Elevated soluble intercellular adhesion molecule-1 levels in obesity: relationship to insulin resistance and tumor necrosis factor-alpha system activity.

Intercellular adhesion molecule-1 (ICAM-1) is 1 of the possible factors linking obesity and diabetes with cardiovascular disease, however, the mechanism of the increase in ICAM-1 concentration in obesity remains unclear. Therefore, the aim of the present study was to assess plasma soluble ICAM-1 (sICAM-1) levels in obese subjects with normal glucose tolerance and to evaluate whether those levels may be related to insulin resistance and tumor necrosis factor-alpha (TNFalpha) system activity. The study was performed in 8 lean and 15 obese subjects. Anthropometric and biochemical parameters were measured, and insulin sensitivity was evaluated using the euglycemic hyperinsulinemic clamp technique (insulin infusion, 50 mU x kg(-1) x h(-1)). Obese subjects were markedly more hyperinsulinemic and insulin resistant and had higher plasma soluble TNF receptor 2 (sTNFR2) and sICAM-1 levels. sICAM-1 was related positively to body mass index (BMI), waist-to-hip ratio (WHR), percent of body fat, glycated hemoglobin (HbA(1c)), plasma insulin and triglycerides (TG), TNFalpha, and sTNFR2 and negatively to insulin sensitivity. Multiple regression analysis showed that only sTNFR2 and insulin sensitivity were independent predictors of sICAM-1 concentrations and were responsible for 66% of sICAM-1 variability. We conclude that an increase in plasma sICAM-1 concentration in obesity is related to TNFalpha system activation and insulin resistance.     

A case report of a patient with dermatomyositis as a prodromal sign of lung cancer

Dermatomyositis (DM) is a connective tissue disease characterized by specific inflammatory lesions in muscle biopsy. It is caused by vasculitis determined by humoral factors with subsequent inflammatory cell accumulation, mainly T CD4+ and B cells, which infiltrate myocytes leading to its vacuolization and degeneration (mainly in the skeletal muscles, rarely in the smooth muscles). The incidence of DM is estimated at 1-10 per million in adults and at 1-3.2 per million in children. The autoimmune mechanism of disease induction is not fully recognized. Several lines of evidence showed the link between DM and neoplastic disease. The first report of dermatomyositis associated with stomach cancer, by Stertz, comes from 1916. In the same time, Kankeleit reported DM associated with breast cancer. Presumably, it is the result of immune reaction against antigens common for muscle and neoplastic cells or some paraneoplastic syndrome underlying mechanism. The report presents the case of a 52-year-old woman with DM (diagnosed according to the Bohan and Peter criteria) and with coexistent squamous lung cancer in situ. The left upper lobectomy was performed. No complications in postoperative period were observed. During more than 2 years of follow-up after the surgery, the patient remained in good condition, without DM symptoms, or cancer relapse. Considering that DM may be associated with lung cancer; extensive diagnostic work-up to exclude neoplastic lesions should be performed. Patients aged 40 years or more should be particularly screened.     

Analysis of efficacy and safety of multiple intravenous infusion of anti-tumor necrosis factor-alpha monoclonal antibody (Remicade) combined with methotrexate compared with sodium aurothiomalate and intramuscular depot methylprednisolone in rheumatoid arthritis

The objective of the paper was compare the effects and tolerability of combined therapy of multiple intravenous infusions of anti-tumour necrosis factor-alfa (TNF-alfa) monoclonal antibody (Remicade) with methotrexate versus treatment with sodium aurothiomalate and intramuscular depot methylprednisolone in rheumatoid arthritis (RA). We investigate also the interval necessary to obtain the improvement in both treatment groups. 36 patients commencing intramuscular sodium aurothiomalate therapy with intramuscular depot methylprednisolone acetate at weeks 0, 4, 8 and 12 in addition to chrysotherapy were compared in retrospective analysis with 32 patients starting with multiple intravenous infusions of infliximab, anti-TNF-alfa monoclonal antibody (Remicade) and methotrexate at a stable dose. Patients were assessed by composite clinical score (DAS 28) and C-reactive protein during 22 weeks of therapy. At week 2 and 6 a significantly greater percentage of infliximab-treated than gold-treated RA patients achieved improvement in each clinical measurement of disease activity. At 22 week of treatment moderate and good response according to EULAR criteria was achieved in 91% of infliximab-treated patients and 58% gold treated patients (p < 0.001). Adverse events were more frequently observed in infliximab-treated patients, but only gold-treated patients discontinued treatment because adverse events (2 patients due to proteinuria, 2 patients due to mucocutaneous changes and one patient due to leucopenia). The higher percentage of adverse events in infliximab-treated patients was caused mainly by the occurrence of infusion reactions (23 reactions out of 160 infusions); most of them were mild (somnolentia and headache) and transient. Viral infections (including herpes simplex and zoster) were more common in patients treated with infliximab and methotrexate. Combination therapy of infliximab and methotrexate is more effective in reducing clinical and biochemical disease activity than gold with methylprednisolone treatment in RA patients during 22 weeks of treatment, especially in the first 6 weeks.     

The Influence of Recombinant Human Erythropoietin on Apoptosis and Cytokine Production of CD4+ lymphocytes from Hemodialyzed Patients

Recombinant human erythropoietin (rhEPO) treatment of hemodialyzed (HD) patients normalizes the altered phenotype of CD4⁺ lymphocytes and restores the balance of Th1/Th2 cytokines. We decided to test how the presence of rhEPO in cell culture modulates cytokine production of CD4⁺ lymphocytes in HD patients with stable hemoglobin level and expression of activation antigens of stimulated CD4⁺ lymphocytes similar to those observed in healthy individuals. We also tested whether the presence of rhEPO in cell culture protects stimulated CD4⁺ lymphocytes of HD patients from apoptosis. Peripheral blood mononuclear cells (PBMC) of HD patients were stimulated with an immobilized anti-CD3 antibody with or without addition of rhEPO. The percentage of apoptotic CD4⁺ lymphocytes and the level of Th1/Th2 cytokines in culture supernatants were measured with flow cytometry. HD patients showed a decrease in the percentage of apoptotic CD4⁺ cells after stimulation with the anti-CD3 antibody combined with rhEPO. The level of IFN-γ and IL-10 was increased while the level of TNF-α was decreased in the presence of rhEPO in cell culture from HD patients. These results confirm the role of rhEPO signaling in T lymphocytes of HD patients.     

Masowe badania molekularne dla identyfikacji dawców ze słabą ekspresją antygenu D

One of the basic rules of transfusion is to prevent alloimmunisation by highly immunogenic RhD antigen and not to transfuse RhD negative individuals with RhD positive blood. In some cases the expression of this antigen is so weak that it is undetectable in routine serological tests. The paper presents an algorithm for mass DNA testing with the purpose of identifying donors with low RhD expression. The screening is based on RHD gene detection (absent in RhD negative Caucasians) in DNA isolated from pools of 96 plasma samples from blood donors identified as RhD negative by the routine serological methods in Blood Transfusion Centers. Such procedure substantially reduces the costs. Plasma samples can be brought from the territory of the whole country, stored and accumulated for testing in one selected center. The cost would amount to approximately 25 PLN per donor. The test is performed once for each RhD negative individual. It is estimated that such persons will represent approximately 0.2% of RhD negative donors.     

Inhibitor kinazy Brutona u chorych z nawrotowym lub opornym na leczenie chłoniakiem z komórek płaszcza – wyniki międzynarodowego,wieloośrodkowego,badania II fazy z ibrutynibem (PCI-32765) – EHA Encore

Bruton's tyrosine kinase (BTK) is a central mediator of B-cell receptor (BCR) signaling essential for normal B-cell development. Ibrutinib is an oral BTK inhibitor that induces apoptosis and inhibits migration and adhesion of malignant B-cells. Updated results of this international, multicenter, phase 2 study of single agent ibrutinib in relapsed or refractory MCL will be presented.Ibrutinib 560 mg PO QD was administered continuously until disease progression. Tumor response was assessed every 2 cycles (one cycle = 28 days). The study enrolled 115 patients (65 bortezomib-naïve, 50 bortezomib-exposed); 111 patients were treated; 110 were evaluable for response. Baseline characteristics included: median age 68 years, time since diagnosis 42 months, number of prior treatments 3; bulky disease (>10 cm) 13%, prior stem cell transplant 10%, high risk MIPI 49%.Median time on treatment was 9.2 months; 53% of patients remain on therapy. Median PFS was 13.9 months and DOR has not yet been reached. Responses increased with longer treatment: comparing to previous data described at ASH 2011, the CR rate increased from 16% to 39%, and the ORR increased from 69% to 75%.     

Vaspin (but not neuropeptide B or neuropeptide W) as a possible predictor of body weight normalization in anorexia nervosa

IntroductionThe aim of the study was to evaluate the correlation between the nutritional status of patients with anorexia nervosa (AN) and levels of vaspin (VASP), neuropeptide B (NPB), neuropeptide W (NPW) and total antioxidant status (TAS).Material and methodsNinety serum samples collected from 30 teenage female patients during the acute stage of AN and 30 healthy persons (CONTR) were subjected to biochemical analysis; patients with AN were examined at the beginning of the study (AN-I) and after hospitalization (AN-II), as a result of which partial stabilization of anthropometric measurements was achieved (an increase of body mass index (BMI) by 3.5 kg/m²).ResultsVaspin levels dropped at the end of the hospitalization (compared to AN-I, p < 0.05), achieving values comparable to the CONTR; moreover there was a positive correlation between VASP level and the achieved body weight in AN-II (p < 0.05). Positive correlations were also noted with regard to VASP vs. NPB in AN-I (p < 0.02) (and AN-II, p < 0.013), as well as in the case of VASP vs. NPW in the same groups (p < 0.02 and p < 0.015, respectively). NPB concentration was higher in AN-I (p < 0.05) and AN-II (p < 0.018) than in CONTR, whereas there were no differences (p > 0.05) with regard to levels of VASP, NPW, or TAS.ConclusionsThe high level of NPB despite treatment and normalization of VASP level may suggest that there are chronic neuroendocrine disorders at play in anorexia nervosa.     

Health-related quality of life in children with immunoglobulin A nephropathy – results of a multicentre national study

IntroductionImmunoglobulin A nephropathy (IgAN) may lead to end stage renal disease and severely affect patient functioning and wellbeing. The aim of the study was to evaluate health-related quality of life (HRQoL) in children and adolescents with IgAN, and compare HRQoL in relation to the disease course, social status and psychological factors, such as expressing anger and perceived personal competence.Material and methodsThe multicentre cross-sectional study included 51 patients ≥ 8 years from 7 paediatric nephrology centres in Poland. Psychometric analysis was performed using the Kidscreen-52 questionnaire to evaluate HRQoL, the Anger Expression Scale to evaluate the severity of anger and the Personal Competence Scale to measure general perception of personal competence.ResultsMean age of patients was 14.54 ±3.69 years; duration since the diagnosis of IgAN was 4.98 ±3.9 years. Patients with IgAN rated their psychological wellbeing as significantly worse compared to healthy peers (p < 0.05). The presence of proteinuria was associated with significantly worse physical wellbeing (58.72 ±18.45 vs. 74.44 ±22.97; p < 0.05). Current therapy (steroids/immunosuppressive drugs) had no effect on HRQoL in the study group. Perceived personal competence was rated high by 49% of children in the study group. Children with IgAN were characterized by lower intensity of expressed anger (p < 0.001) and significantly higher intensity of suppressed anger (p < 0.01) compared to reference ranges. Severity of expressed anger correlated positively with the parent relations and school environment dimensions of HRQoL.ConclusionsWe found lower HRQoL in regard to physical and psychological wellbeing in a group of Polish children with IgAN compared to healthy peers. HRQoL should be monitored in this patient group.     

Time efficiency of direct anterior hip arthroplasty compared to postero-lateral approach in elderly patients

IntroductionPrimary arthroplasty of the hip joint is currently one of the most commonly performed procedures in orthopedics. In Poland we are observing significant changes in the age structure. With the prolonged life more and more elderly patients require musculoskeletal surgery to maintain comfortable and painless mobility. Reducing the duration of the procedure reduces the costs of anesthesiology, surgical and instrument teams, as well as the operating room technical team. The aim of the study was to compare the time required to perform hip joint arthroplasty by the direct anterior approach (DAA) with the postero-lateral approach (PLA) in our hospital.Material and methodsA retrospective analysis of 559 total and bipolar cemented and cementless hip replacement procedures based on two operative approaches – the minimally invasive DAA over the course of 2 years, and the standard PLA over the course of 3 years – was performed.ResultsStatistically significant differences were observed between the approaches used for cementless total arthroplasty with regard to the mean treatment times: 51.9 min for the 272 DAA cases, and 78.3 min for the 190 PLA cases (p < 0.0001). For the cementless hemi-arthroplasty procedure, the mean treatment times were 46.9 min in 36 patients for DAA, and 48.2 min for 61 patients for PLA (p = 0.57).ConclusionsMinimally invasive DAA significantly shortens the time of the procedure in elderly patients compared to PLA. Further study is needed to analyze other aspects of those two approaches.     

The role of NF-κB and Smac/DIABLO proteins in the treatment response and survival of acute myeloid leukemia patients

IntroductionThe misbalance between a family of inhibitor of apoptosis proteins (IAP), regulated by the nuclear factor kappa B (NF-κB) and their natural antagonist second mitochondrial-derived activator of caspases/direct IAP binding protein with low pI (Smac/DIABLO) are important to biology of acute myeloid leukemia (AML).Material and methodsThe aim of the study was to assess NF-κB and Smac/DIABLO proteins expression in blasts of 109 newly diagnosed AML patients using the multicolor flow cytometry and evaluate their influence on AML patients outcome.ResultsExpression of NF-κB and of Smac/DIABLO proteins were found in 95% and 98% of the patients, respectively. A negative correlation between Smac/DIABLO and NF-κB was observed. Age < 60 years old as well as higher Smac/DIABLO expression were associated with a higher probability of complete response achievement in the multivariate analysis. Longer overall survival (OS) in the univariate and multivariate analyses was influenced by age < 60 years old, a favorable or intermediate-risk karyotype and high Smac/DIABLO expression. Additionally, in the survival analysis of the subgroups, the patients aged < 60 years old, with high Smac/DIABLO expression, lower NF-κB expression and < 50% of bone marrow blasts who were treated with standard treatment had better OS.ConclusionsLower NF-κB and higher Smac/DIABLO expression may influence AML patients outcome.