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Serrano-Villar S.,University Hospital Ramon y Cajal | Sainz T.,University Hospital Gregorio Maranon | Lee S.A.,University of California at San Francisco | Hunt P.W.,University of California at San Francisco | And 17 more authors.
PLoS Pathogens | Year: 2014

A low CD4/CD8 ratio in elderly HIV-uninfected adults is associated with increased morbidity and mortality. A subset of HIV-infected adults receiving effective antiretroviral therapy (ART) fails to normalize this ratio, even after they achieve normal CD4+ T cell counts. The immunologic and clinical characteristics of this clinical phenotype remain undefined. Using data from four distinct clinical cohorts and three clinical trials, we show that a low CD4/CD8 ratio in HIV-infected adults during otherwise effective ART (after CD4 count recovery above 500 cells/mm3) is associated with a number of immunological abnormalities, including a skewed T cell phenotype from naïve toward terminally differentiated CD8+ T cells, higher levels of CD8+ T cell activation (HLADR+CD38+) and senescence (CD28- and CD57+CD28-), and higher kynurenine/tryptophan ratio. Changes in the peripheral CD4/CD8 ratio are also reflective of changes in gut mucosa, but not in lymph nodes. In a longitudinal study, individuals who initiated ART within six months of infection had greater CD4/CD8 ratio increase compared to later initiators (>2 years). After controlling for age, gender, ART duration, nadir and CD4 count, the CD4/CD8 ratio predicted increased risk of morbidity and mortality. Hence, a persistently low CD4/CD8 ratio during otherwise effective ART is associated with increased innate and adaptive immune activation, an immunosenescent phenotype, and higher risk of morbidity/mortality. This ratio may prove useful in monitoring response to ART and could identify a unique subset of individuals needed of novel therapeutic interventions. © 2014 Serrano-Villar et al.

Martinez-Martin P.,Carlos III Institute of Health | Martinez-Martin P.,CIBER ISCIII | Osa-Ruiz E.,Multidisciplinary Research Unit | Gomez-Conesa A.,University of Murcia | And 2 more authors.
Journal of Alzheimer's Disease | Year: 2012

A relationship between decline in mobility and walking performance and cognitive impairment exists in the elderly. Therefore, clinical assessment of gait and mobility may be relevant for diagnostic and therapeutic purposes. However, the rating scales used for evaluation of gait disorder in the context of cognitive deterioration were not designed or validated for that setting. The present study was aimed at checking the clinimetric properties of the Rating Scale for Gait Evaluation in Cognitive Deterioration (RSGE-CD), specifically developed for assessment of gait dysfunction across all stages of cognitive decline. Two hundred fifty six subjects were included in the study and classified according to the Global Deterioration Scale (control, subjective/mild cognitive impairment, or dementia). Patients with dementia had a diagnosis of probable Alzheimer's disease (73%) or dementia of combined etiology (27%). Cognitive and functional evaluations, the Tinetti scale, and timed tests were simultaneously applied with the tested scale, which is composed of two subscales: Functional ability and Examination. Exploratory factor analysis showed one factor (70% of the variance). Floor effect and skewness were observed in the control group, whereas internal consistency (Cronbach's alpha = 0.88-0.95), inter-observer and test-retest reliability (intraclass correlation coefficients ≥0.97) were satisfactory. Convergent validity with the other measures was ≥0.60 and the discriminant validity according to classification of subjects by cognitive state and other aspects was also satisfactory (p = 0.0001). The RSGE-CD showed low standard errors of measurement. In this first validation study, the RSGE-CD showed satisfactory clinimetric attributes for assessing gait and mobility across the complete range of cognitive state. © 2012-IOS Press and the authors. All rights reserved.

Miano S.,University of Rome La Sapienza | Castaldo R.,University of Rome La Sapienza | Ferri R.,Oasi Institute for Research on Mental Retardation and Brain Aging IRCCS | Peraita-Adrados R.,University Hospital Gregorio Maranon | And 3 more authors.
Clinical Neurophysiology | Year: 2012

Objective: Non-REM sleep is characterized by a physiologic oscillating pattern that exhibits different levels of arousal, coded as cyclic alternating pattern. The aim of this study was to analyze the development of cyclic alternating pattern parameters in a group of infants with apparent life-threatening events. Methods: A total of 26 infants with apparent life-threatening events (14 females, mean age 3.4. months, 2.37 S.D., age range 0.5-9. months) were studied while they slept in the morning between feedings, by means of a 3-h video-electroencephalographic-polygraphic recording. Sleep was visually scored using standard criteria. The control group was composed of 36 healthy infants (16 females, mean age 3.2. months, 2.17 S.D., age range 0.5-9. months). Results: Children with apparent life-threatening events showed an increased frequency of periodic breathing, gastroesofageal reflux and of other risk conditions. They presented also an increased obstructive apnoea/hypopnea index. A full NREM sleep development was found in a significantly smaller percentage of patients, and they showed a significant reduction of the percentage of REM sleep, of cyclic alternating pattern A1 subtypes, an increased percentage of A2 and A3 subtypes and increased index of A2, A3 subtypes and arousal, compared to normal controls. Cyclic alternating pattern rate showed a significant positive correlation with age, only in controls. Conclusions: Our results show a higher level of arousal and an increased non-REM sleep discontinuity in babies with apparent life-threatening events, compared to controls. Significance: The enhanced mechanism of arousal might counteract life-threatening events and represent an important neurophysiologic distinction from future victims of sudden infant death syndrome who also experience similar events. © 2011 International Federation of Clinical Neurophysiology.

Alvarez M.,University of Habana | Iglesias Fernandez C.,University Hospital Gregorio Maranon | Rodriguez Sanchez A.,University Hospital Gregorio Maranon | Dulin Iniguez E.,University Hospital Gregorio Maranon | Rodriguez Arnao M.D.,University Hospital Gregorio Maranon
Hormone Research in Paediatrics | Year: 2010

Background/Aims: Contradictory results regarding the optimal initial dose of levothyroxine in children with congenital hypothyroidism (CH) hamper the clinical management of these children during their early infancy. We explore the relationships between the initial dose of levothyroxine and endocrine control during the first 6 months and cognition at school age. Subjects and Methods: Fifty children with CH, 14 boys (10 ± 3.1 years) and 36 girls (9.7 ± 2.6 years), at the Pediatric Endocrine Unit of the Hospital Gregorio Marañón in Madrid were studied. Neurocognitive evaluation was carried out exploring alertness and inhibitory control. The number of episodes of overtreatment during the first 6 months, the initial dose of levothyroxine, etiology and sex were the predictor variables. Results: Inhibitory control was significantly lower in children with CH than in controls. An interaction with gender and etiology was obtained. Alertness had an inverse relationship with the number of episodes of overtreatment with no interaction with gender or etiology. Conclusion: Episodes of overtreatment and not the initial dose of levothyroxine are a risk factor for deficit in alertness whereas subtle inhibitory control deficit seems to be a permanent problem with the current therapeutic approach. © 2010 S. Karger AG.

Capa-Grasa A.,Hospital Universitario La Paz | Rojo-Manaute J.M.,Point University | Rodriguez F.C.,University Hospital Gregorio Maranon | Martin J.V.,University Hospital Gregorio Maranon
Orthopaedics and Traumatology: Surgery and Research | Year: 2014

Background: Authors have reported better outcomes, by reducing surgical dissection for carpal tunnel syndromes requiring surgery. Recently, a new sonographically guided technique for ultra minimally invasive (Ultra-MIS) carpal tunnel release (CTR) through 1. mm incision has been described. Hypothesis: We hypothesized that a clinical trial for comparing Ultra-MIS versus Mini-open Carpal Tunnel Release (Mini-OCTR) was feasible. Materials and methods: To test our hypothesis, we conducted a pilot study for studying Ultra-MIS versus Mini-OCTR respectively performed through a 1. mm or a 2. cm incision. We defined success if primary feasibility objectives (safety and efficacy) as well as secondary feasibility objectives (recruitment rates, compliance, completion, treatment blinding, personnel resources and sample size calculation for the clinical trial) could be matched. Score for Quick-DASH questionnaire at final follow-up was studied as the primary variable for the clinical trial. Turnover times were studied for assessing learning curve stability. Results: Forty patients were allotted. Primary and secondary feasibility objectives were matched with the following occurrences: 70.2% of eligible patients finally recruited; 4.2% of randomization refusals; 26.6 patients/month recruited; 100% patients receiving a blinded treatment; 97.5% compliance and 100% completion. A sample size of 91 patients was calculated for clinical trial validation. At final follow-up, preliminary results for Quick-Dash substantially favored Ultra-MIS over Mini-OCTR (average 14.54 versus 7.39) and complication rates were lower for Ultra-MIS (5% versus 20%). A stable learning curve was observed for both groups. Conclusions: The clinical trial is feasible. There is currently no evidence to contraindicate nor withhold the use of Ultra-MIS for CTR. Level of evidence: III. © 2014 Elsevier Masson SAS.

Serrano-Villar S.,University Hospital Ramon jal | Perez-Elias M.J.,University Hospital Ramon jal | Dronda F.,University Hospital Ramon jal | Casado J.L.,University Hospital Ramon jal | And 8 more authors.
PLoS ONE | Year: 2014

Background: A low CD4/CD8 ratio has been identified in the general population as a hallmark of inmmunosenescence and a surrogate of all-cause mortality. We aimed to investigate in treated HIV-infected individuals the relationship between the CD4/CD8 ratio and serious non-AIDS events. Methods: Case-control study within a prospective hospital-based cohort of HIV-infected subjects during at least one year of ART-mediated viral suppression. Cases were patients with serious non-AIDS events (non-AIDS malignancies, cardiovascular disease, and end-stage kidney disease), and controls individuals who did not developed non-AIDS events during follow-up. Data were analyzed using ROC analysis and multivariate logistic regression. Conditional logistic regression was performed in 200 cases/controls matched by age, sex, nadir CD4 and proximal CD4 counts. Results: We analyzed 407 subjects (109 cases, 298 controls). The CD4/CD8 ratio was lower in cases (0.44 vs. 0.70, P<0.0001), with higher discriminatory ability for the detection of non-AIDS events than the CD4 count, CD8 count and nadir CD4. Multivariate analyses (adjusted for age, sex, nadir CD4, proximal CD4 count, year of ART initiation and ART duration) confirmed the independent association of a low CD4/CD8 ratio with the risk of non-AIDS morbidity (per CD4/CD8 ratio quartile decrease, OR, 2.9; 95% CI, 1.3-6.2) and non-AIDS mortality (OR, 2.8; 95% CI, 1.5-5.3). Conclusions: The CD4/CD8 ratio provides additional information to the CD4 counts and nadir CD4 in treated HIV-infected individuals, since it is independently associated with the risk of non-AIDS-related morbidity and mortality. This association is robust and maintained within different subgroups of patients. © 2014 Serrano-Villar et al.

Rojo-Manaute J.M.,University Hospital Gregorio Maranon | Capa-Grasa A.,Hospital Universitario La Paz | Del Cerro-Gutierrez M.,University Hospital Gregorio Maranon | Martinez M.V.,University Hospital Gregorio Maranon | And 2 more authors.
Journal of Ultrasound in Medicine | Year: 2012

Objectives-Trigger digit surgery can be performed by an open approach using classic open surgery, by a wide-awake approach, or by sonographically guided first annular pulley release in day surgery and office-based ambulatory settings. Our goal was to perform a turnover and economic analysis of 3 surgical models. Methods-Two studies were conducted. The first was a turnover analysis of 57 patients allocated 4:4:1 into the surgical models: sonographically guided-office-based, classic open-day surgery, and wide-awake-office-based. Regression analysis for the turnover time was monitored for assessing stability (R2 <.26). Second, on the basis of turnover times and hospital tariff revenues, we calculated the total costs, income to cost ratio, opportunity cost, true cost, true net income (primary variable), break-even points for sonographically guided fixed costs, and 1-way analysis for identifying thresholds among alternatives. Results-Thirteen sonographically guided-office-based patients were withdrawn because of a learning curve influence. The wide-awake (n = 6) and classic (n = 26) models were compared to the last 25% of the sonographically guided group (n = 12), which showed significantly less mean turnover times, income to cost ratios 2.52 and 10.9 times larger, and true costs 75.48 and 20.92 times lower, respectively. A true net income breakeven point happened after 19.78 sonographically guided-office-based procedures. Sensitivity analysis showed a threshold between wide-awake and last 25% sonographically guided true costs if the last 25% sonographically guided turnover times reached 65.23 and 27.81 minutes, respectively. However, this trial was underpowered. Conclusions-This trial comparing surgical models was underpowered and is inconclusive on turnover times; however, the sonographically guided-office-based approach showed shorter turnover times and better economic results with a quick recoup of the costs of sonographically assisted surgery. © 2012 by the American Institute of Ultrasound in Medicine.

Carbone J.,University Hospital Gregorio Maranon | Del Pozo N.,University Hospital Gregorio Maranon | Gallego A.,University Hospital Gregorio Maranon | Sarmiento E.,University Hospital Gregorio Maranon
Expert Review of Anti-Infective Therapy | Year: 2011

Immunosuppressive and biologic therapies are costly and can involve a considerable risk of infection. Noninvasive diagnostic tools for early prediction of infection before and after administration of these therapies are of major interest. Serial longitudinal immune monitoring would provide data on immunocompetence and complement clinical follow-up protocols. Biomarkers of immune response may be useful to identify patients at risk of developing infection and who could be candidates for immunosuppressant dose reduction. This article focuses on the potential use of biomarkers of immune response to predict development of infection after immunosuppressive and biologic therapies in selected settings of autoimmune disease (rituximab for treatment of rheumatoid arthritis) and solid organ transplantation. © 2011 Expert Reviews Ltd.

Rojo-Manaute J.M.,University Hospital Gregorio Maranon | Capa-Grasa A.,Hospital Universitario La Paz | Rodriguez-Maruri G.E.,University Hospital Gregorio Maranon | Moran L.M.,University Hospital Gregorio Maranon | And 2 more authors.
Journal of Ultrasound in Medicine | Year: 2013

Objectives:-The purposes of this study were to measure a safe zone and a path for ultra- minimally invasive sonographically guided carpal tunnel release with a 1-mm incision in healthy volunteers and then test the procedure in cadavers. Methods-First, a previously reported sonographic zone was defined as the space between the median nerve and the closest ulnar vascular structure. Axially, the safest theoretical cutting point for carpal tunnel release was set by bisecting this zone. Magnetic resonance imaging was used for axially determining the limits of the sectors (origin at the cutting point) that did not enclose structures at risk (arteries and nerves) and coronally for determining whether our release path could require directions that could potentially compromise safety (origin at the pisiform's proximal pole). Second, in cadavers, we performed ultra-minimally invasive sonographically guided carpal tunnel release from an intracarpal position through a 1-mm antebrachial approach. Efficacy (deepest fibrous layer release rate), safety (absence of neurovascular or tendon injury), and damage to any anatomy superficial to transverse carpal ligament were assessed by dissection. Results-All 11 of our volunteers (22 wrists) had safe axial sectors located volar and radially of at least 80.4° (considered safe). Release path directions were theoretically safe (almost parallel to the longitudinal axis of the forearm). In 10 cadaver wrists, ultra- minimally invasive sonographically guided carpal tunnel release was effective (100% release rate) and safe without signs of intrusion into the superficial anatomy. Conclusions-Ultra-minimally invasive sonographically guided carpal tunnel release in a safe sonographic zone may be feasible The technique preserves the superficial anatomy and diminishes the damage of a surgical approach. ©2013 by the American Institute of Ultrasound in Medicine.

Rojo-Manaute J.M.,University Hospital Gregorio Maranon | Rodriguez-Maruri G.,University Hospital Gregorio Maranon | Capa-Grasa A.,Hospital Universitario La Paz | Chana-Rodriguez F.,University Hospital Gregorio Maranon | And 2 more authors.
Journal of Ultrasound in Medicine | Year: 2012

Objectives-For trigger digits, intrasheath sonographically guided first annular (A1) pulley release has shown safety and effectiveness in cadavers. This clinical study describes sonographically guided A1 pulley release results in terms of resolution of symptoms, safety, and functional recovery. Methods-Sonographically guided A1 pulley release (11-MHz probe) was used in 48 digits of 48 patients prospectively followed for 11.3 months and examined 1, 3, and 6 weeks, 3 and 6 months, and 1 year later. Resolution of triggering (primary variable of interest) was expressed as the "success rate" per digit. The time for taking postoperative pain killers, range of motion recovery, grip strength, QuickDASH test scores, return to normal activities (including work), cosmetic results, satisfaction, and complications were assessed. Results-The success rate was 100%, and no cases recurred. Mean times were 1.9 days for taking pain killers, 6.6 days for returning to normal activities, and 9.9 and 3.8 days for complete extension and flexion recovery, respectively. Mean QuickDASH scores were 39.8 preoperatively and 7.8, 1.7, and 0 after 6 weeks, 6 months, and 1 year postoperatively. Grip strength reached greater than 90% of the individual's normal strength by the sixth week in men and by the third month in women (P<.001). Radial digital nerve numbness developed in 1 finger, which disappeared by the third week. No other complications were noted. All wounds were cosmetically excellent, and final satisfaction was excellent or good in 98%. Conclusions-With adequate anatomic knowledge, technical training, and a basic ultrasound machine, sonographically guided A1 pulley release can be performed safely and successfully, offering an alternative to classic open surgery in the ambulatory setting. © 2012 by the American Institute of Ultrasound in Medicine.

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