Suboptimal management of rheumatoid arthritis in France: a real-world study based on data from the French National Health Data System.

OBJECTIVES: The emergence of targeted therapy is changing rheumatoid arthritis (RA) management, but real-world data remain limited. This study aimed to describe real-world RA treatment patterns using data from a French national claims database. METHODS: This longitudinal study used the French Permanent Representative Sample (Echantillon Généraliste des Bénéficiaires) claims database. Patients with RA were identified between 2013 and 2017, with treatment patterns, persistence and adherence described. RESULTS: The study population included 2553 patients with RA. Disease-modifying antirheumatic drugs (DMARDs) were prescribed for 1512 (59.2%) patients, of whom 721 (47.6%) did not require discontinuation or treatment switch. There were 377 (24.9%) treatment discontinuations and 114 patients (7.5%) switched to a targeted DMARD (biological and synthetic (Janus kinase inhibitor) DMARDs). Among the 2315 patients with RA in 2017, almost half (n=1102, 47.6%) were not treated with a DMARD. Most (85.7%) received symptomatic treatment (analgesics (81.0%), steroids (49.2%), non-steroidal anti-inflammatory drugs (39.5%)). Of the 1142 treatment initiations identified, 713 (62.4%) were conventional synthetic DMARDs (csDMARDs), with methotrexate being the most frequent (n=553, 48.45%). One-year persistence rates varied between 55.9% (49.2-62.0%) for tumour necrosis factor inhibitors, and 63.4% (59.6-67.0%) for csDMARDs. Treatment adherence, assessed through medication possession ratio, varied between 71.9% and 90.8%, with ≥80% being the adherence cut-off. Almost half of DMARD initiations were associated with long-term (>6 months), high-dose oral steroid use (~7 mg/day prednisone equivalent). CONCLUSION: Despite a diverse therapeutic arsenal, there remains a medical need that is not covered by current RA management, which is frequently compensated for by overprescription of steroids.

Case Report of Bifid Ureter with a Blind Ending: Surgical Laparoscopic Management.

BACKGROUND The blind-ending branch of a bifid ureter is a rare congenital anomaly which is usually asymptomatic but can occasionally give rise to various symptoms, such as chronic abdominal pain. Diagnosis is most often confirmed radiologically, and treatment is usually conservative. Surgical resection of the blind ending of a bifid ureter should be considered in cases of persistent symptoms. CASE REPORT A female patient of 49 years of age presented with intermittent right lumbar pain, repetitive urinary infections and microscopic hematuria. We present here the diagnostic work-up of the case, leading to the identification of the existence of ureteral bifidity located at the lower third of the ureter and of a blind ending of the bifid ureter. Several regimens of various antibiotics failed to resolve the symptoms. It was decided to carry out a laparoscopic resection of the blind ending of the bifid ureter. We describe the practical procedures of the surgical operation and discuss briefly the embryological etiology and the physiopathology of the condition as well as the principal diagnostic modalities. Since the surgery, the patient has been symptom-free. CONCLUSIONS Despite being usually asymptomatic, the rare congenital anomaly of a bifid ureter with a blind ending can occasionally give rise to symptoms such as recurrent infections and persistent abdominal pain. Laparoscopic-based resection of the blind ending should be considered in such cases.

Antioxidant Activities of Co-Encapsulated Natal Plum (Carissa macrocarpa) Juice Inoculated with Ltp. plantarum 75 in Different Biopolymeric Matrices after In Vitro Digestion.

Biopolymeric systems that co-encapsulate probiotics and bioactive compounds ensure timely delivery in the gastrointestinal tract. Cyanidin 3-sambubioside is the dominant anthocyanin in Natal plum (Carissa macrocarpa). This study aims at the co-encapsulation of Natal plum (Carissa macrocarpa) juice inoculated with Lactiplantibacillus plantarum 75 (Ltp. plantarum 75) by freeze-drying using pea protein isolate, maltodextrin, and psyllium mucilage and evaluating their release in vitro. An encapsulation efficiency of >85% was noted in lactic acid bacteria (LAB) survival and anthocyanin content. Freeze-drying produced pinkish-red powder, rich in polyphenols and LAB (>6 Log CFU mL−1) after 14 days of storage. Natal plum juice + maltodextrin + pea protein isolate + psyllium mucilage + Ltp. plantarum 75 (NMPeaPsyB) showed the highest LAB population (6.74 Log CFU mL−1) with a survival rate of 81.9%. After digestion, NMPeaPsyB and NMPeaPsy had the highest LAB survival (>50%) at 67.5% and 67.5 ± 0.75%, respectively, and the highest bioaccessibility of cyanidin 3-sambubioside in Natal plum juice than the other co-encapsulation with other biopolymers. NMPeaPsy and NMPeaPsyB showed phenolic stability in the gastric phase and controlled release in the intestinal simulated phase. The antioxidant activities had strong correlations with cyanidin 3-sambubioside. The results confirmed that microencapsulation is important for improving stability and allowing for the development of functional foods.

Altered expression of the poly(ADP-ribosyl)ation enzymes in uveal melanoma and regulation of PARG gene expression by the transcription factor ERM.

PURPOSE: Poly(ADP-ribosyl)ation is a reversible post-translational modification that requires the contribution of the enzymes poly(ADP-ribose) polymerase-1 (PARP-1) and poly(ADP-ribose) glycohydrolase (PARG). Our study explores expression and activity of PARP-1 and PARG in uveal melanoma cell lines with varying tumorigenic properties. METHODS: Gene profiling on microarrays was conducted using RNA prepared from the uveal melanoma cell lines T97, T98, T108, and T115. The activity of PARP-1 and PARG was monitored by enzymatic assays, whereas their expression was measured by Western blot and PCR. The PARG promoter was analyzed using promoter deletions and site-specific mutagenesis in transfection analyses. The transcription factors binding the PARG promoter were studied by electrophoretic mobility shift assay (EMSA) analyses. Suppression of PARP-1 and PARG expression was performed in T97 and T115 cells by RNAi, and their tumorigenic properties monitored by injections into athymic mice. RESULTS: Expression of PARP-1 was found to vary considerably between uveal melanoma cell lines with distinctive tumorigenic properties in vivo. Sp1 and the ETS protein ERM were shown to bind to the PARG gene promoter to ensure basal transcription in uveal melanoma. Importantly, suppression of PARG gene expression in T97 and T115 cells increased their capacity to form tumors in athymic mice, whereas suppression of PARP-1 significantly reduced or almost entirely abolished tumor formation. CONCLUSIONS: Our results suggest that while overexpression of PARP-1 may confer a proliferative advantage to aggressive uveal melanoma tumors, PARG may, on the other hand, support a tumor suppressor function in vivo.

Interactions between human plasma components and a xenogenic adenovirus vector: reduced immunogenicity during gene transfer.

By the time we are adolescents most of us have been in contact with several of the >50 human adenovirus (HAd) serotypes. These common subclinical infections lead to an efficient anti-adenovirus cross-reacting adaptive immunity. During gene therapy, the ubiquitous anti-adenovirus humoral response and complement activation will modify and dictate vector biodistribution, as well as the response to the virion and transgene(s). In this study, we assayed the interactions of a xenogenic adenovirus derived from canine serotype 2 (CAV-2) with naturally occurring human antibodies (Abs) and the complement system. In our cohort, we found class G immunoglobulins (Igs) that recognized the intact CAV-2 virion and the external virion proteins. However, the majority of donors had low or no neutralizing Abs, class A, or class M Igs. Purified anti-HAd serotype 5 Abs also recognized CAV-2 virion proteins. In addition, in spite of the presence of anti-CAV-2 IgGs, CAV-2 poorly activated the classical and alternative complement cascades. This atypical response was due to a block upstream of the component 3 (C3) convertase and interplay between the component 1 (C1) inhibitor, the C1q-C1r2-C1s2 complex and CAV-2. Our data demonstrate that some xenogenic adenovirus vectors, like CAV-2, could lead to notably different outcomes following systemic delivery.