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[Abstract] Background: Hospitalized COVID-19 patients are prone to develop persistent symptoms and to show reduced quality of life following hospital admission. Methods: Prospective cohort study of COVID-19 patients admitted to a hospital from March 1 to April 30, 2020. The primary outcome was to compare health related quality of life and persistent symptoms six months after hospital admission, of COVID-19 patients who required ICU admission with those who did not. Results: Among the 242 patients hospitalized during the defined period of time, 44 (18.2%) needed ICU admission. Forty (16.5%) patients died during hospital admission. Two hundred and two (83.5%) patients were discharged alive from the hospital. At six months, 183 (75.6%) patients completed the questionnaires (32 ICU patients and 151 non ICU patients). Ninety-six (52.4%) reported decreased quality of life and 143 (78.1%) described persistent symptoms. More ICU patients showed worsening of their quality of life (71.9 vs. 43.7%, P = 0.004). There were no differences in the proportion of patients with persistent symptoms between ICU and non ICU patients (87.5 vs. 76.2%, P = 0.159). ICU patients showed more frequently dyspnea on exertion (78.1 vs. 47.7%, P = 0.02), dyspnea on light exertion (37.5 vs. 4.6%, P < 0.001), and asthenia (56.3 vs. 29.1, P = 0.003). Conclusions: Survivors of COVID-19 needing hospitalization had persistent symptoms and a decline in the quality of life. ICU patients referred a large decrease of their quality of life compared with non ICU patients. [Resumen] Antecedentes/Contexto. Existe una tendencia en los pacientes hospitalizados por COVID-19 a desarrollar síntomas persistentes y a presentar una disminución en su calidad de vida tras el ingreso hospitalario. Métodos. Estudio de cohorte prospectivo de pacientes COVID-19 con ingreso hospitalario entre el 1 de marzo al 30 de abril de 2020. El objetivo primario fue comparar la calidad de vida relacionada con la salud y la presencia de síntomas persistentes seis meses después del ingreso, comparando los pacientes que requirieron ingreso en UCI con los que no lo precisaron. Resultados. De los 242 pacientes hospitalizados durante el período de estudio, 44 (18,2%) necesitaron ingreso en UCI. 40 (16,5%) pacientes fallecieron durante el ingreso hospitalario. 202 (83,5%) pacientes fueron dados de alta del hospital. A los seis meses, 183 (75,6%) pacientes completaron los cuestionarios (32 pacientes UCI y 151 pacientes no UCI). 96 (52,4%) refirieron disminución de la calidad de vida y 143 (78,1%) describieron síntomas persistentes. Un número mayor de pacientes de UCI mostraron un empeoramiento de su calidad de vida (71,9% vs 43,7%, P = 0,004). No hubo diferencias en la proporción de pacientes con síntomas persistentes entre los pacientes con UCI y sin UCI (87,5% vs 76,2%, P = 0,159). Los pacientes de UCI mostraron con mayor frecuencia disnea de esfuerzo (78,1% vs 47,7%, P = 0,02), disnea de pequeños esfuerzos (37,5% vs 4,6%, P < 0,001) y astenia (56,3 vs 29,1, P = 0,003). Conclusiones. Los supervivientes de COVID-19 que necesitaron hospitalización presentaron síntomas persistentes y un deterioro de su calidad de vida. Los pacientes de UCI refirieron una mayor disminución de su calidad de vida en comparación con los pacientes que no precisaron UCI.

• Several cardiovascular/hemostatic disturbances haves been reported in patients with COVID-19, but the real frequency and their potential association with the pathogenic mechanisms of SARS-CoV-19 still remain to be defined. • We investigated the relative frequency of acute coronary syndrome, deep venous thrombosis, pulmonary embolism, stroke and upper gastrointestinal bleeding in COVID patents attending emergency departments (EDs), before hospitalization and compared them with frequencies in the general ED population attending 50 Spanish EDs. • We found that the risk of pulmonary embolism is clearly increased in COVID patients, with an OR of 4.53 with respect to non-COVID patients (95% confidence interval 4.03- 5.10). Additionally, the diagnosis of pulmonary embolism was 2 fold more frequent among ED comers in 2020 compared to 2019, suggesting a SARS-CoV-2 role in such increment of cases.. The remaining entities studied were not found to be unequivocally increased in the present study and need further investigation.

BackgroundLow-dose dexamethasone demonstrated clinical improvement in patients with coronavirus disease 2019 (COVID-19) needing oxygen therapy; however, evidence on the efficacy of high-dose dexamethasone is limited.MethodsWe performed a randomised, open-label, controlled trial involving hospitalised patients with confirmed COVID-19 pneumonia needing oxygen therapy. Patients were randomly assigned in a 1:1 ratio to receive low-dose dexamethasone (6 mg once daily for 10 days) or high-dose dexamethasone (20 mg once daily for 5 days, followed by 10 mg once daily for an additional 5 days). The primary outcome was clinical worsening within 11 days since randomisation. Secondary outcomes included 28-day mortality, time to recovery and clinical status at day 5, 11, 14 and 28 on an ordinal scale ranging from 1 (discharged) to 7 (death).ResultsA total of 200 patients (mean±sd age 64±14 years; 62% male) were enrolled. 32 (31.4%) out of 102 patients enrolled in the low-dose group and 16 (16.3%) out of 98 in the high-dose group showed clinical worsening within 11 days since randomisation (rate ratio 0.427, 95% CI 0.216–0.842; p=0.014). The 28-day mortality was 5.9% in the low-dose group and 6.1% in the high-dose group (p=0.844). There was no significant difference in time to recovery, and in the seven-point ordinal scale at days 5, 11, 14 and 28.ConclusionsAmong hospitalised COVID-19 patients needing oxygen therapy, high dose of dexamethasone reduced clinical worsening within 11 days after randomisation, compared with low dose.

Objective We investigated the incidence, predictor variables, clinical characteristics, and stroke outcomes in patients with COVID-19 seen in emergency departments (EDs) before hospitalization. Methods We retrospectively reviewed all COVID-19 patients diagnosed with stroke during the COVID-19 outbreak in 62 Spanish EDs. We formed two control groups: COVID-19 patients without stroke (control A) and non-COVID-19 patients with stroke (control B). We compared disease characteristics and four outcomes between cases and controls. Results We identified 147 strokes in 74,814 patients with COVID-19 seen in EDs (1.96 parts per thousand, 95% confidence interval [CI] = 1.66 parts per thousand to 2.31 parts per thousand), being lower than in non-COVID-19 patients (6,541/1,388,879, 4.71 parts per thousand, 95% CI = 4.60 parts per thousand to 4.83 parts per thousand; odds ratio [OR] = 0.42, 95% CI = 0.35 to 0.49). The estimated that standardized incidences of stroke per 100,000 individuals per year were 124 and 133 for COVID-19 and non-COVID-19 individuals, respectively (OR = 0.93 for COVID patients, 95% CI = 0.87 to 0.99). Baseline characteristics associated with a higher risk of stroke in COVID-19 patients were hypertension, diabetes mellitus, and previous cerebrovascular and coronary diseases. Clinically, these patients more frequently presented with confusion, decreased consciousness, and syncope and higher D-dimer concentrations and leukocyte count at ED arrival. After adjustment for age and sex, the case group had higher hospitalization and intensive care unit (ICU) admission rates (but not mortality) than COVID-19 controls without stroke (OR = 3.41, 95% CI = 1.27 to 9.16; and OR = 3.79, 95% CI = 1.69 to 8.50, respectively) and longer hospitalization and greater in-hospital mortality than stroke controls without COVID-19 (OR = 1.55, 95% CI = 1.24 to 1.94; and OR = 1.77, 95% CI = 1.37 to 2.30, respectively). Conclusions The incidence of stroke in COVID-19 patients presenting to EDs was lower than that in the non-COVID-19 reference sample. COVID-19 patients with stroke had greater need for hospitalization and ICU admission than those without stroke and longer hospitalization and greater in-hospital mortality than non-COVID-19 patients with stroke.

We aimed to analyze the clinical course of patients discharged from our emergency departament (ED) with pneumonia symptoms compatible with a diagnosis of COVID-19.We followed 102 patients discharged home with a diagnosis of pneumonia compatible with COVID19 between March 12 and 21, 2020, in our hospital in the southern part of the autonomous community of Madrid. Descriptive statistics (medians and interquartile ranges or frequencies, as appropriate) were compiled for the main variables. Treatments and prognoses were compared with 􀁆2, Kruskal-Wallis, or Mann-Whitney tests. The data then underwent logistic regression analysis.Most patients (accounting for 74.5% of the discharges) were treated with hydroxychloroquine alone. The readmission rate was 15.7%; the ED revisiting rate was 25.7%. Admission was associated with an elevated lactate dehydrogenase (LDH) level (P=.011), elevated creatine kinase (CK) (P=.004), and lymphopenia (P=.034). Hypertension and chronic obstructive pulmonary disease were also related to admission. Ischemic heart disease was associated with longer duration of symptoms.Lymphopenia, and elevated LDH and CK levels predicted the need for hospital admission better than other traditional biological markers in patients with mild to moderate symptoms. Telephone follow-up proved useful for dealing with the overloading of health care services.Analizar la evolución de los pacientes que fueron dados de alta del servicio de urgencias (SU) con neumonía compatible con COVID-19.Se realiza el seguimiento de 102 pacientes dados de alta desde SU con diagnóstico de neumonía compatible con COVID-19 entre el 12 y el 21 de marzo de 2020 en un hospital del sur de Madrid. Se describen las principales variables utilizando mediana e intervalo intercuartil o usando frecuencias, según corresponda. La comparación entre tratamientos/pronóstico se realizó utilizando el test ji cuadrado, el test de Kruskal Wallis o el test de Mann-Whitney. Finalmente, se realizó un modelo de regresión logística.La mayoría de los pacientes (74,5%) fueron tratados con hidroxicloroquina en monoterapia. La tasa de reingreso fue de 15,7% y de revisita a urgencias de 25,7%. El ingreso se relacionó con un LDL (lactato deshidrogenasa) elevado (p = 0,011), creatincinasa (CK) elevada (p = 0,004) y linfopenia (p = 0,034). La hipertensión y la enfermedad pulmonar obstructiva crónica se relacionaron con el ingreso, y la cardiopatía isquémica fue la comorbilidad que se asoció a mayor duración de la sintomatología.La linfopenia, LDH y CK pronosticaron mejor la necesidad de ingreso que otros marcadores clásicos en pacientes con clínica leve-moderada. El seguimiento telefónico demostró ser de utilidad ante la sobrecarga de recursos sanitarios.

OBJECTIVE: We investigated the incidence, risk factors, clinical characteristics and outcomes of acute pancreatitis (AP) in patients with COVID-19 attending the emergency department (ED), before hospitalization. METHODS: We retrospectively reviewed all COVID patients diagnosed with AP in 62 Spanish EDs (20% of Spanish EDs, COVID-AP) during the COVID outbreak. We formed two control groups: COVID patients without AP (COVID-non-AP) and non-COVID patients with AP (non-COVID-AP). Unadjusted comparisons between cases and controls were performed regarding 59 baseline and clinical characteristics and 4 outcomes. RESULTS: We identified 54 AP in 74,814 patients with COVID-19 attending the ED (frequency=0.72‰, 95%CI=0.54-0.94‰). This frequency was lower than in non-COVID patients (2,231/1,388,879, 1.61‰, 95%CI=1.54-1.67; OR=0.44, 95%CI=0.34-0.58). Etiology of AP was similar in both groups, being biliary origin in about 50%. Twenty-six clinical characteristics of COVID patients were associated with a higher risk of developing AP: abdominal pain (OR=59.4, 95%CI=23.7-149), raised blood amylase (OR=31.8; 95%CI=1.60-632) and vomiting (OR=15.8, 95%CI=6.69-37.2) being the strongest, and some inflammatory markers (C-reactive protein, procalcitonin, platelets, D-dimer) were more increased. Compared to non-COVID-AP, COVID-AP patients differed in 23 variables; the strongest ones related to COVID symptoms, but less abdominal pain was reported, pancreatic enzymes raise was lower, and severity (estimated by BISAP and SOFA score at ED arrival) was higher. The in-hospital mortality (adjusted for age and sex) of COVID-AP did not differ from COVID-non-AP (OR=1.12, 95%CI=0.45-245) but was higher than non-COVID-AP (OR=2.46, 95%CI=1.35-4.48). CONCLUSIONS: Acute pancreatitis as presenting form of COVID-19 in the ED is unusual (

REIPI-SEIMC COVID-19 group and COVID@HULP group., [Background] The clinical presentation of COVID-19 in patients admitted to hospital is heterogeneous. We aimed to determine whether clinical phenotypes of patients with COVID-19 can be derived from clinical data, to assess the reproducibility of these phenotypes and correlation with prognosis, and to derive and validate a simplified probabilistic model for phenotype assignment. Phenotype identification was not primarily intended as a predictive tool for mortality., [Methods] In this study, we used data from two cohorts: the COVID-19@Spain cohort, a retrospective cohort including 4035 consecutive adult patients admitted to 127 hospitals in Spain with COVID-19 between Feb 2 and March 17, 2020, and the COVID-19@HULP cohort, including 2226 consecutive adult patients admitted to a teaching hospital in Madrid between Feb 25 and April 19, 2020. The COVID-19@Spain cohort was divided into a derivation cohort, comprising 2667 randomly selected patients, and an internal validation cohort, comprising the remaining 1368 patients. The COVID-19@HULP cohort was used as an external validation cohort. A probabilistic model for phenotype assignment was derived in the derivation cohort using multinomial logistic regression and validated in the internal validation cohort. The model was also applied to the external validation cohort. 30-day mortality and other prognostic variables were assessed in the derived phenotypes and in the phenotypes assigned by the probabilistic model., [Findings] Three distinct phenotypes were derived in the derivation cohort (n=2667)—phenotype A (516 [19%] patients), phenotype B (1955 [73%]) and phenotype C (196 [7%])—and reproduced in the internal validation cohort (n=1368)—phenotype A (233 [17%] patients), phenotype B (1019 [74%]), and phenotype C (116 [8%]). Patients with phenotype A were younger, were less frequently male, had mild viral symptoms, and had normal inflammatory parameters. Patients with phenotype B included more patients with obesity, lymphocytopenia, and moderately elevated inflammatory parameters. Patients with phenotype C included older patients with more comorbidities and even higher inflammatory parameters than phenotype B. We developed a simplified probabilistic model (validated in the internal validation cohort) for phenotype assignment, including 16 variables. In the derivation cohort, 30-day mortality rates were 2·5% (95% CI 1·4–4·3) for patients with phenotype A, 30·5% (28·5–32·6) for patients with phenotype B, and 60·7% (53·7–67·2) for patients with phenotype C (log-rank test p, [Interpretation] Patients admitted to hospital with COVID-19 can be classified into three phenotypes that correlate with mortality. We developed and validated a simplified tool for the probabilistic assignment of patients into phenotypes. These results might help to better classify patients for clinical management, but the pathophysiological mechanisms of the phenotypes must be investigated., [Funding] Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation, and Fundación SEIMC/GeSIDA., Funding: Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation, and Fundación SEIMC/GeSIDA.

Highlights • Long outcomes of a large sample of hospitalized CPVID-19 patients were analyzed. • A large proportion of hospitalized COVID-19 patients had a reduced functional status six months after hospitalization. • ICU patients referred a large decrease of their functional status compared with not ICU patients six months after hospitalization. • Female sex, age, length of hospital stay, mechanical ventilation, and ICU admission were associated with limitations in everyday life .

Objective Introducing a new, simple and inexpensive portable equipment for lifeguards, consisting of a pre-assembled full-size plastic blanket with a mask and HEPA filter, which could offer significant time-saving advantages to reduce COVID-19 risk transmission in the first few minutes of CPR after water rescue, avoiding the negative impact of delayed ventilation. Method A pilot study was carried out to determine the feasibility of the pre-assembled kit of face-mask and HEPA filter adapted on a pre-set plastic-blanket. The first step consisted of washing hands, putting on safety glasses and gloves as the first personal protection equipment (PPE) and then covering the victim with an assembled plastic blanket. The second step consisted of 10 min of cardiopulmonary resuscitation (CPR) with PPE and plastic blanket, following the technical recommendations for ventilation during COVID-19. Results Ten rescuers took part in the pilot study. The average time to wear PPE and place the pre-assembly kit on the victim was 82 s [IC 58–105]. After 10 min the quality of the resuscitation (QCPR) was 91% [87–94]. Quality chest compressions (CC) were 22% better than ventilations (V). Most of the rescuers (60%) thought that placing the plastic blanket on the victim on the beach was somewhat simple or very simple. Conclusions Resuscitation techniques in COVID-19 era at the beach have added complexities for the correct use of PPE. Plastic blanket plus basic ventilations equipment resource could be a new alternative to be considered for lifeguards to keep ventilation on use while reducing risk transmission., Highlights • Pre-assembled kit to avoid delaying CPR in the Covid-19 Era • An easy and low-cost equipment • For prehospital environments without immediate EMS assistance

Leprosy, or Hansen’s disease, is a chronic granulomatous disease caused by Mycobacterium leprae and the recently discovered Mycobacterium lepromatosis. In Spain and other countries, where leprosy has been eliminated, an increasing number of imported cases have been documented, especially from South Africa and South America. The diagnosis of leprosy is mainly clinical, based on the signs established by the World Health Organization (WHO), although laboratory tools can be useful for diagnostic confirmation. The treatment is based on the administration of multi-drug therapy, and involves the multidisciplinary work of experts in ophthalmology, orthopedics, and physiotherapy. We studied the confirmed cases by microbiological and /or histopathological diagnosis in the health area of Santiago de Compostela (456,874 inhabitants in Galicia, in the Northwest of Spain), analyzing their clinical, microbiological, and epidemiological characteristics (2006–2015). In our study, we describe five cases of leprosy, four of them imported and one that, in the absence of more data, is native. Although we have only documented five cases during the 10 years of the study, our experience highlights the importance of considering the country of origin, travel history, and contacts in patients or staff working with leprosy patients. Despite the decrease of leprosy in our environment, it is important to enhance suspicion of the disease among health personnel, especially in those patients from countries where leprosy is endemic and those in close contact with the diagnosed patients.

The prognosis of a patient with Covid-19 pneumonia is uncertain. Our objective was to establish a predictive model of disease progression to facilitate early decision-making. A retrospective study was performed of patients admitted with Covid-19 pneumonia, classified as severe (admission to the intensive care unit, mechanic invasive ventilation, or death) or non-severe. A predictive model based on clinical, analytical, and radiological parameters was built. The probability of progression to severe disease was estimated by logistic regression analysis. Calibration and discrimination (receiver operating characteristics curves and AUC) were assessed to determine model performance. During the study period 1,152 patients presented with Covid-19 infection, of whom 229 (19.9%) were admitted for pneumonia. During hospitalization, 51 (22.3%) progressed to severe disease, of whom 26 required ICU care (11.4); 17 (7.4%) underwent invasive mechanical ventilation, and 32 (14%) died of any cause. Five predictors determined within 24 hours of admission were identified: Diabetes, Age, Lymphocyte count, SaO2, and pH (DALSH score). The prediction model showed a good clinical performance, including discrimination (AUC 0.87 CI 0.81, 0.92) and calibration (Brier score = 0.11). In total, 0%, 12%, and 50% of patients with severity risk scores ≤5%, 6-25%, and >25% exhibited disease progression, respectively. A simple risk score based on five factors predicts disease progression and facilitates early decision-making according to prognosis. Carlos III Health Institute, Spain, Ministry of Economy and Competitiveness (SPAIN) and the European Regional Development Fund (FEDER) Instituto de Salud Carlos III

Background: The prognosis of a patient with Covid-19 pneumonia is uncertain. Our objective was to establish a predictive model of disease progression to facilitate early decision-making. Methods: A retrospective study was performed of patients admitted with Covid-19 pneumonia, classified as severe (admission to the intensive care unit, mechanic invasive ventilation, or death) or non-severe. A predictive model based on clinical, analytical, and radiological parameters was built. The probability of progression to severe disease was estimated by logistic regression analysis. Calibration and discrimination (receiver operating characteristics curves and AUC) were assessed to determine model performance. Findings: During the study period 1,152 patients presented with Covid-19 infection, of whom 229 (19.9%) were admitted for pneumonia. During hospitalization, 51 (22.3%) progressed to severe disease, of whom 26 required ICU care (11.4); 17 (7.4%) underwent invasive mechanical ventilation, and 32 (14%) died of any cause. Five predictors determined within 24 hours of admission were identified: Diabetes, Age, Lymphocyte count, SaO2, and pH (DALSH score). The prediction model showed a good clinical performance, including discrimination (AUC 0.87 CI 0.81, 0.92) and calibration (Brier score = 0.11). In total, 0%, 12%, and 50% of patients with severity risk scores ≤5%, 6-25%, and >25% exhibited disease progression, respectively. Interpretation: A simple risk score based on five factors predicts disease progression and facilitates early decision-making according to prognosis. Funding Statement: This project was funded by the Carlos III Health Institute, Spain, Grant/Award Number: COV20/00404; Ministry of Economy and Competitiveness (SPAIN) and the European Regional Development Fund (FEDER). Declaration of Interests: The authors declare no conflicts of interest associated with this publication. Ethics Approval Statement: The study was conducted in accordance with the guidelines of the Declaration of Helsinki and the principles of good clinical practice and was approved by the Institutional Review Board (IRB) of the Galician Health Service on April 3, 2020 (#2020/194). Informed consent forms were waived by the IRB.

In patients with coronavirus disease 2019 (COVID-19) infection, common drugs may exacerbate symptoms and negatively impact outcomes. However, the role of chronic medications on COVID-19 effects remains poorly understood. We hypothesized that certain chronic pain medications would influence outcomes in patients with COVID-19. The main aim is to assess the effect of these medications on the course of the disease in COVID-19 patients. Secondary aims are to compare disease severity and outcomes in patients with COVID-19 receiving chronic treatment with analgesics or other medications versus untreated patients and to determine prevalence of chronic pain medications in specific subgroups of hospitalized patients for COVID-19. Multicenter case-population study in 15 care centers for patients =18 years of age diagnosed and hospitalized with COVID-19. Controls will include patients treated at participating centers for chronic pain during the six-month period prior to March 15th, 2020. Each case will be age- and sex-matched to 10 controls. Patients will be grouped according to disease severity criteria. The primary outcome measures in patients admitted for COVID-19 will be: 1. statistical association between chronic pain medication and disease severity; 2. association between chronic pain treatment and survival. Secondary outcome measures include: 1. prevalence of chronic pain medications in patients with COVID-19 by age and sex; 2. prevalence of chronic pain medications in patients with COVID-19 vs controls. Patients and controls will be paired by age, sex, and geographic residence. Odds ratios with 95% confidence intervals will be calculated to determine the association between each drug and clinical status. Univariate and multivariate analyses will be performed. This is a study protocol. Data is actually being gathered and results are yet not achieved. There is no numerical data presented, so the conclusions cannot be considered solid at this point. Pain medications are likely to influence severity of COVID-19 and patient survival. Identifying those medications that are most closely associated with severe COVID-19 will provide clinicians with valuable data to guide treatment and reduce mortality rates and the long-term sequelae of the disease.

Background B cells exert their pathogenic action in rheumatoid arthritis (RA) locally in the synovium. This study was undertaken to elucidate the chemokines responsible for the recruitment of B cells in the inflamed synovium, taking into account that the rich chemokine milieu present in the synovial tissue can fine-tune modulate discrete chemokine receptors. Methods Expression levels of chemokine receptors from the CC and CXC family, as well as CD27, were assessed by flow cytometry in CD20+ mononuclear cells isolated from the peripheral blood (PB) and synovial fluid (SF) of RA and psoriatic arthritis patients. Transwell experiments were used to study migration of B cells in response to a chemokine or in the presence of multiple chemokines. Results B cells from the SF of arthritis patients showed a significant increase in the surface expression of CCR1, CCR2, CCR4, CCR5 and CXCR4 with respect to PB. Conversely, SF B cells expressed consistently lower amounts of CXCR5, CXCR7 and CCR6, independent of CD27 expression. Analysis of permeabilized B cells suggested internalization of CXCR5 and CCR6 in SF B cells. In Transwell experiments, CCL20 and CXCL13, ligands of CCR6 and CXCR5, respectively, caused a significantly higher migration of B cells from PB than of those from SF of RA patients. Together, these two chemokines synergistically increased B-cell migration from PB, but not from SF. Conclusions These results suggest that CXCL13 and CCL20 might play major roles in RA pathogenesis by acting singly on their selective receptors and synergistically in the accumulation of B cells within the inflamed synovium. Electronic supplementary material The online version of this article (10.1186/s13075-018-1611-2) contains supplementary material, which is available to authorized users.

La presión cricoidea es una maniobra ampliamente recomendada y extendida a la hora de ciertas intubaciones orotraqueales. Pero son pocos los estudios que hayan comparado su realización frente a no realizarla. Por tanto, aquellos profesionales dedicados a la vía aérea deben comprobar su eficacia. El estudio aquí analizado no consigue demostrar la no inferioridad de la intubación sin presión cricoidea durante la inducción de secuencia rápida (ISR). De modo que se alcanza un nuevo reto en el futuro: dejar de hacer lo que hemos aprendido haciendo. Por lo que probablemente serán las generaciones de residentes actuales los que dejarán como anecdótico una práctica cuestionada pero muy realizada. ABSTRACT Cricoid pressure or Sellick. Past and future of a underestimated challenged manoeuvre? Cricoid pressure is an extended maneuver during a rapid sequence induction at certain orotracheal intubations. However, few studies have compared its realization against not doing it. Therefore, there was a need to verify its usefulness or effectiveness. With the present study, which is analyzed with this text, it is not possible to demonstrate the non-inferiority of non-realization. So, a new challenge is achieved in the future: stop doing what we have learned. At least, it will probably be the generations of current residents who will leave as a past practice.

Neutrophils destroy invading microorganisms by phagocytosis by bringing them into contact with bactericidal substances, among which ROS are the most important. However, ROS also function as important physiological regulators of cellular signaling pathways. Here, we addressed the involvement of oxygen derivatives in the regulation of human neutrophil rolling, an essential component of the inflammatory response. Flow experiments using dihydroethidium‐preloaded human neutrophils showed that these cells initiate an early production of intracellular ROS during the rolling phase of the adhesion cascade, a phenomenon that required cell rolling, and the interaction of the chemokine receptor CXCR2 with their ligand CXCL8. Flow cytometry experiments demonstrated that L‐selectin shedding in neutrophils is triggered by ROS through an autocrine–paracrine mechanism. Preincubation of neutrophils with the NADPH oxidase complex inhibitor diphenyleniodonium chloride significantly increased the number of rolling neutrophils on endothelial cells. Interestingly, the same effect was observed when CXCL8 signaling was interfered using either a blocking monoclonal antibody or an inhibitor of its receptor. These findings indicate that, in response to CXCL8, neutrophils initiate ROS production during the rolling phase of the inflammatory response. This very early ROS production might participate in the modulation of the inflammatory response by inducing L‐selectin shedding in neutrophils., This work was supported by grants from the Fondo de Investigaciones Sanitarias of Spain Grants PI12/02499 and PI15/01810 (to. F.D.‐G.), co‐funded by the European Regional Development Fund. This work was also supported by Asociación para la Ayuda a la Investigación en Reumatología del Hospital Universitario de Canarias (REUNINVES) and by the Spanish Society of Rheumatology.

This paper presents certain features of problems and situations closely linked to the risks of exclusion, vulnerability and violence present in the world of women. These were covered by final-year dissertations or projects undertaken by students of the Nuestra Senora del Camino [“Our Lady of the Way”] University School of Social Work during the period 1987 to 2013. These more than ninety pieces of work, deposited in the School's Library, cover a great range of circumstances, some positive, many adverse, relating to women from the Province of Leon. Their topics run from violence and abuse, through women's lack of visibility, problems women face, enduring prejudices, social support and sanctions, to hopes for equality, health, education and the like. They form a panorama in which the ever-present strands are a spirit of struggle and a need for a more decent life.

Primary Sjögren’s syndrome (pSS) is an autoimmune exocrinopathy in which the role that the immune response plays in reducing exocrine gland function, including the glandular microenvironment of cytokines, has not been fully understood. Epithelial cells from biopsies of human parotid gland (HPG) were used to establish a model of human salivary gland in vitro. In this model, the functional consequences of several proinflammatory soluble factors present in the pSS glandular microenvironment were assessed. Stimulation with isoproterenol and calcium produced a significant increase in the basal activity of amylase in the HPG cell supernatants. Under these conditions, the presence of TNF-α and CXCL12 increased amylase mRNA cellular abundance, but reduced the amylase activity in the cell-free supernatant in a dose-dependent manner. IL-1β and IFN-γ, but not TGF-β, also diminished amylase secretion by HPG cells. These results suggest that the glandular microenvironment of cytokine, by acting post-transcriptionally, may be responsible, at least in part, for the reduced exocrine function observed in pSS patients. These data may help to a better understanding of the pathogenesis of SS, which in turn would facilitate the identification of new therapeutic targets for this disorder.

Background: The precise mechanism linking systemic inflammation with insulin resistance (IR) in rheumatoid arthritis (RA) remains elusive. In the present study, we determined whether the incretin-insulin axis and incretin effect are disrupted in patients with RA and if they are related to the IR found in these patients. Methods: We conducted a cross-sectional study that encompassed 361 subjects without diabetes, 151 patients with RA, and 210 sex-matched control subjects. Insulin, C-peptide, glucagon-like peptide-1 (GLP-1), gastric inhibitory polypeptide (GIP), dipeptidyl peptidase 4 (DPP-4) soluble form, and IR indexes by homeostatic model assessment (HOMA2) were assessed. A multivariable analysis adjusted for IR-related factors was performed. Additionally, ten patients and ten control subjects underwent a 566-kcal meal test so that we could further study the postprandial differences of these molecules between patients and control subjects. Results: Insulin, C-peptide, and HOMA2-IR indexes were higher in patients than in control subjects. This was also the case for GLP-1 (0.49 ± 1.28 vs. 0.71 ± 0.22 ng/ml, p = 0.000) and GIP (0.37 ± 0.40 vs. 1.78 ± 0.51 ng/ml, p = 0.000). These differences remained significant after multivariable adjustment including glucocorticoid intake. Disease Activity Score in 28 joints with erythrocyte sedimentation rate (? coefficient 46, 95% CI 6?87, p = 0.026) and Clinical Disease Activity Index (? coefficient 7.74, 95% CI 1.29?14.20, p = 0.019) were associated with DPP-4 serum levels. GLP-1 positively correlated with ?-cell function (HOMA2 of ?-cell production calculated with C-peptide) in patients but not in control subjects (interaction p = 0.003). The meal test in patients with RA revealed a higher total and late response AUC for glucose response, a later maximal response of C-peptide, and a flatter curve in GIP response. Conclusions: The incretin-insulin axis, both during fasting and postprandial, is impaired in patients with RA. This work was supported by grants from the Spanish Ministry of Health, Subdirección General de Evaluación y Fomento de la Investigación, Plan Estatal de Investigación Científica y Técnica y de Innovación 2013–2016 Instituto de Salud Carlos III [ISCIII] PI14/00394) and by the Fondo Europeo de Desarrollo Regional (FEDER) (to IFA). The research of MAGG was supported by European Union FEDER funds and by the “Fondo de Investigación Sanitaria” (grants PI06/0024, PS09/00748, PI12/00060, and PI15/00525) of the Instituto de Salud Carlos III (ISCIII; Spanish Health Ministry). The research of MAGG was also partially supported by RETICS Programs RD12/0009 (RIER) and RD12/0009/0013 from the ISCIII (Spanish Health Ministry).

273 p. El objeto de estudio de esta Tesis Doctoral se centra en conocer si el programa PISA (Programme of International Student Assessment) cumple sus fines: por una parte, que la calidad y riqueza de sus datos constituyan base para la investigación; y, por otra, fomentar el análisis destinado a mejoras en el campo de la educación. Esta investigación abarca los catorce años de vigencia del programa PISA en España. Para ello, la investigación se ha llevado a cabo en dos fases: En primer lugar, se ha analizado el impacto de PISA en las publicaciones académicas internacionales para verificar si el programa constituye base para la investigación. En esta primera fase, se llevó a cabo un análisis bibliométrico de las publicaciones incluidas en las bases de datos de Eric, EBSCOhost y el ISI Web of Knowledge, de 2002 a 2010. La investigación se centró en cuatro cuestiones principales: quiénes publican sobre PISA en las revistas científicas, en qué revistas se ha publicado, cómo ha sido la evolución de estas publicaciones y cuáles han sido los principales temas tratados. En segundo lugar, se ha analizado el impacto en la prensa escrita española para comprobar si PISA contribuye a un debate público en los medios de comunicación para la mejora de las políticas educativas. La metodología utilizada fue el análisis cuantitativo y de contenido de los artículos publicados en cuatro periódicos nacionales: El Mundo, El País, ABC y La Vanguardia, de 2000 a 2014 (n=2634). El estudio se centró en cuatro aspectos: la evolución en la publicación de artículos en prensa, la relación de los artículos con temas educativos, si estos artículos analizan informes de resultados o sólo citan PISA en temas educativos y qué competencias se mencionan. Por una parte, el estudio concluye que PISA ha tenido un impacto considerable en la investigación científica, que se refleja principalmente por autores universitarios de las áreas de la educación y de las ciencias sociales que analizan el desempeño del estudiante. La evolución desde 2007 parece indicar que se publicarán más artículos científicos en los próximos años a través de la iniciativa de los investigadores (en lugar de los consejos editoriales), incluso de otras áreas científicas, lo que aumentará el número de temas de análisis. Por otra parte, este estudio también concluye que la mayor parte de la información publicada en la prensa española sobre PISA es simplista y superficial. La producción de artículos fue aumentando hasta el año 2008 y a partir de ese momento se ha ido observando una disminución. A lo largo de los ciclos PISA, el mayor volumen de artículos siempre se concentra en el año posterior a la publicación de un informe de resultados por parte de la OCDE. Los artículos publicados en la prensa de nuestro país, son mayoritariamente educativos, pero hemos observado un porcentaje elevado de artículos que no tienen vinculación con temas educativos, siendo su principal temática la política general. Además, se ha comprobado que la competencia más mencionada a lo largo del ciclo, no siempre coincide con la tratada prioritariamente en PISA durante ese ciclo

Adrenergic receptors are expressed on the surface of inflammation-mediating cells, but their potential role in the regulation of the inflammatory response is still poorly understood. The objectives of this work were to study the effects of α2-adrenergic agonists on the inflammatory response in vivo and to determine their mechanism of action. In two mouse models of inflammation, zymosan air pouch and thioglycolate-induced peritonitis models, the i.m. treatment with xylazine or UK14304, two α2-adrenergic agonists, reduced neutrophil migration by 60%. The α2-adrenergic antagonist RX821002 abrogated this effect. In flow cytometry experiments, the basal surface expression of L-selectin and CD11b was modified neither in murine nor in human neutrophils upon α2-agonist treatment. Similar experiments in HUVEC showed that UK14304 prevented the activation-dependent upregulation of ICAM-1. In contrast, UK14304 augmented electrical resistance and reduced macromolecular transport through a confluent HUVEC monolayer. In flow chamber experiments, under postcapillary venule-like flow conditions, the pretreatment of HUVECs, but not neutrophils, with α2-agonists decreased transendothelial migration, without affecting neutrophil rolling. Interestingly, α2-agonists prevented the TNF-α–mediated decrease in expression of the adherens junctional molecules, VE-cadherin, β-catenin, and plakoglobin, and reduced the ICAM-1–mediated phosphorylation of VE-cadherin by immunofluorescence and confocal analysis and Western blot analysis, respectively. These findings indicate that α2-adrenoceptors trigger signals that protect the integrity of endothelial adherens junctions during the inflammatory response, thus pointing at the vascular endothelium as a therapeutic target for the management of inflammatory processes in humans.

Non-steroidal anti-inflammatory drugs (NSAIDs) induce the shedding of L-selectin in human neutrophils through a mechanism still not well understood. In this work we studied both the functional effect of NSAIDs on the neutrophils/endothelial cells dynamic interaction, and the potential involvement of reactive oxygen species (ROS) in the NSAIDs-mediated down-regulation of L-selectin. When human neutrophils were incubated with diclofenac, a significant reduction in the number of cells that rolled on activated endothelial cells was observed. Different NSAIDs (flufenamic acid, meclofenamic acid, diclofenac, indomethacin, nimesulide, flurbiprofen, meloxicam, phenylbutazone, piroxicam, ketoprofen and aspirin) caused variable increase in neutrophil intracellular ROS concentration, which was inversely proportional to the change produced in L-selectin surface expression. Pre-incubation of neutrophils with superoxide dismutase, but not with catalase, showed both a significant protective effect on the L-selectin down-regulation induced by several NSAIDs and a diminished effect of diclofenac on neutrophil rolling. Interestingly, diclofenac and flufenamic acid but not piroxicam significantly increased the extracellular superoxide anion production by neutrophils, and inhibition of nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase activity with diphenyleneiodonium prevented the down-regulation of L-selectin by diclofenac. In accordance with these results, neutrophils from patients with chronic granulomatous disease, a hereditary disease in which neutrophils show a reduced capacity to form superoxide radicals, exhibited a lower down-regulation of L-selectin (IC50: 15.3 μg/ml) compared to normal controls (IC50: 5.6 μg/ml) in response to diclofenac. Conclusion A group of NSAIDs is capable of interfering with the ability of neutrophils to interact with endothelial cells by triggering L-selectin-shedding through the NADPH-oxidase-dependent generation of superoxide anion at the plasma membrane.

Diphenylamine-based nonsteroidal antiinflammatory drugs (NSAIDs) are able to cause in vitro the shedding of L-selectin. The aim of this work was to determine the physio-logic relevance of L-selectin shedding in the antiinflammatory effect exerted by NSAIDs in vivo. Chemical compounds structurally related to NSAIDs - including diphenyl-amine, N-phenylanthranilic acid (N-Ph), diphenylacetic acid - as well as the traditional NSAID indomethacin were studied using the zymosan air-pouch mouse model. Animals intramuscularly pretreated with indomethacin or N-Ph, but not with diphenyl-amine or diphenylacetic acid, showed a significant dose-dependent reduction in the number of neutrophils compared with untreated animals (N-Ph, IC50 = 6.7 mg/kg). Except for indomethacin, none of these compounds caused any significant reduction in cyclooxygenase-1 activity in vivo. In flow chamber experiments, N-Ph reduced the capability of human neutrophils to pass across the endothelial barrier by interfering with leukocyte rolling step on HUVEC. N-Ph, but not diphenylacetic acid, induced activation-independent L-selectin shedding in mouse neutrophils. Interestingly, N-Ph exerted an antiinflammatory effect similar to that of the anti-L-selectin blocking antibody Mel-14, although no additive action was observed when both compounds were combined. These data suggest that the L-selectin shedding induced by NSAIDs may be involved in the antiinflammatory action exerted by these compounds in clinical settings.

Servicio de Otorrinolaringologia, Hospital Universitario Nino Jesus, Madrid, Espana Servicio de Anatomia Patologica, Hospital Universitario Nino Jesus, Madrid, Espana Servicio de Otorrinolaringologia, Hospital Universitario Virgen del Rocio, Sevilla, Espana ado de http://www.elsevier.es el 21/06/2016. Copia para uso personal, se prohibe la transmision de este documento por cualquier medio o formato.

Objective.To study the qualitative and quantitative phenotypic changes that occur in molecules involved in antigen presentation and costimulation in synovial B cells from rheumatoid arthritis (RA) and psoriatic arthritis (PsA).Methods.The presence of HLA-DR, CD86, and CD40 in CD20+ cells was studied in RA synovium biopsies using immunohistochemistry and immunofluorescence. Expression was assessed by flow cytometry of the Class II molecules CD40, CD86, CD23, and CD27 on B cells from the synovial fluid (SF), with respect to peripheral blood, from 13 patients with RA and 15 patients with PsA. Expression of interferon-induced protein with tetratricopeptide repeats 4 (IFIT4) in immune-selected CD20+ cells from patients with RA was assessed by quantitative realtime PCR.Results.Infiltrating synovial RA, B cells expressed HLA-DR, CD40, and CD86. Increased expression of CD86, HLA-DR, and HLA-DQ in B cells from SF was found in patients with RA and PsA. HLA-DP was also elevated in rheumatoid SF B cells; conversely, a significantly lower expression was observed in SF from patients with PsA. CD40 expression was increased in SF B cells from PsA, but not in patients with RA. Interestingly, CD20 surface expression level was significantly lower in SF B cells (CD19+, CD138−) from RA, but not in patients with PsA. CD27 upregulation and CD23 downregulation were observed in synovial B cells in both pathologies. Finally, a 4-fold increase in IFIT4 mRNA content was shown in B cells from SF in patients with RA.Conclusion.Synovial B cells from patients with RA and patients with PsA express different antigen-presenting cell phenotypes, suggesting that this cell type plays a dissimilar role in the pathogenesis of each disease.

Objective To explore the potential involvement of the chemokine system in synoviocyte-mediated tissue destruction in rheumatoid arthritis (RA), we studied the expression profile of chemokine receptors and their function in the migration, proliferation, and matrix metalloproteinase (MMP) production of cultured fibroblast-like synoviocytes (FLS) from RA patients. Methods The presence of CC and CXC chemokine receptors on cultured FLS was studied at the messenger RNA (mRNA) level by reverse transcriptase–polymerase chain reaction and at the cell surface expression level by flow cytometry. Variations in cytosolic calcium influx induced by chemokine stimulation were assessed by flow cytometry on Fura Red–preloaded FLS. Two-compartment transwell chambers were used for FLS chemotaxis assays. Cell growth was measured by a fluorescence-based proliferation assay. Gelatinase and collagenase activities were determined by a fibril degradation assay and zymography. Results FLS constitutively expressed the receptors CCR2, CCR5, CXCR3, and CXCR4, both at the cell surface and mRNA levels, but failed to express CCR3 and CCR6. Significant intracytosolic calcium influx was observed on FLS challenged with monocyte chemotactic protein 1 (MCP-1), stromal cell–derived factor 1α (SDF-1α), and interferon-inducible protein 10 (IP-10). Stimulation with MCP-1, SDF-1α, IP-10, and monokine induced by interferon-γ enhanced the migration and proliferation of FLS. These chemokines, in addition to RANTES, increased in a dose- and time-dependent manner the gelatinase and collagenase activities in cell-free supernatants of cultured FLS. Interestingly, the chemokine-mediated up-regulation of MMP activities was significantly abrogated by the presence of anti–interleukin-1β, but not anti–tumor necrosis factor α, blocking antibodies. Conclusion These data suggest that through modulation of the migration, proliferation, and MMP production by FLS, the chemokine system may play a more direct role in the destructive phase of RA than is currently suspected, and thus emphasize the relevance of chemokines and their receptors as potential therapeutic targets in this disease.

The P-selectin glycoprotein ligand-1 (PSGL-1) is involved in the initial contact of leukocytes with activated endothelium, and its adhesive function is regulated through its proteolytic processing. We have found that the metalloprotease ADAM8 is both associated with PSGL-1 through the ezrin-radixin-moesin actin-binding proteins and able to cause the proteolytic cleavage of this adhesion receptor. Accordingly, ADAM8 knockdown increases PSGL-1 expression, and functional assays show that ADAM8 is able to reduce leukocyte rolling on P-selectin and hence on activated endothelial cells. We conclude that ADAM8 modulates the expression and function of PSGL-1. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim., This work was supported by grants from the Spanish Ministry of Health (Fondo de Investigaciones Sanitarias) to A. Urzainqui (FIS-PI080894) and to F. Díaz González (FIS 09/02209), by grants from Ministerio de Ciencia e Innovación to F. S. M. (SAF2008-02635) and to F. M. (SAF2008-02251) and by the Redes RIER, RTICC (RD06/0020/1037) and RECAVA del Instituto de Salud Carlos III and RTICCR.

Legionella infections are not frequent in HIV-infected patients, although clinical manifestations and outcome are particularly severe in this subset. This manuscript analyzes the clinical features and immunological situation of HIV-infected patients with Legionnaires' disease (LD).The clinical files of HIV-infected patients diagnosed with LD from 1983 to December 2003 were reviewed. The incidence of hospital-acquired Legionella pneumonia (HALP) from 1997-2000 in HIV-infected patients was compared with that of non infected patients.Eighteen patients were included. 72.2% were diagnosed by the Legionella urinary antigen assay. The incidence of HALP in HIV-infected and non infected patients was 0.3 and 0.25/1000 admissions/year, respectively (p = 0.42). 83.3% received appropriate antibiotic treatment at the Emergency department. The mean lymphocyte CD4 count was 348.1/microl, 53.8% had an undetectable viral load and 64.7% were on antiretroviral therapy. 72.2% were smokers, 38.8% had cancer and 16.7% were on chemotherapy. 93.8% had cough, 75% dyspnea, 62.5% extrarespiratory symptoms, 76.5% increased AST, 50% increased CK and 56.3% hyponatremia. Moreover, 50% developed bilateral pulmonary infiltrates, 83.3% respiratory failure and 22.2% died.Although LD is not more frequent in HIV-infected than in non infected patients, its clinical severity suggests that it is an opportunistic infection.