Treatment of idiopathic inflammatory myositis associated interstitial lung disease: A systematic review and meta-analysis

Objective

Interstitial lung disease (ILD) is the most severe complication of idiopathic inflammatory myositis (IIM), resulting in significant increase in morbidity and mortality and for which the best treatment remains controversial. We conducted a meta-analysis to evaluate the efficacy of therapies used for the management of IIM-related ILD.

Estrogen receptor alpha-mediated adiposity-lowering and hypocholesterolemic actions of the selective estrogen receptor modulator acolbifene

OBJECTIVE: The selective estrogen receptor (ER) modulator (SERM) acolbifene (ACOL), a potent and pure antiestrogen in the mammary gland and uterus, exerts beneficial pro-estrogenic actions on energy balance, insulin sensitivity and lipid metabolism. ACOL binds ERs alpha and beta, both of which have been involved in the metabolic actions of estrogen. This study aimed at determining the identity of the ER involved in the beneficial metabolic actions of ACOL. DESIGN AND MEASUREMENTS: ACOL was administered for 4 weeks to male and female wild-type and ERalpha knockout (KO) mice, and indices of energy balance as well as plasma and liver lipid concentrations were determined. RESULTS: ERalpha KO mice were heavier, gained more fat mass and had larger adipose depots than their wild-type counterparts. In both genders, ACOL decreased fat gain (50%) and white adipose tissue mass in male and female wild-type, but not in ERalpha KO mice. ACOL reduced plasma cholesterol in female wild-type mice (-27%), whereas the compound remained ineffective in their ERalpha KO counterparts. Plasma triglycerides were unaffected by ACOL. Finally, ACOL decreased liver cholesterol and triglyceride concentrations only in wild-type female animals. CONCLUSION: The beneficial metabolic actions of the SERM ACOL on adiposity and on plasma and liver lipids are entirely due to its interaction with the ERalpha.     

17β-Estradiol and estrogen receptor α protect right ventricular function in pulmonary hypertension via BMPR2 and apelin

Women with pulmonary arterial hypertension (PAH) exhibit better right ventricular (RV) function and survival than men; however, the underlying mechanisms are unknown. We hypothesized that 17β-estradiol (E2), through estrogen receptor α (ER-α), attenuates PAH-induced RV failure (RVF) by upregulating the procontractile and prosurvival peptide apelin via a BMPR2-dependent mechanism. We found that ER-α and apelin expression were decreased in RV homogenates from patients with RVF and from rats with maladaptive (but not adaptive) RV remodeling. RV cardiomyocyte apelin abundance increased in vivo or in vitro after treatment with E2 or ER-α agonist. Studies employing ER-α–null or ER-β–null mice, ER-α loss-of-function mutant rats, or siRNA demonstrated that ER-α is necessary for E2 to upregulate RV apelin. E2 and ER-α increased BMPR2 in pulmonary hypertension RVs and in isolated RV cardiomyocytes, associated with ER-α binding to the Bmpr2 promoter. BMPR2 is required for E2-mediated increases in apelin abundance, and both BMPR2 and apelin are necessary for E2 to exert RV-protective effects. E2 or ER-α agonist rescued monocrotaline pulmonary hypertension and restored RV apelin and BMPR2. We identified what we believe to be a novel cardioprotective E2/ER-α/BMPR2/apelin axis in the RV. Harnessing this axis may lead to novel RV-targeted therapies for PAH patients of either sex.     

CIHR Canadian HIV Trials Network Co-Infection and Concurrent Diseases Core: Updated Canadian guidelines for the treatment of hepatitis C infection in HIV-hepatitis C coinfected adults

BACKGROUND:Hepatitis C virus (HCV) coinfection occurs in 20% to 30% of Canadians living with HIV and is responsible for a heavy burden of morbidity and mortality. Management of HIV-HCV coinfection is more complex due to the accelerated progression of liver disease, the timing and nature of antiretroviral and HCV therapy, mental health and addictions management, socioeconomic obstacles and drug-drug interactions between new HCV direct-acting antiviral therapies and antiretroviral regimens.OBJECTIVE:To update national standards for the management of HCV-HIV coinfected adults in the Canadian context.METHODS:A standing working group with specific clinical expertise in HIV-HCV coinfection was convened by The Canadian Institute of Health Research HIV Trials Network to review recently published data regarding HCV antiviral treatments and to update the Canadian HIV-HCV coinfection guidelines.RESULTS:Recent data suggest that the gap in sustained virological response rates between HCV monoinfection and HIV-HCV coinfection has been eliminated with newer HCV antiviral regimens. All HIV-HCV coinfected individuals should be assessed for HCV therapy. First-line treatment for genotypes 1 through 6 includes pegylated interferon and weight-based ribavirin dosing plus the nucleotide sofosbuvir for 12 weeks. Sofosbuvir in combination with the protease inhibitor simeprevir is another first-line consideration for genotype 1 infection. Sofosbuvir with ribavirin for 12 weeks (genotype 2) and 24 weeks (genotype 3) is also recommended as first-line treatment.DISCUSSION:Recommendations may not supersede individual clinical judgement.     

Evaluation of Care and Surveillance of Cardiovascular Disease: Can We Trust Medico-administrative Hospital Data?

Background

The evaluation of care and the surveillance of disease are important in respect to cardiovascular disease because it is prevalent and costly. In Canada, medico-administrative hospital data are readily available, continuously updated, and offer comprehensive coverage of the patient population. However, there is concern about the quality of the information.

Methods

The reliability and predictive capability of comorbidity data contained within Québec's hospital discharge database were assessed in comparison with data collected by clinical medical record reabstraction in a sample of 1989 patients hospitalized from 2002 to 2006 in a mix of 13 hospitals. Patients either had a principal diagnosis of myocardial infarction or underwent angioplasty or bypass surgery. Twenty-one comorbidities included in the Charlson comorbidity index or known to be associated with mortality were validated via medical record reabstraction.

Results

Of 14 comorbidities with > 2% prevalence, 8 had excellent agreement with medical record review (κ > 0.8) while 6 had substantial agreement (κ > 0.6). In general, positive predictive values were high, while measures of sensitivity were more variable. Univariate associations between comorbidities and 30-day and 1-year mortality were generally similar in the 2 data sources. Comorbidities retained in the final multivariate stepwise regression models from each data source were almost identical, as were the 2 models' abilities to predict mortality.

Conclusions

Hospital discharge data in Québec are, in general, reliably coded and compare favourably with clinical medical record review in their ability to predict mortality. It appears sufficiently reliable to provide useful information about clinical outcomes of cardiac care and to identify problems that warrant investigation.     

First clinical evaluation of a new innovative ureteral access sheath (Re-Trace™): a European study

Purpose

The use of a ureteral access sheath (UAS) during flexible retrograde intrarenal surgery (RIRS) has become increasingly popular. Our aim was to evaluate the accessibility of a new UAS device, allowing the transformation of the working guidewire into a safety guidewire.

Methods

A prospective, multicenter study was conducted between January and February 2010 in six European tertiary reference centers. Patients needing flexible RIRS were eligible to participate in the study. In all cases, insertion of the Re-Trace? (12/14Fr, Coloplast, Denmark) was attempted at the beginning of the procedure. Insertion success was defined as placement of the UAS in the lumbar ureter with successful disengagement of the working guidewire, which turned into a safety guidewire. Influence of gender and pre-stenting status was analyzed by univariate analysis.

Results

137 UASs were used in 75 male and 62 female patients. 25.5 % of ureters were pre-stented: men were 2.17 more often pre-stented than women. The overall Re-Trace? insertion rate was 82.5 %. Success rate was not significantly different between men and women (77.3 vs. 88.7 %, respectively, p = 0.11). Pre-stenting status did not significantly influence the success rate (p = 0.31). When analyzing the combined influence of pre-stenting status and gender, the worst success rates seemed to be obtained in men without pre-stenting, but no significant differences were found between groups.

Conclusions

Re-Trace? UAS showed good overall insertion rates. This evaluation validated the new concept of guidewire disengagement: A single wire automatically switches from working to safety role.