Italian experience with rVIII-single chain: a survey of patients with haemophilia A and their physicians

Journal of Thrombosis and Thrombolysis - rVIII-SingleChain is indicated for treatment and prophylaxis of bleeding in patients with haemophilia A (HA). The safety and efficacy of rVIII-SingleChain...     

Effects of Grape Skin Extract on Age-Related Mitochondrial Dysfunction,Memory and Life Span in C57BL/6J Mice

Dementia contributes substantially to the burden of disability experienced at old age, and mitochondrial dysfunction (MD) was identified as common final pathway in brain aging and Alzheimer’s disease. Due to its early appearance, MD is a promising target for nutritional prevention strategies and polyphenols as potential neurohormetic inducers may be strong neuroprotective candidates. This study aimed to investigate the effects of a polyphenol-rich grape skin extract (PGE) on age-related dysfunctions of brain mitochondria, memory, life span and potential hormetic pathways in C57BL/6J mice. PGE was administered at a dose of 200 mg/kg body weight/d in a 3-week short-term, 6-month long-term and life-long study. MD in the brains of aged mice (19–22 months old) compared to young mice (3 months old) was demonstrated by lower ATP levels and by impaired mitochondrial respiratory complex activity (except for mice treated with antioxidant-depleted food pellets). Long-term PGE feeding partly enhanced brain mitochondrial respiration with only minor beneficial effect on brain ATP levels and memory of aged mice. Life-long PGE feeding led to a transient but significant shift of survival curve toward higher survival rates but without effect on the overall survival. The moderate effects of PGE were associated with elevated SIRT1 but not SIRT3 mRNA expressions in brain and liver tissue. The beneficial effects of the grape extract may have been influenced by the profile of bioavailable polyphenols and the starting point of interventions.     

Cells carrying nonlymphoma-associated bcl-2/IgH rearrangements (NLABR) are phenotypically related to follicular lymphoma and can establish as long-term persisting clonal populations

OBJECTIVE: Nonlymphoma-associated bcl-2/IgH rearrangements (NLABRs) are frequently amplified by PCR in blood of lymphoma-free subjects (LFS), but the temporal kinetics and phenotypic nature of NLABR-positive cells are unknown. To address these issues we prospectively monitored a panel of NLABR-positive LFS. METHODS: LFS have been studied by nested PCR, real-time PCR, and DNA sequencing. Cell selection studies were also performed to define the nature of NLABR-bearing clones. RESULTS: Of 125 donors, 16 (12.8%) were found to be bcl-2/IgH positive and were monitored at least every 6 months for a median time of 22 months (range 6-50). In half of the subjects the same NLABR detected initially was again reamplified at follow-up thrice or more. In 5, the same NLABR was constantly amplified in every follow-up sample. With a median follow-up of 22 months (range 9-50), no stable disappearance of a recurrent clone has been so far recorded. Real-time PCR indicated that persistent NLABR-positive clones are stable over time in the same subject. Cell separation studies indicate that NLABRs belong to CD19+, CD5-, CD23-, CD10+/- cells. CONCLUSIONS: Our results indicate that NLABR-positive clones are persistent populations phenotypically related to follicular lymphoma (FL). This suggests the existence of a FL-related clonal expansion of undetermined significance, which might be either a premalignant or a nonmalignant counterpart of FL.     

18FDG PET/CT in the early assessment of non-small cell lung cancer response to immunotherapy: frequency and clinical significance of atypical evolutive patterns

European Journal of Nuclear Medicine and Molecular Imaging - This prospective study aimed (1) to assess the non-small cell lung cancer (NSCLC) evolutive patterns to immunotherapy using FDG-PET and...     

The impact of pharmacogenetics on radiation therapy outcome in cancer patients. A focus on DNA damage response genes

More than half of cancer patients are treated by radiation therapy, with a wide inter-patient variability in tumour response. Recent advances have been made in understanding molecular mechanisms that govern the behaviour of tumour cells and tissues exposed to ionizing radiation. Accumulating data suggest an important role of DNA damage response genes, including DNA repair (especially double-strand breaks), apoptosis and cell-cycle control genes. It has been hypothesized that frequent germinal polymorphisms, most often single-nucleotide polymorphisms, in DNA damage response genes may impact tumour response and clinical outcome for patients receiving a radiotherapy-based treatment. We reviewed literature covering the relationships between candidate gene polymorphisms in DNA damage response and the efficacy of a radiation-based treatment. Although several methodological limitations may preclude a definitive conclusion, single nucleotide polymorphisms of several candidate genes such as ERCC- or XRCC-family genes seem to be potential predictive biomarkers of radiotherapy efficacy, even though not strictly involved in radiotherapy-induced double-strand breaks repair. In order to improve the relevance of clinical results, and our interpretation of them, we draw a parallel between clinical findings and available preclinical data on polymorphism functionality. Clinical findings require validation in larger replication studies and open the prospect of future clinical trials.     

Lupus anticoagulant: interference with in vivo prostaglandin production and with platelet sensitivity to prostacyclin.

The hypothesis has been made that inhibition of prostacyclin (PG12) production may play a role in the pathogenesis of thrombosis in patients with the lupus anticoagulant (LA), but so far no evidence of reduced PG12 levels in vivo has been produced. We have tested the plasma levels of PG12 and thromboxane A2 (TXA2) and the platelet sensitivity to PG12 in 14 patients with and without LA and in 14 healthy controls. No significant difference in the prostanoid basal levels was detected among the groups; however, in some patients PG12 increments seemed to parallel the clinical course of the disease. Platelet sensitivity to exogenous PG12 was significantly enhanced in the LA + patients and correlated with PG12 values. We suggest that in these subjects additional factors, other than reduced PG12, may predispose to thrombosis.     

Health‐related quality of life and burden of fatigue in patients with primary immune thrombocytopenia by phase of disease

The main objective of this study was to compare health‐related quality of life (HRQOL) of primary immune thrombocytopenia (pITP) patients with that of general population, overall, and by patient group (i.e., newly diagnosed, persistent, and chronic patients). Fatigue was also investigated as a secondary objective. Overall, 424 adult patients were enrolled in a multicenter observational study and the control group consisted of a representative sample from the general population. Propensity score matching plus further multivariate linear regression adjustment was used to compare HRQOL outcomes between pITP patients and general population. Mean age of patients was 54 years. Of those with HRQOL assessment, 99 patients (23.6%) were newly diagnosed, 53 (12.6%) were persistent, and 268 (63.8%) were chronic pITP patients. Comparison by patient group versus their respective peers in the general population revealed greater impairments in persistent pITP patients. Persistent pITP patients reported clinically meaningful impairments in physical functioning (?15; 95% CI ?24.1 to ?5.8; P = 0.002), social functioning (?15.3; 95% CI ?25.5 to ?5.1; P = 0.004), role physical (?28.4; 95% CI ?43.1 to ?13.7; P < 0.001), role emotional (?23.9; 95% CI ?40.1 to ?7.7; P = 0.004), and mental health scales (?11.3; 95% CI ?21.2 to ?1.4; P = 0.026) of the SF‐36 questionnaire. Higher fatigue severity was associated with lower physical and mental HRQOL outcomes. Our findings suggest that the burden of the disease and treatment might depend on the disease phase and that persistent pITP patients are the most vulnerable subgroup. Am. J. Hematol. 91:995–1001, 2016. © 2016 Wiley Periodicals, Inc.