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Successful vascular adult thymus transplant has been reported in different animal models but not in rabbits. These animal models are slightly larger than the murine and substantially smaller than the porcine. We describe in rabbits a supermicrosurgical technique for vascular neonatal thymus transplant and provide histologic evidence of tissue viability.Newborn (New Zealand, n = 12, 6 female) and adult (New Zealand, n = 12, 6 female) rabbits were used as donors and recipients, respectively. Whole thymuses were extracted from donors and grafted into recipients. Immediate direct vascularization was accomplished by anastomosis to the right common carotid artery and the right external vena cava. At day 14, graft sites were surgically explored, and grafted thymuses were explanted for histologic evaluation. All recipients were followed over 2 weeks for clinical signs of graft-vs-host reaction.The vascular pedicles of the thymus grafts ranged 0.5 to 0.8 mm in vessel diameter. From the 12 transplants, 3 recipients (3/12; 25%) died during the surgical procedure because of blood loss after clamp release. On histology, from the 9 (9/12; 75%) successful at revascularization, none (0/9; 0%) had signs of acute rejection or necrosis, and all (9/9; 100%) evidenced normal cytoarchitecture. No clinical signs of graft-vs-host reaction were evidenced during follow-up.Vascular neonatal thymus transplant in rabbits is surgically feasible. This technique will enable a novel approach for studying the biology of the thymus.

Introduction The treatment of non-small cell lung cancer (NSCLC) has profoundly changed on account of the arrival of new therapies, like immunotherapy. Within this group of drugs, those aimed at the programmed cell death-1 or programmed cell death ligand-1(PD1/PDL-1) are very relevant, for example, Pembrolizumab. Although its adverse reactions are generally mild and well tolerated, it has been associated with certain immune-related adverse events (IrAEs) than can be serious and affect any organ. Case report A 62-year-old woman diagnosed with stage IV NSCLC with a single bone metastasis and PD-L1 expression of 60% started treatment with cisplatin-pemetrexed-pembrolizumab, and maintenance with pembrolizumab. Management and outcome The patient attended the ER with pericardial effusion that was assumed to be a Pembrolizumab IrAE and was managed with corticosteroids. The patient fully recovered but immunotherapy was not reintroduced due to the severity of the AE. Discussion The cardiovascular system is among the least affected organs by immunotoxicity, with an incidence between 0.09–0.6%. However, some authors suspect the incidence is underestimated. Median time to onset is highly variable, ranging from 6 weeks since the first dose to 2 years after discontinuation of the treatment. There are not guidelines on the most effective management of the IrAEs, but according to the pharmaceutical reference, corticosteroids should be initiated followed by a progressive reduction. If no response is obtained, another immunosuppressive agent should be added. The determination to restart immunotherapy depends on the severity of the adverse reaction, the availability of other alternative treatments, and the cancer response.

The medical auxiliary Mahboub al-Mahmoud (Tangier, 1888-ca. 1970) remains a neglected figure in the history of Morocco's medical modernization. However, his life and professional trajectory can provide a fruitful standpoint from which to question the persisting nationalist bias that has pervaded the modest postcolonial medical historiography about that farthest corner of North Africa. Mahboub's multiple mobilities-temporal, social, geographical, professional-transcend the "colonial fractures" created by the complex European partition of Morocco, which have resulted in Moroccans playing no significant role in the narratives of the origin and development of modern medicine in the country. This paper is divided into three sections, each of which deals with a distinctive phase of Mahboub's itinerary, his connections with various groups of irregular medical practitioners, and the modernizing initiatives they embodied from the times of Hassan I's late nineteenth-century reforms to the rise of Moroccan anticolonial nationalism in the 1930s.

After more than a year of pandemic, the international medical community has changed the perception of fear to one of respect for SARS-COV-2. This has been the consequence of the integral study of all the dimensions of the disease, from viral recombinant capacity to transmissibility, diagnosis, care and prevention. This document summarizes the main strategic lines of study and approach to the pandemic in Madrid.

We designed a clinical study to analyze patterns of adherence to obeticholic acid, factors influencing the adherence and potential correlation with treatment efficacy by using MEMS® cap in practice daily. Method: A multicenter prospective observational study of patients with primary biliary cholangitis. Adherence will be measured by MEMS® cap, pill count, and patient-reported outcomes during 3 months. The quality of life will be self- reported using the Chronic Liver Disease Questionnaire test, European Quality of Life 5-Dimension Questionnaire test and Itch Severity Scale.We expect to clarify if there is correlation between adherence with treatment efficacy and to identify causes for poor compliance and introduce measures to reduce its prevalence.Diseñamos un estudio clínico para analizar los patrones de adherencia al ácido obeticólico, los factores que influyen en la adherencia y la posible correlación con la eficacia del tratamiento mediante el uso de MEMS® cap en la práctica clínica diaria.Método: Estudio observacional prospectivo multicéntrico de pacientes con colangitis biliar primaria. La adherencia se medirá mediante MEMS® cap, el recuento de comprimidos y se registrarán los resultados comunicados por el paciente durante 3 meses. La calidad de vida será autoinformada utilizando el Cuestionario de Enfermedad Hepática Crónica, el Cuestionario Europeo de Calidad de Vida en cinco dimensiones y la Escala de Intensidad del Picor.Esperamos identificar si existe una relación entre la adherencia con la efectividad del tratamiento e identificar las causas de la falta de adherencia para poder introducir medidas para reducir su prevalencia.

Background Nursing homes for older adults have concentrated large numbers of severe cases and deaths for coronavirus disease 2019 (COVID-19). Methods Point seroprevalence study of nursing homes to describe the demography and characteristic of severe acute respiratory syndrome by coronavirus 2 (SARS-CoV-2) immunoglobulin G (IgG)-positive residents and staff. Results Clinical information and blood samples were available for 9,332 residents (mean age 86.7 ± 8.1 years, 76.4% women) and 10,614 staff (mean age 45.6 ± 11.5, 86.2% women). Up to 84.4% of residents had frailty, 84.9% co-morbidity and 69.3% cognitive impairment; 65.2% of workers were health-aides. COVID-19 seroprevalence was 55.4% (95% confidence interval (CI), 54.4–56.4) for older adults and 31.5% (30.6–32.4) for staff. In multivariable analysis, frailty of residents was related with seropositivity (odds ratio (OR): 1.19, P = 0.02). In the case of staff, age > 50 years (2.10, P Conclusions Level of dependency influences risk of COVID-19 among residents. Individual and work factors, contacts outside the nursing home are associated with COVID-19 exposure in staff members. It is key to strengthen control measures to prevent the introduction of COVID-19 into care facilities from the community.

Las personas mayores residentes en instituciones cumplen criterios de pacientes geriátricos complejos, pero con frecuencia no tienen resueltas sus necesidades sanitarias. La pandemia de COVID-19 ha hecho evidentes los déficits existentes en la atención sanitaria a estas personas. Como respuesta a ello surge la necesidad de mejorar la coordinación entre hospitales y residencias, lo que en Madrid se ha materializado en la implantación de equipos o unidades de Geriatría de Enlace en los hospitales públicos. Respecto a las acciones frente a la pandemia por COVID-19, la Sociedad Española de Geriatría y Gerontología ha definido el papel de los geriatras en esta función y ha dado directrices sobre prevención, detección precoz, aislamiento y sectorización, formación, clasificación de las residencias, coordinación de las derivaciones y papel de los diferentes niveles asistenciales, entre otras. Estas unidades también deben dirigir su actividad hacia otras áreas de atención actualmente deficitarias como la coordinación, las visitas presenciales en los centros, las sesiones de telemedicina, la valoración geriátrica en los servicios de urgencias y la coordinación con atención primaria y salud pública. En este artículo se describe la generación del concepto y la implantación de la Geriatría de Enlace en la Comunidad de Madrid a raíz de la pandemia de COVID-19 y se ilustra con los datos de actividad de una unidad cuyo hospital tiene en su área un elevado número de residencias. El objetivo es ayudar a comprender la necesidad de esta actividad, para evitar la fragmentación de cuidados existente en la actualidad entre hospitales y residencias. Actividad que debería consolidarse y mantenerse en el futuro.

The case of a female who had an accident that caused an open fracture is reported. During hospitalisation, Verona integron-encoded metallo-β-lactamase (VIM)-producing Klebsiella pneumoniae was isolated. Antimicrobial susceptibility testing revealed resistance to β-lactam antibiotics, quinolones, trimethoprim/sulfamethoxazole, and susceptibility to tigecycline, colistin, fosfomycin and aminoglycosides. Synergistic activity of ceftazidime-avibactam and aztreonam was proved in vitro and a combined therapy with tigecycline was started. Combination with aminoglycosides was ruled out as it was not described in the literature and also in order to avoid side effects. Colistin was rejected because of its nephrotoxicity profile. The antibiotic treatment was assessed by a multidisciplinary team with a pharmacist who closely monitored adverse effects and interactions with other drugs. The total duration of this combination was 25 days, without any adverse events reported. Fourteen weeks after the accident the patient was discharged. After 2 months of follow-up neither relapses nor reinfections have been reported.

Assessment of T-cell responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigens may be of value to determine long-lasting protection to breakthrough infections or reinfections. Interferon gamma release assay is a validated method to test cellular immunity in mycobacterial infections and has been proposed for patients with SARS-CoV-2 infection or vaccination. Quantitative IgG to spike and qualitative IgG to nucleocapsid antigens were determined by chemiluminescence microparticle immunoassay using the Architect platform (Abbott), and interferon gamma release assays against two Qiagen proprietary mixes of SARS-CoV-2 spike protein (antigen 1 and antigen 2) were performed for a selected group of subjects. A total of 121 subjects in a cloistered institution after a COVID-19 outbreak was studied. IgG spike levels and interferon gamma concentrations were highest among subjects after two doses of vaccine, followed by patients with a longer history of past COVID-19 and no vaccination. The best cutoff for the interferon gamma assay was 25 IU/L for all subgroups of individuals and the two sets of SARS-CoV-2 antigens studied. Testing T-cell response may be of clinical utility to determine immunity after exposure to SARS-CoV-2 antigens, with the interferon gamma concentration of 25 IU/L as the best cutoff either after infection or vaccination.

The objective of this study was to investigate the efficacy and safety of early treatment with sarilumab, added to standard of care (SOC), in hospitalized adults with COVID-19. Methods included phase II, open-label, randomized, controlled clinical trial of hospitalized patients with COVID-19 pneumonia and interleukin (IL)-6 levels ≥ 40 pg/mL and/or d-dimer > 1,500 ng/mL. Participants were randomized (1:1:1) to receive SOC (control group), SOC plus a single subcutaneous dose of sarilumab 200 mg (sarilumab-200 group), or SOC plus a single subcutaneous dose of sarilumab 400 mg (sarilumab-400 group). The primary outcome variable was the development of acute respiratory distress syndrome (ARDS) requiring high-flow nasal oxygenation (HFNO), non-invasive mechanical ventilation (NIMV) or invasive mechanical ventilation (IMV) at day 28. One-hundred and 15 participants (control group, n = 39; sarilumab-200, n = 37; sarilumab-400, n = 39) were included. At randomization, 104 (90%) patients had supplemental oxygen and 103 (90%) received corticosteroids. Eleven (28%) patients in the control group, 10 (27%) in sarilumab-200, and five (13%) in sarilumab-400 developed the primary outcome (hazard ratio [95% CI] of sarilumab-400 vs control group: 0.41 [0.14, 1.18]; P = 0.09). Seven (6%) patients died: three in the control group and four in sarilumab-200. There were no deaths in sarilumab-400 (P = 0.079, log-rank test for comparisons with the control group). In patients recently hospitalized with COVID-19 pneumonia and features of systemic inflammation, early IL-6 blockade with a single dose of sarilumab 400 mg was safe and associated with a trend for better outcomes. (This study has been registered at ClinicalTrials.gov under identifier NCT04357860.)., This study has been supported by the Consejeria de Salud y Familias, Junta de Andalucia, Spain (COVID-19 Research Program. Project code COVID-0013-2020). B.G.G. and J.T.C. are supported by General Sub-Directorate of Networks and Cooperative Research Centers, Ministry of Science and Innovation, Spanish Network for Research in Infectious Diseases [REIPI RD16/0016/0001, RD16/0016/0008]—co-financed by the European Regional Development Fund “A Way to Achieve Europe, Operational Program Smart Growth 2014–2020.” J.C.G. is supported by SCReN (Spanish Clinical Research Network) funded by the ISCIII-Sub-Directorate General for Research Assessment and Promotion through project PT17/0017/0032 and PT20/0039. R.L.L., C.D.L.F., J.T.-C., and B.G.-G. are supported by the Center of Biomedical Investigation Network for Infectious Diseases (CIBERINFEC) funded by ISCIII through projects CB21/13/00049 and CB21/13/00012.

Emily Keene (London 1849 - Tangier 1941) became a relevant figure in pre-colonial Moroccan history due to her involvement in British policy and to her philanthropic-medical initiatives during the late 19th and early 20th centuries. Such prominence was closely linked with her marriage to the sheriff of Wazzan, a powerful spiritual and political figure. 'Grace', in a triple romantic, political and religious sense, was a defining feature of Keene's marriage and widowhood and explained that, despite her continuing adscription to Christian religion, British imperialism and Western science, she deployed a weakly hegemonic stand towards her country of adoption. This attitude distanced her from the 'civilizing mission' policy that set off in the mid-1880s and from the active proselytising and scientific supremacism of the British missionaries during the same period. After her husband's death in 1892, she showed a strong commitment towards (Western-style) Moroccan social and political emancipation, which she tried to promote in close association with a small circle of women friends and Quakers based in Tangiers. Emily Keene's is thus an excellent case study for exploring the interplay between gender, imperialism and religion in pre-colonial Morocco and also the connection between private life and public activity in 19th century women humanitarians.

Background This study anlyzed whether family caregivers of patients with advanced cancer suffer impaired sleep quality, increased strain, reduced quality of life or increased care burden due to the presence and heightened intensity of symptoms in the person being cared for. Method A total of 41 patient-caregiver dyads (41 caregivers and 41 patients with advanced cancer) were recruited at six primary care centres in this cross-sectional study. Data were obtained over a seven-month period. Caregiver’s quality of sleep (Pittsburgh Sleep Quality Index), caregiver’s quality of life (Quality of Life Family Version), caregiver strain (Caregiver Strain Index), patients’ symptoms and their intensity (Edmonton Symptom Assessment System), and sociodemographic, clinical and care-related data variables were assessed. The associations were determined using non-parametric Spearman correlation. Results Total Edmonton Symptom Assessment System was significantly related to overall score of the Pittsburgh Sleep Quality Index (r = 0.365, p = 0.028), the Caregiver Strain Index (r = 0.45, p = 0.005) and total Quality of Life Family Version (r = 0.432, p = 0.009), but not to the duration of daily care (r = -0.152, p = 0.377). Conclusions Family caregivers for patients with advanced cancer suffer negative consequences from the presence and intensity of these patients’ symptoms. Therefore, optimising the control of symptoms would benefit not only the patients but also their caregivers. Thus, interventions should be designed to improve the outcomes of patient-caregiver dyads in such cases.

This collaborative meta-analysis was supported by the Swiss National Science Foundation and the Laura and John Arnold Foundation (grant supporting the post-doctoral fellowship at the Meta-Research Innovation Center at Stanford (METRICS), Stanford University). The funders had no role in the design of this collaborative meta-analysis; in the collection, analysis, and interpretation of data; or in the report writing., We would like to express our warm gratitude to all participating patients and convalescent plasma donors. We thank Katja Suter and Sina Ullrich, University of Basel, for their administrative assistance. For their helpful contribution to individual trials, we thank Erica Wood, Iain Gosbell, Richard Charlewood, Thomas Hills, Veronica Hoad, Kristina Kairaitis, Aikaj Jindal, John Gerrard, Hong Foo, Adam Stewart, and Nanette Trask (ASCOT trial); Amalia Bravo-Lindoro, Ral Carrillo-Esper, Karla Maldonado-Silva, Catalina Casillas-Suárez, Orlando Carrillo-Torres, Sandra Murrieta, Elizabeth Diaz-Padilla, Eli Omar Zavaleta, Yadira Bejar-Ramirez, and Evelyn Cortina-de la Rosa (CPC-SARS trial); Sheri Renaud, Roel Rolando-Almario, and Jacqueline Day (NCT04385199 trial); Sandra Tingsgrd, MD, Karen Brorup Heje Pedersen, MD, Michaela Tinggaard, MD, Louise Thorlacius-Ussing, MD, Clara Lundetoft Clausen, MD, Nichlas Hovmand, MD, Simone Bastrup Israelsen, MD, Cecilie Leding, MD, Katrine Iversen, MD, Maria Engel Miller, MD, Hkon Sandholdt, MSc biostatistician (CCAP-2 trial). On behalf of the IRCT20200310046736N1 trial, we thank the Khuzestan Blood Transfusion Organization for specialized assistance in the preparation and maintenance of plasma samples. On behalf of the NCT04332835 trial, we thank all the members of the "PC-COVID-19 Group" at the Clinica del Occidente and Hospital Universitario Mayor Mederi in Bogota, and Clinica CES in Medellin. On behalf of the NCT04403477 trial, we thank Miles Carroll for his support regarding the antibody testing in Bangladesh. The Co-CLARITY team would like to extend their gratitude to the Department of Science and Technology Philippine Council for Health Research and Development and the UP-Philippine General Hospital for all their support in the setting up and conduct of the trial. For helpfully communicating details of their trial, we thank members of the PlasmAr trial, NCT04359810 trial (Max O´Donnell), NCT04468009 trial, and CTRI/2020/05/025299 trial. Support for title page creation and format was provided by AuthorArranger, a tool developed at the National Cancer Institute (https://www.cancer.gov/)., During the conduct of the study, the following is reported: Dr. Berry reports being employee with ownership role at Berry Consultants (receives payments for statistical modeling and design of REMAP-CAP). Dr. Castillo reports grants from DOST PCHRD. Dr. Daly reports grants from Medical Research Future Fund (Australian Govt) and RBWH. Dr. Denkinger reports grants from German Ministry for Education and Research. Dr. Dumagay reports grants from Philippine Council for Health Research and Development. Dr. Dunachie reports grants from UK Department of Health and Social Care, grants from UK National Institute of Health Research. Dr. Gauiran reports grants from Department of Science and Technology—Philippine Council for Health Research and Development. Dr. Gordon reports grants from NIHR, grants from NIHR Research Professorship (RP-2015-06-18), and non-financial support from NIHR Clinical Research Network. Dr. Higgins reports grants from NHMRC and from the Minderoo Foundation. Dr. Hills reports grants from Health Research Council of New Zealand. Dr. Holm reports grants from Swedish Government Funds for Clinical Research (ALF). Dr. Janssen and Dr. Müller-Tidow report grants from the Federal Ministry of Education and Research in Germany (BMBF) to the RECOVER clinical trial. Dr. Krapp reports grants from Department of Foreign Affairs, Trade, and Development of Canada, grants from Fundación Telefónica del Perú. Dr. J. Lim reports grants from the Department of Science and Technology, Philippine Council for Health Research and Development. Dr. Lucero reports grants from Philippine Council for Health Research and Development. Dr Manrique reports economic support from Grupo ISA Intercolombia for the project development of trial NCT04332835. Drs. McQuilten and Wood report grants from Medical Research Future Fund. Dr. McVerry reports grants from The Pittsburgh Foundation, Translational Breast Cancer Research Consortium, and from UPMC Learning While Doing Program. Mr. Mouncey reports grants from National Institute for Health Research and from the European Union FP7: PREPARE. Dr. Najdovski reports payment from KUL Leuven to Belgian Red Cross for supply of convalescent plasma. Dr. Nichol reports grants from Health Research Board of Ireland. Dr. D. Roberts reports grants from the National Institute for Health (UKRIDHSC COVID-19 Rapid Response Rolling Call—Grant Reference Number COV19-RECPLAS) and the European Commission (SUPPORT-E #101015756). Dr. Rowan reports grants from the European Commission and from the UK National Institute for Health Research. Dr. Shankar-Hari reports grants from National Institute for Health Research UK, grants from UKRI-National Institute for Health Research UK. Dr. Turgeon reports grants from Canadian Institutes of Health Research. Dr. Venkatesh reports grants from Baxter. Dr. Webb reports grants from National Health and Medical Research Council, grants from Minderoo Foundation. Dr. Zacharowski reports grants from EU Horizon 2020. The ASCOT trial team (Drs Bowen, Daly, Davis, Denholm, Hammond, Jha, L. Lim, McQuilten, Molton, Morpeth, O’Sullivan, Paterson, Perry, Price, Rees, Roberts, Rogers, Sasadeusz, Snelling, Tong, Venkatesh, Wood) is funded by grants from from Royal Brisbane and Women’s Hospital Foundation, Pratt Foundation, Minderoo Foundation, BHP Foundation, Hospital Research Foundation, Macquarie Group Foundation, Health Research Council of New Zealand, Australian Partnership for Preparedness Research on Infectious Disease Emergencies (APPRISE), and the collection and supply of convalescent plasma was conducted within Lifeblood’s funding arrangements. The CONFIDENT trial is funded by the Belgian KCE (blood establishments received payment for the convalescent plasma supplied in the clinical trial). REMAP-CAP was supported in part by funding from UKRIDHSC COVID-19 Rapid Response Rolling Call (Grant Reference Number COV19-RECPLAS). Collection of convalescent plasma for REMAP-CAP was funded by the Department of Health and Social Care, UK. The IRCT20200310046736N1 trial was supported by the Ahvaz Jundishapur University of Medical Sciences (Grant No. R.AJUMS.REC.1399.003, Dr. Pouladzadeh). The PC-COVID-19 Group is supported by the Universidad del Rosario, IDCBIS, ISA Group and Suramericana (Colombia). Outside the submitted work, the following is reported: Dr. Axfors reports postdoctoral grants from the Knut and Alice Wallenberg Foundation, Uppsala University, the Swedish Society of Medicine, the Blanceflor Foundation, and the Sweden-America Foundation. Dr. Aomar reports personal fees from SOBI, GEDEON RICHTER, and GSK. Dr. Benfield reports grants from Novo Nordisk Foundation, Simonsen Foundation, Lundbeck Foundation, Kai Hansen Foundation, Erik and Susanna Olesen’s Charitable Fund; grants and personal fees from GSK, Pfizer, Gilead; and personal fees from Boehringer Ingelheim, MSD, and Pentabase ApS. Dr. Estcourt reports being an investigator on the RECOVERY trial. Dr. Gordon reports personal fees from GlaxoSmithKline, Bristol Myers Squibb, and 30 Respiratory. Dr. Jha reports grants and personal fees from Baxter Healthcare, personal fees from Astra Zeneca, grants from NephroPlus. Dr. Laterre reports personal fees from Adrenomed. Dr. McVerry reports grants from NIH/NHLBI and Bayer Pharmaceuticals, Inc. Dr. Mondragon reports financial activities outside the submitted work (employment at Johnson & Johnson). Dr. Perry reports partner being employed at CSL and owning shares in CSL. Dr. Paterson reports involvement with ALLIANCE trial of COVID-19 treatments. Dr. J. Roberts reports other COVID-19 related trials (in different patient groups): tocilizumab in ICU patients; hydroxychloroquine dosing in ICU patients; planned study of remdesivir pharmacokinetics in patients during expanded access program; and in silico evaluation of ivermectin dosing. Dr Sasadeusz reports grants from various Pharma companies including Gilead Sciences, Abvvie, Merck, and Takeda. Dr. Zacharowski reports personal fees from Biotest AG, CSL Behring, GE Heathcare, and is President of the ESAIC., Background: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, https://doi.org/10.17605/OSF.IO/GEHFX). Methods: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung–Knapp–Sidik–Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. Results: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. Conclusions: Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care., Amalia Bravo-Lindoro, BHP Foundation, Blanceflor Foundation, Department of Foreign Affairs, Trade, and Development of Canada, Eli Omar Zavaleta, Erik and Susanna Olesen’s Charitable Fund, Federal Ministry of Education and Research in Germany, Fundación Telefónica del Perú, IDCBIS, ISA Group and Suramericana, Kai Hansen Foundation, Katja Suter and Sina Ullrich, Khuzestan Blood Transfusion Organization, Macquarie Group Foundation, Medical Research Future Fund, NephroPlus, RBWH, Roel Rolando-Almario NCT04385199, Royal Brisbane, Sheri Renaud, Simonsen Foundation, UKRI-National Institute for Health Research UK, UKRIDHSC COV19-RECPLAS, UP-Philippine General Hospital CTRI/2020/05/025299, NCT04359810, NCT04468009, Women’s Hospital Foundation, National Institutes of Health, National Heart, Lung, and Blood Institute, Pittsburgh Foundation, Pfizer, Baxter International, Stanford University, Gilead Sciences, National Institute on Handicapped Research RP-2015-06-18, Meso Scale Diagnostics, Universität Basel, Laura and John Arnold Foundation, Health Research Board, Pratt Foundation, Canadian Institutes of Health Research, National Institute for Health Research, Department of Health and Social Care, European Commission 101015756, National Health and Medical Research Council, Department of Science and Technology, Ministry of Science and Technology, India, Health Research Council of New Zealand, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Sweden-America Foundation, Bundesministerium für Bildung und Forschung, Lundbeckfonden, Knut och Alice Wallenbergs Stiftelse, Seventh Framework Programme, Ahvaz Jundishapur University of Medical Sciences, Université Pierre et Marie Curie, Uppsala Universitet, Horizon 2020, Svenska Läkaresällskapet, Universidad del Rosario, Pharmaceuticals Bayer, Novo Nordisk Fonden, Department of Science and Technology, Philippines, Philippine Council for Health Research and Development, Minderoo Foundation

2S-Hesperidin is the main flavonoid of orange (Citrus sinensis). Previous researches have pointed its effects in muscle development and fat accumulation reduction, although most of these results have not been assessed in humans. The objective of this study is to evaluate the effect of chronic (8-weeks) intake of 2S-hesperidin on amateur cyclists' body composition. A double-blind, parallel and randomized trial, was carried out with 40 amateur cyclists that were divided in two groups, one taking 2S-hesperidin (500 mg d-1, n = 20) and another taking placebo (500 mg d-1 microcellulose, n = 20) for 8 weeks. Dual-energy X-ray absorptiometry (DXA) and anthropometric measurements were used to assess the effect of both treatments on body composition. In addition, the resting metabolic rate was measured. In comparison to placebo, DXA analysis showed a decrease in percentage body fat (%BF) (-10.4%; p = 0.035) and lower limb fat mass (-10.5%; p = 0.029) in favour of 2S-hesperidin. After evaluation of anthropometric data, a decrease in %BF (-3.7%; p = 0.006), total body fat (-3.0%; p = 0.047), ∑ of 8 skinfolds (-6.1%; p = 0.008) was observed in 2S-hesperidin group, but not in placebo. Additionally, there was an increase in muscle mass percentage (1.0%; p =0.001) and total muscle mass (1.7%; p = 0.011) after ingestion of 2S-hesperidin, with no changes in placebo. Chronic intake of 2S-hesperidin decreased fat mass in amateur cyclists, evaluated through different body composition measurement methodologies (DXA and anthropometry). In addition, 2S-hesperidin supplementation showed a promoting effect on muscle development.

The virological meaning of the different patterns of serology in COVID-19 has been little examined in clinical settings. Asymptomatic subjects with IgM-spike (S) and IgG-nucleocapsid (N) determinations by chemiluminescence were studied for SARS-CoV-2 shedding in respiratory secretions by transcription-mediated amplification (TMA). In subjects showing IgM-S positive and IgG-N negative, IgG-S was determined by lateral flow assay. A total of 712 individuals were tested: 30.0% presented IgM-S(+)/IgG-N(−), 25.8% had IgM-S(+)/IgG-N(+) and 44.2% had IgM-S(−)/IgG-N(+), the proportion with TMA(+) were comparable in these three groups: 12.1, 8.7 and 10.5%, respectively. In individuals with IgM-S(+)/IgG-N(−), IgG-S(+) was detected in 66.5%. The frequency of IgM-S(+)/IgG-S(−) in the total population was 10.0%, of whom 24.1% had TMA(+), the chances for TMA(+) in subjects with an IgM-S(+) alone pattern were 2.4%. Targeting of the same SARS-CoV-2 antigen seems to be better for the characterization of IgM/IgG patterns of response. IgM-S(+) alone reactivity is rare, and a small proportion is associated with viral shedding.

Background Pericardial effusion is a frequent finding in the setting of infective endocarditis. Limited data exists on clinical characteristics and outcomes in this group of patients. We aimed to determine the associated factors, clinical characteristics, and outcomes of patients who had pericardial effusion and native valve infective endocarditis. Methods and results A total of 1205 episodes of infective endocarditis from 25 Spanish centers between June 2007 and March 2013 within the Spanish Collaboration on Endocarditis (GAMES) registry were included. Echocardiogram at admission, clinical and microbiological variables, and one-year follow-up were analyzed. Pericardial effusion was observed in 7.8% (94/1205 episodes) of episodes of infective endocarditis, most of them being mild or moderate (93.6%). The presence of pericardial effusion was associated with a higher risk of heart failure during admission (OR 1.9; CI 95% 1.2–3.0). Patients with pericardial effusion had a higher rate of surgery (53.2% vs. 41.1%; p = 0.02); however, this association was no longer significant after adjusting for possible confounders (OR 1.4; CI 95% 0.9–2.2; p = 0.10). The presence of pericardial effusion was not associated with a higher in-hospital or one-year mortality (33.0% vs. 25.2%; p = 0.10 and 40.2% vs. 37.3%; p = 0.60 respectively). Conclusions The prevalence of pericardial effusion in patients with infective endocarditis was lower than previously reported. The presence of pericardial effusion is associated with the development of heart failure during hospitalization making it a warning sign, possibly reflecting indirectly a mechanical complication, which, however, if treated surgically in a timely manner does not change the final outcome of patients. Sin financiación 3.471 JCR (2018) Q2, 48/136 Cardiac & Cardiovascular Systems 0.990 SJR (2018) Q2, 91/365 Cardiology and Cardiovascular Medicine No data IDR 2018 UEM

Nursing homes have suffered in a particularly pronounced way from the effects of COVID-19 so it is very convenient to know the evolution in them of the disease and the impact of SARS-CoV2 vaccination The objective of this study was to analyze COVID-19 pandemic evolution from the start of the second wave to the end of the vaccination campaign at the nursing homes. A coordination program between Primary Care and Geriatrics and Public Health services was activated.2,668 seniors were followed at 39 nursing homes. Data from new cases, active cases, mortality and place of treatment of COVID-19 were collected. A descriptive analysis was performed with the measurement of the absolute number of positive SARS-CoV-2 cases and the frequency distribution.Between August 7The incidence of COVID-19 at nursing homes after the first wave of the pandemic has apparently been lower. The transmission in these centers has followed a different distribution than at community. Mass vaccination has achieved the practical disappearance of the disease.Los centros residenciales han sufrido de una manera especialmente acusada los efectos de la COVID-19 por lo que es muy conveniente conocer la evolución en ellos de la enfermedad y el impacto de la vacunación frente al SARS-CoV2. El objetivo de este estudio fue conocer la evolución de la pandemia de COVID-19 desde el comienzo de la segunda ola hasta el final del proceso de vacunación en las residencias de personas mayores de un área sanitaria, en la cual se activó un programa de coordinación entre Atención Primaria y los servicios de Geriatría y Salud Publica.Se siguió a 2.668 personas mayores en 39 residencias. Se recogieron datos de casos nuevos, activos, fallecidos y lugar de tratamiento de la COVID-19. Se realizó un análisis descriptivo con la medición del número absoluto de casos positivo de SARS-CoV-2 y la distribución de frecuencias.Entre el 7 de agosto de 2020 y el 26 de febrero de 2021 se produjeron 30 brotes en 21 residencias. Se detectaron 300 casos positivos de SARS-CoV-2 (11% de los residentes totales). La media diaria de casos activos fue 27. Fueron hospitalizados 166 (55%). Fallecieron 66 pacientes (22% de los infectados), 54 de ellos (78%) en el hospital. Se realizaron 1.984 test PCR. El perfil temporal de aparición de casos nuevos no siguió una distribución “en olas” como en la comunidad. Treinta y siete días después del inicio de la segunda dosis de vacunación, no existieron casos activos hasta el 1 de marzo en que aparecieron nuevos casos en estudio por posible escape vacunal.La incidencia de la COVID-19 en las residencias de personas mayores tras la primera ola de la pandemia es aparentemente inferior. La transmisión en estos centros sigue una distribución diferente a la de la comunidad. El efecto de la vacunación masiva consigue la práctica desaparición de la enfermedad.

Currently, there is a greater number of amateurs that practice cycling. However, there is no clear evidence regarding bone health in amateur cyclists compared to professional cyclists, as the latter has shown to have lower bone mineral content and density. Therefore, the aim of this study was to identify the differences in bone variables between professional (PRO) and amateur (AMA) road cyclists, and to see if these differences were related to differences in cycling performance. A parallel trial was carried out with 15 AMA and 10 PRO cyclists. All cyclists visited the laboratory twice: 1) in a fasted state, body composition measured by dual-energy X-ray absorptiometry (DXA) and 2) physiological variables measured using an incremental test until exhaustion. Significantly lower values were found in bone mineral density, bone mineral content and fat free mass in PRO compared to AMA (p 0.05). In addition, significantly higher power was produced in ventilatory thresholds 1 and 2 (VT1 and VT2) and VO

© 2020 The Author(s)., [Objectives]: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters., [Methods]: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs)., [Results]: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22–0.47; p < 0.001) for tocilizumab, 0.82 (0.71–1.30; p 0.82) for IHDC, 0.61 (0.43–0.86; p 0.006) for PDC, and 1.17 (0.86–1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02–0.17; p < 0.001)., [Conclusions]: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situation., IJ has received honoraria for participating in an advisory board from Gilead Sciences, and for educational activities from ViiV. JB has received research grants from AbbVie, Gilead Sciences, Merck, and ViiV, and honoraria for being a speaker or advisory board participation from AbbVie, Gilead Sciences, Janssen, Merck, and ViiV. JRA received fees for participating in an advisory board, being a speaker, and research grant support from Viiv, Janssen, Gilead, MSD, Teva, Alexa and Serono. PR is involved as speaker or advisory board participant for Gilead Sciences, AbbVie and ViiV. JR-B, JP, JC and MY have no conflicts of interest to declare. SAM-COVID was funded by Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III (COV20/01031) co-funded by European Union (ERDF/ESF, “Investing in your future”) and Fundación SEIMC/GeSIDA. In addition, Juan Berenguer, Jesús Rodríguez-Baño, Inmaculada Jarrín, Jordi Carratalá, Jerónimo Pachón, and José R Arribas received funding for research from Plan Nacional de I+D+i 2013-2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades – co- financed by European Development Regional Fund “A way to achieve Europe”, Operative program Intelligent Growth 2014–2020 through the networks: Spanish AIDS Research Network (RIS) [RD16/0025/0017 (JB), RD16/0025/0018 (JRA), RD16/0025/00XX (IJ)] and Spanish Network for Research in Infectious Diseases (REIPI)[RD16/0016/0001 (JRB), RD16/0016/0005 (JC), and RD16/0016/0009 (JP).

[Background] To assess the impact of blood cultures negative infective endocarditis (BCNIE) on in-hospital mortality., [Methods] Prospective multicentre study with retrospective analysis of a Spanish cohort including adult patients with definite IE. Cardiac implantable devices infection were excluded. Comparisons between blood cultures positive and BCNIE groups were performed to analyse in-hospital mortality., [Results] 1001 cases were included of which 83 (8.3%) had BCNIE. Alternative microbiological diagnosis was achieved for 39 (47%) out 83 cases. The most frequent identifications were: Coxiella burnetii (11; 28.2%), Tropheryma whipplei (4; 10.3%), Streptococcus gallolyticus (4;10.3%) and Staphylococcus epidermidis (3; 7.7%). Surgery was performed more frequently in BCNIE group (57.8 vs. 36.9%, p, [Conclusions] In our cohort, BCNIE was not associated to greater in-hospital mortality based in multivariate Cox regression models. The variables most frequently associated with mortality were indicated but not performed surgery (aHR = 2.48, 95% CI 1.73–3.56, p

Background Hyperglycaemia has emerged as an important risk factor for death in coronavirus disease 2019 (COVID-19). The aim of this study was to evaluate the association between blood glucose (BG) levels and in-hospital mortality in non-critically patients hospitalized with COVID-19. Methods This is a retrospective multi-centre study involving patients hospitalized in Spain. Patients were categorized into three groups according to admission BG levels: 180 mg/dL. The primary endpoint was all-cause in-hospital mortality. Results Of the 11,312 patients, only 2128 (18.9%) had diabetes and 2289 (20.4%) died during hospitalization. The in-hospital mortality rates were 15.7% (180 mg/dL), p.001. The cumulative probability of mortality was significantly higher in patients with hyperglycaemia compared to patients with normoglycaemia (log rank, p.001), independently of pre-existing diabetes. Hyperglycaemia (after adjusting for age, diabetes, hypertension and other confounding factors) was an independent risk factor of mortality (BG >180 mg/dL: HR 1.50; 95% confidence interval (CI): 1.31-1.73) (BG 140-180 mg/dL; HR 1.48; 95%CI: 1.29-1.70). Hyperglycaemia was also associated with requirement for mechanical ventilation, intensive care unit (ICU) admission and mortality. Conclusions Admission hyperglycaemia is a strong predictor of all-cause mortality in non-critically hospitalized COVID-19 patients regardless of prior history of diabetes. KEY MESSAGE Admission hyperglycaemia is a stronger and independent risk factor for mortality in COVID-19. Screening for hyperglycaemia, in patients without diabetes, and early treatment of hyperglycaemia should be mandatory in the management of patients hospitalized with COVID-19. Admission hyperglycaemia should not be overlooked in all patients regardless prior history of diabetes., The study was completely support by the Spanish Federation of Internal Medicine.

GAMES Investigators., [Background] Enterococcal endocarditis (EE) is a growing entity in Western countries. However, quality data from large studies is lacking., [Objectives] The purpose of this study was to describe the characteristics and analyze the prognostic factors of EE in the GAMES cohort., [Methods] This was a post hoc analysis of a prospectively collected cohort of patients from 35 Spanish centers from 2008 to 2016. Characteristics and outcomes of 516 cases of EE were compared with those of 3,308 cases of nonenterococcal endocarditis (NEE). Logistic regression and Cox proportional hazards regression analysis were performed to investigate risk factors for in-hospital and 1-year mortality, as well as relapses., [Results] Patients with EE were significantly older; more frequently presented chronic lung disease, chronic heart failure, prior endocarditis, and degenerative valve disease; and had higher median age-adjusted Charlson score. EE more frequently involved the aortic valve and prosthesis (64.3% vs. 46.7%; p < 0.001; and 35.9% vs. 28.9%; p = 0.002, respectively) but less frequently pacemakers/defibrillators (1.5% vs. 10.5%; p < 0.001), and showed higher rates of acute heart failure (45% vs. 38.3%; p = 0.005). Cardiac surgery was less frequently performed in EE (40.7% vs. 45.9%; p = 0.024). No differences in in-hospital and 1-year mortality were found, whereas relapses were significantly higher in EE (3.5% vs. 1.7%; p = 0.035). Increasing Charlson score, LogEuroSCORE, acute heart failure, septic shock, and paravalvular complications were risk factors for mortality, whereas prior endocarditis was protective and persistent bacteremia constituted the sole risk factor for relapse., [Conclusions] Besides other baseline and clinical differences, EE more frequently affects prosthetic valves and less frequently pacemakers/defibrillators. EE presents higher rates of relapse than NEE.

[Background] S. aureus (SA) infective endocarditis (IE) has a very high mortality, attributed to the age and comorbidities of patients, inadequate or delayed antibiotic treatment, and methicillin resistance, among other causes. The main study objective was to analyze epidemiological and clinical differences between IE by methicillin-resistant versus methicillin-susceptible SA (MRSA vs. MSSA) and to examine prognostic factors for SA endocarditis, including methicillin resistance and vancomycin minimum inhibitory concentration (MIC) values > 1 μg/mL to MRSA., [Methods] Patients with SA endocarditis were consecutively and prospectively recruited from the Andalusia endocarditis cohort between 1984 and January 2017., [Results] We studied 437 patients with SA endocarditis, which was MRSA in 13.5% of cases. A greater likelihood of history of COPD (OR 3.19; 95% CI 1.41–7.23), invasive procedures, or recognized infection focus in the 3 months before IE onset (OR 2.9; 95% CI 1.14–7.65) and of diagnostic delay (OR 3.94; 95% CI 1.64–9.5) was observed in patients with MRSA versus MSSA endocarditis. The one-year mortality rate due to SA endocarditis was 44.3% and associated with decade of endocarditis onset (1985–1999) (OR 8.391; 95% CI (2.82–24.9); 2000–2009 (OR 6.4; 95% CI 2.92–14.06); active neoplasm (OR 6.63; 95% CI 1.7–25.5) and sepsis (OR 2.28; 95% CI 1.053–4.9). Methicillin resistance was not associated with higher IE-related mortality (49.7 vs. 43.1%; p = 0.32)., [Conclusion] MRSA IE is associated with COPD, previous invasive procedure or recognized infection focus, and nosocomial or healthcare-related origin. Methicillin resistance does not appear to be a decisive prognostic factor for SA IE.

Background Patients with advanced cancer, receiving at-home palliative care, are subject to numerous symptoms that are changeable and often require attention, a stressful situation that also impacts on the family caregiver. It has been suggested that music therapy may benefit both the patient and the caregiver. We propose a study to analyse the efficacy and cost utility of a music intervention programme, applied as complementary therapy, for cancer patients in palliative care and for their at-home caregivers, compared to usual treatment. Method A randomised, double-blind, multicentre clinical trial will be performed in cancer patients in at-home palliative care and their family caregivers. The study population will include two samples of 40 patients and two samples of 41 caregivers. Participants will be randomly assigned either to the intervention group or to the control group. The intervention group will receive a seven-day programme including music sessions, while the control group will receive seven sessions of (spoken word) therapeutic education. In this study, the primary outcome measure is the assessment of patients’ symptoms, according to the Edmonton Symptom Assessment System, and of the overload experienced by family caregivers, measured by the Caregiver Strain Index. The secondary outcomes considered will be the participants’ health-related quality of life, their satisfaction with the intervention, and an economic valuation. Discussion This study is expected to enhance our understanding of the efficacy and cost-utility of music therapy for cancer patients in palliative care and for their family caregivers. The results of this project are expected to be applicable and transferrable to usual clinical practice for patients in home palliative care and for their caregivers. The approach described can be incorporated as an additional therapeutic resource within comprehensive palliative care. To our knowledge, no previous high quality studies, based on a double-blind clinical trial, have been undertaken to evaluate the cost-effectiveness of music therapy. The cost-effectiveness of the project will provide information to support decision making, thereby improving the management of health resources and their use within the health system. Trial registration The COMTHECARE study is registered at Clinical Trials.gov, NCT04052074. Registered 9 August, 2019.

Objective: To investigate the rate of colorectal neoplasms (CRNs) in patients who have Enterococcus faecalis infective endocarditis (EFIE) with available colonoscopies and to assess whether this is associated with the identification of a focus the infection. Patients and Methods: Retrospective analysis of data from a prospective multicenter study involving 35 centers who are members of the Grupo de Apoyo para el Manejo de la Endocarditis en Espana [Support Group for the Management of Infective Endocarditis in Spain] cohort. A specific set of queries regarding information on colonoscopy and histopathology of colorectal diseases was sent to each participating center. Four-hundred sixty-seven patients with EFIE were included from January 1, 2008, to December 31, 2017, from whom data on colonoscopy performance and results were available in 411 patients. Results: One hundred forty-two (34.5%) patients had a colonoscopy close to the EFIE episode. The overall rate of colorectal diseases was 70.4% (100 of 142), whereas the prevalence of CRN (advanced adenomas and colorectal carcinoma) was 14.8% (21 of 142), with no significant differences between the group of EFIE of unknown focus and that with an identified focus. Conclusion: Our study adds to prior evidence suggesting a much higher rate of CRN among patients with EFIE than in the general population of the same age and sex. In addition, our findings suggest that this phenomenon might take place both in EFIE with an unknown and an identified source of infection.

Purpose: To analyze the influence of adding gentamicin to a regimen consisting of β-lactam or vancomycin plus rifampicin on survival in patients suffering from Staphylococcal prosthetic valve endocarditis (SPVE). Methods: From January 2008 to September 2016, 334 patients with definite SPVE were attended in the participating hospitals. Ninety-four patients (28.1%) received treatment based on β-lactam or vancomycin plus rifampicin and were included in the study. Variables were analyzed which related to patient survival during admission, including having received treatment with gentamicin. Results: Seventy-seven (81.9%) were treated with cloxacillin (or vancomycin) plus rifampicin plus gentamicin, and 17 patients (18.1%) received the same regimen without gentamicin. The causative microorganism was Staphylococcus aureus in 40 cases (42.6%) and coagulase-negative staphylococci in 54 cases (57.4%). Overall, 40 patients (42.6%) died during hospital admission, 33 patients (42.9%) in the group receiving gentamicin and 7 patients in the group that did not (41.2%, P = 0.899). Worsening renal function was observed in 42 patients (54.5%) who received gentamicin and in 9 patients (52.9%) who did not (p = 0.904). Heart failure as a complication of endocarditis (OR: 4.58; CI 95%: 1.84–11.42) and not performing surgery when indicated (OR: 2.68; CI 95%: 1.03–6.94) increased mortality. Gentamicin administration remained unrelated to mortality (OR: 1.001; CI 95%: 0.29–3.38) in the multivariable analysis. Conclusions: The addition of gentamicin to a regimen containing vancomycin or cloxacillin plus rifampicin in SPVE was not associated to better outcome.

Human and animal studies have shown that Hesperidin has the ability to modulate antioxidant and inflammatory state and to improve aerobic performance. The main objective of this study was to assess whether the acute intake of 500 mg of 2S-Hesperidin (Cardiose&reg, ) improves antioxidant status, metabolism, and athletic performance, during and after a rectangular test (aerobic and anaerobic effort). For this, a crossover design was used in 15 cyclists (&gt, 1 year of training), with one week of washout between placebo and Cardiose&reg, supplementation. After the intervention, significant differences in average power (+2.27%, p = 0.023), maximum speed (+3.23%, p = 0.043) and total energy (&sum, 4 sprint test) (+2.64%, p = 0.028) between Cardiose&reg, and placebo were found in the best data of the repeated sprint test. Small changes were also observed in the activity of catalase, superoxide dismutase, reduced glutathione concentration and oxidized/reduced glutathione (GSSG/GSH) ratio, as well as the lipoperoxidation products (thiobarbituric acid reactive substances, TBARS), at different points of the rectangular test, although not significant. Our findings showed improvements in anaerobic performance after Cardiose&reg, intake, but not in placebo, suggesting the potential benefits of using Cardiose&reg, in sports with a high anaerobic component.

Annona purpurea, known in Mexico as “cabeza de negro” or “ilama”, belongs to the Annonaceae family. Its roots are employed in folk medicine in several regions of Mexico. Taking that information into account, a chemical and biological analysis of the components present in the roots of this species was proposed. Our results demonstrated that the dichloromethane (DCM) extract was exclusively constituted by a mixture of five new acetogenins named annopurpuricins A–E (1–5). These compounds have an aliphatic chain of 37 carbons with a terminal α,β unsaturated γ-lactone. Compounds 1 and 2 belong to the adjacent bis-THF (tetrahydrofuran) α-monohydroxylated type, while compounds 3 and 4 belong to the adjacent bis-THF α,α’-dihydroxylated type; only compound 5 possesses a bis-epoxide system. Complete structure analysis was carried out by spectroscopy and chemical methods. All compounds were evaluated for their antiproliferative activity on three human tumor cell lines (MSTO-211H, HeLa and HepG2). Compounds 1–4 inhibited significantly the growth of HeLa and HepG2 cells, showing GI50 values in the low/subnanomolar range, while 5 was completely ineffective under the tested conditions. The investigation of the mechanism of action responsible for cytotoxicity revealed for the most interesting compound 1 the ability to block the complex I activity on isolated rat liver mitochondria (RLM).

A comparative study of the behaviour of left-sided infective endocarditis (left-sided IE) due to Streptococcus agalactiae (GBS) with left-sided IE caused by Staphylococcus aureus (SA). A prospective, multicentre cohort study in eight public hospitals in Spain, from January 1984 to December 2015; comparative analysis and factors associated with mortality. In total, there were 1754 episodes of left-sided IE; 41 (2.3%) caused by GBS vs. 344 (19.6%) due to SA, definitive IE 39 vs. 324 cases, males, 25 vs. 213, respectively. There were no differences in age or comorbidity, and healthcare-associated acquirement was 10% vs. 43%, p 0.001. Transthoracic echocardiogram (TTE) was performed in 95% vs. 96.8% and a transesophageal echocardiogram (TEE) in 61% vs. 56%. Vegetations were detected in 80% and measured > 1 cm in a similar proportion. It affected native valves in 85.4% vs. 82.6% and late prosthetic valve in 14.6% vs. 9.6%. The course was acute in both groups. There were more skin manifestations in SA left-sided IE, 7.3% vs. 32%, p 0.001. Both groups had similar complications, but in SA, there was more renal failure, 24% vs. 45%, p 0.010. Surgical risk and operated patients were similar. Mortality was proportionally higher in the SA group, without significance 29% vs. 43% (150), p 0.09. Heart failure, septic shock and neurological deterioration conditioned mortality: HR 1.96, 1.69 and 1.37 (CI 95% 1.40–2.73; 1.19–2.39 and 0.99–1.88 respectively) and to a lesser degree SA as aetiology agent and age. Left-sided IE caused by GBS is similar in severity to left-sided IE caused by SA.

ObjectivesTo analyse the effectiveness of dalbavancin (DBV) in clinical practice as consolidation therapy in patients with bloodstream infection (BSI) and/or infective endocarditis (IE) produced by gram-positive cocci (GPC), as well as its safety and pharmacoeconomic impact.MethodsA multicentre, observational and retrospective study was conducted of hospitalised patients with IE and/or BSI produced by GPC who received at least one dose of DBV. Clinical response was assessed during hospitalization, at 3 months and at 1 year.ResultsEighty-three patients with median age of 73 years were enrolled; 73.5% were male; 59.04% had BSI and 49.04% IE (44.04% prosthetic valve IE, 32.4% native IE, 23.5% pacemaker lead). The most frequently isolated microorganism wasStaphylococcus aureusin BSI (49%) and coagulase-negative staphylococci in IE (44.1%). All patients with IE were clinically cured in hospital; at 12 months, there was 2.9% loss to follow-up, 8.8% mortality unrelated to IE, and 2.9% therapeutic failure rate. The percentage effectiveness of DBV to treat IE was 96.7%. The clinical cure rate for BSI was 100% during hospital stay and at 3 months; there were no recurrences or deaths during the follow-up. No patient discontinued treatment for adverse events. The saving in hospital stay was 636 days for BSI (315,424.20€) and 557 days for IE (283,187.45€).ConclusionsDBV is an effective consolidation antibiotic therapy in clinically stabilized patients with IE and/or BSI. It proved to be a cost-effective treatment, reducing the hospital stay, thanks to the pharmacokinetic/pharmacodynamic profile of this drug.

Spanish Collaboration on Endocarditis — Grupo de Apoyo al Manejo de la Endocarditis Infecciosa en España (GAMES)., [Aim] To evaluate the effect of the type of surgical indication on mortality in infective endocarditis (IE) patients who are rejected for surgery., [Methods and results] From January 2008 to December 2016, 2714 patients with definite left-sided IE were attended in the participating hospitals. One thousand six hundred and fifty-three patients (60.9%) presented surgical indications. Five hundred and thirty-eight patients (32.5%) presented surgical indications but received medical treatment alone. The indications for surgery in these patients were uncontrolled infection (366 patients, 68%), heart failure (168 patients, 31.3%) and prevention of embolism (148 patients, 27.6%). One hundred and thirty patients (24.2%) presented more than one indication. The mortality during hospital admission was 60% (323 patients). The in-hospital mortality of patients whose indication for surgery was heart failure, uncontrolled infection or risk of embolism was 75.6%, 61.4% and 54.7%, respectively (p, [Conclusions] The type of surgical indication is associated with mortality in IE patients who are rejected for surgical intervention.

To evaluate the quality of sleep in caregivers of patients with advanced cancer receiving home palliative care, basing the analysis on subjective and objective measures, and to develop a predictive model of sleep disturbances among this population.A descriptive cross-sectional study was conducted in six clinical management units within primary healthcare centres. Data were obtained during a period of six months, from a sample population of 41 caregivers. The Pittsburgh Sleep Quality Index (PSQI) and a 7-day accelerometry evaluation were performed to assess sleep quality. Daytime sleepiness, caregiver strain and quality of life were also evaluated.According to the PSQI, 90.2% of participants had poor sleep quality. The average duration of night-time sleep, measured by accelerometry and the PSQI, was 6 h. Taking PSQI as the dependent variable, the study model predicted 40.7% of the variability (p 0.01). The variables "Caregiver strain" and "Daily hours dedicated to care" produced the following results: B coefficient 0.645; p = 0.001; and B coefficient 0.230; p = 0.010, respectively.The caregivers presented significant health-related alterations, including sleep disturbances, which were directly related to two variables: the index of caregiver strain and the number of hours per day dedicated to providing care.

2S-Hesperidin is a flavanone (flavonoid) found in high concentrations in citrus fruits. It has an antioxidant and anti-inflammatory effects, improving performance in animals. This study investigated the effects of chronic intake of an orange extract (2S-hesperidin) or placebo on non-oxidative/glycolytic and oxidative metabolism markers and performance markers in amateur cyclists. A double-blind, randomized, placebo-controlled trial was carried out between late September and December 2018. Forty amateur cyclists were randomized into two groups: one taking 500 mg/day 2S-hesperidin and the other taking 500 mg/day placebo (microcellulose) for eight weeks. All participants completed the study. An incremental test was used to evaluate performance, and a step test was used to measure oxygen consumption, carbon dioxide, efficiency and oxidation of carbohydrates and fat by indirect calorimetry. The anaerobic power (non-oxidative) was determined using Wingate tests (30 s). After eight weeks supplementation, there was an increase in the incremental test in estimated functional threshold power (FTP) (3.2%, p &le, 0.05) and maximum power (2.7%, 0.05) with 2S-hesperdin compared to placebo. In the step test, there was a decrease in VO2 (L/min) (&minus, 8.3%, 0.01) and VO2R (mL/kg/min) (&minus, 8.9%, 0.01) at VT2 in placebo. However, there were no differences between groups. In the Wingate test, there was a significant increase (p &le, 0.05) in peak and relative power in both groups, but without differences between groups. Supplementation with an orange extract (2S-hesperdin) 500 mg/day improves estimated FTP and maximum power performance in amateur cyclists.

Traditionally, anterior accessory great saphenous vein insufficiency was managed by crossectomy and resection of varicose veins. The aim of this paper is to show the safety and efficacy of a new therapeutic strategy for anterior accessory great saphenous varicose veins.This non-randomised prospective study included 65 patients with varicose veins from the anterior accessory great saphenous vein. The novelty of the technique is to avoid the great saphenous vein crossectomy and perform just flebectomy of the visible veins. Venous duplex studies were performed preoperatively, a month and a year postoperatively. The clinical assessment was done by the Fligelstone scale.The baseline CEAP clinical classification was: 58% C2, 26% C3 and 15% C4-6. The new strategy was applied to all cases.3 haematomas, 7 cases of asymptomatic partial anterior saphenous thrombosis. Reduction of the initial average diameter was from 6.4 mm anterior saphenous to 3.4 mm by one year (p0.001). At twelve months a forward flow is maintained in 82% of cases. Recurrence of varicose veins was 8%. All patients improved their clinical status based on the Fligelstone scale. Cases with saphenous diameter bigger than 7.5 mm and obesity were identified as predictors of worse clinical and hemodynamic outcome.This modified surgical strategy for anterior saphenous varicose veins results in better clinical outcomes at one year postoperatively.

To evaluate the course of left-sided infective endocarditis (LsIE) in patients with liver cirrhosis (LC) analyzing its influence on mortality and the impact of surgery.Prospective cohort study, conducted from 1984 to 2013 in 26 Spanish hospitals.A total of 3.136 patients with LsIE were enrolled and 308 had LC: 151 Child-Pugh A, 103 B, 34 C and 20 were excluded because of unknown stage. Mortality was significantly higher in the patients with LsIE and LC (42.5% vs. 28.4%; p0.01) and this condition was in general an independent worse factor for outcome (HR 1.51, 95% CI: 1.23-1.85; p0.001). However, patients in stage A had similar mortality to patients without cirrhosis (31.8% vs. 28.4% p = NS) and in this stage heart surgery had a protective effect (28% in operated patients vs. 60% in non-operated when it was indicated). Mortality was significantly higher in stages B (52.4%) and C (52.9%) and the prognosis was better for patients in stage B who underwent surgery immediately (mortality 50%) compared to those where surgery was delayed (58%) or not performed (74%). Only one patient in stage C underwent surgery.Patients with liver cirrhosis and infective endocarditis have a poorer prognosis only in stages B and C. Early surgery must be performed in stages A and although in selected patients in stage B when indicated.

Although Hispanics of Mexican origin in the United States have been identified as a population with a particularly higher rate of Down syndrome (DS), there is a paucity of studies concerning this topic in Mexico. The aim of this study was to determine the prevalence and risk factors for DS in a population from Western Mexico. For prevalence, 230 liveborn infants with DS were included from a total of 89,332 births occurring during the period 2009-2017 at the Dr. Juan I. Menchaca Civil Hospital of Guadalajara (Mexico). In order to evaluate potential DS risks, a case-control study was conducted among 633 newborns, including those 211 DS patients with full trisomy 21 (cases) and 422 infants without birth defects (controls). Data were analyzed using multivariable logistic regression analysis. The overall prevalence for DS was 25.7 per 10,000 (95% confidence interval [95% CI]: 22.4-29.1). Patients with DS had a significantly higher risk for family history of DS in distant relatives (adjusted odds ratio [aOR] = 4.4, 95% CI: 2.5-7.7), relatives with thyroid disease (aOR = 2.3, 95% CI: 1.2-4.0), maternal age ≤ 19 years (aOR = 5.1, 95% CI: 2.7-9.6) or ≥ 35 years (aOR = 3.3, 95% CI: 1.5-6.9), paternal age ≤ 19 years (aOR = 3.5, 95% CI: 1.7-7.4), pre-pregnancy BMI ≥ 25 kg/m2 (aOR = 1.6, 95% CI: 1.0-2.4), and pre-pregnancy alcohol consumption (aOR = 1.8, 95% CI: 1.1-2.9). The identified risks in family history, and previously mentioned nutritional disadvantages were associated with DS in our sample and probably also to its increased prevalence in our population.

Recent acute studies have shown that high-intensity resistance circuit-based (HRC) training in hypoxia increases metabolic stress. However, no intervention studies have yet proven their effectiveness. This study aimed to analyze the effect of 8 weeks of HRC in hypoxia on aerobic performance, resting energy expenditure (REE), repeat sprint ability (RSA) and hematological variables. Twenty-eight subjects were assigned to hypoxia (FiO2 = 15%; HRChyp : n = 15; age: 24.6 ± 6.8 years; height: 177.4 ± 5.9 cm; weight: 74.9 ± 11.5 kg) and normoxia (FiO2 = 20.9%; HRCnorm : n = 13; age: 23.2 ± 5.2 years; height: 173.4 ± 6.2 cm; weight: 69.4 ± 7.4 kg) groups. Each training session consisted of two blocks of three exercises (Block 1: bench press, leg extension, front pull down; 2: deadlift, elbow flexion, ankle extension). Each exercise was performed at 6 repetitions maximum. Participants exercised twice weekly for 8 weeks and before and after the training program blood test, REE, RSA and treadmill running test were performed. Fatigue index in the RSA test was significantly decreased in the HRChyp (-0.9%; P

Background: There is little information concerning infective endocarditis (IE) in patients with bicuspid aortic valve (BAV) or mitral valve prolapse (MVP). Currently, IE antibiotic prophylaxis (IEAP) is not recommended for these conditions. Objectives: This study sought to describe the clinical and microbiological features of IE in patients with BAV and MVP and compare them with those of IE patients with and without IEAP indication, to determine the potential benefit of IEAP in these conditions. Methods: This analysis involved 3,208 consecutive IE patients prospectively included in the GAMES (Grupo de Apoyo al Manejo de la Endocarditis infecciosa en España) registry at 31 Spanish hospitals. Patients were classified as high-risk IE with IEAP indication (high-risk group; n = 1,226), low- and moderate-risk IE without IEAP indication (low/moderate-risk group; n = 1,839), and IE with BAV (n = 54) or MVP (n = 89). Results: BAV and MVP patients had a higher incidence of viridans group streptococci IE than did high-risk group and low/moderate-risk group patients (35.2% and 39.3% vs. 12.1% and 15.0%, respectively; all p < 0.01). A similar pattern was seen for IE from suspected odontologic origin (14.8% and 18.0% vs. 5.8% and 6.0%; all p < 0.01). BAV and MVP patients had more intracardiac complications than did low/moderate-risk group (50% and 47.2% vs. 30.6%, both p < 0.01) patients and were similar to high-risk group patients. Conclusions: IE in patients with BAV and MVP have higher rates of viridans group streptococci IE and IE from suspected odontologic origin than in other IE patients, with a clinical profile similar to that of high-risk IE patients. Our findings suggest that BAV and MVP should be classified as high-risk IE conditions and the case for IEAP should be reconsidered. Sin financiación 18.639 JCR (2018) Q1, 3/136 Cardiac & Cardiovascular Systems 9.280 SJR (2018) Q1, 1/365 Cardiology and Cardiovascular Medicine No data IDR 2018 UEM

Age is one of the main risk factors for the development of cancer. It is expected that the progressive aging of the population will have an unprecedented impact on the incidence of various tumours. In fact, the management of elderly cancer patients is already a major public health problem in developed countries. However, elderly patients have systematically been excluded from cancer drug studies or protocol development. This has left health professionals in uncharted territory, without proper tools to address the multiple difficulties that arise in the treatment of these patients. A comprehensive geriatric assessment may serve as an ideal tool for the correct detection of hidden problems, facilitating treatment decisions in these complex patients, and integrating the care of patients with comorbidities.

Background— The purpose of this study was to assess the incidence of neurological complications in patients with infective endocarditis, the risk factors for their development, their influence on the clinical outcome, and the impact of cardiac surgery. Methods and Results— This was a retrospective analysis of prospectively collected data on a multicenter cohort of 1345 consecutive episodes of left-sided infective endocarditis from 8 centers in Spain. Cox regression models were developed to analyze variables predictive of neurological complications and associated mortality. Three hundred forty patients (25%) experienced such complications: 192 patients (14%) had ischemic events, 86 (6%) had encephalopathy/meningitis, 60 (4%) had hemorrhages, and 2 (1%) had brain abscesses. Independent risk factors associated with all neurological complications were vegetation size ≥3 cm (hazard ratio [HR] 1.91), Staphylococcus aureus as a cause (HR 2.47), mitral valve involvement (HR 1.29), and anticoagulant therapy (HR 1.31). This last variable was particularly related to a greater incidence of hemorrhagic events (HR 2.71). Overall mortality was 30%, and neurological complications had a negative impact on outcome (45% of deaths versus 24% in patients without these complications; P Conclusions— Moderate to severe ischemic stroke and brain hemorrhage were found to have a significant negative impact on the outcome of infective endocarditis. Early appropriate antimicrobial treatment is critical, and transitory discontinuation of anticoagulant therapy should be considered.

Background Popliteal venous aneurysms are an uncommon clinical entity although they have been the subject of a number of published clinical cases. Herein we have conducted an updated review of reports of these aneurysms while also describing our own experience with 4 such cases over the last 10 years. Methods A systematic search was conducted on MEDLINE and Embase concerning popliteal venous aneurysms. We collected all information mentioned associated with their clinical morphology, diagnosis, treatment, and follow-up. The patients included consisted of all those from the literature reports for whom the presence of an aneurysm in the popliteal region was described, plus the 4 cases in our own series. Results The most significant contribution was made by Sessa et al. in 2000, who recommended that this disorder be actively searched for in conventional echo-Doppler studies and, once detected, surgical repair should be undertaken by tangential aneurysmectomy with lateral venorrhaphy to prevent repeat pulmonary embolisms. In conjunction with their series, we reviewed other publications over the last 10 years to determine whether these recommendations have undergone any changes based on the new findings. We found 91 cases in addition to the 117 cases described by Sessa and colleagues as well as the 4 contributed by our group. Most of these cases do not present any specific symptomatology and are discovered by chance via echo Doppler. They are sometimes detected as a palpable mass in the popliteal fossa, with a tendency toward growth, venous thrombosis, and repeat pulmonary embolisms. Phlebography is usually left to preoperative study, and NMR and CAT are rarely used. The objective of surgical treatment is to eliminate the aneurysm while maintaining venous drainage to the limb, with the technique employed most often being tangential aneurysmectomy with lateral venorrhaphy. There are very few postoperative complications and relapses are rare. Conclusions The most recent publications confirm the recommendations made by Sessa et al. more than 10 years ago. Thus, no further changes should be made to the current approach to treatment of venous aneurysms.

The usefulness of the complete blood count (CBC) during the first week of life in infants with Down syndrome (DS) has been recognized; however, studies are limited and have evaluated only some of the parameters of the CBC. Here, we report a prospective study of 135 infants with cytogenetically confirmed DS and a reference group of 226 infants without birth defects all born during the period 2009-2015 at the Dr. Juan I. Menchaca Civil Hospital of Guadalajara (Guadalajara, Mexico). The goal was to evaluate hematological findings in the CBC during the first 7 days of life, interpreted according to gestational and postnatal age. Data were analyzed using multivariate logistic regression analysis expressed as adjusted odds ratio (aORs) with 95% confidence intervals (95% CIs). Infants with DS had a significantly higher risk for polycythemia (aOR = 12.4, 95% CI: 4.6-33.3), macrocytosis (aOR = 15.9, 95% CI: 1.8-143.4), high values of mean corpuscular hemoglobin (aOR = 36.4, 95% CI: 4.5-294.9), anisocytosis (red blood cells of unequal size) (aOR = 3.9, 95% CI: 2.1-7.6), thrombocytopenia (aOR = 32.4, 95% CI: 15.2-68.9), white blood cell (WBC) count ≥30 × 103 /µl (aOR = 19.4, 95% CI: 4.1-91.5), lymphocytosis (aOR = 73.3, 95% CI: 9.5-565.4), and basophilia (aOR = 16.8, 95% CI: 1.9-151.5). Overall, 74% of infants with DS in our study had polycythemia, thrombocytopenia, WBC count >30 × 103 /µl, or lymphocytosis (aOR = 35.6, 95% CI: 18.8-79.2). Compared with those in other studies, our infants with DS had distinctive hematological findings including a lower frequency of thrombocytopenia, infrequent neutrophilia, and frequent lymphocytosis and neutropenia. This suggests ethnic, socioeconomic, or nutritional differences. © 2017 Wiley Periodicals, Inc.

We evaluate the clinical, echographic and prognostic characteristics of infective endocarditis (IE) in a large population of elderly patients, and the results of surgical approach.Multicentric, prospective, observational cohort study with 961 consecutive left-sided IE: 356 patients aged ≥65 years were compared with 605 younger. Indications for cardiac surgery, potential surgical risk, time and outcome, were compared.Hospital-acquired endocarditis, comorbidity, renal failure and septic shock were more frequent in elderly, but embolisms were less. Intracardiac destruction and ventricular failure were similar in both groups, but significantly fewer elderly patients underwent cardiac surgery (36% vs 51%; p 0.01), and this group showed a worse outcome (43.2% of mortality vs 27% in younger; p 0.01), resulting age as an independent predictor of mortality (OR: 1.02 CI95%: 1.01-1.03). Compared with medical treatment, surgery showed lower percentages of mortality compared with medical treatment (23.3% vs 31.3%; p = 0.03) in younger group, but a high mortality was observed with both procedures (47.6% vs 40.3%; p = 0.1) in the elderly.Although similar percentages of heart failure and intracardiac complications, increasing age is associated with higher mortality in IE. Lower rates of surgical treatment and a worse outcome after operation are common features in elderly patients.

Background and Objective: Metabolic syndrome is common in patients with hypertension and increases the risk of developing diabetes mellitus. The objective of this study (the MARCADOR study) was to compare the effects of manidipine 20 mg with the extemporary combination of manidipine 10mg/lisinopril 10 mg, amlodipine 10 mg and telmisartan 80 mg on insulin sensitivity, as well as metabolic, inflammatory and prothrombotic markers, in hypertensive non-diabetic patients with metabolic syndrome. Methods: This study had a prospective, randomized, open-label, blinded endpoint (PROBE) design. A total of 120 patients aged 35–75 years with stage I—II essential hypertension (systolic blood pressure [BP] 140–179 mmHg, diastolic BP 90–109 mmHg) and metabolic syndrome were recruited from general practitioner clinics in Northern Gran Canaria Island, Spain and randomized to receive amlodipine 10 mg (n = 30), telmisartan 80 mg (n = 30), manidipine 20 mg (n = 30) or (low-dose) manidipine 10 mg/lisinopril 10 mg (n=30), all administered once daily. At baseline and after 14 weeks of treatment, BP, insulin sensitivity, lipid profile, and albumin and metanephrin excretion as well as several other metabolic, inflammatory, prothrombotic and growth/adhesion markers were measured. The primary endpoint was the change in insulin sensitivity. Results: A total of 115 patients completed the study. All treatments significantly lowered BP from baseline. Compared with amlodipine, manidipine had significantly superior effects (p

Background: Cystatin C has emerged as a new biomarker of renal function that has been found to predict adverse cardiovascular outcomes, especially heart failure (HF). Evidence of the usefulness of cystatin C in patients with heart failure with preserved ejection fraction (HFPEF) remains sparse. It is hypothesized that serum cystatin C levels in HFPEF has prognostic value. Methods and Results: Cystatin C, urea nitrogen, creatinine, and N-terminal proBNP-type natriuretic peptidelevelsweremeasuredonadmissionin218consecutivepatientswithHFandleftventricularejectionfraction O45%, as measured by Doppler echocardiography. The primary end point was all-cause mortality and/ or readmission at 1year. We determined the adjusted hazardratio (HR) byCox regressionmodel. During the 1-year follow-up period, 70 patients (32.2%) died, and 126 patients (57.8%) died and/or required rehospitalization. Serum cystatin C levels by quartiles were associated with increased risk for adverse events. KaplanMeier survival curves showed significantly increased primary end point with each quartile of cystatin C (log rank !0.001). Patients in the highest quartile of cystatin C level were at increased adjusted risk for the primary end point (HR 3.40; 95% confidence interval [CI] 1.86e6.21; P ! .0001) and all-cause mortality (HR 8.14; 95% CI 1.21e23.26; P ! .01). Furthermore, high serum cystatin C levels were also associated with poor prognosis despite normal or mildly reduced renal function. Conclusions: Serum cystatin C level on admission in patients with HFPEF is a strong and independent predictor of an unfavorable outcome. This relationship remains in patients without advanced renal dysfunction. (J Cardiac Fail 2011;17:31e38)

This article studies the central role of nation-states in the Red Cross during the interwar period. In the late nineteenth century, Spain pioneered the creation of European-style humanitarian institutions in Morocco. However, its perennial instability as a state, aggravated by the colonial disaster of 1898, put an end to the regenerationist project of a Moroccan Red Cross. When the Spanish protectorate was established in 1912, the Spanish Red Cross was overshadowed by competition from its French counterpart, the internationalization of Tangiers and resistance from the local inhabitants. This culminated in the so-called Rif War of 1921-1927, a mixture of anticolonial revolt and international war that vividly exposed the ingrained deficiencies of the Spanish State and its Red Cross.

Hydroxyapatite (HA) is a calcium phosphate bioceramic widely used for bone grafting and augmentation purposes. The biological response of HA can be improved through chemical and microstructural modifications, as well as by manufacturing it as macroporous implants. In the present study, calcium deficient hydroxyapatite (CDHA) and Si substituted hydroxyapatite (SiHA) macroporous scaffolds have been prepared by robocasting. In order to obtain different microstructural properties, the scaffolds have been treated at 700°C and 1250°C. The scaffolds have been characterized and tested as supports for both osteoblast growth and pre-osteoblast differentiation, as fundamental requisite for their potential use in bone tissue engineering. Morphology, viability, adhesion, proliferation, cell cycle, apoptosis, intracellular content of reactive oxygen species and interleukin-6 production were evaluated after contact of osteoblasts-like cells with CDHA and SiHA materials. An adequate interaction of osteoblasts-like cells and preosteoblasts-like cells with all these scaffolds was observed. However, the higher bone cell proliferation and differentiation on CDHA and SiHA scaffolds treated at 1250°C and the lower adsorption of albumin and fibrinogen on these materials in comparison to those treated at 700°C, suggest a better tissue response to CDHA and SiHA materials treated at high temperature.

Background The aim of this study was to detect DNA of hepatitis B virus (HBV) for reliable diagnosis of HBV infection in sera by means of a validated polymerase chain reaction (PCR) using a 5′ oligonucleotide (primer) previously described and a 3′ primer designed by our investigation group. Methods Sera samples collected from patients with chronic liver disease (CLD) related to HBV infection and negative to hepatitis C virus (HCV) infection were analyzed. Patients were both positive and negative to HBV by serum markers detected by ELISA immunoassay. A 146-base pair (bp) fragment was amplified from highly conserved precore-core region. This procedure enabled us to search for DNA HBV-positive cases. Results Viral replicative state in negative hepatitis B e antigen (HBeAg) (15.7%) cases was verified by PCR technique. This detected infection by HBV in 100% of immunoassay-positive samples. Additionally, sequences of expected size in patients bearing atypical markers in their sera (7.1%) and those with negative serology (4.8%) for HBV markers were detected. Conclusions In this study we have improved a PCR technique successfully applied in hepatitis B prevalence studies in northeastern Mexico. Prevalence of hepatitis B in this region of Mexico is intermediate compared to countries of the northern hemisphere where prevalence is lower, and to countries of Southeast Asia and the Mediterranean region where it is highly endemic.