Judith Cohen-Bittan

Hydroxychloroquine in systemic lupus erythematosus: results of a French multicentre controlled trial (PLUS Study).

Introduction Hydroxychloroquine (HCQ) is an important medication for treating systemic lupus erythematosus (SLE). Its blood concentration ([HCQ]) varies widely between patients and is a marker and predictor of SLE flares. This prospective randomised, double-blind, placebo-controlled, multicentre study sought to compare standard and adjusted HCQ dosing schedules that target [HCQ] ≥1000 ng/ml to reduce SLE flares. Patients and methods [HCQ] was measured in 573 patients with SLE (stable disease and SELENA-SLEDAI≤12) treated with HCQ for at least 6 months. Patients with [HCQ] from 100 to 750 ng/ml were randomised to one of two treatment groups: no daily dose change (group 1) or increased HCQ dose to achieve the target [HCQ] (group 2). The primary end point was the number of patients with flares during 7 months of follow-up. Results Overall, mean [HCQ] was 918±451 ng/ml. Active SLE was less prevalent in patients with higher [HCQ]. A total of 171 patients were randomised and followed for 7 months. SLE flare rates were similar in the two groups (25% in group 1 vs 27.6% in group 2; p=0.7), but a significant spontaneous increase in [HCQ] in both groups between inclusion and randomisation strongly suggested improved treatment adherence. Patients at the therapeutic target throughout follow-up tended to have fewer flares than those with low [HCQ] (20.5% vs 35.1%, p=0.12). Conclusions Although low [HCQ] is associated with higher SLE activity, adapting the HCQ dose did not reduce SLE flares over a 7-month follow-up. ClinicalTrials.gov NCT00413361

Lower vitamin D levels are associated with higher systemic lupus erythematosus activity, but not predictive of disease flare-up

Objectives Growing evidence suggests that vitamin D plays a key role in the pathogenesis and progression of autoimmune diseases, including systemic lupus erythematosus (SLE). Recent studies have found an association between lower serum 25-hydroxyvitamin D (25(OH)D) levels and higher SLE activity. We studied the relationship between 25(OH)D levels and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score, and we assessed for the first time the role of vitamin D in predicting SLE flare-ups. Methods Serum 25(OH)D levels were measured in 170 patients with SLE who were prospectively followed up for 6 months (Plaquenil LUpus Systemic study, ClinicalTrials.gov number NCT00413361). Results The mean SLEDAI score was 2.03±2.43 and 12.3% patients had active disease (SLEDAI ≥6). The mean 25(OH)D level was 20.6±9.8 ng/mL. Deficiency (25(OH)D <10 ng/mL) was observed in 27 (15.9%), insufficiency (10≤25(OH)D<30) in 112 (65.9%) and optimal vitamin D status (25(OH)D≥30) in 31 (18.2%) patients. In multivariate analysis, female gender (p=0.018), absence of defined antiphospholipid syndrome (p=0.002) and higher creatinine clearance (p=0.004) were predictive of lower 25(OH)D levels. In multivariate analysis, lower 25(OH)D levels were associated with high SLE activity (p=0.02). Relapse-free survival rate was not statistically different according to the vitamin D status during the 6-month follow-up (p=0.22). Conclusions We found a low vitamin D status in the majority of patients with SLE, and a modest association between lower 25(OH)D levels and high disease activity. There was no association between baseline 25(OH)D levels and relapse-free survival rate.

Determinants of Hydroxychloroquine Blood Concentration Variations in Systemic Lupus Erythematosus

Blood concentrations of hydroxychloroquine (HCQ) vary widely among patients with systemic lupus erythematosus (SLE). A pharmacokinetic/pharmacodynamic relationship has been found in different situations, and a very low blood concentration of HCQ is a simple marker of nonadherence to treatment. Therefore, interest in blood HCQ concentration measurement has increased, but little is known about factors that influence blood HCQ concentration variability. This study was undertaken to analyze determinants of blood HCQ concentrations.

Quality of life in systemic lupus erythematosus: description in a cohort of French patients and association with blood hydroxychloroquine levels

Objectives Benefits of hydroxychloroquine (HCQ) use on physician reported outcomes are well documented in systemic lupus erythematosus (SLE). We assess for the first time the association and predictive value of blood HCQ levels towards health-related quality of life (HRQOL) in SLE. Methods Data from the PLUS study (a randomized, double-blind, placebo-controlled, multicentre study) were utilized. Blood HCQ levels were quantified by high-performance liquid chromatography along with HRQOL assessments (Medical Outcomes Study-SF-36) at baseline (V1) and month 7 (V2). Results 166 SLE patients’ data were analysed. Mean (SD) age and disease duration were 44.4 (10.7) and 9.3 (6.8) years. Eighty-seven per cent were women. Mean (SD, median, IQR) HCQ concentrations in the blood at V1 were 660 (314, 615, 424) ng/ml and increased to 1020 (632, 906, 781) ng/ml at V2 (mean difference 366 units, 95% confidence interval −472 to −260, p < 0.001). No significant correlations between HCQ concentrations with HRQOL domains at V1 or V2 were noted. There were no differences in HRQOL stratified by HCQ concentrations. HCQ concentrations at V1 or changes in HCQ concentration (V2-V1) were not predictive of HRQOL at V2 or changes in HRQOL (V2-V1). Conclusions No association of HCQ concentrations with current or longitudinal HRQOL were found in SLE.

Prognostic Value of Serum Procalcitonin After Orthopedic Surgery in the Elderly Population

Background Orthopedic surgery is more and more frequent in the older patients and is associated with a high mortality rate. Although serum procalcitonin levels are associated with prognosis in young adults, data are still lacking in the elderly population, and especially after surgery. The main objective of this study was to determine the prognostic value of procalcitonin levels in a large geriatric orthopedic population, and we compared it with clinical variables and biomarkers. Methods This is a prospective study including patients admitted in our dedicated geriatric postoperative unit, after orthopedic surgery with immediate postoperative measured procalcitonin levels. Collected data included age, sex, medical history, functional status (activities of daily living [ADL]), fracture type, Cumulative Illness Rating scale (CIRS), postoperative complications, and biological data. The primary endpoint was the 30-day mortality. Results 436 patients (age 85±6 years) were included. Hip fracture surgery was the most frequent (n = 310; 71%), and the 30-day mortality rate was 6.9%. Compared with C-reactive protein (CRP), albumin, CIRS, and ADL, procalcitonin had the highest area under the receiver operating characteristic curve for predicting 30-day mortality (0.74; 95% CI: 0.70-0.78). Using a cutoff at 1 µg/L, procalcitonin was more specific than CIRS to predict 30-day mortality (92 vs 77%; p < .001). In a multivariable analysis, procalcitonin level higher than 0.39 µg/L is a significant predictor of mortality within 30 days (odds ratio 3.84; 95% CI: 1.61-9.14, p = .002). Conclusion Elevated procalcitonin values were strongly and significantly associated with mortality within 30 days in older patients after orthopedic surgery.

Isolated cardiac troponin rise does not modify the prognosis in elderly patients with hip fracture

Abstract Perioperative myocardial infarction remains a life-threatening complication in noncardiac surgery and even an isolated troponin rise (ITR) is associated with significant mortality. Our aim was to assess the prognostic value of ITR in elderly patients with hip fracture. In this cohort study, all patients admitted between 2009 and 2013 in our dedicated geriatric postoperative unit after hip fracture surgery with a cardiac troponin I determination were included and divided into Control, ITR, and acute coronary syndrome (ACS) groups. The primary end point was a composite criteria defined as 6-month mortality and/or re-hospitalization. Secondary end points included 30-day mortality, 6-month mortality, and 6-month functional outcome. Three hundred twelve patients were (age 85 ± 7 years) divided into Control (n = 217), ITR (n = 50), and ACS (n = 45) groups. There was no significant difference for any postoperative complications between ITR and Control groups. In contrast, atrial fibrillation, acute heart failure, hemorrhage, and ICU admission were significantly more frequent in the ACS group. Compared to the Control group, 6-month mortality and/or rehospitalization was not significantly modified in the ITR group (26% vs. 28%, P = 0.84, 95% confidence interval [CI] of the difference -13%–14%), whereas it was increased in the ACS group (44% vs. 28%, P = 0.02, 95% CI of the difference 2%–32%). ITR was not associated with a higher risk of new institutionalization or impaired walking ability at 6 months, in contrast to ACS group. In elderly patients with hip fracture, ITR was not associated with a significant increase in death and/or rehospitalization within 6 months.

Association between Cognitive Status before Surgery and Outcomes in Elderly Patients with Hip Fracture in a Dedicated Orthogeriatric Care Pathway

BACKGROUND Dementia is associated with a worse prognosis of hip fracture, but the impact of a dedicated geriatric care pathway on the prognosis of these patients has not been evaluated. OBJECTIVE According to the cognitive status before surgery, our main objective was to compare mortality rate at 6 months; secondary outcomes were to compare in-hospital complications, the risk of new institutionalization, and the ability to walk at 6 months. METHODS Between 2009 and 2015, all patients (>70 years) admitted after hip fracture surgery into a dedicated unit of peri-operative geriatric care were included: patients with dementia (DP), without dementia (NDP), and with cognitive status not determined (CSND). Data are expressed as hazard ratio (HR) for multivariate cox analysis or odds ratio (OR) for multivariate logistic regression analysis and their 95% confidence interval (CI). RESULTS We included 650 patients (86±6 years): 168 DP, 400 NDP, and 82 CSND. After adjustment for age, sex, comorbidities, polypharmacy, pre-fracture autonomy, time-to-surgery, and delirium, there were no significant differences for 6-month mortality (DP versus NDP: HR = 0.7[0.4-1.2], DP versus CSND: HR = 0.6[0.3-1.4], CSND versus NDP: HR = 0.8[0.4-1.7]); but DP and CSND were more likely to be newly institutionalized after 6 months compared to NDP (OR DP = 2.6[1.4-4.9], p = 0.003, OR CSND = 2.9[1.4-6.1], p = 0.004). 92% of population was walking after 6 months (63% with assistance): no difference was found between the three groups. CONCLUSION In a dedicated geriatric care pathway, DP and CSND undergoing hip surgery have the same 6-month mortality and walking ability as NDP.

Late-Onset Bing-Neel Syndrome Associated with Delirium and Lewy Body Dementia

four of 12 who did not had ventricular rupture, a 33% incidence of death for each group. In other series, 19% of patients did not have surgery, and none of them suffered ventricular rupture during follow-up. In a recent series of nine chronic pseudoaneurysms that were not repaired, none of the individuals died from cardiac rupture, and the 4-year cumulative survival rate was 74.1%. The current series was a small retrospective one, which limits the value of Kaplan–Meyer analysis, but most knowledge about the management of pseudoaneurysms is based on collections of cases or small single-center experiences. The individuals included in this sample were not representative of the whole population of individuals with MI; they were elderly, and most of them came to the hospital very late or did not come during the acute episode. None was treated with mechanical reperfusion therapy, which reduces the risk of cardiac rupture. They were survivors. Maintained normal physical activity after a MI could increase the risk of cardiac rupture because of an increase in stress on the damaged ventricular wall. This would happen more easily after silent MI, which is more frequent in elderly adults. This, and not only a moreconservative surgical attitude, could help explain why chronic pseudoaneurysms are more frequent in elderly adults and explains the frequent presentation as an incidental finding: 50% in our series and 48% in others. The long-term course of chronic ventricular pseudoaneurysm can be considered to be benign. Incidental finding of this entity is frequent in elderly adults, and surgical repair is not indicated in older, asymptomatic, or high-risk individuals.

Bilateral adrenal necrosis after knee arthroplasty.

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Elevated Neopterin Levels Predict Early Death in Older Hip-fracture Patients

Our society faces a major challenge concerning management of the health and socio-economic burden caused by acute physical stress in the older population (+ 75 years). In particular, hip-fracture surgery (HFS) represents a major health care preoccupation, affecting 1.6 million patients worldwide, resulting in a significant drop in life quality and autonomy. The trauma is associated with 20–30% one-year mortality in the elderly. In the present study, we aim to identify factors, which influence and/or predict the outcome of elderly hip- fracture patients (HFP) post-surgery. Our objective was to identify biomarkers with a prognostic capacity of one-year mortality. We employed an observational cohort of HFP (n = 60) followed-up longitudinally during the first year post fracture. Clinical and biological data (n = 136), collected at arrival to hospital, were then compared to healthy controls (n = 42) and analyzed using a regularized logistic regression model with lasso penalty followed by 10-fold cross-validation of variables. We show that plasmatic neopterin levels, a molecule released by IFN-γ-activated macrophages, is predictive of mortality in HFP (ROC-AUC = 0.859). Moreover, neopterin measured at arrival to the hospital correlated negatively with the time of survival after HFS. Neopterin therefore represents a biomarker, which enables better follow-up of patients at risk of early death.