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.

Recommendations for somatic and germline genetic testing of single pheochromocytoma and paraganglioma based on findings from a series of 329 patients

Abstract: Background Nowadays, 65–80% of pheochromocytoma and paraganglioma (PPGL) cases are explained by germline or somatic mutations in one of 22 genes. Several genetic testing algorithms have been proposed, but they usually exclude sporadic-PPGLs (S-PPGLs) and none include somatic testing. We aimed to genetically characterise S-PPGL cases and propose an evidence-based algorithm for genetic testing, prioritising DNA source. Methods The study included 329 probands fitting three criteria: single PPGL, no syndromic and no PPGL family history. Germline DNA was tested for point mutations in RET and for both point mutation and gross deletions in VHL , the SDH genes, TMEM127 , MAX and FH . 99 tumours from patients negative for germline screening were available and tested for RET , VHL , HRAS , EPAS1 , MAX and SDHB. Results Germline mutations were found in 46 (14.0%) patients, being more prevalent in paragangliomas (PGLs) (28.7%) than in pheochromocytomas (PCCs) (4.5%) (p=6.62×10−10). Somatic mutations were found in 43% of those tested, being more prevalent in PCCs (48.5%) than in PGLs (32.3%) (p=0.13). A quarter of S-PPGLs had a somatic mutation, regardless of age at presentation. Head and neck PGLs (HN-PGLs) and thoracic-PGLs (T-PGLs) more commonly had germline mutations (p=2.0×10−4 and p=0.027, respectively). Five of the 29 metastatic cases harboured a somatic mutation, one in HRAS . Conclusions We recommend prioritising testing for germline mutations in patients with HN-PGLs and T-PGLs, and for somatic mutations in those with PCC. Biochemical secretion and SDHB-immunohistochemistry should guide genetic screening in abdominal-PGLs. Paediatric and metastatic cases should not be excluded from somatic screening.

Clinical remission and/or minimal disease activity in patients receiving adalimumab treatment in a multinational, open-label, twelve-week study.

Abstract: Objective To evaluate the effect of adalimumab treatment on clinical remission and/or minimal disease activity (MDA) in 6,610 patients with active rheumatoid arthritis (RA) who were enrolled in the Research in Active RA trial, a multinational, open-label, 12-week study with an optional extension period. Methods Clinical remission was defined as a Disease Activity Score in 28 joints (DAS28) <2.6, Simplified Disease Activity Index (SDAI) score ≤3.3, or Clinical Disease Activity Index (CDAI) score ≤2.8. MDA required absence of tender and swollen joints plus erythrocyte sedimentation rate (ESR) ≤10 mm/hour; DAS28 score ≤2.85; or achievement of 5 of 7 core criteria for pain, swollen/tender joints, physical function, physician/patient global assessment, and ESR. Time to and time in remission/MDA and response predictors were analyzed using Kaplan-Meier estimates and Cox proportional hazards regression analysis, respectively. Results A total of 38%, 24%, and 27% of patients achieved remission defined as DAS28 <2.6, SDAI ≤3.3, and CDAI ≤2.8, respectively. MDA was observed in 45% of patients by DAS28 ≤2.85, in 43% by the core set of criteria, and in 13% by absence of tender/swollen joints plus ESR ≤10 mm/hour. Median times in continuous remission and MDA were 3.4 and 4.4 months, respectively. Predictors for remission (DAS28 <2.6) and MDA (DAS28 ≤2.85) were male sex; younger age; concomitant disease-modifying antirheumatic drug use; lower baseline DAS28, CRP concentration, and Health Assessment Questionnaire disease index score; ≤1 comorbidity; and tumor necrosis factor antagonist naivety. Conclusion During adalimumab treatment, 25% of patients experienced clinical remission and nearly half achieved MDA. To our knowledge, this analysis represents the largest prospective clinical trial data set to be assessed using Outcome Measures in Rheumatology Clinical Trials MDA criteria.

Failure to implement evidence-based clinical guidelines for sepsis at the ED.

Abstract: Objective The main objective was to evaluate if consensus "bundle" measures to optimize the treatment of sepsis have been integrated in our routine practice. We also tried to identify variables significantly associated to mortality. Methods An observational, unblinded study of those patients who, according to their physicians, met criteria for sepsis under its different stages of severity was conducted. Six items as proposed by surviving sepsis campaign were evaluated: (1) measurement of blood lactate; (2) obtaining blood samples for culture before use of antibiotics; (3) early use of antibiotics (>3h); (4) fluid replacement with at least 20 mL/kg of crystalloids in the first hour, unless contraindicated, if hypotension or blood lactate >4 mmol/L; (5) use of vasoactive drugs, other than dopaminergic doses of dopamine, if hypotension or shock; (6) measurement of central venous pressure and central venous O 2 saturation in shock. Data concerning several aspects of diagnosis, treatment, and consultation to ICU were collected. Results Compliance with published guidelines is poor after evaluating the 6 items proposed: 12.5% of shocked patients had determinations of blood lactate; 15% of septic patients had no blood cultures drawn; 32% had received their first dose of antibiotics in the first 3 hours after admission; 46.6% of the cases of severe sepsis or shock received a fluid aggressive therapy; 43.3% of the patients with an indication for vasoactive drugs received them; no patient had central venous pressure monitoring at the ED. In addition, intensive care specialists were seldom consulted (17%). Having used dopaminergic doses of dopamine and having a respiratory focus as a source of infection were independently associated to mortality, respective OR: 21 ([1.7-254.9]; 95% CI) and 9.6 ([1.7-52]; 95% CI). Conclusions The "bundle" measures proposed in the surviving sepsis campaign seem not to have had enough impact in our ED. This is the start point of a "plan-do-study-act" process directed to improve the outcome of patients with sepsis at our institution.