Hospital General Universitario Gregorio Marañón

About: Hospital General Universitario Gregorio Marañón is a healthcare organization based out in Madrid, Spain. It is known for research contribution in the topics: Population & Transplantation. The organization has 11975 authors who have published 12386 publications receiving 244847 citations.

Tapering biologic and conventional DMARD therapy in rheumatoid arthritis: current evidence and future directions

Abstract: Improvements in the control of inflammation in rheumatoid arthritis (RA) by conventional synthetic and biologic disease-modifying antirheumatic drugs (DMARDs) have led to a substantial change in the clinical outcomes of patients during the last 30 years. Current treatment can lead to sustained remission in some patients raising questions about the optimal management strategies in this subgroup of patients. Today, tapering of DMARDs and even their discontinuation appears as an interesting concept for achieving a more tailored and dynamic treatment approach of RA, especially in patients, who achieved full disease control by DMARD treatment. In this review article, current developments of DMARD tapering are discussed. The article provides an overview of existing studies on this topic and addresses new strategies to reach drug-free remission. Furthermore, concepts for defining patients eligible for DMARD tapering are described and potential future strategies in using biomarkers in predicting the risk for disease relapse after initiation of DMARD tapering are addressed. These findings are finally considered in light of the vision to achieve cure as an ultimate goal in patients with RA achieving full control of inflammation.

Randomized Phase II Study Evaluating Akt Blockade with Ipatasertib, in Combination with Abiraterone, in Patients with Metastatic Prostate Cancer with and without PTEN Loss

Abstract: Purpose: PI3K–Akt–mTOR and androgen receptor (AR) signaling are commonly aberrantly activated in metastatic castration-resistant prostate cancer (mCRPC), with PTEN loss associating with poor prognosis. We therefore conducted a phase Ib/II study of the combination of ipatasertib, an Akt inhibitor, with the CYP17 inhibitor abiraterone in patients with mCRPC. Patients and Methods: Patients were randomized 1:1:1 to ipatasertib 400 mg, ipatasertib 200 mg, or placebo, with abiraterone 1,000 mg orally. Coprimary efficacy endpoints were radiographic progression-free survival (rPFS) in the intent-to-treat population and in patients with PTEN-loss tumors. Results: rPFS was prolonged in the ipatasertib cohort versus placebo, with similar trends in overall survival and time-to-PSA progression. A larger rPFS prolongation for the combination was demonstrated in PTEN-loss tumors versus those without. The combination was well tolerated, with no treatment-related deaths. Conclusions: In mCRPC, combined blockade with abiraterone and ipatasertib showed superior antitumor activity to abiraterone alone, especially in patients with PTEN-loss tumors. See related commentary by Zhang et al., p. 901

An intervention integrated into daily clinical practice reduces the incidence of delirium during hospitalization in elderly patients.

Abstract: OBJECTIVES: To analyze the effectiveness of a multicomponent intervention integrated into daily practice for the prevention of in-hospital delirium in elderly patients. DESIGN: Controlled study comparing an intervention in a geriatric unit (GI) with usual care in two internal medicine services (UC). SETTING: University hospital in Madrid, Spain. PARTICIPANTS: Five hundred forty-two consecutive patients (170 GI, 372 UC), aged 70 and older, with any of the risk criteria for delirium (cognitive impairment, visual impairment, acute disease severity, dehydration). INTERVENTION: Educational measures and specific actions in seven risk areas (orientation, sensory impairment, sleep, mobilization, hydration, nutrition, drug use). Daily monitoring of adherence. MEASUREMENTS: Baseline characteristics, risk factors for delirium, and quality care indicators were analyzed. The primary endpoint was incidence of delirium assessed daily. The secondary endpoint was functional decline, defined as loss of independence in any of the activities of daily living. The intervention effect was evaluated using logistic regression analysis. RESULTS: Delirium affected 11.7% of the GI group and 18.5% of the UC group (P 5.04). After adjustment for confounders, the intervention was associated with lower incidence of delirium (odds ratio 50.4, 95% confidence interval 50.24‐0.77; P 5.005). In the patients who experienced delirium, severity, length, and recurrence of episodes were similar in both groups. Adherence to the intervention protocols was 75.7%. The intervention reduced the rate of functional decline (45.5% in GI vs 56.3% in UC, P 5.03) and improved other quality indicators (e.g., mobilization and physical restraints reduction). CONCLUSION: A multicomponent, nonpharmacological intervention integrated into routine practice reduces delirium during hospitalization in older patients, improves quality of care, and can be implemented without additional resources in a public healthcare system. J Am Geriatr Soc 57:2029–2036, 2009.

ImmunoChip Study Implicates Antigen Presentation to T Cells in Narcolepsy

Abstract: Recent advances in the identification of susceptibility genes and environmental exposures provide broad support for a post-infectious autoimmune basis for narcolepsy/hypocretin (orexin) deficiency. We genotyped loci associated with other autoimmune and inflammatory diseases in 1,886 individuals with hypocretin-deficient narcolepsy and 10,421 controls, all of European ancestry, using a custom genotyping array (ImmunoChip). Three loci located outside the Human Leukocyte Antigen (HLA) region on chromosome 6 were significantly associated with disease risk. In addition to a strong signal in the T cell receptor alpha (TRA@), variants in two additional narcolepsy loci, Cathepsin H (CTSH) and Tumor necrosis factor (ligand) superfamily member 4 (TNFSF4, also called OX40L), attained genome-wide significance. These findings underline the importance of antigen presentation by HLA Class II to T cells in the pathophysiology of this autoimmune disease.