Diagnostic potential of circulating cell-free DNA in patients needing mechanical ventilation: Promises and challenges

Circulating cell-free DNA (cf-DNA) mainly comes from apoptotic cells and can refl ect the extent of cellular damage. Increased plasma levels of cf-DNA have been found in many acute disorders, including septic and clinically ill patients, and usually correlate well with clinical outcome. Acute respiratory failure, the most frequent organ failure in ICU patients, can be related to various acute diseases that may cause cell death and release of DNA into the bloodstream. In a recent issue of Critical Care, Okkonen and colleagues evaluate levels of cf-DNA in plasma as a prognostic marker in patients needing mechanical ventilation. They report that plasma cf-DNA was higher than normal in patients with mechanical ventilation, and even higher in patients who eventually died compared to survivors. However, its usefulness as a death predictor may be limited in the heterogeneous group of mechanically ventilated patients, probably due to confounding eff ects of comorbidities, among other factors

Melhoria da Atenção ao Hipertenso e Diabético na UBS Pastor João Braz, Cruzeiro do Sul, AC

ARNALICH, Yelena Venegas. Melhoria da atenção à saúde do hipertenso e diabético na UBS Pastor João Braz, Cruzeiro Do Sul, AC.2015. Trabalho de Conclusão de Curso – Curso de Especialização em Saúde de Família – Modalidade a Distância, Universidade Federal de Pelotas, Pelotas, 2015. A Hipertensão Arterial Sistêmica e a Diabetes Mellitus representam um grande desafio à Saúde Pública. Estima-se que um em cada três adultos (maior ou igual há 25 anos) tem hipertensão arterial e um em cada dez adultos tem Diabetes Mellitus, estas doenças são muito freqüentes no mundo e no Brasil, quando não são bem tratadas podem ocasionar complicações e ate a morte do portador. O objetivo geral deste trabalho foi melhorar a qualidade da atenção ao hipertenso e diabético na Unidade de Saúde Pastor João Braz, em Cruzeiro do Sul, Acre. Com base nas recomendações do Ministério da Saúde (Cadernos de Atenção Básica 36 (Hipertensão) e 37 (Diabetes Mellitus), 2013), toda a equipe da unidade foi envolvida em um projeto de intervenção na área específica, com duração de 12 semanas. Neste tempo a equipe focou em objetivos específicos (ampliar cobertura, melhorar a adesão, a qualidade do atendimento, a qualidade dos registros, mapearem hipertensos e diabéticos de risco e promoção de saúde), buscando alcançá-los através de metas e ações pré-estabelecidas, nos eixos de monitoramento e avaliação, organização e gestão do serviço, engajamento público e qualificação profissional. Os resultados foram várias mudanças na rotina do serviço com a criação do Programa de Atenção ao Hipertenso e Diabético da Unidade de Saúde (HIPERDIA). A maioria das metas foi alcançada. Um em cada quatro usuários da área adstrita já foi cadastrado no Programa. Apesar das limitações, a intervenção promoveu uma melhora substancial na qualidade de atendimento ao hipertenso e diabético. A maioria das ações previstas já foi incorporada à rotina da unidade

Efecto precoz del B-bloqueante Esmolol sobre la regresión del remodelado coroonario en ratas espontáneamente hipertensas y estudio observacional de la influencia del tratamiento crónico B-bloqueantes en la aparición de complicaciones perioperatorias en cirugía no cardiaca

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Cirugía. Fecha de lectura: 29-04-2016Esta tesis tiene embargado el acceso al texto completo hasta el 29-10-2017La hipertensión arterial produce remodelado de cavidades cardiacas y pared vascular, que conduce a la aparición de complicaciones cardíacas (insuficiencia cardiaca, infarto de miocardio, arritmias graves) con aumento secundario de la morbimortalidad. Varios fármacos antihipertensivos (ARA-II, IECAS, calcioantagonistas y β-bloqueantes) han mostrado su capacidad para revertir el anterior proceso de remodelado en un periodo de tratamiento de meses-años, mejorando así el pronóstico de estos pacientes. El esmolol es un fármaco bloqueante 1-adrenérgico (cardioselectivo) que posee ciertas ventajas farmacocinéticas respecto a otros hipotensores, junto con un efecto bradicardizante e hipotensor rápido y potente. En un estudio experimental previo, realizado en ratas espontáneamente hipertensas (SHR), nuestro grupo demostró que el esmolol reducía significativamente, en tan solo 48 horas de perfusión intravenosa, la hipertrofia ventricular izquierda, siendo el primer fármaco capaz de producir dicho efecto de manera precoz (15). En base a este hallazgo, diseñamos el presente trabajo experimental con el objetivo de investigar si el anterior tratamiento con esmolol revertía el remodelado de la arteria coronaria en la SHR. Nuestros resultados muestran que el fármaco produce dicho efecto y que lo hace a través de los siguientes mecanismos: 1º) reducción del grosor de la pared y de la capa media arterial; 2º) normalización de la reactividad vascular, favorecida por una mayor biodisponibilidad de óxido nítrico; 3º) reducción del estrés oxidativo con un aumento de actividad de la superóxido dismutasa y catalasa; y 4º) disminución de la concentración de dimetilarginina asimétrica que conduce a una mayor producción de óxido nítrico. Adicionalmente, durante una estancia de 3 meses en el hospital St George´s de Londres, hemos diseñado y realizado un estudio clínico observacional con el objetivo de analizar la eficacia del tratamiento crónico -bloqueante en la profilaxis de las complicaciones de la cirugía no cardíaca. Para ello, hemos evaluado retrospectivamente una cohorte de 80 pacientes sometidos a cirugía mayor no cardíaca, e ingresados en la Unidad de Cuidados Intensivos de este hospital. Tras un periodo de seguimiento de 2-4 semanas desde el postoperatorio inmediato hasta el alta hospitalaria/fallecimiento, los pacientes incluidos en el brazo de tratamiento -bloqueante presentaron un mayor número de factores de riesgo cardiovascular y mayor incidencia de arritmias en el postoperatorio. Sin embargo, no se encontraron diferencias en la incidencia de otros eventos cardiacos, complicaciones no cardiacas, duración de la estancia hospitalaria o tasa de mortalidad entre los pacientes tratados o sin tratar con -bloqueantes. Los resultados de este estudio sugieren que el tratamiento crónico con -bloqueantes no induce la aparición de complicaciones perioperatorias (salvo arritmias postoperatorias) en cirugía no cardíaca. No obstante, se necesitan estudios prospectivos y aleatorizados adicionales, con un tamaño muestral mayor, para dilucidar la eficacia real del tratamiento crónico con -bloqueantes en la profilaxis de complicaciones perioperatorias tras cirugía no cardíaca.Hypertension induces remodeling of the cardiac cavities and vascular wall, leading to the onset of cardiac complications (heart failure, myocardial ischemia, serious arrhythmias) and the resulting increase in morbidity and mortality. Several antihypertensive drugs (ARA-II, ACE inhibitors, calcium channel and β- adrenergic receptor blockers) have shown their ability to reverse the above remodeling process within months or years of treatment, thus improving the patients’ prognosis. Esmolol is a -adenergic blocking agent (cardioselective) that possesses certain pharmacokinetic advantages over other antihypertensive drugs, and also has fast and powerful bradycardic and hypotensive effects. In a previous experimental study in spontaneously hypertensive rats (SHRs), our group had shown that esmolol significantly reduced, after just 48 hours of intravenous infusion, left ventricular hypertrophy, being the first drug known to produce this effect in such a short period of time (15). Based on this finding, we designed the present experimental study with the objective of investigating whether the above esmolol treatment revert coronary artery remodeling in SHR. Our results show that the drug produces the above effect, and that it does so through the following mechanisms: 1st) reducing the thickness of the arterial wall and the middle layer; 2nd) normalization of vascular reactivity by increasing nitric oxide bioavailability; 3rd) reducing oxidative stress by increasing the activity of superoxide dismutase and catalase; and 4) decreasing the concentration of the asymmetric dimethylarginine, which leads to increased nitric oxide production. Additionally, during a 3 month stay at St George's Hospital in London, an observational clinical study was designed and performed with the aim of analyzing the effectiveness of chronic therapy with β- blockers in the prophylaxis of perioperative complications of major noncardiac surgery. This was done by retrospectively evaluating a cohort of 80 patients who underwent major noncardiac surgery and were transferred to the Intensive Care Unit of the hospital. After a follow-up period of 2-4 weeks after surgery until discharge/death, the patients who were included in the beta-blocker arm had a greater number of cardiovascular risk factors and a higher incidence of postoperative arrhythmias. However, no differences in relation to the incidence of other cardiac events, noncardiac complications, length of hospital stay or mortality rate were found between patients treated or untreated with β-blockers. The results of this study suggest that chronic treatment with β-blockers does not induce perioperative complications (except postoperative arrhythmias) after noncardiac surgery. However, additional prospective and randomized studies, with a larger sample size, are needed to elucidate the actual effectiveness of chronic treatment with β-blockers as prophylaxis for perioperative complications after noncardiac surgery

Corneal Intrastromal Implantation Surgery by means of MyoRing Corneal Implant for the Treatment of Keratoconus: A Review

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Predicting critical illness on initial diagnosis of COVID-19 based on easily obtained clinical variables: development and validation of the PRIORITY model

Objectives: We aimed to develop and validate a prediction model, based on clinical history and examination findings on initial diagnosis of coronavirus disease 2019 (COVID-19), to identify patients at risk of critical outcomes. Methods: We used data from the SEMI-COVID-19 Registry, a cohort of consecutive patients hospitalized for COVID-19 from 132 centres in Spain (23rd March to 21st May 2020). For the development cohort, tertiary referral hospitals were selected, while the validation cohort included smaller hospitals. The primary outcome was a composite of in-hospital death, mechanical ventilation, or admission to intensive care unit. Clinical signs and symptoms, demographics, and medical history ascertained at presentation were screened using least absolute shrinkage and selection operator, and logistic regression was used to construct the predictive model. Results: There were 10 433 patients, 7850 in the development cohort (primary outcome 25.1%, 1967/7850) and 2583 in the validation cohort (outcome 27.0%, 698/2583). The PRIORITY model included: age, dependency, cardiovascular disease, chronic kidney disease, dyspnoea, tachypnoea, confusion, systolic blood pressure, and SpO2 ≤93% or oxygen requirement. The model showed high discrimination for critical illness in both the development (C-statistic 0.823; 95% confidence interval (CI) 0.813, 0.834) and validation (C-statistic 0.794; 95%CI 0.775, 0.813) cohorts. A freely available web-based calculator was developed based on this model (https://www.evidencio.com/models/show/2344). Conclusions: The PRIORITY model, based on easily obtained clinical information, had good discrimination and generalizability for identifying COVID-19 patients at risk of critical outcomes.No funding was received for this work

The prognostic value of eosinophil recovery in COVID-19: A multicentre, retrospective cohort study on patients hospitalised in spanish hospitals

Artículo con numerosos autores sólo se mencionan el primero, los de la UAM y el grupo colectivoObjectives: A decrease in blood cell counts, especially lymphocytes and eosinophils, has been described in patients with serious Severe Acute Respiratory Syndrome Coronavirus 2 (SARSCoV- 2), but there is no knowledge of their potential role of the recovery in these patients’ prognosis This article aims to analyse the effect of blood cell depletion and blood cell recovery on mortality due to COVID-19. Design: This work was a retrospective, multicentre cohort study of 9644 hospitalised patients with confirmed COVID-19 from the Spanish Society of Internal Medicine’s SEMI-COVID-19 Registry. Setting: This study examined patients hospitalised in 147 hospitals throughout Spain. Participants: This work analysed 9644 patients (57.12% male) out of a cohort of 12,826 patients 18 years of age hospitalised with COVID-19 in Spain included in the SEMI-COVID-19 Registry as of 29 May 2020. Main outcome measures: The main outcome measure of this work is the effect of blood cell depletion and blood cell recovery on mortality due to COVID-19. Univariate analysis was performed to determine possible predictors of death, and then multivariate analysis was carried out to control for potential confounders. Results: An increase in the eosinophil count on the seventh day of hospitalisation was associated with a better prognosis, including lower mortality rates (5.2% vs. 22.6% in non-recoverers, OR 0.234; 95% CI, 0.154 to 0.354) and lower complication rates, especially regarding the development of acute respiratory distress syndrome (8% vs. 20.1%, p = 0.000) and ICU admission (5.4% vs. 10.8%, p = 0.000). Lymphocyte recovery was found to have no effect on prognosis. Treatment with inhaled or systemic glucocorticoids was not found to be a confounding factor. Conclusion: Eosinophil recovery in patients with COVID-19 who required hospitalisation had an independent prognostic value for all-cause mortality and a milder cours

Priming human adipose-derived mesenchymal stem cells for corneal surface regeneration.

Limbal stem cells (LSC) maintain the transparency of the corneal epithelium. Chemical burns lead the loss of LSC inducing an up-regulation of pro-inflammatory and pro-angiogenic factors, triggering corneal neovascularization and blindness. Adipose tissue-derived mesenchymal stem cells (AT-MSC) have shown promise in animal models to treat LSC deficiency (LSCD), but there are not studies showing their efficacy when primed with different media before transplantation. We cultured AT-MSC with standard medium and media used to culture LSC for clinical application. We demonstrated that different media changed the AT-MSC paracrine secretion showing different paracrine effector functions in an in vivo model of chemical burn and in response to a novel in vitro model of corneal inflammation by alkali induction. Treatment of LSCD with AT-MSC changed the angiogenic and inflammatory cytokine profile of mice corneas. AT-MSC cultured with the medium that improved their cytokine secretion, enhanced the anti-angiogenic and anti-inflammatory profile of the treated corneas. Those corneas also presented better outcome in terms of corneal transparency, neovascularization and histologic reconstruction. Priming human AT-MSC with LSC specific medium can potentiate their ability to improve corneal wound healing, decrease neovascularization and inflammation modulating paracrine effector functions in an in vivo optimized rat model of LSCD

Plasma levels of mitochondrial and nuclear DNA in patients with massive pulmonary embolism in the emergency department: A prospective cohort study

Introduction: Cell-free plasma mitochondrial DNA (mt-DNA) and nuclear DNA (n-DNA) are biomarkers with prognostic utility in conditions associated with a high rate of cell death. This exploratory study aimed to determine the plasma levels of both nucleic acids in patients with massive and submassive pulmonary embolism (PE) and to compare them with other biomarkers, such as heart-type fatty acid-binding protein (H-FABP) and troponin I (Tn-I) Methods: This was a prospective observational study of 37 consecutive patients with massive PE, 37 patients with submassive PE, and 37 healthy subjects. Quantifications of plasma mt-DNA and n-DNA with real-time quantitative polymerase chain reaction (PCR), and plasma H-FABP and Tn-I by commercial assays, were done on blood samples drawn within 4 hours after presentation at the emergency department. Results: Plasma mt-DNA and n-DNA concentrations were much higher in patients with massive PE (median, 2,970 GE/ml; interquartile range (IQR), 1,050 to 5,485; and 3,325 GE/ml, IQR: 1,080 to 5,790, respectively) than in patients with submassive PE (870 GE/ml and 1,245 GE/ml, respectively; P < 0.01) or controls (185 GE/ml and 520 GE/ml, respectively). Eighteen patients with massive PE died of a PE-related cause by day 15 of observation. Plasma mt- DNA and n-DNA values were 2.3-fold and 1.9-fold higher in the subgroup of nonsurviving patients than in survivors. H-FABP and Tn-I values were also higher in patients with massive PE who died (7.3 ng/ml and 0.023 ng/ml, respectively) than in those who survived (6.4 ng/ml, and 0.016 ng/ml, respectively). By receiver operating curve (ROC) analysis, the best cutoff values for predicting 15-day mortality were 3,380 GE/ml for mt-DNA, 6.8 ng/ml for H-FABP, 3,625 GE/ml for n-DNA, and 0.020 ng/ml for Tn-I, based on the calculated areas under the curve (AUCs) of 0.89 (95% confidence interval (CI), 0.78 to 0.99), 0.76 (95% CI, 0.69 to 093), 0.73 (95% CI, 0.58 to 0.91), and 0.59 (95% CI, 0.41 to 0.79), respectively. By stepwise logistic regression, a plasma mt-DNA concentration greater than 3,380 GE/ml (adjusted odds ratio (OR), 8.22; 95% CI, 1.72 to 39.18; P 6.8 ng/ml (OR, 5.36; 95% CI, 1.06 to 27.08; P < 0.01) were the only independent predictors of mortality. Conclusions: mt-DNA and H-FBAP might be promising markers for predicting 15-day mortality in massive PE, with mt-DNA having better prognostic accuracy.This work was supported partially by grants from Plan Nacional I+D+I (SAF 2008-05347 and SAF2011-23575) and from Fundación Mutua Madrileña de Investigación Biomédica (2008 and 2011) to Francisco Arnalich and Carmen Montie