Evaluación del perfil de seguridad del medicamento tocilizumab en pacientes sospechosos o confirmados por COVID-19 / Evaluation of the safety profile of the drug tocilizumab in patients suspected or confirmed by COVID-19

Introducción: La enfermedad de COVID-19, es una enfermedad emergente cuya patogénesis se relaciona con la tormenta de citocina, la interleucina 6 juega un papel importante en la tormenta de citocinas. El medicamento tocilizumab, es un anticuerpo monoclonal humanizado, el cual se une al receptor soluble IL-6. En pacientes con COVID-19 se ha observado que el uso de tocilizumab disminuye la inflamación exacerbada. Ante este nuevo uso del medicamento es relevante establecer el balance beneficio-riesgo en estos pacientes con COVID-19, identificando con ello las reacciones adversas a medicamentos que pueden estar relacionadas al uso de tocilizumab. Materiales y métodos: Estudio de farmacovigilancia descriptivo y transversal en una cohorte retrospectiva en pacientes sospechosos o confirmados por COVID-19 en el Instituto Nacional de Cardiología Ignacio Chávez de la Ciudad de México, México en el periodo 05 de mayo del 2020 al 20 de enero del 2021. Resultados: De los 36 pacientes participantes en este estudio, la edad promedio fue 53 años, de los cuales 30 fueron hombres y 6 fueron mujeres. Las comorbilidades identificadas en este estudio fue la hipertensión arterial sistémica, seguida de la diabetes mellitus tipo II. En la evaluación de los estudios de laboratorio se observó que 2 pacientes desarollaron neutropenia moderada, mientras que en 5 pacientes se identificó trombocitopenia leve y 2 pacientes desarrollaron trombocitopenia moderada. Las infecciones bacterianas identificadas en el estudio con el uso del medicamento fueron: 5 aislamientos de Klebsiella oxytoca, 4 a Escherichia coli y 4 a Pseudomonas aeruginosa... (AU)

Introduction: COVID-19 is a new emerging disease which pathogenesis is mediated by a cytokines storm, interleukin 6 plays an important part of this storm. Tocilizumab is a humanized monoclonal antibody that binds to the IL-6 receptor. In patient with COVID-19, exacerbated inflammation has been observed to decrease when given tocilizumab. Due to the new use of this drug is relevant to stablish the risk-benefit ratio in COVID-19 patients, by identifying the drug adverse reactions that may be related to the use of tocilizumab. Material and methods: Descriptive and cross-sectional pharmacovigilance study in a retrospective cohort in patients suspected or confirmed by COVID-19 in the National Institute of Cardiology in Mexico City, Mexico from May 5, 2020 to January 20, 2021. Outcomes: From 36 patients in this study, the average age was 53 years of which 30 were men and 6 were women. The comorbidities identified in this study were systemic arterial hypertension followed by type II diabetes mellitus. Evaluating the laboratory results we observed 2 patients developed moderate neutropenia, 5 patients presented mild thrombocytopenia and 2 patients moderate thrombocytopenia. The bacterial infections identified in the study with the use of the tocilizumab were: 5 isolates Klebsiella oxytoca, 4 isolates Escherichia coli and 4 Pseudomonas aeruginosa. Conclusion: Knowing the possible drug adverse reactions that occurred in patients with COVID-19 who were administered tocilizumab, allow us to the identify the risks associated with the drug, determining the safety profile and be alert of bacterial infections, neutropenia, and thrombocytopenia, throughout a pharmacotherapeutical follow up, thereby identifying possible associated alterations possibly restated with the use of tocilizumab. (AU)

Corticosteroid safety in COVID-19 patients: a pharmacovigilance study / Seguridad de corticoesteroides en pacientes con COVID-19: un estudio de farmacovigilancia

The use of oral and intravenous corticosteroids as a treatment for SARS-CoV-2 infection has been shown to inhibit the exaggerated inflammatory response, reducing symptoms and days of hospitalization of patients. However, its use is controversial because not enough clinical studies have been made to verify the safety of the drugs. Objective: To assess the safety profile of corticosteroids treatment, at high and low doses, in suspected or confirmed patients with COVID-19, determining the most frequent side effects in patients, and assessing whether the administration of the drugs represents a greater benefit than the risk of presenting these effects. Methods: Ambispective study of active pharmacovigilance at a cohort of confirmed or suspected COVID-19 patients, treated with intravenous and oral corticosteroids. 366 patients were evaluated and divided into 3 groups: use of methylprednisolone (155 mg average) every 24 hours for 3 days, dexamethasone (6 mg) every 24 hours for 10 days, and a control group. Results: The distribution of the cases with hyperglycemia was 33 in high doses and 82 with low doses of corticosteroids and both high and low doses have a similar distribution in cases of infections. When evaluating the harshness and severity of hyperglycemia in the two groups with corticosteroids, it is observed that patients with high doses present more harsh (48%). In case of harshness and severity of infections it is observed that patients with high doses present more harsh (62%) and more severe (79%) cases than those who were administered low doses. (AU)

El uso de corticoides orales e intravenosos como tratamiento para la infección por SARS-CoV-2 ha demostrado inhibir la respuesta inflamatoria exagerada, reduciendo los síntomas y los días de hospitalización de los pacientes. Sin embargo, su uso es controvertido porque no se han realizado suficientes estudios clínicos para verificar la seguridad de los medicamentos. Objetivo: Evaluar el perfil de seguridad del tratamiento con corticoides, a dosis altas y bajas, en pacientes con sospecha o confirmación de COVID-19, determinando los efectos secundarios más frecuentes en los pacientes, y valorando si la administración de los fármacos representa un mayor beneficio que el riesgo de presentar estos efectos. Métodos: Estudio ambispectivo de farmacovigilancia activa en una cohorte de pacientes confirmados o sospechosos de COVID-19, tratados con corticoides intravenosos y orales. Se evaluaron 366 pacientes y se dividieron en 3 grupos: uso de metilprednisolona (155 mg promedio) cada 24 horas por 3 días, dexametasona (6 mg) cada 24 horas por 10 días y un grupo control. Resultados: La distribución de los casos con hiperglucemia fue de 33 casos usando dosis altas y 82 con dosis bajas de corticoides, tanto las dosis altas como las bajas tienen la misma distribución en los casos de infecciones. Al evaluar la severidad y gravedad de la hiperglucemia en los dos grupos con corticoides, se observa que los pacientes con dosis altas presentan mayor gravedad (48%). En caso de severidad y gravedad de las infecciones se observa que los pacientes con dosis altas presentan casos más graves (62%) y más severos (79%) que los que recibieron dosis bajas. (AU)

Evaluación del perfil de seguridad del medicamento lopinavir/ritonavir (Lpv/r) en los pacientes sospechosos o confirmados por COVID-19 / Evaluation of the safety profile of the drug lopinavir/ritonavir (Lpv/r) in suspected or confirmed COVID-19 patients

Introducción: El nuevo SARS-CoV-2, es el agente causal de la enfermedad COVID-19. La Organización Mundial de la Salud (OMS) ha referenciado el uso del lopinavir/ritonavir (Lpv/r), es un inhibidor de la proteasa del virus de inmunodeficiencia humana adquirida (VIH-1). El estudio clínico de Cao et al., identificó que el uso de Lpv/r no se asociaron con un mayor número de eventos adversos en comparación con el tratamiento estándar.Materiales y métodos: Estudio retrospectivo de farmacovigilancia en una cohorte en pacientes sospechosos o confirmados de COVID-19 en un hospital de tercer Nivel de la Ciudad de México en el periodo 01 abril 2020 al 30 julio 2020. Resultados: El tratamiento de Lpv/r incluyó 140 pacientes, de los cuales 91 pacientes completaron el tratamiento, mientras que 50 pacientes no terminaron el esquema. Los principales motivos de la suspensión del esquema del medicamento fueron: alta por mejoría (11 casos), defunciones (10 casos) y por inicio de ruxolitinib (9 casos). Además, se identificaron 8 reacciones adversas al medicamento, de las cuales 5 son reacciones asociadas a los trastornos gastrointestinales (diarreas) y las otras 3 reacciones asociadas a trastornos hepatobiliares (hipertransaminasemia).Conclusión: El perfil de seguridad del medicamento Lpv/r demostró una coherencia con las observaciones de estudios previos en relación en los eventos adversos presentados de tipo gastrointestinales y hepáticos, estos últimos se encuentran relacionados a interacción fármaco-fármaco, por lo que sugerimos un seguimiento farmacoterapéutico para identificar las interacciones y las reacciones adversas durante el uso Lpv/r. (AU)

Abstract: The new SARS-CoV-2 is the causal agent for COVID-19. The World Health Organization (WHO) referenced the use of lopinavir/ritonavir (Lpv/r), which is a protease inhibitor of human inmunodeficiency virus (HIV-1). The Clinical trial by Cao et al. identified that the use of Lpv/r has not been associated with any increase of adverse drug reactions within compared to the standard of care.Materials and methods: Pharmacovigilance retrospective study of patients suspected or confirmed with COVID-19 in a 3rd level hospital in Mexico City from April, 01 2020 to July, 30 2020.Results: Lopinavir/ritonavir treatment was prescribed 140 patients from which 91 patients completed the treatment, while 50 patients did not completed the treatment. The cause suspensions were: patient discharge for improvement (11 cases), deaths (10 cases) and start of ruxolitinib (9 cases). In addition, were identify 8 adverse drug reaction from which 5 were associated to gastrointestinal disorders (diarrhea) and 3 hepatobiliary disorders (hypertransaminasemia).Conclusion: The safety profile of the Lpv/r demonstrated consistency with the observations of previous studies in relation to gastrointestinal and hepatic adverse events, which were related to drug-drug interaction, so we suggest a pharmacotherapeutic monitoring to identify them as well as adverse drug reactions due to Lpv/r. (AU)

Presurgical Identification of the Central Sulcus Using GE EPI Sequences in Combination with 3D Reconstruction is a Useful and Easy Technique for Functional Identification of the Sensorimotor Cortex.

Functional magnetic resonance imaging (fMRI) is a noninvasive neuroimaging technique that enables the visualization of vascular changes originating in the cortex on the execution of a simple motor task. We aimed to assess the usefulness of sensorimotor fMRI using echo-planar imaging (EPI) techniques and assess its clinical usefulness in the identification of the central sulcus. We studied 32 candidates for neurosurgery who had centrally located space-occupying lesions with fMRI using EPI images with blood oxygen level-dependent (BOLD) gradient-echo (GE) sequences acquired on a 1.5T scanner while patients repeatedly opened and closed their hands. Statistical activation images (t images) corresponding to the movements of the right and left hands were compared using cancellation analysis. Three-dimensional reconstruction of the cranium and brain of each patient showed the relative position of the expansive lesion and of non-damaged cortical tissue. Reproducible and selective functional sensorimotor activation was observed in 32 patients. Validation was carried out by intraoperative mapping in 19 patients. Based on intraoperative confirmation data we assumed that functional MR imaging (fMRI) is a valid method for identifying the motor cortex. Nevertheless, a limitation to our study is that not all the patients received invasive cortical stimulation. It is also relevant to indicate that fMRI and intraoperative procedures coincide in the sulcus identified as the sensorimotor cortex. Neurological examination did not reveal postoperative motor/sensitive deterioration in the remaining patients. fMRI using GE EPI sequences in combination with three-dimensional reconstruction is a useful and easy technique for functional identification of the sensorimotor cortex.

Síndromes depresivos asociados a deterioro cognitivo / Depressive syndromes associated to cognitive deterioration

La presencia de síntomas depresivos y cuadros depresivos clínicamente significativos es frecuente entre los pacientes con deterioro cognitivo. Las muestras clínicas indican que entre el 30-50 por ciento de los pacientes con deterioro cognitivo presentan síntomas depresivos. Los síntomas depresivos son una fuente importante de discapacidad funcional adicional a la causada por el deterioro cognitivo. Por otra parte, los pacientes de edad avanzada con episodios depresivos mayores sin demencia presentan habitualmente déficits cognitivos que también empeoran el funcionamiento general. Aunque los síntomas depresivos y el deterioro cognitivo pueden darse de forma independiente o coexistir sin aparente conexión, cada vez existen más datos que sugieren una correlación que pudiera llegar incluso a ser etiológica. El nihilismo terapéutico ha sido la reacción más frecuente ante estos cuadros. Sin embargo, los tratamientos específicos o sintomáticos han demostrado ser eficaces en el tratamiento de los síntomas depresivos de los pacientes con alteraciones cognitivas, mejorando de forma significativa el funcionamiento general de los mismos. (AU)

Trastornos afectivos: análisis de su comorbilidad en los trastornos psiquiátricos más frecuentes / Affective disorders: analysis of their comorbility in the more frequent psychiatric disorders

La comorbilidad se define por la presencia de dos o más enfermedades independientes en un mismo sujeto. En este trabajo se revisa la comorbilidad de los trastornos afectivos con otros trastornos mentales y se centra en los trastornos de ansiedad, esquizofrenia, dependencia de sustancias psicoactivas, trastornos de alimentación, trastornos de personalidad y trastornos obsesivo-compulsivos. Para ello hemos realizado una extensa revisión teniendo en cuenta numerosos estudios, así como diferentes orientaciones diagnósticas (categorial o dimensional). En general, la presencia de síntomas y/o trastornos afectivos en el contexto de otras patologías mentales es alta. Además la comorbilidad tiene una alta transcendencia en cuanto al pronóstico clínico (peor respuesta a los tratamientos, mayor persistencia sintomática, mayor tendencia a la cronicidad y mayor riesgo de mortalidad) y las consecuencias sociales (disminución del rendimiento laboral y mayor uso de recursos). No obstante, tenemos que tener en cuenta que el análisis de la comorbilidad de los trastornos afectivos en otros trastornos mentales es complejo y controvertido, no sólo por su alta frecuencia sino por la existencia de un solapamiento sintomático, la escasez de signos y síntomas patognomónicos, la variabilidad de los criterios diagnósticos, las diferencias metodológicas aplicadas así como la escasez de estudios longitudinales y prospectivos. (AU)

[Depressive syndromes associated to cognitive deterioration]. / Síndromes depresivos asociados a deterioro cognitivo.

The presence of depressive symptoms and clinically significant depressive pictures is frequent amongst patients with cognitive deterioration. Clinical samples indicate that between 30-50% of patients with cognitive deterioration show depressive symptoms. Depressive symptoms are an important source of functional disability additional to that caused by cognitive deterioration. On the other hand, elderly patients with serious depressive episodes without dementia normally show cognitive deficits that also worsen general functioning. Although depressive symptoms and cognitive deterioration can arise independently, or co-exist without apparent connection, there is an increasing body of data suggesting a correlation that might even be etiological. Therapeutic nihilism has been the most frequent reaction to these pictures. Nonetheless, specific or symptomatic treatments have shown themselves to be efficient in treating the depressive symptoms of patients with cognitive alterations, significantly improving their general functioning.

[Affective disorders: analysis of their comorbidity in the more frequent psychiatric disorders]. / Trastornos afectivos: análisis de su comorbilidad en los trastornos psiquiátricos más frecuentes.

Comorbidity is defined as the presence of two or more independent diseases in the same subject. This paper reviews the comorbidity of affective disorders with other mental disorders. We focus on the disorders of anxiety, schizophrenia, dependence on psychoactive substances, eating disorders, personality disorders and obsessive-compulsive disorder. To this end, we have carried out an extensive review that has taken account of numerous studies, as well as of different diagnostic orientations (categorical or dimensional). In general the presence of affective symptoms and/or disorders in the context of other mental pathologies is high. Moreover, comorbidity has a high transcendence with respect to clinical prognosis (worse response to treatments, greater symptomatic persistence, greater tendency to chronicity and greater risk of mortality) and the social consequences (decline in work performance and greater use of resources). Nonetheless, we must bear in mind that the analysis of the comorbidity of affective disorders in other mental disorders is complex and controversial, not only because of its high frequency, but also because of the existence of symptomatic overlap, scarcity of signs and pathognomonic symptoms, variability of diagnostic criteria, applied methodological differences, as well as a scarcity of longitudinal and prospective studies.

Classification issues in catatonia.

Kahlbaum described catatonia as a disorder in which mood syndromes were the primary features and the characteristic symptoms were the motor signs. In the present study, we examined the relationship between motor features and other syndromes of psychosis, the clinical validity of Kahlbaum's concept of catatonia, its relationship to schizophrenia and mood disorder, and its nosological position in relation to DSM-III-R, DSM-IV and Leonhard's classification of endogenous psychoses. Patients with Kahlbaum's catatonia differed from patients with schizophrenia or mood disorder in various demographic and clinical variables. Positive and negative motor syndromes, although interrelated, showed a different correlational pattern with other psychotic syndromes. Catatonia did not appear to fit into any particular nosological category, although this issue largely depends on whether schizophrenia and mood disorders are broadly or restrictively defined. When definitions are more restrictive as in Leonhard's system, catatonia seems to be better accommodated as a "third psychosis", i.e. described by the concept of cycloid psychosis.

Percutaneous transgastric cystoduodenostomy in the treatment of a pancreatic pseudocyst: a new approach.

A case of an infected pseudocyst in the head of the pancreas is presented. Due to its small size and fistulization to the duodenum, a drainage catheter was placed through the fistulous tract from a distant transgastric approach. The fistula was balloon dilated to improve its emptying. Sixteen months later the patient remains asymptomatic with no recurrence of the pseudocyst.

Renal biopsy with forceps through the femoral vein.

PURPOSE: To evaluate the usefulness of a new technique of transvascular renal biopsy with a flexible forceps in high-risk patients and compare its results with those reported for other techniques of renal biopsy. PATIENTS AND METHODS: Sixteen transfemoral renal biopsies were performed in 13 high-risk patients. Indications included severe bleeding disorders, combined renal-hepatic biopsy, morbid obesity, solitary kidney, and poor clinical condition. The technique was performed through the femoral vein; a 7-F Mullins introducer sheath was placed in a subcortical renal vein, and the biopsy was performed with a flexible biopsy forceps. RESULTS: Renal tissue was obtained in 15 of 16 procedures (93.7%) with at least one glomerulus in 14 of 16 (87.5%), and at least six glomeruli in 11 of 16 procedures (69%). Samples adequate for diagnosis were obtained in 13 of 16 procedures (81%). Mean number of glomeruli per procedure was 12.6 (range, 0-39). Aside from transient hematuria in two patients, no other complications were known to have occurred. CONCLUSIONS: Transfemoral renal biopsy is a safe technique for acquisition of renal samples in high-risk patients. The procedure can be performed at the same time as other vascular techniques. The histopathologic results, although worse than those obtained with the percutaneous approach, are better than those reported with other transvascular techniques.

Percutaneous vascular and nonvascular puncture under US guidance: role of color Doppler imaging.

Although ultrasound guidance is extensively used in percutaneous interventional procedures, the limitations of B-mode, gray-scale sonographic guidance can restrict clinical use. Little attention has been paid to the use of color Doppler sonography during such procedures. There are several ways in which color Doppler sonography can facilitate percutaneous procedures that involve insertion of a needle or catheter. The advantages of color Doppler sonography include the following: (a) better visualization of the shaft and tip of the needle, especially in solid, echogenic lesions, when the needle is moving, or when the beam-needle angle is narrow; (b) improved targeting of either vessels or non-vascular structures (ie, biliary ducts) to be punctured; (c) avoidance of interposed vascular structures and highly vascular areas during puncture of lesions; (d) improved visualization of poorly echogenic catheters, allowing proper placement; and (e) prompt detection of complications, including active bleeding, after withdrawal of the needle.