 72-year-old patient with multiple myeloma was admitted to the intensive care unit because of hypercalcemic crisis and acute renal failure. After 7 days of comprehensive therapy including diuretics steroids, calcitonin, and intermittent hemodialysis (IHD) with low-calcium dialysate, calcium still reached high levels between IHD treatments and thrombocytopenia developed after chemotherapy. CVVHDF with calcium-free bicarbonate dialysate was started. Anticoagulation with 2.2% citrate was performed in order to chelate calcium, and thus treat the hypercalcemia, and to provide regional anticoagulation, and thus reduce the risk of bleeding due to thrombocytopenia. CVVHDF with citrate anticoagulation was continued for 6 days, and standard heparin anticoagulation was started when the hypercalcemia and thrombocytopenia abated.

[Treatment of glioblastoma multiforme]. / Zkusenosti s lécbou multiformního glioblastomu.

The authors evaluate therapeutic results in 31 patients with the diagnosis of multiform glioblastoma. The comprehensive therapeutic procedure used as a rule which involves surgery, radiotherapy and in some instances also chemotherapy still gives very unsatisfactory results. The mean survival period of patients after surgery was 26.7 weeks and the mortality of patients within one month was 22.6%. Even radical surgery does not produce more favourable therapeutic results. Contemporary trends of preclinical and clinical research are focused in particular on different immunotherapeutic methods.

Intrabronchial brachytherapy using 226-radium source.

Present work reports on results of manual brachytherapy in lung cancer using intrabronchial catheter and 226-radium source. Expected dosage was 18 Gy at 1 cm from the source. This therapy was combined with external radiotherapy by 60-cobalt till the dosage about 65 Gy. 19 men were treated, the mean survival was 14.3 months. Advantages and disadvantages of the method are discussed.