Hospital General Universitario De Valencia

BACKGROUND\nTreatment with peginterferon alfa-2a alone produces significantly higher sustained virologic responses than treatment with interferon alfa-2a alone in patients with chronic hepatitis C virus (HCV) infection. We compared the efficacy and safety of peginterferon alfa-2a plus ribavirin, interferon alfa-2b plus ribavirin, and peginterferon alfa-2a alone in the initial treatment of chronic hepatitis C. METHODS\nA total of 1121 patients were randomly assigned to treatment and received at least one dose of study medication, consisting of 180 μg of peginterferon alfa-2a once weekly plus daily ribavirin (1000 or 1200 mg, depending on body weight), weekly peginterferon alfa-2a plus daily placebo, or 3 million units of interferon alfa-2b thrice weekly plus daily ribavirin for 48 weeks. RESULTS\nA significantly higher proportion of patients who received peginterferon alfa-2a plus ribavirin had a sustained virologic response (defined as the absence of detectable HCV RNA 24 weeks after cessation of therapy) than of patients who received interferon alfa-2b plus ribavirin (56 percent vs. 44 percent, P CONCLUSIONS\nIn patients with chronic hepatitis C, once-weekly peginterferon alfa-2a plus ribavirin was tolerated as well as interferon alfa-2b plus ribavirin and produced significant improvements in the rate of sustained virologic response, as compared with interferon alfa-2b plus ribavirin or peginterferon alfa-2a alone.

DOCUMENT REVIEWERS: Luis Alcocer (Mexico), Christina Antza (Greece), Mustafa Arici (Turkey), Eduardo Barbosa (Brazil), Adel Berbari (Lebanon), Luís Bronze (Portugal), John Chalmers (Australia), Tine De Backer (Belgium), Alejandro de la Sierra (Spain), Kyriakos Dimitriadis (Greece), Dorota Drozdz (Poland), Béatrice Duly-Bouhanick (France), Brent M. Egan (USA), Serap Erdine (Turkey), Claudio Ferri (Italy), Slavomira Filipova (Slovak Republic), Anthony Heagerty (UK), Michael Hecht Olsen (Denmark), Dagmara Hering (Poland), Sang Hyun Ihm (South Korea), Uday Jadhav (India), Manolis Kallistratos (Greece), Kazuomi Kario (Japan), Vasilios Kotsis (Greece), Adi Leiba (Israel), Patricio López-Jaramillo (Colombia), Hans-Peter Marti (Norway), Terry McCormack (UK), Paolo Mulatero (Italy), Dike B. Ojji (Nigeria), Sungha Park (South Korea), Priit Pauklin (Estonia), Sabine Perl (Austria), Arman Postadzhian (Bulgaria), Aleksander Prejbisz (Poland), Venkata Ram (India), Ramiro Sanchez (Argentina), Markus Schlaich (Australia), Alta Schutte (Australia), Cristina Sierra (Spain), Sekib Sokolovic (Bosnia and Herzegovina), Jonas Spaak (Sweden), Dimitrios Terentes-Printzios (Greece), Bruno Trimarco (Italy), Thomas Unger (The Netherlands), Bert-Jan van den Born (The Netherlands), Anna Vachulova (Slovak Republic), Agostino Virdis (Italy), Jiguang Wang (China), Ulrich Wenzel (Germany), Paul Whelton (USA), Jiri Widimsky (Czech Republic), Jacek Wolf (Poland), Grégoire Wuerzner (Switzerland), Eugene Yang (USA), Yuqing Zhang (China).

BACKGROUND: Treatment with pegylated interferon (peginterferon) and ribavirin for 48 weeks is more effective than conventional interferon and ribavirin in patients with chronic hepatitis C. OBJECTIVE: To assess the efficacy and safety of 24 or 48 weeks of treatment with peginterferon-alpha2a plus a low or standard dose of ribavirin. DESIGN: Randomized, double-blind trial. SETTING: 99 international centers. PATIENTS: 1311 patients with chronic hepatitis C. INTERVENTION: Peginterferon-alpha2a, 180 microg/wk, for 24 or 48 weeks plus a low-dose (800 mg/d) or standard weight-based dose (1000 or 1200 mg/d) of ribavirin. MEASUREMENT: Sustained virologic response: undetectable HCV RNA concentration at the end of treatment and during 12 to 24 weeks of follow-up. RESULTS: Overall and in patients infected with HCV genotype 1, 48 weeks of treatment was statistically superior to 24 weeks and standard-dose ribavirin was statistically superior to low-dose ribavirin. In patients with HCV genotype 1, absolute differences in sustained virologic response rates between 48 and 24 weeks of treatment were 11.2% (95% CI, 3.6% to 18.9%) and 11.9% (CI, 4.7% to 18.9%), respectively, between standard- and low-dose ribavirin. Sustained virologic response rates for peginterferon-alpha2a and standard-dose ribavirin for 48 weeks were 63% (CI, 59% to 68%) overall and 52% (CI, 46% to 58%) in patients with HCV genotype 1. In patients with HCV genotypes 2 or 3, the sustained virologic response rates in the 4 treatment groups were not statistically significantly different. CONCLUSION: Treatment with peginterferon-alpha2a and ribavirin may be individualized by genotype. Patients with HCV genotype 1 require treatment for 48 weeks and a standard dose of ribavirin; those with HCV genotypes 2 or 3 seem to be adequately treated with a low dose of ribavirin for 24 weeks.

BACKGROUND: Activating mutations in the epidermal growth factor receptor gene (EGFR) confer hypersensitivity to the tyrosine kinase inhibitors gefitinib and erlotinib in patients with advanced non-small-cell lung cancer. We evaluated the feasibility of large-scale screening for EGFR mutations in such patients and analyzed the association between the mutations and the outcome of erlotinib treatment. METHODS: From April 2005 through November 2008, lung cancers from 2105 patients in 129 institutions in Spain were screened for EGFR mutations. The analysis was performed in a central laboratory. Patients with tumors carrying EGFR mutations were eligible for erlotinib treatment. RESULTS: EGFR mutations were found in 350 of 2105 patients (16.6%). Mutations were more frequent in women (69.7%), in patients who had never smoked (66.6%), and in those with adenocarcinomas (80.9%) (P<0.001 for all comparisons). The mutations were deletions in exon 19 (62.2%) and L858R (37.8%). Median progression-free survival and overall survival for 217 patients who received erlotinib were 14 months and 27 months, respectively. The adjusted hazard ratios for the duration of progression-free survival were 2.94 for men (P<0.001); 1.92 for the presence of the L858R mutation, as compared with a deletion in exon 19 (P=0.02); and 1.68 for the presence of the L858R mutation in paired serum DNA, as compared with the absence of the mutation (P=0.02). The most common adverse events were mild rashes and diarrhea; grade 3 cutaneous toxic effects were recorded in 16 patients (7.4%) and grade 3 diarrhea in 8 patients (3.7%). CONCLUSIONS: Large-scale screening of patients with lung cancer for EGFR mutations is feasible and can have a role in decisions about treatment.

BACKGROUND: Covalent attachment of a 40-kd branched-chain polyethylene glycol moiety to interferon alfa-2a results in a compound (peginterferon alfa-2a) that has sustained absorption, a slower rate of clearance, and a longer half-life than unmodified interferon alfa-2a. We compared the clinical effects of a regimen of peginterferon alfa-2a with those of a regimen of interferon alfa-2a in the initial treatment of patients with chronic hepatitis C. METHODS: We randomly assigned 531 patients with chronic hepatitis C to receive either 180 microg of peginterferon alfa-2a subcutaneously once per week for 48 weeks (267 patients) or 6 million units of interferon alfa-2a subcutaneously three times per week for 12 weeks, followed by 3 million units three times per week for 36 weeks (264 patients). All the patients were assessed at week 72 for a sustained virologic response, defined as an undetectable level of hepatitis C virus RNA (<100 copies per milliliter). RESULTS: In the peginterferon group, 223 of the 267 patients completed treatment and 206 completed follow-up. In the interferon group, 161 of the 264 patients completed treatment and 154 completed follow-up. In an intention-to-treat analysis in which patients who missed the examination at the end of treatment or follow-up were considered not to have had a response at that point, peginterferon alfa-2a was associated with a higher rate of virologic response than was interferon alfa-2a at week 48 (69 percent vs. 28 percent, P=0.001) and at week 72 (39 percent vs. 19 percent, P=0.001). Sustained normalization of serum alanine aminotransferase concentrations at week 72 was also more common in the peginterferon group than in the interferon group (45 percent vs. 25 percent, P=0.001). The two groups were similar with respect to the frequency and severity of adverse events, which were typical of those associated with interferon alfa. CONCLUSIONS: In patients with chronic hepatitis C, a regimen of peginterferon alfa-2a given once weekly is more effective than a regimen of interferon alfa-2a given three times weekly.

BACKGROUND: Available treatments for hepatitis B e antigen (HBeAg)-negative chronic hepatitis B are associated with poor sustained responses. As a result, nucleoside and nucleotide analogues are typically continued indefinitely, a strategy associated with the risk of resistance and unknown long-term safety implications. METHODS: We compared the efficacy and safety of peginterferon alfa-2a (180 microg once weekly) plus placebo, peginterferon alfa-2a plus lamivudine (100 mg daily), and lamivudine alone in 177, 179, and 181 patients with HBeAg-negative chronic hepatitis B, respectively. Patients were treated for 48 weeks and followed for an additional 24 weeks. RESULTS: After 24 weeks of follow-up, the percentage of patients with normalization of alanine aminotransferase levels or hepatitis B virus (HBV) DNA levels below 20,000 copies per milliliter was significantly higher with peginterferon alfa-2a monotherapy (59 percent and 43 percent, respectively) and peginterferon alfa-2a plus lamivudine (60 percent and 44 percent) than with lamivudine monotherapy (44 percent, P=0.004 and P=0.003, respectively; and 29 percent, P=0.007 and P=0.003, respectively). Rates of sustained suppression of HBV DNA to below 400 copies per milliliter were 19 percent with peginterferon alfa-2a monotherapy, 20 percent with combination therapy, and 7 percent with lamivudine alone (P<0.001 for both comparisons with lamivudine alone). Loss of hepatitis B surface antigen occurred in 12 patients in the peginterferon groups, as compared with 0 patients in the group given lamivudine alone. Adverse events, including pyrexia, fatigue, myalgia, and headache, were less frequent with lamivudine monotherapy than with peginterferon alfa-2a monotherapy or combination therapy. CONCLUSIONS: Patients with HBeAg-negative chronic hepatitis B had significantly higher rates of response, sustained for 24 weeks after the cessation of therapy, with peginterferon alfa-2a than with lamivudine. The addition of lamivudine to peginterferon alfa-2a did not improve post-therapy response rates.

Oral potentially malignant disorders (OPMDs) are associated with an increased risk of occurrence of cancers of the lip or oral cavity. This paper presents an updated report on the nomenclature and the classification of OPMDs, based predominantly on their clinical features, following discussions by an expert group at a workshop held by the World Health Organization (WHO) Collaborating Centre for Oral Cancer in the UK. The first workshop held in London in 2005 considered a wide spectrum of disorders under the term "potentially malignant disorders of the oral mucosa" (PMD) (now referred to as oral potentially malignant disorders: OPMD) including leukoplakia, erythroplakia, proliferative verrucous leukoplakia, oral lichen planus, oral submucous fibrosis, palatal lesions in reverse smokers, lupus erythematosus, epidermolysis bullosa, and dyskeratosis congenita. Any new evidence published in the intervening period was considered to make essential changes to the 2007 classification. In the current update, most entities were retained with minor changes to their definition. There is sufficient evidence for an increased risk of oral cancer among patients diagnosed with "oral lichenoid lesions" and among those diagnosed with oral manifestations of 'chronic graft-versus-host disease'. These have now been added to the list of OPMDs. There is, to date, insufficient evidence concerning the malignant potential of chronic hyperplastic candidosis and of oral exophytic verrucous hyperplasia to consider these conditions as OPMDs. Furthermore, due to lack of clear evidence of an OPMD in epidermolysis bullosa this was moved to the category with limited evidence. We recommend the establishment of a global research consortium to further study the natural history of OPMDs based on the classification and nomenclature proposed here. This will require multi-center longitudinal studies with uniform diagnostic criteria to improve the identification and cancer risk stratification of patients with OPMDs, link them to evidence-based interventions, with a goal to facilitate the prevention and management of lip and oral cavity cancer.

The three monokines interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha (TNF alpha), and interleukin-6 (IL-6) modulate acute phase plasma protein synthesis in adult human hepatocytes. Only IL-6 stimulates the synthesis of the full spectrum of acute phase proteins as seen in inflammatory states in humans, i.e. synthesis and secretion of C-reactive protein, serum amyloid A, fibrinogen, alpha 1-antitrypsin, alpha 1-antichymotrypsin and haptoglobin are increased while albumin, transferrin and fibronectin are decreased. IL-1 beta as well as TNF alpha, although having a moderate effect on the positive acute phase proteins and inhibiting the synthesis of fibrinogen, albumin and transferrin, fail to induce serum amyloid A and C-reactive protein. These data suggest that IL-6 plays the key role in the regulation of acute phase protein synthesis in human hepatocytes.

This document summarizes the available evidence and provides recommendations on the use of home blood pressure monitoring in clinical practice and in research. It updates the previous recommendations on the same topic issued in year 2000. The main topics addressed include the methodology of home blood pressure monitoring, its diagnostic and therapeutic thresholds, its clinical applications in hypertension, with specific reference to special populations, and its applications in research. The final section deals with the problems related to the implementation of these recommendations in clinical practice.

Collaborators: Lucas Aparicio (Argentina), Kei Asayama (Japan), Roland Asmar (France), Grzegorz Bilo (Italy), Jean-Marc Boivin (France), Alejandro de la Sierra (Spain), Eamon Dolan (Ireland), Jan Filipovsky (Czech Republic), Geoffrey Head (Australia), Yutaka Imai (Japan), Kazuomi Kario (Japan), Anastasios Kollias (Greece), Efstathios Manios (Greece), Klaus Matthias (Germany), Richard McManus (UK), Anastasia Mihailidou (Australia), Paul Muntner (USA), Martin Myers (Canada), Teemu Niiranen (Finland), Angeliki Ntineri (Greece), Takayoshi Ohkubo (Japan), Aleksander Prejbisz (Poland), Athanase Protogerou (Greece), Menno Pruijm (Switzerland), Aletta Schutte (Australia), Daichi Shimbo (USA), Joseph Schwartz (USA), James Sharman (Australia), Andrew Shennan (UK), Jan Staessen (Belgium), Markus van der Giet (Germany), Liffert Vogt (The Netherlands), Jiguang Wang (China), Paul Whelton (USA), William White (USA).

Hypertension in children and adolescents has gained ground in cardiovascular medicine, thanks to the progress made in several areas of pathophysiological and clinical research. These guidelines represent a consensus among specialists involved in the detection and control of high blood pressure in children and adolescents. The guidelines synthesize a considerable amount of scientific data and clinical experience and represent best clinical wisdom upon which physicians, nurses and families should base their decisions. They call attention to the burden of hypertension in children and adolescents, and its contribution to the current epidemic of cardiovascular disease, these guidelines should encourage public policy makers, to develop a global effort to improve identification and treatment of high blood pressure among children and adolescents.

Human hepatocytes in primary culture were used as a model system to investigate the mechanism(s) involved in the induction of the acute-phase response in human liver. Hepatocytes were incubated with increasing amounts of recombinant human interleukin-1 beta, recombinant interleukin-6 and tumor necrosis factor-alpha. Synthesis of C-reactive protein was studied at the mRNA and protein levels. Only recombinant interleukin-6 was capable of inducing C-reactive protein-mRNA and C-reactive protein-protein synthesis. Also, fibrinogen and alpha-1-antitrypsin synthesis measured by immunoprecipitation with specific antisera increased in a dose-dependent, time-dependent manner, whereas albumin synthesis decreased to about 50% of controls. Maximal effects were observed at 100 to 300 units of recombinant interleukin-6/ml culture medium after 20 hr of incubation. Although the synthetic glucocorticoid dexamethasone slightly modulated the effect of recombinant interleukin-6, it was not an absolute requirement for the induction of acute-phase protein synthesis in human hepatocytes. In pulse-chase experiments it was shown that the time course of the disappearance of the acute-phase proteins from the cells and their appearance in the medium is not influenced by recombinant interleukin-6. This finding suggests that recombinant interleukin-6 exerts its regulatory effect on acute-phase protein synthesis at the pretranslational level.

BACKGROUND: Patients with type 1 diabetes mellitus and microalbuminuria often have elevated blood pressure while they are asleep, but it is not known whether the elevation develops concomitantly with microalbuminuria or precedes it. METHODS: We monitored 75 adolescents and young adults who had had type 1 diabetes with normal urinary albumin excretion and blood pressure for more than five years. Ambulatory blood-pressure monitoring was used to assess blood pressure at the initial evaluation and about two years later, at which time all subjects had normal urinary albumin excretion. Subsequently, subjects were monitored for the development of microalbuminuria. RESULTS: Microalbuminuria developed in 14 subjects, whereas the other 61 continued to have normal urinary albumin excretion. The mean (+/-SD) systolic pressure during sleep increased significantly in the subjects who ultimately had microalbuminuria (from 109.9+/-11.3 to 114.9+/-11.7 mm Hg, P=0.01) but not in the subjects with normal albumin excretion (from 106.0+/-8.8 to 106.4+/-14.8 mm Hg). The risk of progression to microalbuminuria was examined in relation to the ratio of systolic pressure during sleep to systolic pressure in the daytime. A ratio of 0.9 or lower, used to define a normal fall in nocturnal pressure, had a negative predictive value of 91 percent for the development of microalbuminuria. Moreover, the risk of microalbuminuria was 70 percent lower (95 percent confidence interval, 44 to 110 percent) in subjects with a ratio of 0.9 or less than in those with a ratio higher than 0.9 (P=0.01). CONCLUSIONS: In persons with type 1 diabetes, an increase in systolic blood pressure during sleep precedes the development of microalbuminuria. In those whose blood pressure during sleep decreases normally, the progression from normal albumin excretion to microalbuminuria appears to be less likely.

BACKGROUND: Severe trauma represents a major global public health burden and the management of post-traumatic bleeding continues to challenge healthcare systems around the world. Post-traumatic bleeding and associated traumatic coagulopathy remain leading causes of potentially preventable multiorgan failure and death if not diagnosed and managed in an appropriate and timely manner. This sixth edition of the European guideline on the management of major bleeding and coagulopathy following traumatic injury aims to advise clinicians who care for the bleeding trauma patient during the initial diagnostic and therapeutic phases of patient management. METHODS: The pan-European, multidisciplinary Task Force for Advanced Bleeding Care in Trauma included representatives from six European professional societies and convened to assess and update the previous version of this guideline using a structured, evidence-based consensus approach. Structured literature searches covered the period since the last edition of the guideline, but considered evidence cited previously. The format of this edition has been adjusted to reflect the trend towards concise guideline documents that cite only the highest-quality studies and most relevant literature rather than attempting to provide a comprehensive literature review to accompany each recommendation. RESULTS: This guideline comprises 39 clinical practice recommendations that follow an approximate temporal path for management of the bleeding trauma patient, with recommendations grouped behind key decision points. While approximately one-third of patients who have experienced severe trauma arrive in hospital in a coagulopathic state, a systematic diagnostic and therapeutic approach has been shown to reduce the number of preventable deaths attributable to traumatic injury. CONCLUSION: A multidisciplinary approach and adherence to evidence-based guidelines are pillars of best practice in the management of severely injured trauma patients. Further improvement in outcomes will be achieved by optimising and standardising trauma care in line with the available evidence across Europe and beyond.

BACKGROUND: An important determinant of successful cardiac resynchronization therapy for heart failure is the position of the left ventricular (LV) pacing lead. The aim of this study was to analyze the impact of the LV lead position on outcome in patients randomized to cardiac resynchronization-defibrillation in the Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy (MADIT-CRT) study. METHODS AND RESULTS: The location of the LV lead was assessed by means of coronary venograms and chest x-rays recorded at the time of device implantation. The LV lead location was classified along the short axis into an anterior, lateral, or posterior position and along the long axis into a basal, midventricular, or apical region. The primary end point of MADIT-CRT was heart failure (HF) hospitalization or death, whichever came first. The LV lead position was assessed in 799 patients, (55% patients ≥65 years of age, 26% female, 10% LV ejection fraction ≤25%, 55% ischemic cardiomyopathy, and 71% left bundle-branch block) with a follow-up of 29±11 months. The extent of cardiac resynchronization therapy benefit was similar for leads in the anterior, lateral, or posterior position (P=0.652). The apical lead location compared with leads located in the nonapical position (basal or midventricular region) was associated with a significantly increased risk for heart failure/death (hazard ratio=1.72; 95% confidence interval, 1.09 to 2.71; P=0.019) after adjustment for the clinical covariates. The apical lead position was also associated with an increased risk for death (hazard ratio=2.91; 95% confidence interval, 1.42 to 5.97; P=0.004). CONCLUSION: LV leads positioned in the apical region were associated with an unfavorable outcome, suggesting that this lead location should be avoided in cardiac resynchronization therapy. Clinical Trial Registration- URL: http://clinicaltrials.gov. Unique identifier: NCT00180271.

OBJECTIVE: To evaluate the efficacy and safety of perampanel 2, 4, and 8 mg/day added to 1-3 concomitant antiepileptic drugs (AEDs) in patients with uncontrolled partial-onset seizures. METHODS: During this double-blind, placebo-controlled trial, patients with persisting seizures on 1-3 AEDs were randomized to perampanel 2, 4, and 8 mg/day or placebo following a 6-week baseline phase. Perampanel was titrated weekly by 2 mg/day and maintained at the dose achieved for 13 weeks. Primary endpoints were median percent change in seizure frequency and 50% responder rate. Analysis of covariance was performed on all treated patients with any seizure data (recorded in daily diaries) in the double-blind phase. RESULTS: A total of 706 patients were randomized and received trial medication; 623 completed the trial. Median percent change in seizure frequency-the primary efficacy endpoint-was -10.7%, -13.6%, -23.3%, and -30.8% for placebo, perampanel 2, 4, and 8 mg/day, respectively. The difference from placebo was statistically significant for perampanel 4 mg/day (p = 0.0026) and 8 mg/day (p < 0.0001). The corresponding 50% responder rates were 17.9%, 20.6%, 28.5%, and 34.9%. The difference from placebo was statistically significant for perampanel 4 mg/day (p = 0.0132) and 8 mg/day (p = 0.0003). An apparent dose response was suggested for dizziness, which was the most frequent treatment-emergent adverse event. CONCLUSIONS: This trial demonstrated that adjunctive perampanel effectively reduced seizure frequency and possessed a favorable tolerability profile in patients ≥12 years with partial-onset seizures (with or without secondary generalization), with a minimum effective dose of 4 mg/day. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that 4 and 8 mg/day doses of adjunctive perampanel are effective and tolerated in reducing partial-onset seizures.

Oral lichen planus (OLP) is a relatively common chronic inflammatory disorder affecting stratified squamous epithelia. Whereas in the majority of instances, cutaneous lesions of lichen planus (LP) are self-limiting and cause itching, oral lesions in OLP are chronic, rarely undergo spontaneous remission, are potentially premalignant and are often a source of morbidity. Current data suggest that OLP is a T cell-mediated autoimmune disease in which auto-cytotoxic CD8+ T cells trigger apoptosis of oral epithelial cells. The characteristic clinical aspects of OLP may be sufficient to make a correct diagnosis if there are classic skin lesions present. An oral biopsy with histopathologic study is recommended to confirm the clinical diagnosis and mainly to exclude dysplasia and malignancy. The most commonly employed and useful agents for the treatment of lichen planus (LP) are topical corticosteroids but other newer agents are available.

Human dental pulp contains precursor cells termed dental pulp stem cells (DPSC) that show self-renewal and multilineage differentiation and also secrete multiple proangiogenic and antiapoptotic factors. To examine whether these cells could have therapeutic potential in the repair of myocardial infarction (MI), DPSC were infected with a retrovirus encoding the green fluorescent protein (GFP) and expanded ex vivo. Seven days after induction of myocardial infarction by coronary artery ligation, 1.5 x 10(6) GFP-DPSC were injected intramyocardially in nude rats. At 4 weeks, cell-treated animals showed an improvement in cardiac function, observed by percentage changes in anterior wall thickening left ventricular fractional area change, in parallel with a reduction in infarct size. No histologic evidence was seen of GFP+ endothelial cells, smooth muscle cells, or cardiac muscle cells within the infarct. However, angiogenesis was increased relative to control-treated animals. Taken together, these data suggest that DPSC could provide a novel alternative cell population for cardiac repair, at least in the setting of acute MI.

Coeliac disease (CD) is the most common immune-mediated enteropathy characterized by chronic inflammation of the small intestinal mucosa. The ingestion of gluten is responsible for the symptoms of CD, but other environmental factors are also thought to play a role in this disorder. In this study, the composition of the duodenal microbiota of coeliac children with active disease, symptom-free CD patients on a gluten-free diet and control children was determined. Bacteriological analyses of duodenal biopsy specimens were carried out by fluorescent in situ hybridization coupled with flow cytometry. The proportions of total bacteria and Gram-negative bacteria were significantly higher in CD patients with active disease than in symptom-free CD patients and controls. Bacteroides and Escherichia coli groups were significantly more abundant in CD patients with active disease than in controls, whilst these bacterial deviations were normalized in symptom-free CD patients. The ratio of Lactobacillus--Bifidobacterium to Bacteroides--E. coli was significantly reduced in coeliac patients with either active or inactive disease compared with controls. The differences in Atopobium, Eubacterium rectale--Clostridium coccoides, Clostridium histolyticum, Clostridium lituseburense, sulphate-reducing bacteria and Faecalibacterium prausnitzii populations among the three groups of children were less relevant. Overall, the higher incidence of Gram-negative and potentially pro-inflammatory bacteria in the duodenal microbiota of coeliac children was linked to the symptomatic presentation of the disease and could favour the pathological process of the disorder.

RATIONALE: Obstructive sleep apnea (OSA) is an independent risk factor for stroke, but little is known about the role of continuous positive airway pressure (CPAP) on mortality in patients with stroke. OBJECTIVES: To analyze the independent impact of long-term CPAP treatment on mortality in patients with ischemic stroke. METHODS: Prospective observational study in 166 patients with ischemic stroke. Sleep study was performed in all of them and CPAP treatment was offered in the case of moderate to severe cases. Patients were followed-up for 5 years to analyze the risk of mortality. MEASUREMENTS AND MAIN RESULTS: Of 223 patients consecutively admitted for stroke, a sleep study was performed on 166 of them (2 mo after the acute event). Thirty-one had an apnea-hypopnea index (AHI) of less than 10; 39 had an AHI between 10 and 19, and 96 had an AHI of 20 or greater. CPAP treatment was offered when AHI was 20 or greater. Patients were followed up in our outpatient clinic at 1, 3, and 6 months, and for every 6 months thereafter for 5 years (prospective observational study). Mortality data were recorded from our computer database and official death certificates. The mean age of subjects was 73.3 +/- 11 years (59% males), and the mean AHI was 26 (for all patients with a predominance of obstructive events). Patients with an AHI of 20 or greater who did not tolerate CPAP (n = 68) showed an increase adjusted risk of mortality (hazards ratio [HR], 2.69; 95% confidence interval [CI], 1.32-5.61) compared with patients with an AHI of less than 20 (n = 70), and an increased adjusted risk of mortality (HR, 1.58; 95% CI, 1.01-2.49; P = 0.04) compared with patients with moderate to severe OSA who tolerated CPAP (n = 28). There were no differences in mortality among patients without OSA, patients with mild disease, and patients who tolerated CPAP. CONCLUSIONS: Our results suggest that long-term CPAP treatment in moderate to severe OSA and ischemic stroke is associated with a reduction in excess risk of mortality.