Changes in Adhesion and the Expression of Adhesion Molecules in PBMCs after Aneurysmal Subarachnoid Hemorrhage: Relation to Cerebral Vasospasm.

Aneurysmal subarachnoid hemorrhage (aSAH) is a neurovascular disease produced by extravasation of blood to the subarachnoid space after rupture of the cerebral vessels. After bleeding, the immune response is activated. The role of peripheral blood mononuclear cells (PBMCs) in this response is a current subject of research. We have analysed the changes in PBMCs of patients with aSAH and their interaction with the endothelium, focusing on their adhesion and the expression of adhesion molecules. Using an in vitro adhesion assay, we observed that the adhesion of PBMCs of patients with aSAH is increased. Flow cytometry analysis shows that monocytes increased significantly in patients, especially in those who developed vasospasm (VSP). In aSAH patients, the expression of CD162, CD49d, CD62L and CD11a in T lymphocytes and of CD62L in monocytes increased. However, the expression of CD162, CD43, and CD11a decreased in monocytes. Furthermore, monocytes from patients who developed arteriographic VSP had lower expression of CD62L. In conclusion, our results confirm that after aSAH, monocyte count and adhesion of PBMCs increase, especially in patients with VSP, and that the expression of several adhesion molecules is altered. These observations can help predict VSP and to improve the treatment of this pathology.

HDL anti-inflammatory function is impaired and associated with high SAA1 and low APOA4 levels in aneurysmal subarachnoid hemorrhage.

Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating disease with high morbidity and mortality rates. Within 24 hours after aSAH, monocytes are recruited and enter the subarachnoid space, where they mature into macrophages, increasing the inflammatory response and contributing, along with other factors, to delayed neurological dysfunction and poor outcomes. High-density lipoproteins (HDL) are lipid-protein complexes that exert anti-inflammatory effects but under pathological conditions undergo structural alterations that have been associated with loss of functionality. Plasma HDL were isolated from patients with aSAH and analyzed for their anti-inflammatory activity and protein composition. HDL isolated from patients lost the ability to prevent VCAM-1 expression in endothelial cells (HUVEC) and subsequent adhesion of THP-1 monocytes to the endothelium. Proteomic analysis showed that HDL particles from patients had an altered composition compared to those of healthy subjects. We confirmed by western blot that low levels of apolipoprotein A4 (APOA4) and high of serum amyloid A1 (SAA1) in HDL were associated with the lack of anti-inflammatory function observed in aSAH. Our results indicate that the study of HDL in the pathophysiology of aSAH is needed, and functional HDL supplementation could be considered a novel therapeutic approach to the treatment of the inflammatory response after aSAH.

Immunomodulation of Oxidative Stress during Organ Donation Process: Preliminary Results.

The objective was to quantify oxidative stress resulting from ischemia during the donation process, using malondialdehyde (MDA) measurement, and its modulation by the administration of melatonin. We designed a triple-blind clinical trial with donors randomized to melatonin or placebo. We collected donors by donation after brain death (DBD) and controlled donation after circulatory death (DCD), the latter maintained by normothermic regional perfusion (NRP). Melatonin or placebo was administered prior to donation or following limitation of therapeutic effort (LTE). Demographic variables and medical history were collected. We also collected serial measurements of MDA, at 60 and 90 min after melatonin or placebo administration. A total of 53 donors were included (32 from DBD and 21 from DCD). In the DBD group, 17 donors received melatonin, and 15 placebo. Eight DCD donors were randomized to melatonin and 13 to placebo. Medical history and cause for LTE were similar between groups. Although MDA values did not differ in the DBD group, statistical differences were observed in DCD donors during the 0-60 min interval: -4.296 (-6.752; -2.336) in the melatonin group and -1.612 (-2.886; -0.7445) in controls. Given the antioxidant effect of melatonin, its use could reduce the production of oxidative stress in controlled DCD.

Metrics of Sexual Behavior Stigma Among Cisgender Men Who Have Sex With Men in 9 Cities Across the United States.

Men who have sex with men (MSM) in the United States are stigmatized for their same-sex practices, which can lead to risky sexual behavior, potentiating risk for human immunodeficiency virus (HIV) infection. Improved measurement is necessary for accurately reporting and mitigating sexual behavior stigma. We added 13 sexual behavior stigma items to local surveys administered in 2017 at 9 sites in the Centers for Disease Control and Prevention's National HIV Behavioral Surveillance system, which uses venue-based, time-sampling procedures to survey cisgender MSM in US Census Metropolitan Statistical Areas. We performed exploratory factor analytical procedures on site-specific (Baltimore, Maryland; Denver, Colorado; Detroit, Michigan; Houston, Texas; Nassau-Suffolk, New York; Portland, Oregon; Los Angeles, California; San Diego, California; and Virginia Beach-Norfolk, Virginia) and pooled responses to the survey items. A 3-factor solution-"stigma from family" (α = 0.70), "anticipated health-care stigma" (α = 0.75), and "general social stigma" (α = 0.66)-best fitted the pooled data and was the best-fitting solution across sites. Findings demonstrate that MSM across the United States experience sexual behavior stigma similarly. The results reflect the programmatic utility of enhanced stigma measurement, including tracking trends in stigma over time, making regional comparisons of stigma burden, and supporting evaluation of stigma-mitigation interventions among MSM across the United States.

Effectiveness Factors of Organ Donation in Andalusia.

OBJECTIVES: Donation effectiveness is one of the most important factors for the sustainability of the donation transplant process. The aim of this study was to characterize and identify hypothetical factors associated with effective donation (at least one organ transplanted) in the Andalusian population. METHOD: Cross-sectional descriptive observational study of a sample of 4144 potential organ donors registered in the Andalusian Information System of Transplant from January 2006 to December 2018. Donors were categorized according to the result of the donation and analyzed depending their effectiveness. RESULTS: The Andalusian donors were mainly men (60%) and were between 55 and 75 years of age (47.6%). The majority died of brain death (87.45%) caused by a cerebrovascular accident (63.5%). They had cardiovascular risk factors such as hypertension (38.3%), diabetes mellitus (14.8%), dyslipidemia (11.1%), smoking (20.4%), and overweight with a median body mass index of 27.1 kg/m2 (IQR, 24.6-29.4). Effective donor rate was 84.5%. Increasing age, diabetes mellitus, increasing body mass index, and the presence of antibodies against hepatitis C virus were hypothetical predictors of an ineffective donation. CONCLUSIONS: In view of our results, we can say that the Andalusian donor population has a high effectiveness rate, presenting hypothetical factors that could allow one to predict the outcome of an effective donation.

Interobserver and Intertest Agreement in Telemedicine Glaucoma Screening with Optic Disk Photos and Optical Coherence Tomography.

Purpose: To evaluate interobserver and intertest agreement between optical coherence tomography (OCT) and retinography in the detection of glaucoma through a telemedicine program. Methods: A stratified sample of 4113 individuals was randomly selected, and those who accepted underwent examination including visual acuity, intraocular pressure (IOP), non-mydriatic retinography, and imaging using a portable OCT device. Participants' data and images were uploaded and assessed by 16 ophthalmologists on a deferred basis. Two independent evaluations were performed for all participants. Agreement between methods was assessed using the kappa coefficient and the prevalence-adjusted bias-adjusted kappa (PABAK). We analyzed potential factors possibly influencing the level of agreement. Results: The final sample comprised 1006 participants. Of all suspected glaucoma cases (n = 201), 20.4% were identified in retinographs only, 11.9% in OCT images only, 46.3% in both, and 21.4% were diagnosed based on other data. Overall interobserver agreement outcomes were moderate to good with a kappa coefficient of 0.37 and a PABAK index of 0.58. Higher values were obtained by experienced evaluators (kappa = 0.61; PABAK = 0.82). Kappa and PABAK values between OCT and photographs were 0.52 and 0.82 for the first evaluation. Conclusion: In a telemedicine screening setting, interobserver agreement on diagnosis was moderate but improved with greater evaluator expertise.

Normothermic Regional Perfusion and Donation After Circulatory Death (Controlled and Uncontrolled): Metabolic Differences and Kidney Transplantation Evolution.

OBJECTIVE: To analyze metabolic differences during normothermic regional perfusion (NRP) between the dissimilar types of donation after circulatory death, uncontrolled (uDCD) and controlled (cDCD), and the evolution of the transplanted kidneys. METHODS: Observational, prospective, cohort study. We included patients from uDCD and cDCD maintained with NRP in 2017. Six consecutive blood gases were collected with determination of pH and lactic acid. Creatinine levels were monitored at 24 hours, 3 months, and 6 months after transplant and the need for renal replacement therapy was evaluated. Descriptive statistical analysis was performed, presenting the qualitative variables as frequencies and percentages, and quantitative as mean ± SD or median (interquartile range [IQR]). We used χ2 testing for bivariate analysis of qualitative variables. RESULTS: We collected 18 donors. Fifteen out of 18 (83.3%) were men with a median of 51 years (IQR, 46-60). Eleven out of 18 (61.1%) were cDCD and 7 out of 18 (38.9%) were uDCD. The blood gas results are illustrated in Table 1. A total of 28 renal transplants were obtained with a median age of 47 years (IQR, 45-57); 83% were male. Ten out of 28 (35.7%) came from uDCD and 18 out of 28 (64.7%) from cDCD. Table 2 shows the monitoring of the creatinine values of the recipients after the transplantation. CONCLUSIONS: There are more metabolic disorders in our series in uDCD organ donation compared with cDCD. The recovery of the renal function of organs from uDCD is slower than that of cDCD, however; the tendency is toward normality.

APACHE II y SAPS II como predictores de evolución a muerte encefálica en pacientes neurocríticos / APACHE II and SAPS II as predictors of brain death development in neurocritical care patients

Objetivo. Evaluar si las escalas pronósticas APACHE II (Acute Physiology and Chronic Health Evaluation II) y SAPS II (Simplified Acute Physiology Score II) son capaces de predecir la evolución a muerte encefálica en pacientes neurocríticos. Pacientes y métodos. Estudio retrospectivo, observacional, realizado en un hospital de tercer nivel. Se incluyó a 508 pacientes mayores de 16 años, ingresados con patología neurocrítica aguda, con estancia en la unidad de cuidados intensivos de al menos 24 horas. Las variables de interés fueron: datos demográficos, factores de riesgo, APACHE II, SAPS II y resultado pronóstico. Resultados. Mediana de edad: 41 años (rango intercuartílico: 25-57). Varones: 76,2%. Motivo de ingreso más frecuente: traumatismo (55,3%). Medianas: escala de coma de Glasgow (GCS), 10 puntos; APACHE II, 13 puntos; SAPS II, 31 puntos; y estancia en cuidados intensivos, cinco días. La mortalidad en la unidad de cuidados intensivos fue de 145 (28,5%). De ellos, 44 (8,7%) evolucionaron a muerte encefálica. El análisis de regresión logística univariante mostró que la GCS, las escalas APACHE II y SAPS II, y los días de estancia en la unidad de cuidados intensivos se comportaron como variables predictoras de evolución a muerte encefálica. Sin embargo, en el análisis multivariante realizado con APACHE II y SAPS II, se evidenció que sólo APACHE II mantiene significación estadística, a pesar de la buena discriminación de ambas escalas. Conclusión. Los coordinadores de trasplantes podrían usar la escala APACHE II como una herramienta para detectar pacientes con riesgo de evolución a muerte encefálica, minimizando la pérdida de potenciales donantes

Aim. To assess the prognostic value of APACHE II and SAPS II scales to predict brain death evolution of neurocritical care patients. Patients and methods. Retrospective observational study performed in a tertiary hospital. Include 508 patients over 16 years old, hospitalized in ICU for at least 24 hours. The variables of interest were: demographic data, risk factors, APACHE II, SAPS II and outcome. Results. Median age: 41 years old (IR: 25-57). Males: 76.2%. Most frequent reason for admission: trauma (55.3%). Medians: Glasgow Coma Scale (GCS), 10 points; APACHE II, 13 points; SAPS II, 31 points; and ICU stay, 5 days. Mortality in the ICU was 28.5% (n = 145) of whom 44 (8.7%) evolved to brain death. Univariate logistic regression analysis showed that GCS, APACHE II and SAPS II scores, as well as ICU stay days behaved as predictors of brain death evolution. However, the multivariate analysis performed including APACHE II and SAPS II scores showed that only APACHE II maintained statistical significance, despite the good discrimination of both scores. Conclusion. Transplant coordinators might use the APACHE II score as a tool to detect patients at risk of progression to brain death, minimizing the loss of potential donors

Relation of RhoA in Peripheral Blood Mononuclear Cells With Severity of Aneurysmal Subarachnoid Hemorrhage and Vasospasm.

BACKGROUND AND PURPOSE: Rho-kinase, an effector of RhoA, is associated with various cardiovascular diseases in circulating blood cells. However, the role of RhoA/Rho-kinase in peripheral blood mononuclear cells from patients with spontaneous aneurysmal subarachnoid hemorrhage (aSAH) has not yet been studied in relation to the severity of this disease. Therefore, we analyzed the expression and activity of RhoA as a possible biomarker in aSAH. METHODS: Twenty-four patients with aSAH and 15 healthy subjects were examined. Peripheral blood mononuclear cells were collected, and RhoA activity and expression were determined by RhoA activation assay kit (G-LISA) and enzyme-linked immunosorbent assay tests, respectively. The severity of aSAH was determined from the World Federation of Neurological Surgeon scale, and vasospasm was evaluated using clinical symptoms, arteriography, and sonography. RESULTS: RhoA expression was significantly increased in peripheral blood mononuclear cells from patients on days 0, 2, and 4 after aSAH versus healthy subjects (P=0.036, 0.010, and 0.018, respectively, by U Mann-Whitney analysis). There was a significant correlation between RhoA expression and injury severity on days 2 and 4 (Spearman test, day 2: r=0.682, n=14, P=0.007; day 4: r=0.721, n=14, P=0.004). No significant correlation was observed on day 0 (day 0: r=0.131, n=6, P=0.805). Active RhoA was not significantly different in patients and healthy subjects on days 0, 2, and 4 (P=0.243, 0.222, and 0.600, respectively) nor did it increase significantly on days 0 and 2 in patients with vasospasm versus patients without vasospasm (P=0.064 and 0.519, respectively). In contrast, active RhoA was significantly higher on day 4 in patients who developed vasospasm versus patients without vasospasm (P=0.028). CONCLUSIONS: Our preliminary results indicate that RhoA expression and activity in peripheral blood mononuclear cells might be related with aSAH severity and cerebral vasospasm. RhoA is a potential biomarker of the risks associated with aSAH.

Short-term Results From a Training Program to Improve Organ Donation in Uncontrolled Donation After Circulatory Death.

BACKGROUND: In all organ transplantation programs, election of the proper protocol relies primarily on the professionals involved in the detection of potential donors. The objective of our study was to assess the impact of a series of prehospital training sessions, as well as to develop several positive feedback strategies within the uncontrolled organ donation after circulatory death (uDCD) program in our city. METHODS: A before-after intervention study was carried out in 3 steps. First, professionals enrolled in the Emergency Health Services Agency-061 (EPES-061) program underwent specific training to identify potential donors. Second, a specific logotype was designed to alert emergency health care professionals that in cases where cardiopulmonary resuscitation was ineffective and after treatment of all potentially reversible causes, the "chain of survival" should be considered a "chain of opportunities." Third, a positive feedback strategy was put in place, whereby each time a donation was procured, the EPES-061 personnel that had identified the potential donor were notified by phone and in a personal letter. RESULTS: The mean age for donors was 50.5 years of age (interquartile range 37-52.5), and 89.5% of all donations came from male subjects. Positive feedback letters and phone calls, including information on final outcome, were provided to the appropriate personnel in 100% of the cases. Postintervention information showed an increase in both eligible and utilized donors. CONCLUSIONS: Interventions outside the hospital setting that facilitate optimal implementation of the uDCD program are an essential part of this strategy to increase the donor pool and make the wait shorter for transplant patients.

El proceso de donación tras reanimación cardiopulmonar fallida / Organ donation process after unsuccessful cardiopulmonary resuscitation

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Calidad de vida tras el trasplante renal / Quality of life after kidney transplant

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S100B and Neuron-Specific Enolase as mortality predictors in patients with severe traumatic brain injury.

OBJECTIVE: To determine temporal profile and prognostic ability of S100B protein and neuron-specific enolase (NSE) for prediction of short/long-term mortality in patients suffering from severe traumatic brain injury (sTBI). METHODS: Ninety-nine patients with sTBI were included in the study. Blood samples were drawn on admission and on subsequent 24, 48, 72, and 96 h. RESULTS: 15.2% of patients died in NeuroCritical Care Unit, and 19.2% died within 6 months of the accident. S100B concentrations were significantly higher in patients who died compared to survivors. NSE levels were different between groups just at 48 h. In the survival group, S100B levels decreased from 1st to 5th sample (p < 0.001); NSE just from 1st to 3rd (p < 0.001) and then stabilized. Values of S100B and NSE in non-survival patients did not significantly vary over the four days post sTBI. ROC-analysis showed that all S100B samples were useful tools for predicting mortality, the best the 72 h sample (AUC 0.848 for discharge mortality, 0.855 for six-month mortality). NSE ROC-analysis indicated that just the 48-h sample predicted mortality (AUC 0.733 for discharge mortality, 0.720 for six-month mortality). CONCLUSION: S100B protein showed higher prognostic capacity than NSE to predict short/long-term mortality in sTBI patients.

Papel de la corticoterapia en la neuropatía periférica del paciente con enfermedad pulmonar obstructiva crónica / Role of corticosteroids in peripheral neuropathy of chronic obstructive pulmonary disease patients

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Biomarkers of vasospasm development and outcome in aneurysmal subarachnoid hemorrhage.

Aneurysmal subarachnoid hemorrhage (SAH) is a neurologic emergency caused by a brain aneurysm burst, resulting in a bleeding into the subarachnoid space. Its incidence is estimated between 4 and 28/10,000 inhabitants and it is the main cause of sudden death from stroke. The prognosis of patients with SAH is directly related to neurological status on admission, to the magnitude of the initial bleeding, as well as to the development of cerebral vasospasm (CVS). Numerous researchers have studied the role of different biomarkers in CVS development. These biomarkers form part of the metabolic cascade that is triggered as a result of the SAH. Hence, among these metabolites we found biomarkers of oxidative stress, inflammation biomarkers, indicators of brain damage, and markers of vascular pathology. However, to the author knowledge, none of these biomarkers has been demonstrated as a useful tool for predicting neither CVS development nor outcome after SAH. In order to reach success on future researches, firstly it should be stated which pathophysiological process is mainly responsible for CVS development. Once this process has been determined, the temporal course of this pathophysiologic cascade should be characterized, and then, perform further studies on biomarkers already analyzed, as well as on new biomarkers not yet studied in the SAH pathology, focusing attention on the temporal course of the diverse metabolites and the sampling time for its quantification.