To compare drugs that are recommended in national and international clinical guidelines with those reimbursed and actually used in the treatment of pancreatic adenocarcinoma in Poland. Websites of relevant clinical associations, the List of reimbursed drugs authorized by the Ministry of Health in Poland (LMoH) and database made available by Polish public payer as of October 2015 were screened in search for drugs used in the treatment of pancreatic adenocarcinoma. All guidelines consequently recommended gemcitabine or its doublets with nab-paclitaxel (with the highest category of evidence) and in patients with good performance status – FOLFIRINOX (oxaliplatin, irinotecan and fluorouracil). Some also indicated gemcitabine in combination with erlotinib, capecitabine or cisplatin, as well as doublets of oxaliplatin with fluoropiridine (classified as less effective). According to LMoH the following chemotherapeutics were reimbursed in the treatment of adenocarcinomas of pancreas: carboplatin, cisplatin, cyclophosphamide, dacarbazine, doxorubicin, etoposide, fluorouracil, gemcitabine, ifosfamide, irinotecan, mitomicin, oxaliplatin, vinblastine, vincristine and vinorelbine. Database of Polish public payer showed that from 2013 to 2015 (as for first half of the year) 1138 patients with the mentioned malignancies were treated with reimbursed drugs and gemcitabine was used in a great majority of them (n=923). Among less commonly utilized drugs were fluorouracil (n=224), oxaliplatin (n=189) and cisplatin (n=125). Other were administered to single patients (irinotecan n=23, etoposide n=11, carboplatin, vinorelbine n=4 each, doxorubicin n=3, cyclophosphamide, vinblastine and vinorelbine n=1 each). There were also 20 patients from 2014 to 2015 treated with nab-paclitaxel reimbursed outside standard fashion (i.e. outside LMoH). There is a strong adherence of recommended, reimbursed and actually used drugs in pancreatic adenocarcinoma if it comes to gemcitabine, fluorouracil, oxaliplatin and cisplatin in Poland.
To systematically review the currently available clinical and cost-effectiveness evidence of non-pegylated liposomal doxorubicin (NPLD) for non-Hodgkin lymphoma (nHL). The hypothesis under verification was that the administration of NPLD lowers the cardiotoxicity typical for conventional anthracyclines while being able to sustain the clinical effect of treatment. A systematic literature search was conducted for clinical and cost-effectiveness data for the nHL population treated with NPLD, using the main medical databases (PubMed, EMBASE, Cochrane Library). In addition, clinical trial registries were searched, reference lists of included studies and reviews were screened for missed studies. Searches took place in September 2012. The review generated 9 one-arm clinical trials and 1 retrospective study which met the inclusion criteria. One comparative parallel trial comparing R-CHOP with R-COMP in the DLBCL population is ongoing, with no results published. Generally, available evidence is poor – studies identified are characterized by many limitations, i.e.: small and heterogeneous study populations, relatively short observation period, not always specified inclusion and exclusion criteria, diversified treatment regimens (with R-CHOP dominating), shortened or/and presented selectively safety data. The majority of studies was performed in the DLBCL population. Cumulative interpretation of data was hindered due to essential differences in between trials. Lowering of LVEF was observed with a frequency of 0% to 31,7% of cases, while symptomatic lowering of LVEF with the development of chronic ischemic heart disease occurred with the frequency of 0 to 10%. The second most frequent cardiological event observed was arrhythmia. Clinical efficacy focused on surrogate endpoints (radiological responses), defined differently in between trials. No economic evaluations studies were found. There is limited evidence on the effectiveness and safety of NPLD in patients with nHL due to the lack of well-designed and well-reported comparative studies. Further research is needed to explore the hypothesis in question.
Neutrophil migration did not change during normal menstrual cycles but was significantly reduced during controlled ovarian hyperstimulation (COH). Correlations between neutrophil migration and serum hormone concentrations could not be established. (C)2004 by American Society for Reproductive Medicine.
Objectives: We investigated the association of impaired blood polymorphonuclear Leukocyte (PMN) migration with the incidence of bacterial infections in patients with severe trauma.Method: Twenty-six intensive-care patients with different injury severity scores were enrolled in a prospective study. PMN migration was measured daily using 300 fit fresh whole blood in a membrane filter assay. Migration was evaluated in an automated image analyzer that recorded numbers and distribution of the immigrant PMNs within a filter. The relevant parameter was the percentage of PMNs that migrated from the blood samples into the filters upon f-Met-Leu-Phe stimulation.Results: Nine patients developed posttraumatic infections verified microbiologically. These patients showed a reduced PMN migratory capacity in comparison with the 17 patients without infections. A migrating portion of six per cent or Less at least three days in succession preceded infections by one to 19 days and indicated infection in eight true positive versus three false positive cases, and 14 true negative versus one false negative case, i.e. specificity was 82.3% and sensitivity 88.8%, p = 0.0008. Trauma severity had no influence on PMN migration.Conclusions: Trauma patients with impaired PMN migration are at risk for bacterial infections. Whole-blood migration tests can define the infection risk and thus may be useful predictive markers for infections. (C) 2003 The British Infection Society. Published by Elsevier Science Ltd. ALL rights reserved.
We have developed an improved method for measuring the filamentous (F) actin content of human blood polymorphonuclear leukocytes (PMNs). The essential feature of the method is the immediate fixation of the F-actin cytoskeleton. Fresh whole blood (100 µl) is shock-cooled by the addition of 1.0 ml of a mixture of 18.75% glycerol and 5% formaldehyde in phosphate buffer pre-cooled to –8°C and subsequently fixed at 4°C for 15 min. After lysis in distilled water and removal of the red blood cells by centrifugation, the F-actin cytoskeleton of the PMNs is stained with fluorescein isothiocyanate (FITC)-phalloidin and quantified by means of flow cytometry. In healthy test subjects, PMN stimulation by the chemotactic peptide formyl-methionyl-leucyl-phenylalanine (FMLP) for 20 s resulted in a significantly increased F-actin assembly, while in patients with multiple organ failure, two subpopulations arose: one with greater F-actin content and a second with lower F-actin content in comparison with the unstimulated blood sample. This simple and fast method may be a useful tool in basic and clinical research.
The aim of the study was to demonstrate an activation of polymorpho-nuclear leukocytes (PMNs) in chronic progressive atherosclerosis (ATH). A group of patients with ATH, and a group of ATH patients under aspirin (ASA) therapy were compared with control persons without atherosclerotic alterations (healthy controls). Each group comprised 15 male age-matched subjects. The following inflammatory parameters related to PMN activities were measured: the polymorphonuclear leukocyte (PMN) blood count; blood PMN migration and reactive oxygen species release in vitro; the blood levels of PMN elastase, malondialdehyde, antibodies to oxidized LDL and soluble ICAM-1. In ATH patients, the PMN blood counts and the share of blood PMNs migrating upon platelet activating factor and leukotriene B4 stimulation were significnatly above the values of the healthy controls, while the other parameters were not significantly altered. ASA treatment attenuated the inflammatory response and reduced the differences between ATH and the healthy controls. It can be concluded that, in patients with chronic progressive atherosclerosis, PMNs are involved in the inflammatory process underlying the disease.
Infectious complications are still a major cause of morbidity and mortality after organ transplantation, and early therapy would certainly reduce the risk associated with severe infections. We therefore investigated the significance of polymorphonuclear leukocyte (PMN) functional tests as predictive markers for infection in transplant patients under immunosuppressive therapy in a longitudinal study. In 41 patients, blood PMN migration and reactive oxygen species release, the blood levels of PMN elastase, malondialdehyde, neopterin, sICAM-1 and sVCAM-1, and urine neopterine were measured in 3- and 4-day intervals after liver-, kidney-, kidney-pancreas-, and heart and lung transplantation. PMN migration was determined in whole blood and estimated by the amount of PMNs to penetrate into a membrane filter upon FMLP stimulation. Three groups of patients were formed according to their postoperative course. Group I patients (n - 23) had no or only minor local infection, group II patients (n= 11) had infections with distinct systemic involvement, and group III patients (n - 7) developed sepsis. A first elastaselevel of over 100 mg/L after surgery, followed by a drop in the amount of blood PMNs ready to migrate, on FMLP stimulation, to below 12%, turned out to be a marker for impending infection, whereas all other parameters tested were not predictive. In six of seven group III patients, this marker became positive (sensitivity 85.7%) up to 15 days before clinical manifestation of sepsis. In group I (largely uneventful recovery) only one of 23 patients was positive (specificity 95.6%), whereas group II patients were in between (4 of 11 positive). By this method it seems possible to diagnose severe infections in the preclinical phase, which may help prevent them if treatment is begun promptly.