Estudio observacional retrospectivo de eventos adversos asociados al tratamiento de COVID-19 / Retrospective observational study of adverse events associated with the treatments used for COVID-19

Objetivos: Cuantificar y clasificar los eventos adversos (EA) asociados a los tratamientos empleados para la COVID-19. Describir los medicamentos empleados y su frecuencia de utilización. Material y métodos: Estudio retrospectivo, unicéntrico, que incluye pacientes adultos con infección confirmada por SARS-CoV-2 con fecha de ingreso hospitalario entre el 13/03/2020 y 13/04/2020 y con fecha de alta o exitus anterior a 31/05/2020. El período de estudio fue el ingreso y los 30 días posteriores al alta. Se registraron datos demográficos, clínicos, relativos al tratamiento y a los EA. Se categorizó la probabilidad de causalidad del fármaco mediante el algoritmo de Karch y Lasagna modificado. Resultados: Se incluyeron 183 pacientes de los cuales en el 51% se registró algún evento adverso. Se utilizaron hasta 9 fármacos diferentes. La combinación más utilizada fue hidroxicloroquina más azitromicina (57,5%). Se notificaron 142 EA durante el ingreso, siendo los más prevalentes los trastornos hematológicos (24,6%) y gastrointestinales (15,5%). Un 29,6% son producidos probable o posiblemente por fármacos usados para el tratamiento de la COVID-19. El medicamento que produjo más reacciones adversas fue el lopinavir-ritonavir (25% de pacientes). Se detectaron 7 interacciones farmacológicas que produjeron alargamiento del intervalo QT del electrocardiograma. En el período de estudio, la prevalencia de tromboembolismo es del 13,1%. Conclusiones: Casi un tercio de los eventos adversos registrados durante la primera fase de la pandemia, pudieron ser debidos a los tratamientos empleados. La profilaxis anticoagulante adecuada y evitar las interacciones, son las principales claves para evitar problemas relacionados con medicamentos en los pacientes con COVID-19. (AU)

Objectives: Quantify and classify adverse events (AE) associated with the treatments used for COVID-19. Describe the medication used and its frequency of use. Material and methods: A retrospective, single-center study, including adult patients with confirmed SARS-CoV-2 infection, hospital admission date between March 13th, 2020 and April 13th, 2020 and with a discharge or death date prior to May 31st, 2020. The study period was from the admission date and until 30 days after discharge. Demographic data, clinical data, treatment and adverse events were recorded. The probability of drug causality was categorized using the modified Karch and Lasagna algorithm. Results: 183 patients were included of which 51% had some adverse event. Up to 9 different drugs were used. The most used combination was hydroxychloroquine plus azithromycin (57.5%). 142 AE were reported during admission, being haematological (24.6%) and gastrointestinal (15.5%) disorders the most prevalent. 29.6% are probably or possibly produced by drugs used for the treatment of COVID-19. The drug that caused the most adverse reactions was lopinavir-ritonavir (25% of patients). Seven drug interactions were detected that produced lengthening of the QT interval of the electrocardiogram. In the study period, the prevalence of thromboembolism is 13.1%. Conclusions: Almost a third of the adverse events registered during the first phase of the pandemic could be due to the treatment used. Adequate anticoagulant prophylaxis and avoiding interactions are the main keys to prevent drug-related problems in patients with COVID-19. (AU)

Melatonin in sleep disorders.

Melatonin is the main hormone involved in the control of the sleep-wake cycle. It is easily synthesisable and can be administered orally, which has led to interest in its use as a treatment for insomnia. Moreover, as production of the hormone decreases with age, in inverse correlation with the frequency of poor sleep quality, it has been suggested that melatonin deficit is at least partly responsible for sleep disorders. Treating this age-related deficit would therefore appear to be a natural way of restoring sleep quality, which is lost as patients age. However, despite the undeniable theoretical appeal of this approach to insomnia, little scientific evidence is available that supports any benefit of this substitutive therapy. Furthermore, the most suitable dose ranges and pharmaceutical preparations for melatonin administration are yet to be clearly defined. This review addresses the physiology of melatonin, the different pharmaceutical preparations, and data on its clinical usefulness.

Melatonina en los trastornos de sueño / Melatonin in sleep disorders

La melatonina es la principal hormona implicada en la regulación de la oscilación entre sueño y vigilia. Es fácilmente sintetizable y administrable por vía oral, lo que ha propiciado el interés para usarla en el tratamiento de una de las patologías humanas más prevalentes, el insomnio. Además, el hecho de que su producción se reduzca con la edad, en una relación inversamente proporcional a la frecuencia de mala calidad de sueño, ha reforzado la idea de que su déficit es, al menos en parte, responsable de estos trastornos. En esta línea de pensamiento, remontar el déficit que se va instaurando a medida que transcurre la vida sería un modo natural de restaurar la integridad del sueño, que se va perdiendo con la edad. Sin embargo, a pesar del innegable atractivo teórico de esta aproximación al problema del insomnio, la evidencia científica que sustenta el posible beneficio de esta terapia sustitutiva es escasa. Ni siquiera están bien definidos los rangos de dosis a los que administrarla o la formulación farmacológica más adecuada. En la presente revisión se repasa la fisiología de la melatonina, se revisan las características farmacológicas de su administración exógena y se analizan los datos existentes sobre su utilidad clínica. (AU)

Melatonin is the main hormone involved in the control of the sleep-wake cycle. It is easily synthesisable and can be administered orally, which has led to interest in its use as a treatment for insomnia. Moreover, as production of the hormone decreases with age, in inverse correlation with the frequency of poor sleep quality, it has been suggested that melatonin deficit is at least partly responsible for sleep disorders. Treating this age-related deficit would therefore appear to be a natural way of restoring sleep quality, which is lost as patients age. However, despite the undeniable theoretical appeal of this approach to insomnia, little scientific evidence is available that supports any benefit of this substitutive therapy. Furthermore, the most suitable dose ranges and pharmaceutical preparations for melatonin administration are yet to be clearly defined. This review addresses the physiology of melatonin, the different pharmaceutical preparations, and data on its clinical usefulness. (AU)

Thriving in Oxygen While Preventing ROS Overproduction: No Two Systems Are Created Equal.

From 2.5 to 2.0 billion years ago, atmospheric oxygen concentration [O2] rose thousands of times, leading to the first mass extinction. Reactive Oxygen Species (ROS) produced by the non-catalyzed partial reduction of O2 were highly toxic eliminating many species. Survivors developed different strategies to cope with ROS toxicity. At the same time, using O2 as the final acceptor in respiratory chains increased ATP production manifold. Thus, both O2 and ROS were strong drivers of evolution, as species optimized aerobic metabolism while developing ROS-neutralizing mechanisms. The first line of defense is preventing ROS overproduction and two mechanisms were developed in parallel: 1) Physiological uncoupling systems (PUS), which increase the rate of electron fluxes in respiratory systems. 2) Avoidance of excess [O2]. However, it seems that as avoidance efficiency improved, PUSs became less efficient. PUS includes branched respiratory chains and proton sinks, which may be proton specific, the mitochondrial uncoupling proteins (UCPs) or unspecific, the mitochondrial permeability transition pore (PTP). High [O2] avoidance also involved different strategies: 1) Cell association, as in biofilms or in multi-cellularity allowed gas-permeable organisms (oxyconformers) from bacterial to arthropods to exclude O2. 2) Motility, to migrate from hypoxic niches. 3) Oxyregulator organisms: as early as in fish, and O2-impermeable epithelium excluded all gases and only exact amounts entered through specialized respiratory systems. Here we follow the parallel evolution of PUS and O2-avoidance, PUS became less critical and lost efficiency. In regard, to proton sinks, there is fewer evidence on their evolution, although UCPs have indeed drifted in function while in some species it is not clear whether PTPs exist.

Melatonin in sleep disorders. / Melatonina en los trastornos de sueño.

Melatonin is the main hormone involved in the control of the sleep-wake cycle. It is easily synthesisable and can be administered orally, which has led to interest in its use as a treatment for insomnia. Moreover, as production of the hormone decreases with age, in inverse correlation with the frequency of poor sleep quality, it has been suggested that melatonin deficit is at least partly responsible for sleep disorders. Treating this age-related deficit would therefore appear to be a natural way of restoring sleep quality, which is lost as patients age. However, despite the undeniable theoretical appeal of this approach to insomnia, little scientific evidence is available that supports any benefit of this substitutive therapy. Furthermore, the most suitable dose ranges and pharmaceutical preparations for melatonin administration are yet to be clearly defined. This review addresses the physiology of melatonin, the different pharmaceutical preparations, and data on its clinical usefulness.

[Sustained upgaze in a patient who ingested high doses of bupropion. Report of one case]. / Supraversión de la mirada en intoxicación mortal por bupropión.

Upgaze or sustained elevation of the eyes, is an alteration of ocular motility initially described in hypoxic coma. We report a 65-year-old woman admitted with hypotension and alteration of sensorium due to the ingestion of 9.5 g of Bupropion. She presented two seizures of short duration, without epileptic activity on the EEG. She had a persistent asynchronous myoclonus in extremities, tachycardia and prolonged Q-t. She suffered a cardiac arrest caused by asystole, which recovered quickly in five minutes. At that moment, upgaze appeared, associated with a persistent ocular opening, which persisted for days, but finally disappeared, without remission of coma. A magnetic resonance imaging done at the eighth day, showed hyperintensity of the oval center and corpus callosum which disappeared in a new imaging study done 30 days later, where images of hypoxia in the basal nuclei and cortex appeared. The patient died forty seven days after admission. Up-gaze is an ominous oculomotor alteration linked to an important but incomplete damage in the cerebral cortex, a condition that perverts some sequences of the ocular opening, reversing the Bell phenomenon and producing eyelid retraction.

Supraversión de la mirada en intoxicación mortal por bupropión / Sustained upgaze in a patient who ingested high doses of bupropion: report of one case

Upgaze or sustained elevation of the eyes, is an alteration of ocular motility initially described in hypoxic coma. We report a 65-year-old woman admitted with hypotension and alteration of sensorium due to the ingestion of 9.5 g of Bupropion. She presented two seizures of short duration, without epileptic activity on the EEG. She had a persistent asynchronous myoclonus in extremities, tachycardia and prolonged Q-t. She suffered a cardiac arrest caused by asystole, which recovered quickly in five minutes. At that moment, upgaze appeared, associated with a persistent ocular opening, which persisted for days, but finally disappeared, without remission of coma. A magnetic resonance imaging done at the eighth day, showed hyperintensity of the oval center and corpus callosum which disappeared in a new imaging study done 30 days later, where images of hypoxia in the basal nuclei and cortex appeared. The patient died forty seven days after admission. Up-gaze is an ominous oculomotor alteration linked to an important but incomplete damage in the cerebral cortex, a condition that perverts some sequences of the ocular opening, reversing the Bell phenomenon and producing eyelid retraction.

Sterility and Safety Validation for Transport Packaging of Organs and Tissues.

The bags used in the transport of organs and tissues must be sterile, nontoxic, pyrogen free, and must serve as a barrier throughout their useful life. The goal of this study was to show the sterility, safety, and functionality of the bags subjected to irradiation, through validated procedures and techniques. The selected sterilization method was the use of gamma radiation. The sterilization dose was determined based on validated standards for the sterilization of medical products, ISO 11137-2: 2013 and ISO/TS 13004: 2013, using the Verification Dose Maximum method on samples belonging to 3 manufacturing lots. The ISO 10993-5: 2009 standard was used in the cytotoxicity tests, by means of extracts test and quantitative technique of MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide. The tests to determine the expiration date of the kit were performed by ASTM F1980, accelerated aging, and ASTM D3078 to evaluate hermeticity. The irradiation dose validated to reach the required sterility safety level was 22.5 kGy. The constituent materials and the sterilization method do not generated cellular toxicity, and the product was not modified during the simulated time of 5 years. Sterilization by irradiation is a method that leaves no residue, does not harm the properties of the material because it is conducted in cold, and as the sterilizing agent, the energy absorbed by the product is highly penetrating and can be treated in its final packaging, with no risk of postcontamination. It is for this reason that it is prioritized over other methods of sterilization.

Sleep biosignature of Type 2 diabetes: a case-control study.

AIM: To determine whether or not the sleep disturbances associated with Type 2 diabetes affect the structure of sleep. METHODS: We designed a case-control study in 76 patients with Type 2 diabetes and 76 control subjects without Type 2 diabetes, matched by age, gender, BMI and waist and neck circumferences. A subgroup of 32 patients with Type 2 diabetes was also matched with 64 control subjects without Type 2 diabetes according to apnoea-hypopnoea index score. Examination included an overnight full polysomnography. RESULTS: No differences in the percentage of time spent in either rapid eye movement or non-rapid eye movement sleep were observed between groups; however, patients with Type 2 diabetes had more microarousal events during sleep than control subjects [41.4 (total range 4.0-104.4) vs 20.7 (total range 1.3-94.5) events/h; P < 0.001]. These differences were mainly observed during the non-rapid eye movement sleep [7.4 (total range 0-107.2) vs 0.2 (total range 0-65.2) events/h; P < 0.001]. In addition, sleep variables related to oxygen saturation measures, such as the percentage of time spent with oxygen saturation ≤90%, were significantly greater during the rapid eye movement sleep in patients with Type 2 diabetes [20.3 (total range 0-99.2) vs. 10.5 (total range 0-94.0)%; P = 0.047]. This pattern was maintained in the subgroup of patients matched by apnoea-hypopnaea index. Finally, stepwise regression analyses showed that apnoea-hypopnoea index, the presence of Type 2 diabetes and fasting plasma glucose value were independently associated with the number of microarousals (R2 =0.667). CONCLUSIONS: Type 2 diabetes is associated with an altered sleep structure, with different effects according to rapid eye movement (increase in nocturnal hypoxia) or non-rapid eye movement (increase in sleep fragmentation) sleep.

Sensitization of retinoids and corticoids to epigenetic drugs in MYC-activated lung cancers by antitumor reprogramming.

Components of the SWI/SNF chromatin remodeling complex, including BRG1 (also SMARCA4), are inactivated in cancer. Among other functions, SWI/SNF orchestrates the response to retinoid acid (RA) and glucocorticoids (GC) involving downregulation of MYC. The epigenetic drugs SAHA and azacytidine, as well as RA and GC, are currently being used to treat some malignancies but their therapeutic potential in lung cancer is not well established. Here we aimed to determine the possible therapeutic effects of azacytidine and SAHA (A/S) alone or in combination with GC plus RA (GC/RA) in lung cancers with either BRG1 inactivation or MYC amplification. In vitro, responses to GC/RA treatment were more effective in MYC-amplified cells. These effects were mediated by BRG1 and involved a reprogramming towards prodifferentiation gene expression signatures and downregulation of MYC. In MYC-amplified cells, administration of GC/RA enhanced the cell growth inhibitory effects of A/S which, in turn, accentuated the prodifferentiation features promoted by GC/RA. Finally, these treatments improved overall survival of mice orthotopically implanted with MYC-amplified, but not BRG1-mutant, cells and reduced tumor cell viability and proliferation. We propose that the combination of epigenetic treatments with retinoids and corticoids of MYC-driven lung tumors constitute a strategy for therapeutic intervention in this otherwise incurable disease.

Cryptic Caribbean species of Scorpaena (Actinopterygii: Scorpaeniformes) suggested by cytogenetic and molecular data.

Cytogenetic and molecular analyses enabled identification of two cytotypes among individuals of the spotted scorpion fish Scorpaena plumieri from Margarita Island, Venezuela. Cytotype 1 was characterized by 48 subtelo-acrocentric chromosomes and fundamental number (number of chromosome arms; FN) equalled 48, while cytotype 2 was characterized by two metacentric and 46 subtelo-acrocentric chromosomes and FN was 50. These cytotypes also differed in the location of the ribosomal gene clusters and in the distribution of the constitutive heterochromatin. Moreover, fish from the cytotypes 1 and 2 were found to belong to distinct mitochondrial lineages. The presence of two S. plumieri cytotypes from two lineages separated by high genetic distance suggests that they correspond to sympatric cryptic species.

BRG1/SMARCA4 is essential for neuroblastoma cell viability through modulation of cell death and survival pathways.

Neuroblastoma (NB) is a neoplasm of the sympathetic nervous system, and is the most common solid tumor of infancy. NBs are very heterogeneous, with a clinical course ranging from spontaneous regression to resistance to all current forms of treatment. High-risk patients need intense chemotherapy, and only 30-40% will be cured. Relapsed or metastatic tumors acquire multi-drug resistance, raising the need for alternative treatments. Owing to the diverse mechanisms that are responsible of NB chemoresistance, we aimed to target epigenetic factors that control multiple pathways to bypass therapy resistance. We found that the SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a, member 4 (SMARCA4/BRG1) was consistently upregulated in advanced stages of NB, with high BRG1 levels being indicative of poor outcome. Loss-of-function experiments in vitro and in vivo showed that BRG1 is essential for the proliferation of NB cells. Furthermore, whole-genome transcriptome analysis revealed that BRG1 controls the expression of key elements of oncogenic pathways such as PI3K/AKT and BCL2, which offers a promising new combination therapy for high-risk NB.

Detección de cortisol salival nocturno en una muestra de sujetos de Santiago de Chile, mediante la técnica deelectroquimioluminicencia / Night salivary cortisol measurement in a sample of volunteers from Santiago using an electroquimioluminicence technique

Cortisol is a glucocorticoid hormone with circadian cycle, it shows high levels in the morning and lower in the night. The salivary cortisol is the biologically active fraction and night measurement has been very useful for improving the diagnosis of Cushing’s syndrome, an endocrine disorder characterized by high levels of cortisol and loss of their circadian cycle. A disadvantage of this measurement is the establishment of reference ranges, which depends on the population and technique. Therefore the night salivary cortisol values were determined in a sample of 75 healthy volunteers, aged 18-75 years old. Each volunteer collects two samples in consecutive days and these samples were analyzed by electrochemiluminescence. The average of night salivary cortisol of volunteers was 0.165 +/- 0.059 ug/dL with a range from 0.082 to 0.352 ug/dL and no significant differences were found between two samples of cortisol in day 1 and 2. Our results suggest that the proposed cut-off limit 0.32 ug/dL between patients with and without Cushing Syndrome would be suitable for this technique and in our population.

Dealing with inter-expert variability in retinopathy of prematurity: A machine learning approach.

BACKGROUND AND OBJECTIVE: Understanding the causes of disagreement among experts in clinical decision making has been a challenge for decades. In particular, a high amount of variability exists in diagnosis of retinopathy of prematurity (ROP), which is a disease affecting low birth weight infants and a major cause of childhood blindness. A possible cause of variability, that has been mostly neglected in the literature, is related to discrepancies in the sets of important features considered by different experts. In this paper we propose a methodology which makes use of machine learning techniques to understand the underlying causes of inter-expert variability. METHODS: The experiments are carried out on a dataset consisting of 34 retinal images, each with diagnoses provided by 22 independent experts. Feature selection techniques are applied to discover the most important features considered by a given expert. Those features selected by each expert are then compared to the features selected by other experts by applying similarity measures. Finally, an automated diagnosis system is built in order to check if this approach can be helpful in solving the problem of understanding high inter-rater variability. RESULTS: The experimental results reveal that some features are mostly selected by the feature selection methods regardless the considered expert. Moreover, for pairs of experts with high percentage agreement among them, the feature selection algorithms also select similar features. By using the relevant selected features, the classification performance of the automatic system was improved or maintained. CONCLUSIONS: The proposed methodology provides a handy framework to identify important features for experts and check whether the selected features reflect the pairwise agreements/disagreements. These findings may lead to improved diagnostic accuracy and standardization among clinicians, and pave the way for the application of this methodology to other problems which present inter-expert variability.

Synthesis of a heterogeneous artificial metallolipase with chimeric catalytic activity.

A solid-phase strategy using lipase as a biomolecular scaffold to produce a large amount of Cu(2+)-metalloenzyme is proposed here. The application of this protocol on different 3D cavities of the enzyme allows creating a heterogeneous artificial metallolipase showing chimeric catalytic activity. The artificial catalyst was assessed in Diels-Alder cycloaddition reactions and cascade reactions showing excellent catalytic properties.

IgE sérica e IgA salival, total y específica para Dermatophagoides pteronyssinus y subpoblaciones leucocitarias en niños atópicos y no atópicos con asma y/o rinitis / Total and Dermatophagoides pteronyssinus specific IgE and salivary IgA and leukocyte populations in atopic and nonatopic children with asthma and/or rhinitis

Objetivo. Investigar inmunológicamente niños con problemas respiratorios de asma y/o rinitis (atópicos o no atópicos) en la búsqueda de evidencias que permitan una mejor comprensión del desbalance que padecen estos niños en su sistema inmune. Materiales y métodos. Se estudiaron 47 niños de ambos sexos, con edades comprendidas entre los 6 y 15 años, que concurrieron a la consulta por afecciones respiratorias compatibles con asma y/o rinitis a la División de Alergia e Inmunología del Hospital de Niños de la Santísima Trinidad de la Ciudad de Córdoba. Según la información obtenida en la anamnesis, examen físico y prick tests, fueron divididos en dos grupos: atópicos (n=25) y no atópicos (n=22). Luego que los padres firmaron el consentimiento informado y los niños mayores a 7 años dieron su asentimiento para participar del trabajo de investigación, se tomaron muestras de sangre y saliva, para determinar concentración y actividad específica en inmunoglobulinas (Igs) así como estudiar poblaciones leucocitarias y subpoblaciones linfocitarias. Resultados. Como era previsible, los niveles de IgE sérica total y los porcentajes relativos de eosinófilos sanguíneos se mostraron significativamente elevados en el grupo de los niños atópicos (A) con respecto a los no atópicos (NA). El estudio de IgE sérica específica para Dermatophagoides pteronyssinus solo arrojó resultados positivos en los pacientes A y se observó una correlación significativa entre los niveles de IgE total y específica para dicho alérgeno, y entre los niveles de prick y RAST. Los niveles séricos de IgG e IgA no demostraron diferencias de significación entre ambos grupos. El estudio de la IgA salival (IgAs) total permitió observar en el grupo de los niños NA concentraciones significativamente mayores que las correspondientes al grupo de pacientes A. Sin embargo, al estudiar la IgAs específica para el D. pteronyssinus, se observó lo inverso: los pacientes A tienen casi el doble de IgAs específica para el alérgeno respecto del grupo NA. En el estudio de subpoblaciones de células T (CD3, CD4 y CD8), no se observaron diferencias significativas entre ambos grupos. Las subpoblaciones de linfocitos B CD27-y linfocitos B CD27+ tuvieron valores similares en ambos grupos (aproximadamente 80% y 20%, respectivamente). En ambos grupos, alrededor de un 50% de los linfocitos B CD27+ expresaron IgD y el 50% restante fueron IgD­. Sin embargo, el grupo de niños A tuvo dos veces menos de linfocitos B que expresan alta densidad de la molécula CD27 (CD27+++) con respecto a los niños NA (p=0,044). Conclusión. Entre los parámetros inmunológicos investigados encontramos diferencias significativas entre niños A y NA en las concentraciones totales y específicas para el D. pteronyssinus en los isotipos de IgE e IgAs, y en una subpoblación de linfocitos B CD27+++. Dichos hallazgos son analizados en la discusión del manuscrito. (AU)

Purpose. To perform an immunologically investigation in children with respiratory problems of asthma and/or rhinitis (atopic or non atopic) in order to get a better understanding of the immune system imbalance in these patients. Materials and methods. 47 children of both sexes, aged between 6 and 15 years, who were attended for respiratory diseases at the Division of Allergy and Immunology at Children's Hospital de la Santísima Trinidad from Córdoba city were studied. According to information obtained on clinical history, physical examination and prick tests they were divided into two groups: Atopics (n=25) and non-atopic (n=22). After parents signed informed consent and children over 7 years assent to participate in the research work, samples of blood and saliva were taken to determine immune globulins concentrations and specific activities as well as to study leukocyte populations and lymphocytes subpopulations. Results. As expected, levels of total serum IgE and the relative percentages of blood eosinophils were significantly higher in the group of atopic (A) children with regard to non¬atopic (NA) children. The study of specific serum IgE for Dermatophagoides pteronissynus only showed positive results in the A group, and positive correlations between the levels of total and specific IgE, as well as prick and RAST values. Serum IgG and IgA levels showed no significant differences between both groups. Total salivary IgA concentrations were significantly higher in the group of NA children than in the group of A patients. Surprisingly, when specific salivary IgA for D. pteronyssinus was studied, the opposite was observed: Atopic patients have nearly twice specific salivary IgA for this allergen than the NA children. In the study of T cells subpopulations (CD3, CD4 and CD8), no significant differences between groups were observed. The subpopulations of CD27-B cells and CD27+ B cells were similar in both groups (roughly 80% and 20%, respectively). In both groups, approximately 50% of CD27+ B cells expressed IgD and the remaining 50% were IgD­. However, atopic children had less than half B cells expressing high density of CD27 molecule (CD27+++) with respect to the NA children (p=0.044). Conclusion: Among the immunological parameters investigated, we found significant differences between A and NA children in the concentrations of total and specific IgE and salivary IgA to the allergen, and in a subpopulation of CD27+++ B cells. These findings are debated in the discussion of the manuscript(AU)

¿Son la anemia y la transfusión de glóbulos rojos factores de riesgo para enterocolitis necrotizante en prematuros? / Are anemia and red blood cell transfusion risk factors for necrotizing enterocolitis in premature infants?

Introducción: La enterocolitis necrotizante es una emergencia gastrointestinal en prematuros debido a la necrosis transmural del intestino, cuya etiología sigue siendo desconocida. Metodología: Para identificar la asociación entre enterocolitis necrotizante, anemia y transfusión de glóbulos rojos en prematuros menores de 34 semanas de edad gestacional, se realizó un estudio de casos y controles, donde se compararon 45 prematuros con enterocolitis necrotizante estadio II o mayor según criterios de Bell modificados con 90 controles sin enterocolitis necrotizante. Se creó una regresión logística para evaluar el efecto sobre el riesgo. Resultados: A través de una regresión logística multivariable, controlando Apgar al 5° minuto, sepsis, síndrome de dificultad respiratoria, alimentación completa, SNAP-PE II como factores de confusión, se identificó que la presencia de hematocrito menor de 30% incrementa el riesgo de enterocolitis necrotizante en prematuros menores de 34 semanas (OR: 1,5; 95% IC 1,0-9,5; p = 0,01); además, el riesgo de enterocolitis necrotizante se incrementó en 2,1 veces (95% IC 1,7-6,4; p = 0,04) con transfusión de glóbulos rojos en las 48 horas previas al diagnóstico. El grupo control recibió 1 ± 1 transfusiones y el grupo con enterocolitis necrotizante recibió 3 ± 1 transfusiones de glóbulos rojos antes del diagnóstico (OR: 3,2; 95% IC 2,3-8,6; p < 0,01). Conclusión: La anemia puede incrementar el riesgo de desarrollo de enterocolitis necrotizante en prematuros, este riesgo se incrementa significativamente en las 48 horas posteriores a la transfusión y después de un aumento en la frecuencia de transfusiones de glóbulos rojos

Introduction: Necrotizing enterocolitis is an emergency gastrointestinal disease in neonates due to transmural necrosis of the bowel, whose etiology remains unknown. Methodology: To determine association of anemia and red blood cell transfusions with necrotizing enterocolitis in preterm infants, a study of cases and controls was designed, were compared 45 infants with necrotizing enterocolitis stage II or greater than stage II on the modified Bell’s criteria with 90 controls without necrotizing enterocolitis. A logistic regression model was created to evaluate the effect on the risk of necrotizing enterocolitis. Results: Through multivariate logistic regression corrected for Apgar score at 5° minute, sepsis, respiratory difficulty syndrome, full feeds achieved, SNAP-PE II as confounding factors, was identified the presence of hematocrit less than 30% increased risk of necrotizing enterocolitis in infants less than 34 weeks (OR: 1.5; 95% CI 1.0-9.5, p = 0.01); also, the risk of necrotizing enterocolitis increased 2.1 times (95% CI 1.7-6.4, p = 0.04) with transfusion 48 hours before the necrotizing enterocolitis diagnosis. The control group received 1 ± 1 transfusions, and the necrotizing enterocolitis group received 3 ± 1 red blood cell transfusions before the necrotizing enterocolitis diagnosis (OR: 3.2; 95% CI 2.3-8.6, p < 0.01). Conclusion: Anemia may increase the risk of developing necrotizing enterocolitis in preterm infants. The risk for necrotizing enterocolitis increased significantly with increased transfusion frequency before the necrotizing enterocolitis diagnosis or during the 48 hours after red blood cell transfusion