Vincristine efficacy and safety in treating immune thrombocytopenia: a retrospective study of 35 patients

Although vincristine (VCR) is sometimes prescribed for newly diagnosed immune thrombocytopenia (ITP), its efficacy in refractory ITP and sustained efficacy has yet to be demonstrated. We describe our clinical experience and recommend vincristine's correct place in ITP management. This retrospective study analysed data from 35 patients with newly diagnosed (ND), persistent (P) or chronic (C) ITP treated with VCR. The initial response rate, defined as >30 × 10⁹ platelets/L, reached 86% after a median of 7 [interquartile range (IQR) 6–13] days. In ND and P ITP, even when previous therapies were inefficient, initial response was 87.5%, suggesting that this treatment could be used particularly in rescue. Median survival time, without failure or relapse, was 15 months (Kaplan–Meier curve). Predictive factors (univariate analysis) of an initial and long‐term response were a small number of prior treatments received. However, at 2 yr, only seven patients had sustained response. Eight (23%) patients experienced adverse events: neuropathy for seven and bowel obstruction for one. Vincristine efficacy in ITP was confirmed, and it could be a good strategy for treating resistant ITP, especially in emergencies. In this era of new therapeutics, VCR deserves to remain on the list of ITP treatments because of its initial efficacy, safety and low cost.     

Phthalimido-thiazole as privileged scaffold: activity against immature and adult worms of Schistosoma mansoni

Parasitology Research - Phthalimide, 1,3-thiazole, and thiazolidinone cores are considered privileged scaffolds and represent an attractive starting point to design new bioactive compounds for...     

Targeted next-generation sequencing in steroid-resistant nephrotic syndrome: mutations in multiple glomerular genes may influence disease severity

Genetic diagnosis of steroid-resistant nephrotic syndrome (SRNS) using Sanger sequencing is complicated by the high genetic heterogeneity and phenotypic variability of this disease. We aimed to improve the genetic diagnosis of SRNS by simultaneously sequencing 26 glomerular genes using massive parallel sequencing and to study whether mutations in multiple genes increase disease severity. High-throughput mutation analysis was performed in 50 SRNS and/or focal segmental glomerulosclerosis (FSGS) patients, a validation cohort of 25 patients with known pathogenic mutations, and a discovery cohort of 25 uncharacterized patients with probable genetic etiology. In the validation cohort, we identified the 42 previously known pathogenic mutations across NPHS1, NPHS2, WT1, TRPC6, and INF2 genes. In the discovery cohort, disease-causing mutations in SRNS/FSGS genes were found in nine patients. We detected three patients with mutations in an SRNS/FSGS gene and COL4A3. Two of them were familial cases and presented a more severe phenotype than family members with mutation in only one gene. In conclusion, our results show that massive parallel sequencing is feasible and robust for genetic diagnosis of SRNS/FSGS. Our results indicate that patients carrying mutations in an SRNS/FSGS gene and also in COL4A3 gene have increased disease severity.     

Familial recurrent bilateral panuveitis: efficiency of alpha interferon

INTRODUCTION: There is no consensus for the treatment of severe recurrent uveitis. Immunosuppressive drugs have inconstant efficiency and may result in serious adverse effects. We report the cases of two brothers suffering from severe recurrent idiopathic panuveitis dramatically improved following alpha interferon therapy. EXEGESIS: Two 28 and 32 years old brothers presented with an idiopathic recurrent panuveitis for 4 and 5 years respectively. They both had a HLA B5 haplotype. However they had no clinical symptoms of Beh?et's disease. In both cases panuveitis recurred three or four times yearly despite corticosteroid and cyclosporin therapies. The treatment with alpha interferon improved visual acuity in both cases. The older brother had no recurrence throughout the period of treatment and after a 1 year follow-up. The other one was improved and the ocular lesions have been stabilised for nine months follow-up. CONCLUSION: - Alpha interferon therapy seems efficient in severe idiopathic panuveitis. This treatment is well tolerated without ophthalmologic adverse effects. The optimal posology and the duration of treatment need to be determined.     

New insights on IgA vasculitis with underlying solid tumor: a nationwide French study of 30 patients

Clinical Rheumatology - IgA vasculitis (IgAV) frequently occurs during or after a mucosal infection; it also rarely occurs in patients with cancer. We hypothesized that cancer could impact the...     

Segment-embedded frame definition affects the hip joint centre precision during walking

Due to marker-specific soft tissue artefacts, the choice of the markers defining the segment-embedded frame affects the functional joint centre location, with subsequent error propagation to joint kinematics and kinetics in gait analysis. Our aim was to assess the effect of the number and placement of markers on the precision of the hip joint centre (HJC) location during walking.Twelve markers (2 x 6) were attached to the pelvis and left thigh of 15 young male subjects. Set-up movements were collected to locate an optimised functional HJC. For all permutations of three from six markers, a HJC was located and subsequently reconstructed in a static trial and during walking. Precision measures with two different definitions of the origin, namely a single maker or their mean-point, and using three, four, five and six were calculated. Finally, marker triads that reduced the variability of the HJC location were determined. Both the number of markers and method for defining the origin significantly affected the HJC precision during static and walking trials. For walking, precision of 39 mm using three markers improved to 5 mm using redundant markers and the mean marker position as the segment origin. Markers placed close to the joint gave more consistent results.     

Compliance, safety, and effectiveness of fixed-dose artesunate-amodiaquine for presumptive treatment of non-severe malaria in the context of home management of malaria in Madagascar

Home management of malaria is recommended for prompt, effective antimalarial treatment in children less than five years of age. Compliance, safety, and effectiveness of the new fixed-dose artesunate-amodiaquine regimen used to treat suspected malaria were assessed in febrile children enrolled in a 24-month cohort study in two settings in Madagascar. Children with fever were asked to visit community health workers. Presumptive antimalarial treatment was given and further visits were scheduled for follow-up. The primary endpoint was the risk of clinical/parasitologic treatment failure. Secondary outcomes included fever/parasite clearance, change in hemoglobin levels, and frequency of adverse events. The global clinical cure rate was 98.4% by day 28 and 97.9% by day 42. Reported compliance was 83.4%. No severe adverse effects were observed. This study provides comprehensive data concerning the clinical cure rate obtained with artesunate-amodiaquine and evidence supporting the scaling up of home management of malaria.