Ethik,Kommunikation und interdisziplinäre Zusammenarbeit – per Gesetz?!

Die Onkologie - Die Corona-Pandemie hat in den letzten Monaten verdeutlicht, dass das Thema Sterblichkeit trotz erheblicher Fortschritte im Bereich der Hospiz- und Palliativversorgung zu...     

Effects of social stress on behavior and corpus luteum in female golden hamsters (Mesocricetus auratus)

The consequences of group-keeping as a social stressor on the solitary-living golden hamster were studied. Two females at the same stage of the estrous cycle were kept together for 5 weeks. Behavioral observations showed that the dominance structures within groups were unstable. Intensity of aggression was highest at metestrous, whereas the greatest activity was observed during the estrous stage. After 1 week, the body masses of singly kept and group-kept hamsters were different. Five weeks after the onset of the experiment, the body mass of the singly kept hamsters had increased by 3.6%, and that of the group-kept hamsters by 25%. The plasma progesterone level of group-kept females was 60 to 70% higher than that of singly kept females. The absolute masses of the adrenal glands and the ovaries were higher in group-kept females. Nevertheless, the relative masses did not differ. Whereas a significant positive correlation between the weights of both organs and the body mass was observed in singly kept females, in group-kept females such a correlation was only observed between body and ovary weight. Number and size of corpora lutea were enlarged in group-kept individuals, and this seems to be responsible for elevated plasma progesterone titres. These results indicate social stress in group-kept female hamsters.     

Live now--pay by ageing: high performance mitochondrial activity in youth and its age-related side effects

Radical oxygen species are a byproduct of normal energy metabolism in mitochondria. The short-lived radicals cause damage to their immediate surrounding, i.e. the mitochondria. While most of this damage will be removed by normal mitochondrial turnover, damage to mitochondrial DNA (mtDNA) can persist and may accumulate with age. Recent evidence indicates that mutant mtDNA molecules can accumulate within individual cells, potentially hampering mitochondrial function.     

Undernutrition is associated with mortality,exacerbation, and poorer quality of life in patients with chronic obstructive pulmonary disease: A systematic review with meta-analysis of observational studies

Impaired nutrition status is recognized as a risk factor for worse clinical outcomes in patients with chronic obstructive pulmonary disease (COPD). The aims of this study were to investigate how undernutrition is diagnosed, its prevalence, and whether there is an association between this condition and clinical outcomes in patients with COPD. The search for this systematic review of observational studies (PROSPERO: CRD42020191888) was performed in the PubMed, Embase, and Scopus databases, with no date or language restrictions. The studies had to report data on the diagnosis of undernutrition and its association with mortality, exacerbation, length of hospital stay, or quality of life in adult patients with COPD. A meta-analysis with a random-effects model was performed to combine data. Forty-nine studies were included (20 of them classified as having a low risk of bias), and the most common diagnostic method of undernutrition was body mass index (BMI) (n = 36). The pooled prevalence of undernutrition was equal to 20% (95% CI, 0.15–0.25; I² = 100%), and it was associated with mortality (risk ratio = 1.97; 95% CI, 1.55–2.50; I² = 98%), exacerbation (risk ratio = 1.73; 95% CI, 1.03–2.91; I² = 96%), and poorer quality of life (mean difference = 8.25; 95% CI, 5.40–11.10; I² = 79%). For all outcomes, the certainty of evidence was very low. In conclusion, undernutrition is prevalent and is associated with poorer outcomes in patients with COPD. However, undernutrition is mainly diagnosed by BMI, which underreports its prevalence, and the certainty of the evidence is very low.     

Refinement of the international prognostic scoring system (IPSS) by including LDH as an additional prognostic variable to improve risk assessment in patients with primary myelodysplastic syndromes (MDS).

The international prognostic scoring system (IPSS) is considered the gold standard for risk assessment in primary myelodysplastic syndromes (MDS). This score includes several prognostic factors except serum lactate dehydrogenase (LDH). We evaluated the prognostic power of LDH as an additional variable in IPSS-based risk assessment. For this purpose, a total of 892 patients with primary MDS registered by the Austrian-German cooperative MDS study group was analyzed retrospectively. Multivariate analysis confirmed the value of established parameters such as medullary blasts, karyotype and peripheral cell counts and showed that elevated LDH was associated with decreased overall survival (P<0.00005) and increased risk of AML development (P<0.00005), independent of the system used to classify MDS (FAB or WHO). Moreover, elevated LDH was found to be a significant predictor of poor survival within each IPSS risk group and within each FAB group except RAEB-T. To exploit these results for refined prognostication, each IPSS risk group was split into two separate categories (A=normal LDH vs B=elevated LDH). Using this LDH-assisted approach, it was possible to identify MDS patients with unfavorable prognosis within the low and intermediate IPSS risk groups. We propose that the IPSS+LDH score should improve clinical decision-making and facilitate proper risk stratification in clinical trials.     

Clinical Benefit-Risk Profile of Lenalidomide in Patients With Lower-risk Myelodysplastic Syndromes Without del(5q): Results of a Phase III Trial

BackgroundIn the phase III MDS-005 study of patients with lower-risk, non-del(5q) myelodysplastic syndromes, lenalidomide was associated with a higher rate of ≥ 8 weeks red blood cell transfusion independence (RBC-TI) compared with placebo, but also with a higher risk of hematologic adverse events (AEs).Patients and MethodsThis analysis evaluated the ratio of clinical benefit-risk in patients treated with lenalidomide or placebo, and assessed the effect of lenalidomide dose reductions on response. Clinical benefit was a composite endpoint defined as RBC-TI, transfusion reduction ≥ 4 units packed red blood cells, hemoglobin increase ≥ 1.5 g/dL, or cytogenetic response.ResultsThe rate of clinical benefit was higher with lenalidomide than with placebo (31.9% vs. 3.8%). The ratio of response (RBC-TI and clinical benefit) to risk (hematologic AEs) favored lenalidomide over placebo. Patients who underwent ≥ 1 lenalidomide dose reduction had a longer duration of treatment, received a higher cumulative dose, and were more likely to experience clinical benefit versus patients without dose reductions.ConclusionDespite the occurrence of hematologic AEs, the overall benefit-risk profile supported lenalidomide treatment. Appropriate management of hematologic AEs by dose reductions may help patients with myelodysplastic syndromes to remain on treatment and achieve clinical benefit.     

Hematologic responses to deferasirox therapy in transfusion-dependent patients with myelodysplastic syndromes

Background

Reductions in transfusion requirements/improvements in hematologic parameters have been associated with iron chelation therapy in transfusion-dependent patients, including those with myelodysplastic syndromes; data on there reductions/improvements have been limited to case reports and small studies.

Design and Methods

To explore this observation in a large population of patients, we report a post-hoc analysis evaluating hematologic response to deferasirox in a cohort of iron-overloaded patients with myelodysplastic syndromes enrolled in the Evaluation of Patients’ Iron Chelation with Exjade^® (EPIC) study using International Working Group 2006 criteria.

Results

Two-hundred and forty-seven, 100 and 50 patients without concomitant medication for myelodysplastic syndromes were eligible for analysis of erythroid, platelet and neutrophil responses, respectively. Erythroid, platelet and neutrophil responses were observed in 21.5% (53/247), 13.0% (13/100) and 22.0% (11/50) of the patients after a median of 109, 169 and 226 days, respectively. Median serum ferritin reductions were greater in hematologic responders compared with non-responders at end of study, although these differences were not statistically significant. A reduction in labile plasma iron to less than 0.4 μmol/L was observed from week 12 onwards; this change did not differ between hematologic responders and non-responders.

Conclusions

This analysis suggests that deferasirox treatment for up to 1 year could lead to improvement in hematologic parameters in some patients with myelodysplastic syndromes.     

Angioimmunoblastic lymphadenopathy (AILD) may respond to thalidomide treatment: two case reports

The histological morphology of AILD-type T-cell lymphoma shows proliferation of small, arborizing high endothelial venules. Patients typically have generalized lymphadenopathy, fever, weight loss, skin rash, polyclonal hypergammaglobulinemia and autoimmune phenomena, and are susceptible to infections. The clinical course is usually aggressive. About 30% of patients have an initial remission on steroids alone, but most require some form of cytotoxic chemotherapy. Median survival ranges from 15 to 24 months, and it appears that the disease cannot be cured. We have used anti-angiogenetic therapy with thalidomide in two AILD patients and observed remarkable responses.