Rituximab decreases the risk of lymphoma in patients with HIV-associated multicentric Castleman disease

HIV-associated multicentric Castleman disease (MCD) is associated with a high risk of developing non-Hodgkin lymphoma (NHL). Rituximab is effective in HIV-MCD, but its impact on NHL incidence remains unknown. From a single-center prospective cohort, 113 patients were identified with a diagnosis of HIV-MCD for the present study. To compare the incidence of NHL between patients who had received a rituximab-based treatment (R+ group) and those who had not (R- group), data were analyzed before and after matching on propensity scores and after multiple imputation. The mean follow-up was 4.2 years. In the R- group (n = 65), 17 patients developed NHL (incidence, 69.6 of 1000 person years). In the R+ group (n = 48), only 1 patient developed NHL (incidence, 4.2 of 1000 person years). Based on the propensity score-matching method, a significant decrease in the incidence of NHL was observed in patients who had been treated with rituximab (hazard ratio, 0.09; 95% confidence interval, 0.01-0.70). Ten Kaposi sarcoma (KS) exacerbations and 1 newly diagnosed KS were observed in 9 patients after rituximab therapy. Rituximab was associated with an 11-fold lower risk of developing lymphoma. KS exacerbation was the most challenging adverse event after rituximab therapy.     

Unbiased plasma proteomics for novel diagnostic biomarkers in cardiovascular disease: identification of quiescin Q6 as a candidate biomarker of acutely decompensated heart failure

Aims Biochemical marker testing has improved the evaluation and management of patients with cardiovascular diseases over the past decade. Natriuretic peptides (NPs), used in clinical practice to assess cardiac dysfunction, exhibit many limitations, however. We used an unbiased proteomics approach for the discovery of novel diagnostic plasma biomarkers of heart failure (HF). Methods and results A proteomics pipeline adapted for very low-abundant plasma proteins was applied to clinical samples from patients admitted with acute decompensated HF (ADHF). Quiescin Q6 (QSOX1), a protein involved in the formation of disulfide bridges, emerged as the best performing marker for ADHF (with an area under the receiver operator characteristic curve of 0.86, 95% confidence interval: 0.79-0.92), and novel isoforms of NPs were also identified. Diagnostic performance of QSOX1 for ADHF was confirmed in 267 prospectively collected subjects of whom 76 had ADHF. Combining QSOX1 to B-type NP (BNP) significantly improved diagnostic accuracy for ADHF by particularly improving specificity. Using thoracic aortic constriction in rats, QSOX1 was specifically induced within both left atria and ventricles at the time of HF onset. Conclusion The novel biomarker QSOX1 accurately identifies ADHF, particularly when combined with BNP. Through both clinical and experimental studies we provide lines of evidence for a link between ADHF and cardiovascular production of QSOX1.     

Comparable outcomes between unrelated and related donors after reduced-intensity conditioning allogeneic hematopoietic stem cell transplantation in patients with high-risk multiple myeloma

The purpose of this study was to assess the results of allogeneic stem cell transplantation (allo-SCT) after reduced-intensity conditioning (RIC) from matched related donors (MRD) and unrelated donors (URD) in 40 patients with high-risk multiple myeloma (MM) in a single centre. Seventeen (43%) (Group 1) and 23 patients (57%) (Group 2) had URD and MRD, respectively. Thirty-nine patients (98%) received one or more autologous transplantation. The median follow-up was 22 months (1-49). None of our patient experienced a graft rejection. The cumulative incidence of grade II-IV acute GVHD was higher (47%) for the URD vs. (17%) for the MRD (P = 0.092). The cumulative incidence of chronic GVHD was no different between the two groups (24% vs. 30%, respectively). At 2 yr, the TRM probabilities were lower in the unrelated group 12% vs. 22% in the related group (P = 0.4). Also at 2 yrs, for patients receiving unrelated transplantation overall and progression-free survivals, 59% and 42%, respectively compared to patients with related donor transplantation, 66% and 44% (P = 0.241). In conclusion, these results suggest that URD in MM is feasible. The small number of patients with URD emphasizes the need to delineate indications and perform prospective protocols.     

Peroxisome proliferator activating receptor alpha and gamma polymorphisms and metabolic abnormalities in HIV-infected patients receiving highly active antiretroviral therapy: the ANRS CO8 APROCO-COPILOTE study

Highly active antiretroviral therapy (HAART) is associated with fat redistribution and metabolic disorders. The present study was undertaken to evaluate the association between peroxisome proliferator activated receptor (PPAR)α and PPARγ polymorphisms, two genes involved in lipid metabolism and adipocyte differentiation, and elements of the metabolic syndrome, lipodystrophy, or carbohydrate metabolism abnormalities in patients receiving HAART. The frequency distribution of rare alleles for PPARα (L162V) and PPARγ (P12A and H449H) was compared using the chi square test in 363 HIV-1-infected patients classified according to the presence or absence of the metabolic syndrome after 48 months of follow-up on their first PI-containing regimen. The P12A rare g allele was present in 12% patients with normal glucose metabolism, 11% patients with impaired glucose tolerance or impaired fasting glucose, and 35% patients with diabetes (p=0.014). The rare g allele for L162V was present in 14% of patients free of hypertriglyceridemia and in 7% patients with hypertriglyceridemia (p=0.04). The rare g allele for L162V was found in 15% of patients free of any sign of lipodystrophy and 8% with at least one sign of lipodystrophy (p=0.04) and the rare t allele for H449H was found in 14% of patients free of any sign of lipodystrophy and 23% of patients with at least one sign of lipodystrophy (p=0.05). There was no convincing association between any polymorphism of PPARα and PPARγ and each individual component of the metabolic syndrome, except for the relationship of the P12A polymorphism with diabetes. Confirmatory studies on a larger number of individuals are needed.