Benjamin Granger

Matrix to predict rapid radiographic progression of early rheumatoid arthritis patients from the community treated with methotrexate or leflunomide: results from the ESPOIR cohort

IntroductionEarly rheumatoid arthritis (RA) patients may show rapid radiographic progression (RRP) despite rapid initiation of synthetic disease-modifying anti-rheumatic drugs (DMARDs). The present study aimed to develop a matrix to predict risk of RRP despite early DMARD initiation in real life settings.MethodsThe ESPOIR cohort included 813 patients from the community with early arthritis for < 6 months; 370 patients had early RA and had received methotrexate or leflunomide during the first year of follow-up. RRP was defined as an increase in the van der Heijde-modified Sharp score (vSHS) ≥ 5 points at 1 year. Determinants of RRP were examined first by bivariate analysis, then multivariate stepwise logistic regression analysis. A visual matrix model was then developed to predict RRP in terms of patient baseline characteristics.ResultsWe analyzed data for 370 patients. The mean Disease Activity Score in 28 joints was 5.4 ± 1.2, 18.1% of patients had typical RA erosion on radiographs and 86.4% satisfied the 2010 criteria of the American College of Rheumatology/European League Against Rheumatism. During the first year, mean change in vSHS was 1.6 ± 5.5, and 41 patients (11.1%) showed RRP. A multivariate logistic regression model enabled the development of a matrix predicting RRP in terms of baseline swollen joint count, C-reactive protein level, anti-citrullinated peptide antibodies status, and erosions seen on radiography for patients with early RA who received DMARDs.ConclusionsThe ESPOIR matrix may be a useful clinical practice tool to identify patients with early RA at high risk of RRP despite early DMARD initiation.

Hyaluronic acid liposomal gel sustains delivery of a corticoid to the inner ear.

The inner ear is one of the most challenging organs for drug delivery, mainly because of the blood-perilymph barrier. Therefore, local rather than systemic drug delivery methods are being developed for inner ear therapy. In this work, we have evaluated the benefit of a hyaluronic acid liposomal gel for sustained delivery of a corticoid to the inner ear after local injection into the middle ear in a guinea pig model. The liposomal gel was easily injectable as a result of the shear-thinning behavior of hyaluronic acid. A prolonged residence time at the site of injection as well as in the round window were achieved without any negative effect on the hearing thresholds of the animals. The presence of liposomes in the formulation resulted in sustained release of the drug in the perilymph for 30days and promoted the conversion of the prodrug loaded within the liposomes (dexamethasone phosphate) into its active form (dexamethasone). In this way, therapeutic doses were attained in the perilymph. A small amount of intact liposomes was visualized in the perilymph, whereas the main proportion of liposomes seemed to be trapped in the round window resulting in a reservoir effect. Thus, the administration of hyaluronic acid liposomal gel to the middle ear is an efficient strategy for delivering corticoids to the inner ear in a sustained manner.

An update on topical haemostatic agents in liver surgery: systematic review and meta analysis.

Mortality and morbidity in hepatic surgery are affected by blood loss and transfusion. Topical haemostatic agents (THA) are composed by a matrix and/or fibrin sealants, and their association known as “carrier‐bound fibrin sealant” (CBFS): despite widely used for secondary haemostasis, the level of evidence remains low. To realize a meta‐analysis on the results of CBFS on haemostasis and postoperative complications. Searches in PubMed, PubMed Central, Cochrane and Google Scholar using keywords: “topical_haemostasis” OR “haemostatic_agents” OR “sealant_patch” OR “fibrin_sealant” OR “collagen_sealant” AND “liver_surgery” OR “hepatic_surgery” OR “liver_transplantation”. Randomized clinical trials, large retrospective cohort studies, case control studies evaluating THA on open/laparoscopic liver surgery and transplantation. From 1993 to 2016 were found 22 studies for qualitative synthesis and 13 for quantitative meta‐analysis. The time to haemostasis was lower in the CBFS group (mean difference −2.33 min; P = 0.00001). The risk of receiving blood transfusion, developing collections and bile leak was not influenced by the use of CBFS (OR 0.75; P = 0.25), (OR 0.72; P = 0.52), (OR 0.74; P = 0.30) respectively. The use of CBFS in liver surgery significantly reduce the time to haemostasis, but does not decrease transfusion, postoperative collection and bile leak.

Thrombocytopenia, splenomegaly, and portal blood flow in patients who have undergone liver transplantation for cirrhosis

The platelet count (PC), the spleen size (SS), and the portal blood flow (PBF) have been independently studied in the perioperative period after orthotopic liver transplantation (OLT) for cirrhosis, but these parameters have not been described and analyzed in combination. We analyzed PC data and Doppler sonography measurements of SS and PBF from 125 adult patients before OLT and 1, 3, 6, 9, and 12 months after transplantation. A linear mixed model with fixed subject random intercepts was used. PCs increased significantly from 101.5 ± 68.5 × 109/L before OLT to 162.4 ± 86 × 109/L 1 month after OLT and remained stable for 1 year after the operation. PBF increased significantly from 619 ± 239 mL/minute before OLT to 1379 ± 491 mL/minute after OLT and remained stable during the first year. SS slowly decreased after OLT, but the decrease became significant only 9 months after the operation (13.8 ± 4.2 cm before OLT versus 11.7 ± 3.7 cm at 9 months, P < 0.05). The cirrhosis etiology did not influence the evolution of the parameters. With or without replication or interferon treatment before OLT, the hepatitis C group viruses did not influence PCs postoperatively. The evolution of SS was correlated to the evolution of PCs in the year after transplantation. In conclusion, PCs and PBF increase rapidly after OLT, whereas SS slowly decreases. The cirrhosis etiology does not influence the evolution of PCs. Thrombocytopenia and splenomegaly are 2 results of portal hypertension, but the rapid normalization of PBF does not completely or rapidly reverse these 2 phenomena. Liver Transpl 18:340–346, 2012.

Brief Report: Nonsteroidal Antiinflammatory Drug–Sparing Effect of Tumor Necrosis Factor Inhibitors in Early Axial Spondyloarthritis: Results From the DESIR Cohort

To evaluate the effect of tumor necrosis factor (TNF) inhibitors on nonsteroidal antiinflammatory drug (NSAID) intake in a cohort of patients with early axial spondyloarthritis (SpA) over the first 2 years of followup.

Liver Preservation with SCOT 15 Solution Decreases Posttransplantation Cholestasis Compared with University of Wisconsin Solution: A Retrospective Study

BACKGROUND SCOT 15 is a new solution to preserve abdominal organs for transplantation. Its principal characteristic is the use of polyethylene glycol. Herein We report our experience using SCOT 15 compared with the reference University of Wisconsin (UW) solution for hepatic transplantation. METHODS We compared 2 groups: SCOT 15 (n = 33; 2009-2010) versus UW (n = 34; 2008-2010), which were paired for cold and warm ischemic times, donor ages, and graft weights. Endpoints were biologic tests in the first 2 months after the operation. A linear mixed model was used to evaluate longitudinal changes and influences of each solution. RESULTS No primary failure was observed. At postoperative day 0, transaminase values were higher in the SCOT 15 than in the UW group: aspartate transaminase: 2,435 ± 399 vs 589 ± 83 IU/L (P < .01); alanine transaminase: ALT: 1,207 ± 191 vs 484 ± 64 IU/L (P < .05), then returned to low levels in both groups. From day 0 to 8, coagulation factors reached normal values; there was no difference between the 2 groups. Total bilirubin decreased similarly in the 2 groups. However, from the second postoperative week (W1) to W8, the SCOT 15 group showed a slow decrease in the mean values of gamma-glutamyltranspeptidase (gGT) from 233 ± 125 to 130 ± 161 IU/L, which were significantly lower than those in the UW group, where the gGT remained around 300 IU/L (P < .01). The End-Stage Liver Disease, Child-Pugh, or United Network for Organ Sharing scores, primary liver diseases, hepatitic C virus status, arterial or biliary complications, and male/female ratio, which was different in the 2 groups, did not statistically influence these results. CONCLUSIONS The main effect of cold storage of human liver using SCOT 15 compared with UW solution was to decrease cholestasis following transplantation.

Supramaximal stimulation during intraoperative facial nerve monitoring as a simple parameter to predict early functional outcome after parotidectomy

Abstract Conclusion: A supramaximal stimulation at 2 mA during intraoperative electromyographic (EMG) facial nerve monitoring appears to be a simple and effective parameter to predict immediate postoperative injury. Objectives: To assess the role of systematic intraoperative facial nerve monitoring in predicting the early functional outcomes obtained after parotidectomy. Methods: Data were collected from patients who underwent parotidectomy. Intraoperative EMG monitoring of the facial nerve was performed by registering two parameters, event intensity (>100 μV) and amplitude of response after a supramaximal stimulation at 2 mA, at the beginning and end of gland removal. Early postoperative clinical functional facial nerve disorder was assessed at day 2. Results: Overall, 50 patients were included and an early facial dysfunction was detected in 27 cases (54%). The maximal response amplitude after supramaximal stimulation at the trunk of the facial nerve was higher in patients with normal facial function compared with those with poor outcomes at the end of surgery (p < 0.01). The postdissection to predissection ratios of maximal response amplitude, but not the stimulation thresholds, were indicative of a nerve conduction block and were significantly lower in the patient group with a poor outcome compared with the group with a normal facial outcome (p < 0.02).

Performance of matrices developed to identify patients with early rheumatoid arthritis with rapid radiographic progression despite methotrexate therapy: an external validation study based on the ESPOIR cohort data

Introduction Use of prediction matrices of risk or rapid radiographic progression (RRP) for early rheumatoid arthritis (RA) in clinical practice could help to better rationalise the first line of treatment. Before use, they must be validated in populations that have not participated in their construction. The main objective is to use the ESPOIR cohort to validate the performance of 3 matrices (ASPIRE, BEST and SONORA) to predict patients at high risk of RRP at 1 year of disease despite initial treatment with methotrexate (MTX). Methods We selected from the ESPOIR cohort 370 patients receiving MTX or leflunomide (LEF) for ≥3 months within the first year of follow-up. Patients were assessed clinically every 6 months, and structural damage progression seen on radiography was measured by the van der Heijde-modified Sharp score (vSHS) at 1 year. RRP was defined as an increase in the vSHS≥5 points during the first year. Results At 1 year, the mean vSHS score was 1.7±5.0 and 46 patients had RRP. The ASPIRE matrix had only moderate validity in the ESPOIR population, with area under the receiver operating characteristic curve (AUC) <0.7. The AUC for the BEST and SONORA matrices were 0.73 and 0.76. Presence of rheumatoid factor (RF)—or anti-citrullinated protein antibodies (ACPAs) and initial structural damage were always predictive of RRP at 1 year. Disease Activity Score in 28 joints (DAS28) and C reactive protein (ASPIRE threshold) were not associated with RRP. Conclusions Matrices to identify patients at risk of RRP tested in the ESPOIR cohort seem to perform moderately. There is no matrix that shows clearly superior performance.

Cost-effectiveness analysis of strategies using new immunological diagnostic tests of latent tuberculosis infection before TNF-blockers therapy

Several tests have been proposed to detect latent tuberculosis (LTB). OBJECTIVE To evaluate the cost-effectiveness of different interferon-gamma release assays based strategies used to screen LTB before tumour necrosis factor (TNF) blockers initiation. METHODS Consecutive patients with rheumatoid arthritis, spondyloarthritis or Crohns disease for whom TNF-blockers were considered, were recruited in 15 tertiary care centres. All were screened for LTB with tuberculin skin test (TST), QuantiFERON TB Gold® in tube (QFT) and T-SPOT.TB® (TSpot) on the same day. Cost-minimization and cost-effectiveness analysis, testing 8 screening test combinations, were conducted. Effectiveness was defined as the percentage of LTB treatment avoided and compared with TST alone. Cost were elicited in the payer perspective, included all the costs related to the screening procedure. RESULTS No tuberculosis reactivation was observed after TNF-blocker initiation. TST followed by QFT if TST was positive was found as the best screening strategy, i.e. the less costly (-54€ compared to reference) and most effective (effectiveness 0.93), resulting in an incremental cost-effectiveness ratio of -192€ per treatment avoided. A probabilistic sensitivity analysis confirmed this result in 72.3% of simulations. CONCLUSION TST followed by QFT if TST was positive is the most cost-effective strategy in screening for LTB in patients before starting anti-TNF therapy. TRIALREGNO NCT00811343.

Evolution of platelet functions in cirrhotic patients undergoing liver transplantation: A prospective exploration over a month

This prospective observational study was designed to analyze platelet functions across time in 50 patients scheduled for liver transplantation (LT) secondary to decompensated cirrhosis or hepatocellular carcinoma. Platelet functions were assessed before LT (pre-LT), one week (D7) and 1 month (D28) after LT. Platelet count significantly increased from pre-LT time to day 28 as well as circulating CD34+hematopoietic stem cells. To avoid any influence of platelet count on assays, platelet function was evaluated on platelet-rich-plasma adjusted to pre-LT platelet count. Although platelet secretion potential did not differ between time-points, as evaluated by the expression of CD62P upon strong activation, platelet aggregation in response to various agonists significantly increased along time, however with no concomitant increase of circulating markers of platelet activation: platelet microvesicles, platelet-leukocyte complexes, soluble CD40L and soluble CD62P. In the multivariate analysis, hepatic function was associated with platelet count and function. A lower platelet aggregation recovery was correlated with Child C score. History of thrombosis or bleeding was associated with respective higher or lower values of platelet aggregation. This longitudinal analysis of platelet functions in LT patients showed an improvement of platelet functions along time together with platelet count increase, with no evidence of platelet hyperactivation at any time-point.