A multicenter retrospective study of 223 patients with t(14;16) in multiple myeloma.

The t(14;16) translocation, found in 3%-5% of newly diagnosed (ND) multiple myeloma (MM), has been associated with adverse outcomes. However, the studies establishing the characteristics of t(14;16) included solely small cohorts. The goal of the current international, multicenter (n = 25 centers), retrospective study was to describe the characteristics and outcomes of t(14;16) patients in a large, real-world cohort (n = 223). A substantial fraction of patients had renal impairment (24%) and hemoglobin <10 g/dL (56%) on initial presentation. Combined therapy of both immunomodulatory drug and proteasome inhibitor (PI) in the first line was used in 35% of patients. Autologous stem cell transplantation was performed in 42% of patients. With a median follow up of 4.1 years (95% CI 3.7-18.7), the median progression-free survival (PFS) and overall survival (OS) from first line therapy were 2.1 years (95% CI 1.5-2.4) and 4.1 years (95% CI 3.3-5.5), respectively. Worse OS was predicted by age > 60 years (HR = 1.65, 95% CI [1.05-2.58]), as well as revised International Scoring System (R-ISS) 3 (vs R-ISS 2; HR = 2.59, 95% CI [1.59-4.24]). In conclusion, based on the largest reported cohort of t(14;16) patients, quarter of this subset of MM patients initially presents with renal failure, while older age and the R-ISS 3 predict poor survival.

The expression of p63 and Ck HMW in magnum and infundibulum of Gallus domesticus oviduct.

The potential for proliferation and differentiation has a critical meaning in terms of the long-term in vitro culture of oviductal target cells. Therefore, it is important to characterize the oviduct epithelial cells, using approved markers. There is scarce data describing the epithelial cells lining the avian oviduct, most of it referring only to the magnum section of the oviduct. This study presents a comprehensive analysis of both magnum and infundibulum tissues, as the most preferred sources of epithelial cells for research on production of recombinant proteins in oviducts of birds. The main objective was to evaluate the expression of p63 and high molecular weight cytokeratins (anti- p63 antibody and anti- High Molecular Weight Cytokeratins) in epithelial cells (EC) of 2 oviduct sections: magnum (proximal and middle) and infundibulum (distal). IHC analysis and western blotting were performed using the mouse monoclonal anti- p63 antibody and anti-Ck HMW. Immunoreactivity was quantified based on the Remmele - Stegner scoring system (0-12). The expression of p63 in nuclei of luminal cells was significantly higher in the infundibulum (P < 0.05), compared to the magnum section. Cytokeratins were also highly expressed in the infundibulum, but the difference was non-significant. These findings reveal new characteristics of the oviduct EC and designate the location of the source of cells in the oviduct tissue for in vitro culture.

Characteristics of selected peripheral blood parameters in polar fox (Alopex lagopus L.) fed diets with inulin.

This study aimed at investigating changes in selected peripheral blood parameters in male polar foxes fed diets with different supplementation of inulin: 0.25% (group El), 0.5% (E2) and 1% (E3). The blood for analysis was sampled from the brachial vein. The study showed that adding 0.25 and 0.5% of inulin to fox feed resulted in a lower content of haemoglobin (Hb) as well as mean mass of Hb in red blood cells in the 0.5% inulin group. The total count of thrombocytes decreased significantly with a higher level of prebiotic, while the total number of white blood cells and the percentage of different leukocytes tested remained invariable. The lowest supplementation of inulin affected the partial pressure of carbon dioxide, however, the remaining acid-base parameters did not change. The present study provides the first preliminary information about the effect of dietary inulin on some haematological indices and acid-base parameters in adult polar foxes. The results may be helpful in practice to improve the health condition of farmed polar foxes.

Changes in the diagnosis and non-invasive treatment of chronic coronary syndromes in the last three European Society of Cardiology guidelines.

One of the most common forms of ischemic heart disease is chronic coronary syndromes (CCS), formerly known as stable coronary artery disease. During the last 15 years, the European Society of Cardiology has modified the guidelines for the diagnosis and treatment of CCS three times. The aim of this study was to analyze the changes in non-invasive diagnostics and pharmacotherapy of CCS that occurred in the last three guidelines. In non-invasive diagnostics, the most important change was reduction of the role of the electrocardiographic exercise test in favor of non-invasive stress imaging tests and computed tomography angiography. In pharmacotherapy, the role of ß-blockers and calcium channel blockers has increased in controlling heart rate and symptoms. Intensive hypolipemic treatment for prevention of cardiovascular events and treatment with low doses of novel oral anticoagulants for those at high risk of cardiovascular events with sinus rhythm are among the recommendations.

Evaluation of the hepatotoxicity of the novel GPR40 (FFAR1) agonist CPL207280 in the rat and monkey.

GPR40 (FFAR1) is a promising target for the managing type 2 diabetes (T2D). The most advanced GPR40 agonist TAK-875 exhibited satisfactory glucose-lowering effects in phase II and III studies. However, the phase III studies of TAK-875 revealed drug-induced liver injury (DILI). It is unknown whether DILI is a consequence of a specific GPR40 agonist or is an inherent feature of all GPR40 agonists. CPL207280 is a novel GPR40 agonist that improves diabetes in Zucker Diabetic Fatty (ZDF) rats, Goto Kakizaki (GK) rats and db/db mice. In this report, the DILI-related toxicity of CPL207280 was compared directly with that of TAK-875. In vitro studies evaluating hepatic biliary transporter inhibition, mitochondrial function, and metabolic profiling were performed in hepatocytes from different species. The long term toxicity of CPL207280 was studied in vivo in rats and monkeys. Activity of CPL207280 was one order of magnitude lesser than that of TAK-875 for the inhibition of bile acid transporters. CPL207280 had a negligible effect on the hepatic mitochondria. In contrast to TAK-875, which was metabolized through toxic glucuronidation, CPL207280 was metabolized mainly through oxidation. No deleterious hepatic effects were observed in chronically treated healthy and diabetic animals. The study presents promising data on the feasibility of creating a liver-safe GPR40 agonist. Additionally, it can be concluded that DILI is not a hallmark of GPR40 agonists; it is linked to the intrinsic properties of an individual agonist.

Mean Platelet Volume Has Prognostic Value in Chronic Lymphocytic Leukemia.

PURPOSE: Mean platelet volume (MPV) is a readily accessible and commonly tested hematological indicator. Recent studies revealed a significant impact of MPV on the course and prognosis of many diseases, including some types of cancer, as well as on the incidence of atrial fibrillation and bleeding. The study aimed to perform a retrospective analysis of MPV in terms of time to first treatment (TTFT) and to determine its prognostic value in the group of patients with chronic lymphocytic leukemia (CLL). Moreover, the study includes a retrospective analysis of platelet parameters in patients treated with ibrutinib concerning bleeding and atrial fibrillation. PATIENTS AND METHODS: The study included 523 patients with CLL, for 344 the most important cytogenetic aberrations were reported. The Mann-Whitney, Kruskal-Wallis, Kaplan-Meier, chi-squared, log­rank tests and multivariate Cox proportional hazard regression model were used to analyze collected data. RESULTS: The receiver operating characteristic curve analysis was performed to identify optimal cut-off value for MPV. The analysis of survival curves showed that in the group of patients with higher values of MPV TTFT was significantly longer than in the group with lower MPV (17.9 vs 36 months, p=0.0015, cut-off value for MPV= 10.4 fl). In multivariate Cox proportional hazard regression model low MPV, the presence of del11q and del13q provided independent prognostic value for TTFT (HR=0.69, 95%-CI, 0.5293 to 0.9081; p=0.0078; HR=1.76, 95%-CI, 1.3000 to 2.3882, p=0.0003, HR=0.74, 95%-Cl, 0.5674 to 0.9588, p=0.0229, respectively). In the group treated with ibrutinib, 59 patients had no significant correlation between MPV level and the incidence of therapy complications, although in the group of patients with low MPV there was a tendency for more frequent occurrence of atrial fibrillation (p=0.259). CONCLUSION: Low MPV values are associated with unfavorable prognosis and might represent a novel, independent prognostic factor in CLL.

Different MAF translocations confer similar prognosis in newly diagnosed multiple myeloma patients.

The MAF translocations, t(14;16) and t(14;20), are considered as adverse prognostic factors based on few studies with small sample sizes. We report on their prognostic impact in a large group of 254 patients - 223 (87.8%) with t(14;16) and 31 (12.2%) with t(14;20). There were no intergroup differences in survival estimates. Median progression-free survival was 16.6 months for t(14;16) and 24.9 months for t(14;20) (p = 0.28). Median overall survival (OS) was 54.0 months and 49.0 months, respectively (p = 0.62). Median OS in patients who underwent double autologous stem cell transplantation (ASCT) was 107.0 months versus 60.0 months in patients who received single ASCT (p < 0.001). ISS 3 was associated with shorter OS (HR = 1.89; 95% CI 1.24-3.19; p = 0.005) in Cox analysis. Our study suggests that t(14;20) should be considered as an adverse factor of equal prognostic implication to t(14;16).

Generation of transgenic chickens by the non-viral, cell-based method: effectiveness of some elements of this strategy.

Transgenic chickens have, in general, been produced by two different procedures. The first procedure is based on viral transfection systems. The second procedure, the non-viral method, is based on genetically modified embryonic cells transferred directly into the recipient embryo. In this review, we analyzed the effectiveness of important elements of the non-viral, cell-based strategy of transgenic chicken production. The main elements of this strategy are: isolation and cultivation of donor embryonic cells; transgene construction; cell transfection in vitro; and chimera production: injection of cells into recipient embryos, raising and identification of germline chimeras, mating germline chimeras, transgene inheritance, and transgene expression. In this overview, recent progress and important limitations in the development of transgenic chickens are presented.