Long-term safety and efficacy of rituximab in 248 adults with immune thrombocytopenia: Results at 5 years from the French prospective registry ITP-ritux

Rituximab is a second-line option in adults with immune thrombocytopenia (ITP), but the estimated 5-year response rate, only based on pooled retrospective data, is about 20%, and no studies have focused on long-term safety. We conducted a prospective multicenter registry of 248 adults with ITP treated with rituximab with 5 years of follow-up to assess its long-term safety and efficacy. The median follow-up was 68.4 [53.7-78.5] months. The incidence of severe infections was only 2/100 patient-years. Profound hypogammaglobulinemia (<5 g/L) developed in five patients at 15 to 31 months after the last rituximab infusion. In total, 25 patients died at a median age of 80 [69.5-83.9] years, corresponding to a mortality rate of 2.3/100 patient-years. Only three deaths related to infection that occurred 12 to 14 months after rituximab infusions could be due in part to rituximab. At 60 months of follow-up, 73 (29.4%) patients had a sustained response. On univariate and multivariate analysis, the only factor significantly associated with sustained response was a previous transient response to corticosteroids (P = .022). Overall, 24 patients with an initial response and then relapse received retreatment with rituximab, which gave a response in 92%, with a higher duration of response in 54%. As a result of its safety profile and its sustained response rate, rituximab remains an important option in the current therapeutic armamentarium for adult ITP. Retreatment could be an effective and safe option.     

Vulnerabilities and Caregiving in an Ethnically Diverse HIV-Infected Population

The current study aimed to identify the primary informal caregivers of a group of urban HIV+ adults (n = 250) and to determine relationships between demographic, medical, and substance use characteristics and caregivers types. Reported caregiver types included 36.8% familial, 22.4% significant other, and 22.8% institutional or other caregiver relationships. The remaining 18% of the sample reported having no individual that rendered informal care. Factors associated with the absence of an informal caregiver included African American race and low education. Hispanic participants reported the highest frequency of family caregivers while participants with a history of substance disorder were less likely to identify a significant other as a caregiver. This study demonstrates the evolving nature of informal caregiving in HIV, race- and education-related disparities in the absence of primary caregivers, and the importance of sociocultural and demographic factors in the study of HIV caregiving. Research supported by R24MH59724 from the National Institutes of Health.     

Prevention of atrial fibrillation onset by beta-blocker treatment in heart failure: a meta-analysis.

AIMS: Atrial fibrillation (AF) is an important morbidity-mortality risk factor, especially in patients with heart failure (HF). Beta-blockers reduce morbidity and mortality in HF. The study was designed to estimate the preventive efficacy of beta-blocker treatment on AF occurrence in patients with HF. METHODS AND RESULTS: A systematic review of the literature was performed to identify all clinical trials evaluating beta-blockers' efficacy in HF. Eligible studies had to be randomized, placebo-controlled and providing information on the incidence of AF during follow-up among those with sinus rhythm at baseline. A total of seven studies which included 11 952 patients receiving a background treatment with angiotensin-converting enzyme-inhibitors could be found. Overall, beta-blockers significantly reduced incidence of onset of AF from 39 to 28 per 1000 patient-years: relative risk reduction=27% (95% confidence interval 14-38, P<0.001); heterogeneity test: P=0.096. A same trend of efficacy was observed in all trials except the SENIORS study. In this trial which included aged patients (>70 years) with systolic or diastolic HF, a higher prevalence of AF at baseline (35%) was observed compared with the mean baseline prevalence (13%). CONCLUSION: Beta-blockers appear to effectively prevent occurrence of AF in patients with systolic HF.     

Fibrolipoma of the median nerve

Neural fibrolipoma or fibrolipomatous hamartoma is an uncommon benign tumor that usually arises in the median nerve. Fibrofatty tissue proliferates around the nerve and infiltrates the epineurium and perineurium. We report a case of fibrolipomatous hamartoma of the left median nerve in an 18-year-old woman. Our objective was to describe the pathognomonic magnetic resonance imaging features, whose presence obviates the need for a diagnostic biopsy.     

A peptide selected by biopanning identifies the integrin alphavbeta6 as a prognostic biomarker for nonsmall cell lung cancer

The development of new modes of diagnosis and targeted therapy for lung cancer is dependent on the identification of unique cell surface features on cancer cells and isolation of reagents that bind with high affinity and specificity to these biomarkers. We recently isolated a 20-mer peptide which binds to the lung adenocarcinoma cell line, H2009, from a phage-displayed peptide library. We show here that the cellular receptor for this peptide, TP H2009.1, is the uniquely expressed integrin, alphavbeta6, and the peptide binding to lung cancer cell lines correlates to integrin expression. The peptide is able to mediate cell-specific uptake of a fluorescent nanoparticle via this receptor. Expression of alphavbeta6 was assessed on 311 human lung cancer samples. The expression of this integrin is widespread in early-stage nonsmall cell lung carcinoma (NSCLC). Log-rank test and Cox regression analyses show that expression of this integrin is significantly associated with poor patient outcome. Preferential expression is observed in the tumors compared with the surrounding normal lung tissue. Our data indicate that alphavbeta6 is a prognostic biomarker for NSCLC and may serve as a receptor for targeted therapies. Thus, cell-specific peptides isolated from phage biopanning can be used for the discovery of cell surface biomarkers, emphasizing the utility of peptide libraries to probe the surface of a cell.     

Association of khellin and 308-nm excimer lamp in the treatment of severe alopecia areata in a child

Alopecia areata (AA) is an autoimmune inflammatory disorder of hair, characterized by non-scarring hair loss. A 308-nm excimer lamp (EL) has been reported as one effective modality in the treatment of AA. Khellin is a furanochromone photosensitizer whose chemical structure is close to psoralens and has previously proven its efficacy in vitiligo in association with ultraviolet A. We evaluated the efficacy and safety of a combination of topical khellin and 308-nm EL in the treatment of a refractory ophiasic AA, of 1-year evolution, in a 5-year-old boy. Treatment consisted in topical application of khellin 45 mn before irradiation with EL (starting dose 50 mJ/cm²) twice a week for 3 months. The result was a complete regrowth of hair with no recurrence 1 year later. Further studies should be carried out to confirm this promising result and to propose khellin–excimer as a new alternative treatment for resistant cases of AA in children.     

Internal translation initiation stimulates expression of the ARF/core+1 open reading frame of HCV genotype 1b

The hepatitis C virus possesses an alternative open reading frame overlapping the Core gene, whose products are referred to as Core+1 or alternative reading frame (ARF) or F protein(s). Extensive studies on genotype HCV-1a demonstrated that ribosomal frameshifting supports the synthesis of core+1 protein, when ten consecutive As are present within core codons 9-11 whereas, in the absence of this motif, expression of the core+1 ORF is mediated mainly by internal translation initiation. However, in HCV-1b, no Core+1 isoforms produced by internal translation initiation have been described. Using constructs which contain the Core/Core+1(342-770) region from previously described HCV-1b clinical isolates from liver biopsies, we provide evidence for the synthesis of Core+1 proteins by internal translation initiation in transiently transfected mammalian cells using nuclear or cytoplasmic expression systems. Site directed mutagenesis analyses revealed that (a) the synthesis of Core+1 proteins is independent from the polyprotein expression, as we observed an increase of Core+1 protein expression from constructs lacking the polyprotein translation initiator, (b) the main Core+1 product is expressed from AUG(85), similarly to the Core+1/S protein of HCV-1a, (c) synthesis of Core+1 isoforms is also mediated from GUG(58) or under certain conditions GUG(26) internal codons, albeit at lower efficiency. Finally, comparable to HCV-1a Core+1 proteins, the HCV-1b Core+1 products are negatively regulated by core expression and the proteaosomal pathway. The expression of Core+1 ORF from HCV-1b clinical isolates and the preservation of translation initiation mechanism that stimulates its expression encourage investigating the role of these proteins in HCV pathogenesis.