Determinants of lenalidomide response with or without erythropoiesis-stimulating agents in myelodysplastic syndromes: the HOVON89 trial.

A randomized phase-II study was performed in low/int-1 risk MDS (IPSS) to study efficacy and safety of lenalidomide without (arm A) or with (arm B) ESA/G-CSF. In arm B, patients without erythroid response (HI-E) after 4 cycles received ESA; G-CSF was added if no HI-E was obtained by cycle 9. HI-E served as primary endpoint. Flow cytometry and next-generation sequencing were performed to identify predictors of response. The final evaluation comprised 184 patients; 84% non-del(5q), 16% isolated del(5q); median follow-up: 70.7 months. In arm A and B, 39 and 41% of patients achieved HI-E; median time-to-HI-E: 3.2 months for both arms, median duration of-HI-E: 9.8 months. HI-E was significantly lower in non-del(5q) vs. del(5q): 32% vs. 80%. The same accounted for transfusion independency-at-week 24 (16% vs. 67%), but similar in both arms. Apart from presence of del(5q), high percentages of bone marrow lymphocytes and progenitor B-cells, a low number of mutations, absence of ring sideroblasts, and SF3B1 mutations predicted HI-E. In conclusion, lenalidomide induced HI-E in patients with non-del(5q) and del(5q) MDS without additional effect of ESA/G-CSF. The identified predictors of response may guide application of lenalidomide in lower-risk MDS in the era of precision medicine. (EudraCT 2008-002195-10).

Solid-state drawing of post-consumer isotactic poly(propylene): Effect of melt filtration and carbon black on structural and mechanical properties.

Post-consumer plastic waste obtained via mechanical recycling is usually applied in thick-walled products, because of the low mechanical strength due to the presence of contaminants. In fact, sorted post-consumer isotactic poly(propylene) (i-PP) can be considered as a blend of 95% i-PP and 5% poly(ethylene), with traces of poly(ethylene terephthalate) (PET). By applying a treatment such as solid-state drawing (SSD) after melt extrusion, the polymer chains can be oriented in one direction, thereby improving the stiffness and tensile strength. In this research, molecular processes such as crystal break-up and chain orientation of these complex blends were monitored as a function of draw ratio. The melt filter mesh size - used to exclude rigid PET particles - and the addition of carbon black (CB) - often added for coloration in the recycling industry - were varied to investigate their influence on the SSD process. This research shows that despite the blend complexity, the molecular processes during SSD compare to virgin i-PP and that similar draw ratios can be obtained (λmax=20), albeit at reduced stiffness and strength as a result of the foreign polymers present in post-consumer i-PP. It is observed that the process stability improves with decreasing mesh size and that higher draw ratios can be obtained. The addition of carbon black, which resides in the dispersed PE phase, also stabilizes the SSD process. Compared to isotropic post-consumer i-PP, the stiffness can be improved by a factor 10 to over 11GPa, while the tensile strength can be improved by a factor 15-385MPa, which is approx. 70% of the maximum tensile strength achieved for virgin i-PP.

Collagenous colitis: description of a single centre series of 83 patients.

INTRODUCTION: Collagenous colitis can be the cause of chronic diarrhoea. AIM: Assess the prevalence of collagenous colitis in a single centre. PATIENTS: All records of patients with diarrhoea in whom histological examination showed collagenous colitis, were retrieved. Demographic data, clinical presentation, associated diseases and treatment were studied. RESULTS: In a period of 15 years 83 patients were identified with collagenous colitis. These were 16 men and 67 women, mean age 60 years (range 20-87) at time of diagnosis. Thirty four patients (38%) complained of mushy stools and 49 (62%) of watery diarrhoea. Eight patients had rectal bleeding. Mucous discharge was noted by 18 patients. There was no weight loss in 55 patients. Six patients complained of loss of appetite, 9 had nausea, and 2 complained of vomitus. A macroscopically normal colon was present in 63 patients. Associated diseases, like celiac disease and hypothyroidism, only were seen in women. Twenty eight patients did not receive any treatment, ten patients received mesalazine. One patient was treated with steroids. Fourteen patients were treated for accompanying bacterial overgrowth. Fourteen patients used loperamide. Budesonide was applied with success in 17 patients. During follow-up 58 patients had no complaints anymore, 21 had mild diarrhoea, 3 moderate, while it was unknown in one patient. CONCLUSION: Collagenous colitis has a higher prevalence as usually reported. There is an association with auto-immune disorders and dysbacteriosis.

Cytochrome c dependent, antimycin-A resistant respiration in mitochondria from potato tuber (Solanum tuberosum L.). Influence of wounding and storage time on outer membrane NADH-cytochrome-c-reductase.

Cytochrome c has two stimulatory effects on respiration of mitochondria especially those from wounded potato tuber. In the first place a stimulation of succinate- and NADH-consuming, antimycin-A-sensitive respiration, which reaches a maximal value at low cytochrome c concentrations, has been found. In the second place, at higher concentrations of cytochrome c a stimulation of NADH-consuming respiration occurs, which is antimycin-A-resistant, but KCN-sensitive. This antimycin-A-resistant, NADH-consuming respiration is absent, when no cytochrome c is added to the reaction medium. It is insensitive to metal chelators, to which the antimycin-A-and KCN-resistant plant mitochondrial alternative oxidase is sensitive. By measurements of NADH-cytochrome c reductase activities a corresponding antimycin-A-resistant NADH-cytochrome c reductase has been found, which is insensitive to osmotic shock treatment. A localization of this antimycin-A-resistant electron transport with NADH as the electron donor in the outer mitochondrial membrane is likely. In the mitochondrial preparations cytochrome c might stimulate by acting as an electron-carrier between the outer membrane reductase and the inner membrane cytochrome oxidase. A big increase of the outer membrane mediated electron transport in the mitochondria has been observed after wounding of potato tuber tissue. The ability of the tissue to produce this electron transport pathway after wounding disappeared after prolonged storage of the tubers. A possible function of this electron transport pathway in fatty acid desaturation during the wound-reaction is suggested.