Ultrasound imaging of the carpal tunnel during median nerve compression

Median nerve (MN) compression is a recognized component of carpal tunnel syndrome (CTS). In order to document compressive changes in the MN during hand activity, the carpal tunnel was imaged with neuromuscular ultrasound (NMUS). Ten patients with CTS and five normal controls underwent NMUS of the MN at rest and during dynamic stress testing (DST). DST maneuvers involve sustained isometric flexion of the distal phalanges of the first three digits. During DST in the CTS patients, NMUS demonstrated MN compression between the contracting thenar muscles ventrally and the taut flexor tendons dorsally. The mean MN diameter decreased nearly 40%, with focal narrowing in the mid-distal carpal canal. Normal controls demonstrated no MN compression and a tendency towards MN enlargement, with an average diameter increase of 17%. Observing the pathologic mechanism of MN injury during common prehensile hand movements could help better understand how to treat and prevent CTS

Genetic Kinship and Social Structure in a Herd of Square-Lipped Rhinoceroses

Zoos and zoological parks serve as genetic and demographic reserves for strengthening endangered populations and reestablishing extinct populations in the wild. Knowing the genetic ties within captive populations is a very helpful tool for successful reproductive management. In the present study we addressed kinship relationships and behavior among rhinoceroses (Ceratotherium simum simum) raised at the Zoological Center, Tel Aviv/Ramat Gan, Israel, with the hope of identifying reasons for the declining rate of reproduction within the herd. We used the random amplified polymorphic DNA (RAPD) technique to reveal the paternity of the rhinos born at the park. In this way, we identified the paternity of five out of seven young born in the herd, which are currently in Ramat Gan. One male accounted for three (37.5%) births, and two other males accounted for one each. The paternity of the two other animals is unknown and may be of animals that are no longer in the Zoological Center. The genetic determinations were accompanied by behavioral observations, which enabled us to determine the social dynamics in the herd. This study suggests that there are at least three contributing factors to the reproductive decline in the herd: 1) a surplus of males, 2) exclusion of potentially reproductive males from the breeding stock, and 3) specific behavioral and physiological problems in some members of the herd

Development and preliminary validation of the Sjögren’s Tool for Assessing Response (STAR): a consensual composite score for assessing treatment effect in primary Sjögren’s syndrome

Objectives: To develop a composite responder index in primary Sjögren’s syndrome (pSS): the Sjögren’s Tool for Assessing Response (STAR). Methods: To develop STAR, the NECESSITY consortium used data-driven methods, based on 9 randomized controlled trials (RCTs), and consensus techniques, involving 78 experts and 20 patients. Based on reanalysis of rituximab trials and literature, the Delphi panel identified a core set of domains with their respective outcome measures. STAR options combining these domains were proposed to the panel to select and improve them. For each STAR option, sensitivity to change was estimated by the C-index in 9 RCTs. Delphi rounds were run for selecting STAR. For the options remaining before the final vote, meta-analyses of the RCTs were performed. Results: The Delphi panel identified 5 domains (systemic activity, patient symptoms, lachrymal function, salivary gland function and biological parameters). A total of 227 STAR options, combining these domains, were selected to be tested for sensitivity to change in the 9 RCTs. After 2 Delphi rounds, meta-analyses of the 20 remaining options were performed. Then, the candidate STAR was selected by a final vote. Conclusion: The candidate STAR is a composite responder index, including in a single tool all main disease features, and dedicated for use as a primary endpoint in pSS RCTs. Its rigorous and consensual development process ensures its face and content validity. The candidate STAR showed a good sensitivity to change. The candidate STAR and its derived options will be prospectively validated in the dedicated RCT of the NECESSITY consortium

Tocilizumab as an add-on therapy to glucocorticoids during the first 3 months of treatment of Giant cell arteritis: A prospective study

IF 3.282International audienceBackgroundThe aim of this study was to evaluate tocilizumab (TCZ) as an add-on therapy to glucocorticoids (GC) during the first 3 months of treatment of giant cell arteritis (GCA).MethodsGCA patients, as defined by ≥3/5 ACR criteria and positive temporal artery biopsy (TAB) or angio-CT-scan or PET-scan-proven aortitis, were included in this prospective open-label study. Prednisone was started at 0.7 mg/kg/day and then tapered according to a standardized protocol. All patients received four infusions of TCZ (8 mg/kg/4 weeks) after inclusion. The primary endpoint was the percentage of patients in remission with ≤0.1 mg/kg/day of prednisone at week 26 (W26). Patients were followed for 52 weeks and data prospectively recorded.ResultsTwenty patients with a median (IQR) age of 72 (69–78) years were included. TAB were positive in 17/19 (90%) patients and 7/16 (44%) had aortitis. Remission was obtained in all cases. At W26, 15 (75%) patients met the primary endpoint. Ten patients experienced relapse during follow-up, mainly patients with aortitis (P = 0.048), or CRP >70 mg/L (P = 0.036) or hemoglobin ≤10 g/dL (P = 0.015) at diagnosis. Among 64 adverse events (AE) reported in 18 patients, three were severe and 30, mostly non-severe infections (n = 15) and hypercholesterolemia (n = 8), were imputable to the study.ConclusionThis study shows that an alternative strategy using a short-term treatment with TCZ can be proposed to spare GC for the treatment of GCA. However, 50% of patients experienced relapse during the 9 months following TCZ discontinuation, especially patients with aortitis, or CRP > 70 mg/L or Hb ≤ 10 g/dL at diagnosis.Trial registration: ClinicalTrials.gov (NCT01910038)

Examining the biological pathways underlying clinical heterogeneity in Sjogren’s syndrome: proteomic and network analysis

Objectives Stratification approaches are vital to address clinical heterogeneity in Sjogren’s syndrome (SS). We previously described that the Newcastle Sjogren’s Stratification Tool (NSST) identified four distinct clinical subtypes of SS. We performed proteomic and network analysis to analyse the underlying pathobiology and highlight potential therapeutic targets for different SS subtypes. Method We profiled serum proteins using O-link technology of 180 SS subjects. We used 5 O-link proteomics panels which included a total of 454 unique proteins. Network reconstruction was performed using the ARACNE algorithm, with differential expression estimates overlaid on these networks to reveal the key subnetworks of differential expression. Furthermore, data from a phase III trial of tocilizumab in SS were reanalysed by stratifying patients at baseline using NSST. Results Our analysis highlights differential expression of chemokines, cytokines and the major autoantigen TRIM21 between the SS subtypes. Furthermore, we observe differential expression of several transcription factors associated with energy metabolism and redox balance namely APE1/Ref-1, FOXO1, TIGAR and BACH1. The differentially expressed proteins were inter-related in our network analysis, supporting the concept that distinct molecular networks underlie the clinical subtypes of SS. Stratification of patients at baseline using NSST revealed improvement of fatigue score only in the subtype expressing the highest levels of serum IL-6. Conclusions Our data provide clues to the pathways contributing to the glandular and non-glandular manifestations of SS and to potential therapeutic targets for different SS subtypes. In addition, our analysis highlights the need for further exploration of altered metabolism and mitochondrial dysfunction in the context of SS subtypes

Clinical presentation, course, and prognosis of patients with mixed connective tissue disease : a multicenter retrospective cohort

International audienceObjectives: The objective of this study is to better characterize the features and outcomes of a large population of patients with mixed connective tissue disease (MCTD). Methods: We performed an observational retrospective multicenter cohort study in France. Patients who fulfilled at least one diagnostic criterion set for MCTD and none of the criteria for other differentiated CTD (dCTD) were included. Results: Three hundred and thirty patients (88% females, median [interquartile range] age of 35 years [26–45]) were included. The diagnostic criteria of Sharp or Kasukawa were met by 97.3% and 93.3% of patients, respectively. None met other classification criteria without fulfilling Sharp or Kasukawa criteria. After a median follow-up of 8 (3–14) years, 149 (45.2%) patients achieved remission, 92 (27.9%) had interstitial lung disease, 25 (7.6%) had pulmonary hypertension, and 18 (5.6%) died. Eighty-five (25.8%) patients progressed to a dCTD, mainly systemic lupus erythematosus (15.8%) or systemic sclerosis (10.6%). Median duration between diagnosis and progression to a dCTD was 5 (2–11) years. The presence at MCTD diagnosis of an abnormal pattern on nailfold capillaroscopy (odds ratio [OR] = 2.44, 95% confidence interval [95%CI] [1.11–5.58]) and parotid swelling (OR = 3.86, 95%CI [1.31–11.4]) were statistically associated with progression to a dCTD. Patients who did not progress to a dCTD were more likely to achieve remission at the last follow-up (51.8% vs. 25.9%). Conclusions: This study shows that MCTD is a distinct entity that can be classified using either Kasukawa or Sharp criteria, and that only 25.8% of patients progress to a dCTD during follow-up

Gender, memory and Jewish identity: reading a family history from medieval southern Italy

This article combines recent work on memory in the early and central Middle Ages to read the Scroll of Ahimaaz, a well-known eleventh-century Jewish text from southern Italy. It suggests that previous readings of the text have been shaped by the dominant tradition of intellectual history within Jewish studies, and that Ahimaaz's work has been overlooked for the information it contains about gender and family history. It concludes that whilst the primarily Jewish identity of Ahimaaz and his family is reinforced by the text, they were at the same time as much a product of the southern Italian environment in which they lived