HLA genetic polymorphisms and prognosis of patients with COVID-19 / Polimorfismos genéticos de los HLA y pronóstico de pacientes con COVID-19

OBJECTIVE: Different genetic polymorphisms of human leukocyte antigen (HLA) have been associated with the risk and prognosis of autoimmune and infectious diseases. The objectives of this study were to determine whether there is an association between HLA genetic polymorphisms and the susceptibility to and mortality of coronavirus disease 2019 (COVID-19) patients. DESIGN: Observational and prospective study. SETTING: Eight Intensive Care Units (ICU) from 6 hospitals of Canary Islands (Spain). PATIENTS: COVID-19 patients admitted in ICU and healthy subjects. INTERVENTIONS: Determination of HLA genetic polymorphisms. MAIN VARIABLE OF INTEREST: Mortality at 30 days. RESULTS: A total of 3886 healthy controls and 72 COVID-19 patients (10 non-survivors and 62 survivor patients at 30 days) were included. We found a trend to a higher rate of the alleles HLA-A*32 (p = 0.004) in healthy controls than in COVID-19 patients, and of the alleles HLA-B*39 (p = 0.02) and HLA-C*16 (p = 0.02) in COVID-19 patients than in healthy controls; however, all these p-values were not significant after correction for multiple comparisons. Logistic regression analysis showed that the presence of certain alleles was associated with higher mortality, such as the allele HLA-A*11 after controlling for SOFA (OR = 7.693; 95% CI = 1.063-55.650; p = 0.04) or APACHE-II (OR = 11.858; 95% CI = 1.524-92.273; p = 0.02), the allele HLA-C*01 after controlling for SOFA (OR = 11.182; 95% CI = 1.053-118.700; p = 0.04) or APACHE-II (OR = 17.604; 95% CI = 1.629-190.211; p = 0.02), and the allele HLA-DQB1*04 after controlling for SOFA (OR = 9.963; 95% CI = 1.235-80.358; p = 0.03). CONCLUSIONS: The new finding from our preliminary study of small sample size was that HLA genetic polymorphisms could be associated with COVID-19 mortality; however, studies with a larger sample size before definitive conclusions can be drawn

OBJETIVO: Diferentes polimorfismos genéticos de los antígenos leucocitarios humanos (HLA) están asociados con el riesgo y el pronóstico de enfermedades autoinmunes e infecciosas. Los objetivos de estudio fueron determinar si existe una asociación entre polimorfismos genéticos de HLA y la susceptibilidad y mortalidad de pacientes con la enfermedad del coronavirus 2019 (COVID-19). DISEÑO: Estudio observacional y prospectivo. ÁMBITO: Ocho unidades de cuidados intensivos (UCI) de 6 hospitales de las Islas Canarias (España). PACIENTES: Pacientes COVID-19 ingresados en la UCI y sujetos sanos. INTERVENCIONES: Se determinaron los polimorfismos genéticos de los HLA. VARIABLE DE INTERÉS PRINCIPAL: Mortalidad a los 30 días. RESULTADOS: Se incluyeron 3.886 sujetos sanos y 72 pacientes COVID-19 (10 fallecidos y 62 supervivientes a 30 días). Encontramos una tendencia a una mayor frecuencia de los alelos HLA-A*32 (p = 0,004) en sujetos sanos que en pacientes COVID-19, y de los alelos HLA-B*39 (p = 0,02) y HLA-C*16 (p = 0,02) en pacientes COVID-19 que en sujetos sanos; sin embargo, no fueron significativos al corregir por comparaciones múltiples. En la regresión logística encontramos que la presencia de ciertos alelos estuvo asociada con mayor mortalidad, como el alelo HLA-A*11 controlando por SOFA (OR = 7.693; IC del 95% = 1.063-55.650; p = 0,04) o APACHE-II (OR = 11.858; IC del 95% = 1.524-92.273; p = 0,02), el alelo HLA-C*01 controlando por SOFA (OR = 11.182; IC del 95% = 1.053-118.700; p = 0,04) o APACHE-II (OR = 17.604; IC del 95% = 1.629-190.211; p = 0,02) y el alelo HLA-DQB1*04 controlando por SOFA (OR = 9.963; IC del 95% = 1.235-80.358; p = 0,03). CONCLUSIONES: Los nuevos hallazgos de nuestro preliminar estudio de pequeño tamaño muestral fueron que determinados polimorfismos genéticos de los HLA podrían estar asociados con la mortalidad de pacientes COVID-19; sin embargo, son necesarios estudios de mayor tamaño muestral para concluirlo definitivamente

Síndrome de Kleefstra. Importancia del estudio genético / Kleefstra syndrome. Importance of genetic study

El síndrome de Kleefstra se caracteriza por una facies peculiar y la presencia de hipotonía, déficit intelectual y retraso grave en la expresión oral, aunque pueden aparecer otras anomalías: cardiacas, de audición, defectos genitales en varones, epilepsia, infecciones respiratorias severas, sobrepeso y alteraciones del comportamiento. Se trata de una enfermedad genética poco frecuente, ocasionada por mutaciones puntuales en el gen histona-lisina-N-metiltransferasa 1 eucromática (EHMT1) o por una microdeleción cromosómica en 9q34.3 (en el 75% de los casos). Este gen codifica una enzima que modifica la función de la histona, esencial para el desarrollo normal. Presentamos el caso clínico de un niño con hipotonía, retraso psicomotor, ausencia de habla y facies peculiar, cuyo diagnóstico se obtuvo gracias a las nuevas técnicas de genética molecular

The Kleefstra syndrome is characterized by a peculiar facies, intelectual deficit and severe delay in the oral expression. Other anomalies that may occur are cardiac, hearing, genital defects in men, epilepsy, severe respiratory infections, overweight and behavioral abnormalities. It’s a rare genetic disorder caused by mutations in the eucromatic histone-lysine-N-methyltransferase 1 (EHMT1) or a chromosome microdeletion 9q34.3 (in 75% of the cases). This gene encodes an enzyme that modifies the function of histone, essential for normal development. We present the case of a child with hypotonia, psychomotor retardation, absence of speech and peculiar facies, whose diagnosis was obtained due to the new techniques in molecular genetics

Correlación de niveles del factor de crecimiento transformante Beta-1 con severidad de vitreorretinopatía proliferativa en pacientes con desprendimiento de retina regmatógeno / Correlation of transforming growth factor Beta-1 vitreous levels with clinical severity of proliferative vitreoretinopathy in patients with rhegmatogenous retinal detachment

Objetivo: Correlacionar la concentración vítrea del factor de crecimiento transformante Beta-1 (TGFBeta-1), con el grado de severidad clínica de la vitreorretinopatía proliferativa (VRP). Diseño: Se realizó un estudio prospectivo, observacional, transversal de casos y controles. Participantes: Se incluyeron 40 pacientes con diagnóstico de VRP secundaria a desprendimiento de retina regmatógeno. Métodos: Se obtuvo vítreo en pacientes sometidos a vitrectomía pars plana por desprendimiento de retina regmatógeno, que fueron atendidos durante el periodo de agosto del 2015 a junio del 2016, en un centro de referencia nacional para la atención oftalmológica en la Ciudad de México, México. Se cuantificaron los niveles de TGFBeta-1 mediante técnica de ELISA. Se realizó una prueba ANOVA para la comparación de los distintos grupos junto con una prueba de Dunns post hoc. Se consideró una diferencia estadísticamente significativa al obtener p < 0,05. Resultados: Se cuantificaron los niveles de TGFBeta-1 y se encontraron las siguientes medias para cada grupo. En el grupo con VRP grado A, 1150,6 ± 452,08 pg/ml, VRP grado B: 1129,6 ± 365,54 pg/ml y VRP grado C: 1146,4 ± 330,21 pg/ml. El análisis estadístico no encontró diferencias significativas cuando se comparan los diferentes grupos de VRP (p = 0,53). Sin embargo, al realizar el análisis diferencial para cada grado de severidad, se observó un aumento estadísticamente significativo en la expresión de TGFBeta-1 en el grupo de pacientes con VRP-A, en relación con mayor número de días de evolución del desprendimiento (p = 0,03). Diferencias que no fueron estadísticamente significativas para VRP-B y C (p = 0,16) (p = 0,16). Conclusión: El comportamiento del TGFβ-1 no guardó relación directa con la severidad clínica, esto sugiere que debe haber otros factores involucrados en las etapas avanzadas de VRP, mientras que podría ser que el TGFβ-1 tenga mayor relevancia durante las etapas iniciales de la evolución clínica promoviendo la transición epitelial-mesenquimatosa debido a su mayor expresión en las etapas iniciales. De lo cual se puede concluir que cada isoforma desempeña un papel muy particular en el complejo proceso de la VRP

Objective: To correlate the vitreous concentration of transforming growth factor β-1 (TGF Beta-1) with the degree of clinical severity of proliferative vitreoretinopathy (PVR). Design: A prospective, observational, cross-sectional study carried out on cases and controls. Participants: The study included 40 patients with a diagnosis of PVR secondary to rhegmatogenous retinal detachment. Methods: Vitreous was obtained in patients undergoing pars plana vitrectomy by rhegmatogenous retinal detachment, who were treated during the period from August 2015 to June 2016, in a national reference centre for ophthalmological care in Mexico City, Mexico. The levels of TGFBeta-1 were quantified by ELISA technique. An ANOVA test was performed for the comparison of the different groups, together with a post-hoc Dunns test. A statistically significant difference was considered when obtaining P <.05. Results: The levels of TGFBeta-1 were quantified, and the following means were found for each group: In the group with PVR grade A, 1150.6 ± 452.08 pg / ml, PVR grade B: 1129.6 ± 365.54 pg / ml, and PVR grade C: 1146.4 ± 330.21 pg / ml. The statistical analysis did not find significant differences when comparing the different PVR groups. (P=.53). However, when performing the differential analysis for each level of severity, a statistically significant increase in the expression of TGFBeta-1 was observed in the group of patients with PVR-A at a greater number of days of evolution of the detachment. (P=.03). There were no statistically significant differences for PVR-B and PVR-C (P=.16 and P=.16, respectively). Conclusion: Although the levels of TGFBeta-1 are not directly related to the clinical severity grade, suggesting that there must be other factors involved in the advanced stages of PVR, TGFBeta-1 may have greater relevance during the initial stages of the clinical course by promoting the epithelial-mesenchymal transition due to its greater expression in PVR-A. Thus, it can be concluded that each isoform plays a very particular role in the complex process of PVR

Neuropatía craneal múltiple: descripción de tres pacientes pediátricos / Multiple cranial neuropathy: a case report of three paediatric patients

No disponible

Complicaciones neurológicas en trasplantados de órgano sólido / Neurological complications in patients receiving solid organ transplants

Introducción: Las complicaciones neurológicas (CN) suponen una parte importante de la morbimortalidad del postoperatorio del trasplante pediátrico de órgano sólido (TPOS).El objetivo fue exponer la experiencia de nuestro hospital, un centro de referencia de trasplante pediátrico cardiaco, hepático y pulmonar. Pacientes y métodos: Estudio descriptivo retrospectivo de 140 pacientes receptores de TPOS en el periodo 2000-2011. Resultados: Presentaron CN 23 pacientes receptores de TPOS (16,4% de casos), con una mediana de edad de 6 años. Las sintomatologías más frecuentes fueron: crisis epilépticas sintomáticas agudas (12 pacientes) y encefalopatía aguda (11 pacientes), seguidas por debilidad neuromuscular (4 niños), temblor (4 niños), cefalea (2 niños), dolor neuropático (2 niños) y alteraciones visuales (2 niños). Las principales etiologías de las CN fueron: neurotoxicidad de los inmunosupresores (12 casos), hipoxia-isquemia cerebral (6 casos), infecciones (2 casos), compresión mecánica de nervio periférico durante la cirugía (2 casos) y trastorno metabólico (un caso). Cinco pacientes presentaron síndrome de encefalopatía posterior reversible (SEPR). Fallecieron 7 pacientes, 4 por encefalopatía hipóxico-isquémica grave. Los pacientes con SEPR evolucionaron favorablemente. Conclusiones: Las CN que se presentan en el postoperatorio del TPOS tienen una incidencia considerable, siendo las crisis epilépticas y la encefalopatía aguda las manifestaciones más comunes. No encontramos diferencia de CN en los diferentes tipos de trasplante. La neurotoxicidad de los inmunosupresores y la hipoxia-isquemia cerebral son las principales causas de CN, teniendo un manejo y evolución diferentes. El pronóstico en la mayoría de casos es favorable, salvo en los afectados por encefalopatía hipóxico-isquémica moderada o grave(AU)

Introduction: Neurological complications (NC) are a significant cause of morbidity and mortality in paediatric patients receiving solid organ transplants. Our aim was to describe the experience of our hospital with NC in paediatric patients receiving heart, lung and liver transplants. Patients and methods: A retrospective study was conducted on 140 paediatric patients who received a solid organ transplant during the period 2000-2011. Results: A total of 23 paediatric solid organ transplant recipients (16.4% of cases), with a median age of 6 years, had NC. The symptoms were, in order of frequency: acute symptomatic seizures (12 patients); acute encephalopathy (11 patients); neuromuscular weakness (4 children), tremor (4 children), headache (2 children), neuropathic pain (2 children), and visual disturbances (2 children). The aetiologies of NC were: the neurotoxicity of the immunosuppressive drugs (12 patients), post-hypoxic-ischaemic encephalopathy (6 patients), infections (2 cases), mechanical compression of peripheral nerve during surgery (2 cases), and a metabolic complication (1 case). The five patients who met the criteria of posterior reversible encephalopathy syndrome had a favourable outcome. Seven patients died, four of them due to hypoxic-ischaemic encephalopathy. Conclusions: NC are common in paediatric patients receiving heart, liver, lung, and renal transplants, with acute symptomatic seizures and acute encephalopathy being the most common clinical signs. No differences were found in the NC with the different types of transplants. Neurotoxicity of the immunosuppressive drugs and hypoxic-ischaemic encephalopathy were the main causes of NC, having different management and outcomes. The prognosis was favourable in most of the patients, except for those who had moderate or severe post-hypoxic-ischaemic damage(AU)

Symptom-relieving and neuroprotective effects of the phytocannabinoid Δ9-THCV in animal models of Parkinson's disease.

BACKGROUND AND PURPOSE: Previous findings have indicated that a cannabinoid, such as Δ(9)-THCV, which has antioxidant properties and the ability to activate CB(2) receptors but to block CB(1) , might be a promising therapy for alleviating symptoms and delaying neurodegeneration in Parkinson's disease (PD). EXPERIMENTAL APPROACH: The ability of Δ(9)-THCV to reduce motor inhibition and provide neuroprotection was investigated in rats lesioned with 6-hydroxydopamine and in mice lesioned with lipopolysaccharide (LPS). KEY RESULTS: Acute administration of Δ(9)-THCV attenuated the motor inhibition caused by 6-hydroxydopamine, presumably through changes in glutamatergic transmission. Moreover, chronic administration of Δ(9)-THCV attenuated the loss of tyrosine hydroxylase-positive neurones caused by 6-hydroxydopamine in the substantia nigra, through an effect related to its antioxidant properties (it was reproduced by cannabidiol -enriched botanical extract). In addition, CB(2) receptor-deficient mice responded to 6-hydroxydopamine in a similar manner to wild-type animals, and CB(2) receptors were poorly up-regulated in the rat substantia nigra in response to 6-hydroxydopamine. By contrast, the substantia nigra of mice that had been injected with LPS exhibited a greater up-regulation of CB(2) receptors. In these animals, Δ(9)-THCV also caused preservation of tyrosine hydroxylase-positive neurones. This effect probably involved CB(2) receptors as it was also elicited by the selective CB(2) receptor agonist, HU-308, and CB(2) receptor-deficient mice were more vulnerable to LPS lesions. CONCLUSIONS AND IMPLICATIONS Given its antioxidant properties and its ability to activate CB(2) but to block CB(1) receptors, Δ(9)-THCV has a promising pharmacological profile for delaying disease progression in PD and also for ameliorating parkinsonian symptoms.

Síntomas que contribuyen a la percepción de la intensidad sintomatológica depresiva. Un estudio preliminar / Symptoms that contribute to the perception of depressive symptom intensity. A preliminary study

Introducción. Los psiquiatras utilizan pocos síntomas para hacer el diagnóstico de depresión. El objetivo planteado por esta investigación es conocer los síntomas que utilizan los psiquiatras para valorar la gravedad de un enfermo depresivo en comparación a cómo lo hace un instrumento estandarizado como la Escala de Hamilton para la depresión (EHD-17). Metodología. Cien pacientes deprimidos atendidos consecutivamente en régimen ambulatorio que reunían los criterios CIE-10 para episodio depresivo, distimia o trastorno adaptativo tipo depresivo, expresaban su situación clínica sobre una Escala analógico visual (EAV) cuyos valores extremos eran los adjetivos BIEN y MAL. El psiquiatra los evaluaba utilizando una Impresión clínica global (ICG) sobre el estado de ánimo deprimido del paciente, y la Escala de Hamilton para la depresión (EHD-17). Se correlacionan(r Pearson) las puntuaciones totales obtenidas con esos instrumentos y con las puntuaciones parciales de los factores melancólico y ansioso de la EHD-17. Resultados. Los psiquiatras dan más importancia a los síntomas melancólicos que a los ansiosos para establecer la gravedad de un paciente deprimido. Los pacientes deprimidos dan la misma importancia a sus síntomas ansiosos y melancólicos. Y la puntuación total de la EHD-17 está más influida y comparte una mayor proporción de varianza con los síntomas ansiosos que con los melancólicos. Todas las correlaciones calculadas son estadísticamente significativas (p = 0,000).Conclusiones. Los autores plantean la influencia que puede tener ese comportamiento de la EHD-17 sobre resultados aparentemente precoces ofrecidos por algunos ensayos clínicos de fármacos antidepresivos (AU)

Introduction. Psychiatrists use few symptoms when diagnosing depression. This study has aimed to know what symptoms are used by the psychiatrists to evaluate the severity of a depressive person compared to how they are evaluated when using a standardized instrument such as Hamilton’s Rating Scale for Depression (HRSD-17).Methodology. A total of 100 depressed outpatients attended consecutively who met the ICD-10 criteria for depressive episode, dysthymia or adjustment disorders depressive types were studied. The depressed outpatients expressed their clinical situation on a Visual Analogue Scale (VAS) whose extreme values were the adjectives WELL and BAD. The psychiatrist evaluated them using a Clinical Global Impression (CGI) scale on the state of the patient's depressed mood, and Hamilton's Rating Scale for Depression (HRSD-17). The total scores obtained with those instruments and with the partial scores of the melancholic and anxious factors of the HRSD-17 were correlated (Pearson's R). Results. Psychiatrists give more importance to melancholic symptoms than to anxious ones to establish the severity of a depressed outpatient. Depressed outpatients give the same importance to their anxious and melancholic symptoms. In addition, the total score of theHRSD-17 is more influenced and shares a larger variance proportion with anxious symptoms than with melancholic ones. All the correlations calculated are statistically significant (p = 0.000).Conclusions. The authors discuss the influence that the HRSD-17 can have on seemingly precocious results offered by some clinical trials of antidepressants drugs (AU)

Neuroartropatía diabética / No disponible

No disponible

Complicaciones psicóticas del consumo de cocaína / No disponible

Dentro de las complicaciones psicopatológicas del consumo de cocaína los síntomas psicóticos son muy habituales, siendo la paranoia transitoria el más común. También pueden producirse las clásicas alucinaciones de formicación, aunque son poco frecuentes. La cocaína puede precipitar la aparición de psicosis en pacientes vulnerables. En este sentido se ha relacionado el consumo de cocaína con peor evolución, mayor número de recaídas, peor respuesta a los tratamientos convencionales y mayor posibilidad de aparición de efectos adversos e indeseados en los pacientes con trastornos mentales como psicosis esquizofrénica o trastorno bipolar. El tratamiento de los pacientes que presentan este tipo de patología dual, psicosis y consumo de cocaína debe enfocarse desde una perspectiva global con tratamiento psicofarmacológico y psicoterapéutico (AU)

Psychotic symptoms are very usual among the psychopathological complications of cocaine use, being transient paranoia the most common of these symptoms. The typical tactile hallucinations of formication, although rather infrequent, can also occur. Cocaine can trigger the appearance of psychosis in vulnerable patients. In this respect, cocaine use has been linked to impaired evolution, increased number of relapses, poor responsiveness to conventional treatments and increased chances of appearance of side and unwanted effects in patients with mental disorders like schizophrenic psychosis or bipolar disorder. The treatment of patients who show this kind of dual pathology, psychotic and cocaine use, needs to be approached from a global perspective including psychopharmacological and psychotherapeutical treatments (AU)

Involvement of GABA(B) receptors in the motor inhibition produced by agonists of brain cannabinoid receptors.

The present study was designed to investigate the possibility of activation of GABA(B) receptors during the motor inhibition caused by cannabimimetics. Adult male rats were injected with an acute dose of arachidonylethanolamide (AEA), Delta(9)- tetrahydrocannabinol (THC), beclofen or vehicle, after pretreatment with CGP 35348, a specific antagonist for GABA(B) receptors, or vehicle, and the behavioral response produced by these compounds tested in an open field. As expected, the administration of either AEA or THC produced a very pronounced motor inhibition, reflected by decreased ambulation and increased time spent in inactivity. The administration of baclofen also produced a marked motor deficit, with similar changes to those observed with both cannabimimetics. Pretreatment with the GABA(B) antagonist, CGP 35348, prevented the motor inhibition induced by baclofen and also attenuated the motor deficit caused by both cannabimimetics, suggesting a role for this receptor. In summary, a GABAergic influence, acting through GABA(B) receptors, seems to be involved in mediating motor effects of cannabimimetics, since the blockade of these receptors attenuates cannabimimetic-induced signs of motor inhibition.