Emergence of innovations in networked populations with reputation-driven interactions.

In this work, we analyze how reputation-based interactions influence the emergence of innovations. To do so, we make use of a dynamic model that mimics the discovery process by which, at each time step, a pair of individuals meet and merge their knowledge to eventually result in a novel technology of higher value. The way in which these pairs are brought together is found to be crucial for achieving the highest technological level. Our results show that when the influence of reputation is weak or moderate, it induces an acceleration of the discovery process with respect to the neutral case (purely random coupling). However, an excess of reputation is clearly detrimental, because it leads to an excessive concentration of knowledge in a small set of people, which prevents a diversification of the technologies discovered and, in addition, leads to societies in which a majority of individuals lack technical capabilities.

Neutralization of Centruroides tecomanus scorpion venom by the use of two human recombinant antibody fragments.

The first toxic component identified against mammals in the venom from Centruroides tecomanus scorpion from Colima, Mexico was Ct1a toxin, which was neutralized by human single chain variable fragment (scFv) RAS27. Venom characterization from these scorpions collected on the Pacific coast of Colima, enabled the identification of a second component of medical importance named Ct71 toxin. Amino acid sequence of Ct71 shares a high identity with Chui5 toxin from C. huichol scorpion, which was neutralized by scFv HV. For this reason, the kinetic parameters of interaction between Ct71 toxin and scFv HV were determined by surface plasmon resonance. Results showed a significantly higher affinity for Ct71 as compared to Chui5. As expected, this toxin was neutralized by scFv HV. The injection of a mixture of scFvs HV and RAS27, resulted in the neutralization of C. tecomanus venom, corroborating that human recombinant antibody fragments can efficiently contribute to the neutralization of medically important toxins and their respective venoms from Mexican scorpions.

Synergistic Combination of NAPROC-13 and NMR 13C DFT Calculations: A Powerful Approach for Revising the Structure of Natural Products.

This article describes the structure revision of nine triterpenoids that have been reported corresponding to the same 13C NMR data set. In addition, 13C NMR calculation shows that some chemical shift assignments must be swapped. Our analysis improves the fit between the experimental and calculated data. Correcting misassigned structures and correctly assigning each signal is essential for elucidating new structurally related compounds. Furthermore, the ambiguity of several compounds, the structure of which differs in the literature and the Sci-Finder database, has been eliminated. Misassigned structures were found by chemical shift searches in NAPROC-13, and the results provide two or more different compounds with the same 13C NMR data. The process to determine the correct, most likely structural proposal in agreement with the experimental 13C NMR data was carried out by DFT calculations.

PRDM16 Deletion Is Associated With Sex-dependent Cardiomyopathy and Cardiac Mortality: A Translational, Multi-Institutional Cohort Study.

BACKGROUND: 1p36 deletion syndrome can predispose to pediatric-onset cardiomyopathy. Deletion breakpoints are variable and may delete the transcription factor PRDM16. Early studies suggest that deletion of PRDM16 may underlie cardiomyopathy in patients with 1p36 deletion; however, the prognostic impact of PRDM16 loss is unknown. METHODS: This retrospective cohort included subjects with 1p36 deletion syndrome from 4 hospitals. Prevalence of cardiomyopathy and freedom from death, cardiac transplantation, or ventricular assist device were analyzed. A systematic review cohort was derived for further analysis. A cardiac-specific Prdm16 knockout mouse (Prdm16 conditional knockout) was generated. Echocardiography was performed at 4 and 6 to 7 months. Histology staining and qPCR were performed at 7 months to assess fibrosis. RESULTS: The retrospective cohort included 71 patients. Among individuals with PRDM16 deleted, 34.5% developed cardiomyopathy versus 7.7% of individuals with PRDM16 not deleted (P=0.1). In the combined retrospective and systematic review cohort (n=134), PRDM16 deletion-associated cardiomyopathy risk was recapitulated and significant (29.1% versus 10.8%, P=0.03). PRDM16 deletion was associated with increased risk of death, cardiac transplant, or ventricular assist device (P=0.04). Among those PRDM16 deleted, 34.5% of females developed cardiomyopathy versus 16.7% of their male counterparts (P=0.2). We find sex-specific differences in the incidence and the severity of contractile dysfunction and fibrosis in female Prdm16 conditional knockout mice. Further, female Prdm16 conditional knockout mice demonstrate significantly elevated risk of mortality (P=0.0003). CONCLUSIONS: PRDM16 deletion is associated with a significantly increased risk of cardiomyopathy and cardiac mortality. Prdm16 conditional knockout mice develop cardiomyopathy in a sex-biased way. Patients with PRDM16 deletion should be assessed for cardiac disease.

Neurolupus como manifestación de primer brote psicótico Reporte de caso / Neurolupus as a manifestation of the first psychotic episode: case report

Resumen Antecedentes: El lupus eritematoso sistémico (LES) es una enfermedad auto inmunitaria crónica multisistémica con diversas manifestaciones clínicas. Siendo las mujeres la pobla ción vulnerable y con mayor afectación a nivel neurológico, al presentar mayor riesgo de convulsiones. Las manifestaciones neuropsiquiátricas ocurren en etapas tempranas de la enfermedad y del diagnóstico, ya que pueden presentarse junto con manifestaciones sistémicas o no. La frecuencia de manifestaciones neuropsiquiátricas en el lupus eritematoso sistémico se ha descrito del 14 al 75%, siendo las alteraciones cognitivas uno de los grandes síntomas a destacar1. La cual puede ir acompañada de trastornos afectivos de tipo depresión y ansiedad. Ya que la psicosis secundaria a LES se remarca por su baja prevalencia (10%)2, los estudios de laboratorio nos suelen orientar hacia el diagnóstico definitivo, siendo los anticuerpos ribosomales P los que se han relacionado más específicamente con la psicosis lúpica. La resonancia magnética es la prueba de elección y las lesiones cerebrales están dominadas por hiperintensidades de materia blanca en forma de punción3. En el siguiente reporte de caso, presentamos a una paciente de 20 años, la cual contaba con antecedentes de esteatosis hepática diagnosticado, diabetes tipo MODY y resección de ovario derecho por teratoma maduro de 9 años de evolución, pero sin antecedentes psiquiátricos de importancia para el momento de su valoración. Sin embargo, de forma aguda presentó un brote psicótico caracterizado por ideas delirantes de grandiosidad y referencia, así como alteraciones conductuales, cognitivas y afectivas. Por las que tuvieron que acudir a hospital de 3er nivel durante el periodo de contingencia sanitaria en el 2020. Tras el antecedente de presentar infección por SARS-CoV-2 tres meses antes de su patología neuropsiquiátricas. Se sospechó en síntomas neurológicos secundarios a infección por COVID-19, así como patología psiquiátrica aislada. Por lo que se realizó abordaje de estudio de primer brote psicótico, diagnosticándose lupus eritematoso sistémico con manifestaciones neuropsiquiátricas. El tratamiento se basó en un bolo de metilprednisolona y antipsicóticos, luego modificada por terapia con corticoesteroides orales y antipsicótico de depósito. Conclusión: El lupus eritematoso sistémico con manifestaciones neuropsiquiátricas es una presentación poco frecuente del padecimiento, por la amplia variación en la aparición de este, los pacientes con síntomas psiquiátricos en contexto de hospital general deben de ser tomados en cuenta para abordajes extensos4. De la misma forma, el tener este conocimiento del caso podrá ampliar nuestro conocimiento sobre las complicaciones de esta patología reumatológica. Y una de sus complicaciones más graves como la psicosis lúpica para poder realizar un mejor abordaje del primer brote psicótico en hospitales generales, donde la valoración de un especialista puede ser más complicada para mejorar las condiciones médicas de estos pacientes.

Abstract Background: Systemic lupus erythematosus is a chronic multisystemic autoimmune disease with diverse clinical manifestations. Women are the most vulnerable population and have the greatest neurological involvement with a higher risk of seizures. Neuropsychiatric manifestations occur in early stages of the disease and diagnosis since they can occur together with systemic manifestations or not. The frequency of neuropsychiatric manifestations in systemic lupus erythematosus has been described from 14 to 75%; being cognitive alterations one of the major symptoms to highlight. Which, in the same way can be accompanied by affective disorders such as depression and anxiety. Since psychosis, secondary to SLE, stands out for its low prevalence (10%), laboratory studies usually guide us towards a definitive diagnosis, being ribosomal P antibodies the ones that have been more specifically related to lupus psychosis. MRI is the test of choice and brain lesions are dominated by punctate white matter hyperintensities. In the following case report, we present a 20-year-old patient who had a history of diagnosed hepatic steatosis, MODY type diabetes and resection of the right ovary for mature teratoma of 9 years of evolution; but with no psychiatric history of importance at the time of her evaluation. However, she acutely presented a psychotic outbreak characterized by delusions of grandiosity and reference; as well as behavioral, cognitive, and affective alterations. For which she had to go to a 3rd level hospital during the period of health contingency in 2020. After a history of SARS-CoV-2 infection three months before her neuropsychiatric pathology, neurological symptoms secondary to COVID-19 infection were suspected, as well as isolated psychiatric pathology. Therefore, a study approach of the first psychotic outbreak was performed, diagnosing systemic lupus erythematosus with neuropsychiatric manifestations. Treatment was based on a bolus of methylprednisolone and antipsychotics; later modified by therapy with oral corticosteroids and depot antipsychotic. Conclusion: Systemic lupus erythematosus with neuropsychiatric manifestations is an infrequent presentation of the disease, because of the wide variation in its appearance, patients with psychiatric symptoms in a general hospital setting should be considered for extensive approaches. In the same way, having this knowledge of this case may broaden our knowledge about the complications of this rheumatologic pathology. And one of its most serious complications such as lupus psychosis to be able to make a better approach to the first psychotic outbreak in general hospitals, where the assessment of a specialist can be more complicated.

Detection of Depression-Related Tweets in Mexico Using Crosslingual Schemes and Knowledge Distillation.

Mental health problems are one of the various ills that afflict the world's population. Early diagnosis and medical care are public health problems addressed from various perspectives. Among the mental illnesses that most afflict the population is depression; its early diagnosis is vitally important, as it can trigger more severe illnesses, such as suicidal ideation. Due to the lack of homogeneity in current diagnostic tools, the community has focused on using AI tools for opportune diagnosis. Unfortunately, there is a lack of data that allows the use of IA tools for the Spanish language. Our work has a cross-lingual scheme to address this issue, allowing us to identify Spanish and English texts. The experiments demonstrated the methodology's effectiveness with an F1-score of 0.95. With this methodology, we propose a method to solve a classification problem for depression tweets (or short texts) by reusing English language databases with insufficient data to generate a classification model, such as in the Spanish language. We also validated the information obtained with public data to analyze the behavior of depression in Mexico during the COVID-19 pandemic. Our results show that the use of these methodologies can serve as support, not only in the diagnosis of depression, but also in the construction of different language databases that allow the creation of more efficient diagnostic tools.

Computational Structural Revision of Elaeophorbate and Other Triterpenoids with the Help of NAPROC-13. A New Strategy for Structural Revision of Natural Products.

A considerable number of natural products have been published in recent years with misassigned structure, even though they had been correctly elucidated in the past. The availability of databases containing revised structures can prevent the amplification of errors in structural elucidation. NAPROC-13, a dereplication tool based on the 13C chemical shift, has been used to search for substances that, possessing the same chemical shifts, have been described with different structures. The correct structure of these different structural proposals is verified by computational chemistry. This paper reports the structural revision of nine triterpenoids following this methodology.

Longitudinal effect of disease-modifying therapy on left ventricular diastolic function in children with sickle cell anemia.

Cardiac abnormalities seen in sickle cell anemia (SCA) include diastolic dysfunction, which has been shown to be associated with high morbidity and early mortality. The effect of disease-modifying therapies (DMT) on diastolic dysfunction is poorly understood. We prospectively evaluated the effects of hydroxyurea and monthly erythrocyte transfusions on diastolic function parameters over 2 years. A total of 204 subjects with HbSS or HbSß0-thalassemia (mean age 11 ± 3.7 years), unselected for disease severity, had diastolic function assessed with surveillance echocardiograms twice, 2 years apart. During this 2-year observation period, 112 participants received DMTs (hydroxyurea, n = 72, monthly erythrocyte transfusions, n = 40), 34 initiated hydroxyurea, and 58 did not receive any DMT. The entire cohort showed an increase in left atrial volume index (LAVi) of 3.40 ± 10.86 mL/m2, p = .001 over 2 years. This increase in LAVi was independently associated with anemia, high baseline E/e' or LV dilation. Individuals not exposed to DMT were younger (mean age 8.8 ± 2.9 years), but at baseline their prevalence of abnormal diastolic parameters was similar to that of the DMT-exposed participants who were older (mean age 12 ± 3.8 years). Participants on DMTs saw no improvement in diastolic function over the study period. In fact, participants on hydroxyurea saw a possible worsening in diastolic parameters (14% increase in LAVi and ~5% decrease in septal e') but also a ~9% decrease in fetal hemoglobin (HbF) levels. Further studies are needed to evaluate if exposure to DMT for a longer duration or achieving higher HbF might be beneficial in alleviating diastolic dysfunction.

Biomarker sST2 in Adults with Transposition of the Great Arteries Palliated by Mustard Procedure: A Five-Year Follow-up.

The Mustard procedure was an early cardiac surgery for transposition of the great arteries (TGA). Despite being successful, it has been associated with long-term arrhythmias and heart failure. A key factor complicating management in adults with congenital heart disease (CHD) is the deficiency of biomarkers predicting outcome. Soluble suppression of tumorogenicity-2 (sST2) is secreted by cardiomyocytes in response to mechanical strain and fibrosis. We hypothesized that adults with a Mustard procedure would have higher levels of sST2 than healthy individuals, and this would correlate with clinical outcome. We performed a single-center study in patients managed during childhood with a Mustard procedure versus age-matched controls. Clinical and demographic data were collected and biomarkers (sST2, cTnI, BNP, lipid panel, insulin, and glucose) were obtained. There were 18 patients (12 male) in the Mustard cohort and 18 patients (6 male) in the control group (22-49 years, mean of 35.8 vs. mean 32.6 years, respectively, p = ns). Nine Mustard subjects were NYHA class II, and 9 subjects were class III. The control group was asymptomatic. sST2 in the Mustard group was elevated in 56% vs. 17% in controls (p = 0.035). Of the Mustard subjects with elevated sST2, 60% had elevated cTnI and BNP, and 90% had low HDL. Over five years, the Mustard patients with elevated sST2 values had greater medication use, arrhythmias, hospitalizations, and ablation/pacer implantations than Mustard subjects with normal sST2. Mustard subjects with elevated sST2 had other biomarker abnormalities and clinically worse outcomes. Thus, sST2 may add a predictive value to cardiac-related morbidity and mortality.

Hidatidosis pulmonar: Reporte de casos y preludio endémico de la equinococosis quística humana en Paraguay / Pulmonary hydatidosis: Case report and endemic prelude to human cystic echinococcosis in Paraguay

El Paraguay integra la Iniciativa Sudamericana para el Control y Vigilancia de Equinococosis Quística. Con el fin de optimizar los informes epidemiológicos sobre hidatidosis, presentamostres casos clínicos vistos en centros nacionales y realizamos una revisión de la literatura local sobre el tópico. Desde 1969 hasta la fecha se describen 70casos de equinococosis quística. Se requieren estudios epidemiológicos sistemáticos para evaluar el grado de penetración, la distribución geográfica y las características de transmisión de esta enfermedad en nuestro país.Palabras clave: equinococosis;equinococosispulmonar; equinococosis hepática; equinococcus granulosus; zoonosis.

Paraguay is a member of the South American Initiative for the Control and Surveillance of Cystic Echinococcosis. In order to optimize the epidemiological reports on hydatidosis, we present three clinical cases seen in national centers and we carry out a review of the local literature on the topic. From 1969 to date, 70cases of cystic echinococcosis have been described. Systematic epidemiological studies are required to assess the degree of penetration, geographic distribution, and transmission characteristics of this disease in our country.Key words:echinococcosis;echinococcosispulmonar;echinococcosishepatic;echinococcus granulosus; zoonoses.

Hidatidosis pulmonar: Reporte de casos y preludio endémico de la equinococosis quística humana en Paraguay

El Paraguay integra la Iniciativa Sudamericana para el Control y Vigilancia de Equinococosis Quística. Con el fin de optimizar los informes epidemiológicos sobre hidatidosis, presentamos tres casos clínicos vistos en centros nacionales y realizamos una revisión de la literatura local sobre el tópico. Desde 1969 hasta la fecha se describen 70 casos de equinococosis quística. Se requieren estudios epidemiológicos sistemáticos para evaluar el grado de penetración, la distribución geográfica y las características de transmisión de esta enfermedad en nuestro país.

Paraguay is a member of the South American Initiative for the Control and Surveillance of Cystic Echinococcosis. In order to optimize the epidemiological reports on hydatidosis, we present three clinical cases seen in national centers and we carry out a review of the local literature on the topic. From 1969 to date, 70 cases of cystic echinococcosis have been described. Systematic epidemiological studies are required to assess the degree of penetration, geographic distribution, and transmission characteristics of this disease in our country.

Exploring the Regulation and Function of Rpl3l in the Development of Early-Onset Dilated Cardiomyopathy and Congestive Heart Failure Using Systems Genetics Approach.

BACKGROUND: Cardiomyopathies, diseases affecting the myocardium, are common causes of congestive heart failure (CHF) and sudden cardiac death. Recently, biallelic variants in ribosomal protein L3-like (RPL3L) have been reported to be associated with severe neonatal dilated cardiomyopathy (DCM) and CHF. This study employs a systems genetics approach to gain understanding of the regulatory mechanisms underlying the role of RPL3L in DCM. METHODS: Genetic correlation, expression quantitative trait loci (eQTL) mapping, differential expression analysis and comparative functional analysis were performed using cardiac gene expression data from the patients and murine genetic reference populations (GRPs) of BXD mice (recombinant inbred strains from a cross of C57BL/6J and DBA/2J mice). Additionally, immune infiltration analysis was performed to understand the relationship between DCM, immune cells and RPL3L expression. RESULTS: Systems genetics analysis identified high expression of Rpl3l mRNA, which ranged from 11.31 to 12.16 across murine GRPs of BXD mice, with an ~1.8-fold difference. Pathways such as "diabetic cardiomyopathy", "focal adhesion", "oxidative phosphorylation" and "DCM" were significantly associated with Rpl3l. eQTL mapping suggested Myl4 (Chr 11) and Sdha (Chr 13) as the upstream regulators of Rpl3l. The mRNA expression of Rpl3l, Myl4 and Sdha was significantly correlated with multiple echocardiography traits in BXD mice. Immune infiltration analysis revealed a significant association of RPL3L and SDHA with seven immune cells (CD4, CD8-naive T cell, CD8 T cell, macrophages, cytotoxic T cell, gamma delta T cell and exhausted T cell) that were also differentially infiltrated between heart samples obtained from DCM patients and normal individuals. CONCLUSIONS: RPL3L is highly expressed in the heart tissue of humans and mice. Expression of Rpl3l and its upstream regulators, Myl4 and Sdha, correlate with multiple cardiac function traits in murine GRPs of BXD mice, while RPL3L and SDHA correlate with immune cell infiltration in DCM patient hearts, suggesting important roles for RPL3L in DCM and CHF pathogenesis via immune inflammation, necessitating experimental validations of Myl4 and Sdha in Rpl3l regulation.

Importancia del estigma en epilepsia / Importance of Stigma in Epilepsy

Resumen El estigma es un fenómeno caracterizado por una respuesta negativa hacia una persona poseedora de un atributo diferente dentro del grupo social en el que se desarrolla. Se han descrito dos tipos de estigma: el percibido (sentido o interiorizado) y el promovido (social o promulgado). Dentro de las enfermedades con más carga asociada a estigma se encuentra la epilepsia, una de las enfermedades neurológicas más prevalentes a nivel mundial y de curso crónico. En los últimos años, se ha mostrado mayor interés en el estudio de este fenómeno, ya que afecta de manera directa la calidad de vida de las personas con epilepsia, influyendo en su desarrollo personal, escolar, laboral y pronóstico.

Abstract Stigma is a phenomenon characterized by a negative response to a person possessing a different attribute within the social group it develops. Two types of stigmas have been described: perceived (felt) and promoted (enacted). Among the diseases with the greatest burden associated with stigma is epilepsy, one of the most prevalent neurological diseases worldwide and with a chronic course. In recent years, greater interest has been shown in the study of this phenomenon since it directly affects the quality of life of people with epilepsy, influencing their personal, academic and work development and prognosis.

Clinical approach to antibody-mediated rejection from the pediatric heart transplant society.

OBJECTIVE: This document is designed to outline the definition, pathogenesis, diagnostic modalities and therapeutic measures to treat antibody-mediated rejection in children postheart transplant METHODS: Literature review was conducted by a Pediatric Heart Transplant Society (PHTS) working group to identify existing pediatric and adult studies on antibody-mediated rejection (AMR). In addition, the centers participating in PHTS were asked to submit their approach to diagnosis and management of pediatric AMR. This document synthesizes information gathered from both these sources to highlight a practical approach to diagnosing and managing a child with AMR postheart transplant. This document may not represent the practice at all centers in the PHTS and serves as a starting point to understand an approach to this clinical scenario.

Use and management of disinfectants by dentists in San Luis Potosi, Mexico, during the covid-19 pandemic / Uso y manejo de desinfectantes por odontólogos de San Luis Potosí, México durante la pandemia covid-19

Introduction: Chlorine, ethyl alcohol, and quaternary ammonium are disinfectants with antiviral activity against SARS-Cov2. However, there are no previous reports of their use and handling for cleaning and disinfection in dental offices. Objetive: To determine the use and management of disinfectants in critical and non-critical areas used by dentists in San Luis Potosí, Mexico, during the COVID-19 pandemic. Material and Methods: A validated cross-sectional survey was applied online to 100 dentists in San Luis Potosí between February and June 2021. Participants were informed about the handling of personal data according to the standard DOF regulations (DOF 07-05-2010). Results: A total of 100 dentists were included in the study, 63% female and 37% male, with a mean age of 26 years. The most widely used disinfectants during the pandemic in critical areas were Lysol® and 0.1% sodium hypochlorite in non-critical areas. Eighty-five percent of dentists know the adverse effects of inappropriate use of disinfectants, 72% did not have any sign or symptom associated with the use of disinfectants. The most used protection barrier was gloves (97%). Sixty-seven per cent of dentists disposed of disinfectant waste down the drain. Conclusion: Sodium hypochlorite and quaternary ammonium compounds and/or ethanol are used to clean non-critical and critical areas in dental offices. However, appropriate measures for their management are not adopted. It is necessary to implement educational strategies to improve the use and management of disinfectants in dental practice.

Introducción: Cloro, alcohol etílico y amonio cuaternario son desinfectantes que muestran actividad antiviral contra el SARS-Cov2, sin embargo, no existen reportes previos de su uso y manejo para la limpieza y desinfección en clínicas dentales. Objetivo: Determinar el uso y manejo de los desinfectantes en áreas críticas y no críticas empleados por los odontólogos en San Luis Potosí durante la COVID-19. Material y Métodos: Encuesta transversal validada y aplicada on-line a 100 odontólogos de San Luis Potosí durante febrero-junio 2021. Se informó a los participantes sobre el manejo de datos personales de acuerdo a la norma (DOF 05-07-2010). Resultados: Se incluyeron un total de 100 odontólogos, 63% del sexo femenino y 37% del sexo masculino, con una edad promedio de 26 años. Los desinfectantes más utilizados durante la pandemia en las áreas críticas fueron el Lysol® y el hipoclorito de sodio al 0.1% en áreas no críticas. El 85% de los odontólogos conocen los efectos adversos del uso inadecuado de los desinfectantes, 72% no tuvieron algún signo o síntoma asociado al uso de desinfectantes. La barrera de protección más utilizada fueron los guantes (97%). El 67% de los odontólogos eliminó los desechos de desinfectantes por la coladera. Conclusión: Para la limpieza de las áreas no críticas y críticas en las clínicas dentales se utilizan el hipoclorito de Sodio y compuestos de amonio cuaternario y/o etanol, sin embargo, no se utilizan las medidas adecuadas para su manejo. Es necesario implementar estrategias educativas para mejorar el uso y manejo de desinfectantes en la práctica dental.

Selumetinib for Refractory Pulmonary and Gastrointestinal Bleeding in Noonan Syndrome.

A 15-year-old-boy with Noonan syndrome and status post orthoptic heart transplant developed mixed mitral valve disease and underwent mechanical mitral valve replacement 6 months before presentation with acute respiratory distress. He developed massive pulmonary hemorrhage that required veno-venous extracorporeal membrane oxygenation (ECMO) support. He had a prolonged anticoagulation free ECMO course of 4 weeks, with ongoing recurrent pulmonary hemorrhage and underwent several rounds of coil embolization of aortopulmonary collaterals. ECMO course was complicated by significant nasopharyngeal bleeding that required embolization of the sphenopalatine artery. Shortly after decannulation, he developed massive gastrointestinal and peritoneal hemorrhage that was treated by embolization of the left gastric artery and a branch of the internal iliac artery. His bleeding was attributed to neo-angiogenesis. Initial treatment with propranolol was unsuccessful. Subsequent treatment with interferon α 2b demonstrated efficacy, but severe neutropenia required cessation of therapy. Because functional alterations of the rat sarcoma virus-mitogen activated protein kinase signaling pathway and protein tyrosine phosphatase nonreceptor type (PTPN11) mutations in Noonan syndrome are known to be associated with neo-angiogenesis, we used the mitogen-activated protein kinase inhibitor selumetinib as a gene-targeted therapy with the hope of controlling bleeding and inhibiting neo-angiogenesis. After initiation of selumetinib, bleeding stopped and allowed the patient to be discharged from the hospital on dipyridamole as antiplatelet prophylaxis for his mechanical mitral valve. He had no further bleeding episodes through 1 year after hospital discharge.

Factores predictores de evolución clínica en pacientes hospitalizados con nefritis lúpica

RESUMEN Introducción: la nefritis lúpica es una complicación frecuente en pacientes diagnosticados con lupus eritematoso sistémico, sobre todo a edad temprana. Objetivos: determinar factores predictores que intervienen en la evolución clínica de pacientes internados con nefritis lúpica. Metodología: estudio observacional, retrospectivo, de corte transverso con componente analítico. Se incluyeron a pacientes de ambos sexos, mayores de 18 años, con diagnóstico de nefritis lúpica, que acuden al Hospital Nacional, Itauguá, Paraguay, en el periodo 2018-2021. Fueron excluidas los pacientes con fichas médicas incompletas. La investigación fue aprobada por el Comité de Ética de la Universidad Nacional de Itapúa. Resultados: fueron estudiados 82 pacientes con diagnóstico reciente o conocido de nefritis lúpica, con media de edad 31 ± 11 años (rango 16 - 75 años), 68 pacientes eran de sexo femenino y 46 de ellos eran de escolaridad primaria. La actividad de la enfermedad promedio, medido por SLEDAI-2K fue 16 ± 6 (rango 4 - 32), al momento de la internación 49 clasificaron como actividad severa. Al ingreso, el valor medio de creatinina fue 3,22 ± 3,33 mg/mL, de proteinuria 1820 ± 2177 mg/día, C3 58 ± 35 mg/dL y C4 11 ± 9 mg/dL. La mortalidad se presentó en 18 pacientes (22%). Las causas de óbito más frecuente fueron las infecciones. Los predictores de mortalidad fueron la evolución de la enfermedad mayor a 4 años y la proteinuria en rango nefrótico (p <0,05). Conclusiones: los predictores de mortalidad de los pacientes con nefritis lúpica fueron la proteinuria en rango nefrótico y el tiempo de enfermedad menor de 4 años de evolución.

ABSTRACT Introduction: Lupus nephritis is a frequent complication in patients diagnosed with systemic lupus erythematosus, especially at an early age. Objective: To determine predictive factors that intervene in the clinical evolution of hospitalized patients with lupus nephritis. Methodology: Observational, retrospective, cross-sectional study with an analytical component. Men and women, older than 18 years, with a diagnosis of lupus nephritis, who attended the Hospital Nacional of Itauguá, Paraguay, in the period 2018-2021, were included. Patients with incomplete medical records were excluded. The research was approved by the Ethics Committee of the National University of Itapúa. Results: Eighty-two patients with a recent or known diagnosis of lupus nephritis were studied, with a mean age of 31 ± 11 years (range 16-75 years), 68 patients were female and 46 of them had primary school. The average disease activity, measured by SLEDAI-2K, was 16±6 (range 4 - 32), and at the time of hospitalization 49 classified as severe activity. On admission, the mean creatinine value was 3.22±3.33 mg/mL, proteinuria 1820±2177 mg/day, C3 58±35 mg/dL and C4 11±9 mg/dL. Mortality occurred in 18 patients (22%). The most frequent causes of death were infections. The predictors of mortality were the evolution of the disease greater than 4 years and proteinuria in the nephrotic range (p <0.05). Conclusions: The predictors of mortality in patients with lupus nephritis were proteinuria in the nephrotic range and disease time of less than 4 years of evolution.