Intoxicación por cianuro posterior a infusión prolongada de Nitroprusiato de sodio: a propósito de un caso / Cyanide poisoning following prolonged infusion of Sodium Nitroprusside: A case report / Intoxicação por cianeto após infusão prolongada de nitroprussiato de sódio: a propósito de um caso

El nitroprusiato de sodio fue aprobado desde 1974 como medicamento para las crisis hipertensivas. Desde entonces existe controversia sobre el potencial tóxico del mismo. La toxicidad por cianuro es una complicación poco común del nitroprusiato de sodio, que puede ser difícil de diagnosticar en pacientes críticamente enfermos. Dentro de los factores de riesgo está la utilización de infusiones prolongadas y dosis altas, por lo que se sugiere que la dosis no exceda 2 µg/kg/min. A continuación, se reporta el caso de un paciente de 49 años que ingresa a un servicio de urgencias después de un síndrome cerebrovascular y una emergencia hipertensiva que requirió infusión de nitroprusiato de sodio, seguida de signos y síntomas, los cuales sugirieron toxicidad. Entre dichos síntomas predominaban los cambios neurológicos, por lo cual fue manejado con hiposulfito de sodio y hubo una buena respuesta. El objetivo de este reporte de caso es sensibilizar al personal de salud sobre la necesidad de un uso adecuado del nitroprusiato y sobre la importancia de sospechar toxicidad en paciente con factores de riesgo.

Sodium Nitroprusside has been approved since 1974 as a medication for hypertensive crises. However, there has been ongoing controversy regarding its potential toxicity. Cyanide toxicity is a rare complication of Sodium Nitroprusside, which can be challenging to diagnose in critically ill patients. Risk factors include prolonged infusions and high doses; hence it is suggested that the dose should not exceed 2 µg/kg/min. Here, we present the case of a 49-year-old patient who entered the emergency department after a cerebrovascular event and a hypertensive emergency that required Sodium Nitroprusside infusion, followed by signs and symptoms suggestive of toxicity. Neurological changes were predominant among these symptoms, and the patient was managed with sodium thiosulfate, resulting in a good response. The objective of this case report is to raise awareness among healthcare professionals about the need for appropriate use of Sodium Nitroprusside and the importance of suspecting toxicity in patients with risk factors.

O nitroprussiato de sódio foi aprovado desde 1974 como medicamento para crises hipertensivas. Desde então tem havido controvérsia sobre o seu potencial tóxico. A toxicidade por cianeto é uma complicação rara do nitroprussiato de sódio, que pode ser difícil de diagnosticar em pacientes gravemente enfermos. Entre os fatores de risco está o uso de infusões prolongadas e altas doses, por isso sugere-se que a dose não ultrapasse 2 µg/kg/min. Relata-se a seguir o caso de uma paciente de 49 anos admitida em pronto-socorro após síndrome cerebrovascular e emergência hipertensiva com necessidade de infusão de nitroprussiato de sódio acompanhada de sinais e sintomas sugestivos de toxicidade. Dentre esses sintomas, predominaram as alterações neurológicas, para as quais foi tratado com hipossulfito de sódio e apresentou boa resposta. O objetivo deste relato de caso é sensibilizar os profissionais de saúde sobre a necessidade do uso adequado do nitroprussiato e sobre a importância de suspeitar de toxicidade em pacientes com fatores de risco.

Frequency of Acid-Base Derangements Among the Neonates Admitted to the Intensive Care Unit

Background: Every year deranged acid-base physiology drives admission to a critical care arena for a vast number of neonates. The neonatal intensive care unit is a fundamental sector for the survival of high-risk newborns. The acid-base disorder must always be considered in the clinical setting. The clinician should, in most cases, be able to predict the type of acid-base imbalance before the blood gas is available. Arterial blood gases (ABG-s) are the gold standard for assessing the adequacy of oxygen delivery, ventilation, and pH. This study aimed to assess the frequency of acid-base derangements among neonates admitted to the intensive care unit. Material & Methods: This was an observational cohort study that was conducted in the Neonatal Intensive Care Unit (I.C.U.) of Dhaka Shishu Hospital, Dhaka, Bangladesh during the period from October 2009 to September 2010. In total 230 neonates admitted to the Neonatal Intensive Care Unit, after fulfilling the inclusion criteria were enrolled in this study as study subjects. For each baby, a detailed history was recorded in a questionnaire form (enclosed herewith) from the mother or other caregiver. It was filled up by the researcher himself containing history (including antenatal history), physical examinations and laboratory findings. Arterial blood gas analysis was done (in a clinical biochemistry laboratory using an automatic analyzer machine) for each neonate at admission and that report was recorded for this study. Results: Among the total study subjects, 127 newborn babies (55.2%) had acid-base imbalances. Mixed acidosis prevailed in the highest frequency (23.9%) Then metabolic acidosis cases were at 17.8% and respiratory acidosis was at 13.9%. Metabolic alkalosis and respiratory alkalosis were absent. Normal blood gas was observed in 44.3% of newborns. All the neonates with pH <7 were dead. After Chi-Square analysis (at df=1), we found a highly significant correlation between mortality outcome with pH <7.35, CO2 >45, HCO3 < 22 mol/l and Base deficit >-10. All modalities of acid-base imbalances were significantly associated with mortality. Conclusion: In this study, a significant number of neonates who were admitted to the intensive care unit, can develop acid-base derangement. Mixed acidosis was found in the highest frequency. Metabolic, respiratory and mixed acidosis all has a significant correlation with death in a NICU. Metabolic alkalosis and respiratory alkalosis were found absent at admission

Sjogren’s syndrome presenting as hypokalemic periodic paralysis, a rare manifestation: A case series

Sjogren’s syndrome is a chronic and slowly progressing autoimmune disease characterized by lyphocytic infiltration of exocrine glands resulting in Sicca syndrome (xerostomia and keratocunjuntivitis sicca). The disease can present alone or along with other autoimmune diseases leading to significant organ specific and systemic disease. Middle aged women (Female: Male: 9:1) are primarily affected. Extraglandular (systemic) manifestations are seen in one third of patients with Sjogren’s syndrome. Among the extraglandular manifestations, renal involvement is commonly seen. Renal involvement in the form of tubulointerstitial nephritis (TIN) is more common compared to glomerular involvement. Distal renal tubular acidosis (RTA) is more common manifestation of TIN presenting as mild hypokalemia, metabolic acidosis, and rarely with hypokalemic periodic paralysis. We report three cases of hypokalemic periodic paralysis with metabolic acidosis, two in respiratory paralysis, diagnosed as distal RTA. On further evaluation of distal RTA, the patient diagnosed to have Sjogren’s syndrome and managed accordingly. Our report shows that Sjogren’s syndrome is a rare but important cause of hypokaemic periodic paralysis due to RTA.

Don’t pin it all on a stereotype

Hypercalcemia is one of the most frequently encountered problems in endocrinology OPD. Although the evaluation may not always be straightforward in all scenarios. Common factors affecting calcium levels such as dehydration, improper sample collection, and vitamin D supplementation may mask a serious underlying disorder. Here, we discuss a case of an elderly female who had symptoms of myelopathy and hypercalcemia whose etiology was initially attributed to excessive sup

Hipomineralización Incisivo Molar en paciente pediátrico con acidosis tubular renal distal. Reporte de caso. Control y seguimiento por 14 años

Introducción: la hipomineralización incisivo molar es un defecto sistémico del desarrollo que afecta a uno o más primeros molares permanentes, se asocia con frecuencia a los incisivos permanentes, de etiología multifactorial y con diversas opciones de tratamiento. Objetivo: se presenta el caso de un paciente que presenta hipomineralización incisivo molar en sus primeros molares permanentes con antecedentes de haber padecido de acidosis tubular renal distal, dicha entidad puede ocasionar defectos en el esmalte. Reporte del caso: masculino de 7 años de edad diagnosticado con acidosis tubular distal a los 4 meses de edad, al momento de la consulta ya superado. En sus primeros molares permanentes se observan lesiones sugestivas de hipomineralización incisivo molar. Se evalúa clínica y radiográficamente. Se le realizan restauraciones con vidrio ionomérico revisadas en controles semestrales y a los 10 años se decide colocar resinas compuestas en los molares afectados. Se indican controles periódicos a los cuales asiste regularmente por 14 años. Conclusión: la identificación temprana de la Hipomineralización incisivo molar permitirá la aplicación de medidas preventivas para asegurar la permanencia de los dientes afectados en boca. Es Importante afianzar las prácticas higiénicas especialmente en las superficies afectadas, concomitantemente con la aplicación de materiales restauradores.

Introdução: a hipomineralização molar incisivo é um defeito sistémico do desenvolvimento que afeta um ou mais primeiros molares permanentes, está frequentemente associada a incisivos permanentes, de etiologia multifatorial e com várias opções de tratamento. Objetivo: é apresentado o caso de um paciente que apresenta hipomineralização molar incisivo em seus primeiros molares permanentes com histórico de ter sofrido acidose tubular renal distal, esta entidade pode causar defeitos de esmalte. Relato de caso: menino de 7 anos de idade diagnosticado com acidose tubular distal aos 4 meses de idade, à época da consulta já ultrapassado. Em seus primeiros molares permanentes, foram observadas lesões sugestivas de hipomineralização molar incisivo. É avaliado clínica e radiograficamente. Restaurações de ionômero de vidro foram realizadas, revisadas em controles semestrais, e aos 10 anos foi decidido colocar resinas compostas nos molares afetados. São indicados controles periódicos, que frequenta regularmente há 14 anos. Conclusão: a identificação precoce da hipomineralização molar incisivo permitirá a aplicação de medidas preventivas para garantir a permanência dos dentes acometidos na boca. É importante reforçar as práticas de higiene, principalmente nas superfícies afetadas, então com a aplicação de materiais restauradores.

Summary Introduction: molar incisor hypomineralization is a systemic developmental defect that affects one or more permanent first molars, is frequently associated with permanent incisors, of multifactorial etiology and with various treatment options. Objective: the case of a patient who presents molar incisor hypomineralization in his first permanent molars with a history of having suffered from distal renal tubular acidosis is presented, this entity can cause enamel defects Case report: 7-year-old male diagnosed with distal tubular acidosis at 4 months of age, at the time of the consultation he had already passed. In his first permanent molars, lesions suggestive of molar incisor hypomineralization were observed. It is evaluated clinically and radiographically. Glass ionomer restorations were performed, reviewed at six-monthly controls, and at 10 years it was decided to place composite resins on the affected molars. Periodic controls are indicated, which he regularly attends for 14 years. Conclusion: early identification of molar incisor hypomineralization will allow the application of preventive measures to ensure the permanence of affected teeth in the mouth. It is important to strengthen hygienic practices, especially on affected surfaces, concomitantly with the application of restorative materials.

Prenatal diagnosis of pyruvate dehydrogenase E1-α deficiency: a case report / 中华围产医学杂志

This article reported a case of pyruvate dehydrogenase E1-α deficiency suggested by abnormal brain development during prenatal ultrasound imaging. Prenatal ultrasound revealed a mild enlargement of bilateral cerebral ventricles and the possibility of intracranial hemorrhage in the fetus at 25 +1 weeks of gestation. MRI showed the fetus with absent corpus callosum, enlarged bilateral cerebral ventricles and paraventricular cysts. After genetic counseling and careful consideration, the couple opted for pregnancy termination. To clarify the cause of the disease, whole-exome sequencing was performed on the fetal skin to detect possible variants, and which revealed a frameshift mutation c.924_930dup(p.R311Gfs*5) in exon 10 of the PDHA1 gene. Sanger sequencing confirmed the mutation was a de novo pathogenic variant, indicating that the fetus was affected by pyruvate dehydrogenase E1-α deficiency.

Fanconi syndrome secondary to primary biliary cholangitis: a case report / 中华肾脏病杂志

Primary biliary cirrhosis/cholangitis is an autoimmune disease. Renal tubular acidosis is a common form in PBC cases, but Fanconi syndrome is rarely reported. The paper reported a 66-year-old female patient with fatigue, renal insufficiency and elevated bile duct enzymes. The patient presented with type 2 proximal renal tubular acidosis and complete Fanconi syndrome. Laboratory examinations showed high-titer-positive anti-mitochondrial antibodies, elevated serum IgM, and type 3 cryoglobulinemia. Renal biopsy revealed interstitial nephritis, and electron micrographs showed abnormal mitochondria in proximal tubular epithelial cells. The patient's renal function ameliorated, and acid-base imbalance and electrolyte disturbances were corrected after high-dose glucocorticoid treatment.

¿Bicarbonato de sodio en terapia intensiva es útil o no?

La acidosis metabólica se ha convertido en un problema muy serio, tanto en las áreas críticas, como de medicina interna y emergencias, sobre todo por la innumerable cantidad de patologías que la presentan; que ha encaminado a muchos profesionales a usar el bicarbonato de Na (NaHCO3-), que definitivamente tiene un efecto en el ascenso del pH y el HCO3-, asociado a un sosiego inverosímil del profesional médico y probablemente a un escaso beneficio por parte de los pacientes; este estudio trata de explicar en forma concisa a la etiología de la acidosis metabólica y la real indicación de esta droga, que hasta el momento podría tener más perjuicios que beneficios.

Metabolic acidosis has become a very serious problem, both in critical areas, such as internal medicine and emergencies, especially due to the innumerable number of pathologies that present it; which has led many professionals to use Na bicarbonate (NaHCO3-), which definitely has an effect on the rise in pH and HCO3-, associated with an unlikely calmness of the medical professional and probably with little benefit on the part of the patients. patients; This study tries to concisely explain the etiology of metabolic acidosis and the real indication of this drug, which up to now could have more harm than good.

Advancing in the understanding of coagulopathy during hemorrhagic shock: From the triad to the deadly pentad / Avanzando en el entendimiento de la coagulopatía durante el choque hemorrágico: de la tríada a la pentada mortal

Abstract The deadly triad concept represented a dogma in the definition of poor outcomes and death associated with major bleeding in trauma. This model of end-stage disease was then rapidly transferred to other major bleeding scenarios. However, and notwithstanding the fact that it represented a severe scenario, the original triad fails to establish a sequence, which would be relevant when defining the objectives during the initial treatment of severe bleeding. Likewise, this model admits only one scenario where all the conditions shall co-exist, knowing that each one of them contributes with a different risk burden. Based on a structured review, we propose a pentad model that includes a natural pattern of events occurring with hypoxemia as the main trigger for the development of hypocalcemia, hyperglycemia, acidosis and hypothermia, as surrogates of multi-organ impairment. This severity model of major bleeding considers coagulopathy as a result of the failure to restore the initial components of damage.

Resumen El concepto de la tríada mortal significó un dogma en la definición de malos desenlaces y muerte asociados al sangrado mayor en trauma. Este modelo de afectación terminal fue luego rápidamente trasladado a otros escenarios de sangrado mayor. Sin embargo y a pesar de significar un escenario de gravedad, la tríada original falla en adjudicar una secuencialidad, lo cual sería importante a la hora de definir los objetivos durante el tratamiento inicial de la hemorragia grave. De igual forma, solo admite un único escenario en donde deben coexistir todas las condiciones, cuando se sabe que cada una atribuye una carga diferencial de riesgo. A partir de una revisión estructurada proponemos un modelo de pentada que incluye un patrón natural de eventos que se implantan sobre la hipoxemia como principal detonante para el desarrollo de hipocalcemia, hiperglucemia, acidosis e hipotermia como representantes del deterioro en múltiples sistemas. Este modelo de gravedad del sangrado mayor culmina con la coagulopatía como resultante de la falla en la resolución de los demás componentes previos.

Physiological variables of the "metabolic component" of acid-base balance and mortality in intensive care patients / Variables fisiológicas del "componente metabólico" del estado ácido base y mortalidad en pacientes de cuidados intensivos

Abstract Introduction: Metabolic acidosis is a frequent pathophysiological condition in critically ill patients. It can be assessed using different physiological variables, but their prognostic value has not yet been well established. Objective: To evaluate the association between the variables that allow assessing the metabolic component of acid-base balance (ABB) and 28-day mortality in patients admitted to an intensive care unit (ICU) in Bogotá, D.C., Colombia. Materials and methods: Prospective cohort study conducted in 122 patients admitted to an ICU between January and June 2013 and with a stay >24 hours. On admission to the ICU, blood samples were taken, and an arterial blood gas test was performed in order to calculate the following variables: anion gap (AG), corrected anion gap (AGc), standard base excess (BEst), metabolic H+, base excess-unmeasurable anions (BEua), arterial pH, arterial lactate, standard HCO3-st, and strong ion difference (SID). APACHE II and SOFA scores were also calculated. A bivariate analysis was performed in which ORs and their respective 95%CI were calculated, and then a multivariate analysis was conducted using a logistic regression model to identify the variables associated with 28-day mortality; a significance level of p<0.05 was considered. Results: Out of the 122 patients, 33 (27.05%) died at 28 days and 51 (48.80%) were women. Participants' mean age was 46.5 years (±15.7). The following variables were significantly associated with 28-day mortality in the bivariate analysis: SID (OR=1.150; p=0.008), BEua (OR=0.897; p=0.023), AG (OR=1.231; p=0.002), AGc (OR=1.232; p=0.003), blood pH (OR=0.001; p=0.023), APACHE II (OR=1.180; p=0.001), HCO3-st (OR=0.841; p=0.015). In the multivariate analysis, only the APACHE II score variable was significantly associated with 28-day mortality (OR=1.188; p=0.008). Conclusion: The physiological variables that allow assessing the metabolic component of ABB, both from the Henderson model and the Stewart model, were not significantly associated with 28-day mortality.

Resumen Introducción. La acidosis metabólica es una condición fisiopatológica frecuente en pacientes críticamente enfermos. Esta alteración es evaluada mediante diferentes variables fisiológicas; sin embargo, su valor pronóstico aún no está bien definido. Objetivo. Evaluar la asociación entre, por una parte, las variables del componente metabólico que permiten valorar el estado ácido base (EAB) y, por la otra, la mortalidad a 28 días en pacientes hospitalizados en una unidad de cuidados intensivos (UCI) en Bogotá D.C., Colombia. Materiales y métodos. Estudio de cohorte prospectivo realizado en 122 pacientes hospitalizados en una UCI entre enero y junio de 2013 y con una estancia mayor a 24 horas. Se tomaron muestras sanguíneas y gases arteriales de ingreso a UCI para el cálculo de las siguientes variables: anion gap (AG), anion gap corregido (AGc), base exceso estándar (BEst), H+ metabólicos, base exceso-aniones no medibles (BEua), pH arterial, lactato arterial, HCO3-st y brecha de iones fuertes (BIF). También se calcularon el puntaje APACHE II y el puntaje SOFA. Se realizó un análisis bivariado en el que se calcularon OR y sus respectivos IC95%, y luego uno multivariado, mediante un modelo de regresión logística, para identificar las variables asociadas con la mortalidad a 28 días; se consideró un nivel de significancia de p<0.05 Resultados. De los 122 pacientes, 33 (27.05%) fallecieron a 28 días y 51 (48.80%) eran mujeres. La edad promedio fue 46.5 años (±15.7). En el análisis bivariado, las siguientes variables se asociaron significativamente con la mortalidad a 28 días: BIF (OR=1.150; p=0.008), BEua (OR=0.897; p=0.023), AG (OR=1.231; p=0.002), AGc (OR=1.232; p=0.003), pH arterial (OR=0.001; p=0.023), APACHE II (OR=1.180;p=0.001), HCO3-st (OR=0.841;p=0.015). En el análisis multivariado, solo el puntaje APACHE II se asoció significativamente con la mortalidad a 28 días (OR=1.188; p=0.008). Conclusión. Las variables fisiológicas que permiten evaluar el componente metabólico del EAB, tanto las del modelo de Henderson, como las del modelo de Stewart, no se asociaron significativamente con la mortalidad a 28 días.

Acidosis láctica grave en una mujer embarazada con síndrome HELLP parcial y COVID-19 / Severe lactic acidosis in a pregnant woman with partial HELLP syndrome and COVID-19

Resumen Se presenta el caso de una mujer embarazada secundigesta, cursando la semana 36.5 de gestación, que concurrió a guardia general por tos seca y disnea progresiva de 3 días de evolución, asociadas a cefalea y mialgias. Se realizó hisopado nasofaríngeo para reacción en cadena de la polimerasa (PCR) para SARS-CoV-2, resultando positivo. La saturación de oxígeno era normal, al igual que la radiografía de tórax. En el laboratorio presentó elevación de bilirrubina, transaminasas, fosfatasa alcalina y LDH, además de plaqueto penia leve. Poco después de su ingreso, comenzó con trabajo de parto. Frente a la falta de progresión del mis mo se decidió la finalización del embarazo por cesárea. La gasometría arterial reveló la presencia de acidosis láctica grave. Nunca hubo evidencia clínica de hipoperfusión tisular o sepsis que pudieran explicarla. Cursó su postoperatorio en la unidad de terapia intensiva, realizándose tratamiento de sostén. Todos los parámetros de laboratorio se normalizaron al cabo de 72 horas, evolucionando favorablemente desde el punto de vista clínico. Se interpretó que cursó un síndrome HELLP parcial. La acidosis láctica no es un componente descripto en este síndrome. Tampoco puede adscribirse a la enfermedad leve por SARS-CoV-2. Podría deberse a una sumatoria de causas, incluidas la hiperproducción de ácido láctico en el marco del trabajo de parto, como la disminución de su aclaramiento por la disfunción hepática asociada al síndrome HELLP.

Abstract The present report describes the case of a 23-year old pregnant woman who was in the 36.5th week of gestation of her second pregnancy. She was attended at the emergency room because of dry cough and progressive dyspnea, in association with headache and myalgia. The nasopharyngeal swab for SARS-CoV-2 polymerase chain reaction (PCR) was positive. Oxygen saturation and chest x-ray were normal. Laboratory tests showed elevated values of bilirubin, aminotransferases, alkaline phosphatase and lactic dehydrogenase, and mild thrombocytopenia. Shortly after being admitted she began with labor. Faced with the lack of progression, the termination of the pregnancy by cesarean section was decided. Arterial blood gases showed severe lactic acidosis. She never presented evidence of clinical signs of tissue hypoperfusion or sepsis that could explain it. The patient completed her postoperative period in the intensive care unit, undergoing supportive treatment. All laboratory parameters were normalized after 72 hours, evolving favorably from the clinical point of view. It was interpreted that she had a partial HELLP syndrome. Lactic acidosis is not a component of this syndrome. Nor can it be ascribed to a mild disease by SARS-Cov-2. It probably responded to a summation of causes, including hyperproduction of lactic acid during labor, as well as its reduced clearance because of liver dysfunction related to HELLP syndrome.

Bicarbonato de sodio intravenoso ¿Cuándo, cómo y por qué utilizarlo? / Intravenous sodium bicarbonate. When, how and why to use it?

Severe metabolic acidosis is defined by a pH < 7.2 with HCO3− < 8 mE- q/L in plasma. Its best treatment is to correct the underlying cause. However, acidemia produces multiple complications such as resistance to the action of catecholamines, pulmonary vasoconstriction, impaired cardiovascular function, hyperkalemia, immunological dysregulation, respiratory muscle fatigue, neurological impairment, cellular dysfunction, and finally, it contributes to multisystemic failure. Intravenous NaHCO3 buffers severe acidemia, preventing the associated damage and gains time while the causal disease is corrected. Its indication requires a risk-benefit assessment, considering its complications. These are hypernatremia, hypokalemia, ionic hypocalcemia, rebound alkalosis, and intracellular acidosis. For this reason, therapy must be "adapted" and administered judiciously. The patient will require monitoring with serial evaluation of the internal environment, especially arterial blood gases, plasma electrolytes, and ionized calcium. Isotonic solutions should be preferred instead of hypertonic bicarbonate. The development of hypernatremia must be prevented, calcium must be provided for hypocalcemia to improve cardiovascular function. Furthermore, in mechanically ventilated patients, a respiratory response similar to the one that would develop physiologically, must be established to be able to extract excess CO2 and thus avoid intracellular acidosis. It is possible to estimate the bicarbonate deficit, speed, and volume of its infusion. However, the calculations are only for reference. More important is to start intravenous NaHCO3 when needed, administer it judiciously, manage its side effects, and continue it to a safe goal. In this review we address all the necessary elements to consider in the administration of intravenous NaHCO3, highlighting why it is the best buffer for the management of severe metabolic acidosis.

Predictores de mortalidad precoz en pacientes con trauma complejo hemorrágico / Early mortality predictors in patients with complex hemorrhagic trauma

RESUMEN Fundamento: El trauma complejo es un problema de salud a nivel mundial y cuando es de tipo hemorrágico la mortalidad es superior a los otros tipos de traumas complejos. Objetivo: Determinar las variables predictoras de mortalidad precoz en pacientes hospitalizados con trauma complejo hemorrágico en una institución hospitalaria del segundo nivel de atención en Cuba. Metodología: Se realizó un estudio transversal en el Hospital General Provincial Camilo Cienfuegos de Sancti Spíritus, durante 6 años. Se incluyeron 207 pacientes. Las variables se agruparon en sociodemográficas, enfermedades crónicas asociadas, mecanismo lesional, tipo de trauma, localización topográfica, tiempo entre admisión hospitalaria, diagnóstico y tratamiento, complicaciones precoces, tratamiento médico y quirúrgico, y mortalidad precoz. Se elaboró un árbol de decisión mediante el método Chaid exhaustivo, la variable dependiente fue la mortalidad por trauma complejo hemorrágico. Resultados: Predominaron los pacientes del sexo masculino (85 %), con 60 años y menos (83 %), con trauma contuso (57.5 %) y politraumatizados (42.5 %). Predominaron también los que presentaron acidosis metabólica (66.7 %), coagulopatía aguda (44.4 %), hipotermia (41.5 %). El 30 % de los pacientes falleció precozmente. El árbol de decisión tuvo una sensibilidad de 82.3 %, una especificidad de 97.2 % y un porcentaje global de pronóstico correcto del 92.8 %. Se identificaron 4 variables predictores de mortalidad: hipotermia, acidosis metabólica, coagulopatía aguda y trauma penetrante. Conclusiones: La probabilidad más alta de fallecer precozmente durante un trauma complejo hemorrágico se da entre pacientes con hipotermia, acidosis metabólica, coagulopatía aguda y trauma penetrante.

ABSTRACT Background: Complex trauma is a worldwide health problem and when hemorrhagic, mortality is higher than other types of complex trauma. Objective: To determine predictive variables of early mortality in hospitalized patients with complex hemorrhagic trauma in a second care level hospital in Cuba. Methodology: A cross-sectional study was conducted at Camilo Cienfuegos Provincial General Hospital in Sancti Spíritus, for 6 years. 207 patients were included. The variables were grouped into sociodemographic, associated chronic diseases, injury mechanism, type of trauma, topographic location, time between hospital admission, diagnosis and treatment, early complications, medical and surgical treatment, and early mortality. A decision tree was developed using the exhaustive Chaid method, the dependent variable was mortality due to complex hemorrhagic trauma. Results: Male patients (85 %), 60 years and younger (83 %), with blunt trauma (57.5 %) and polytraumatized patients (42.5 %) predominated. Those who presented metabolic acidosis (66.7 %), acute coagulopathy (44.4 %), and hypothermia (41.5 %) also predominated. 30 % of patients died early. The decision tree had a sensitivity of 82.3 %, a specificity of 97.2 % and an overall percentage of correct forecast of 92.8 %. Four variables that predicted mortality were identified: hypothermia, metabolic acidosis, acute coagulopathy, and penetrating trauma. Conclusions: The highest probability of early dying during a complex hemorrhagic trauma occurs among patients with hypothermia, metabolic acidosis, acute coagulopathy and penetrating trauma.

Designing of promising Tromethamine-Diflunisal-Pyrrole combinations based on COX binding, drug-properties and safety-Supplementary Data

Gastric issues that accompany the use of NSAIDs (Non-steroid anti-inflammatory drugs) are always a serious global concern. The inhibition of the Cycloxygenase enzyme (COX) limits the prostaglandin synthesis and thereby facilitates the control of pains, inflammation etc. But this creates gastric issues due to the reduction of mucin formation in the stomach. The present work was performed to create a modification in the structure of NSAID drug Diflunisal, to reduce the gastric effect of acidic moiety in the structure and elevate the overall biological properties. The drug Tromethamine, a base used in acidosis treatment was substituted to reduce the acidic issues. The heterocyclic compound pyrrole was substituted to elevate the properties. Neutral, salt, amide and ester combinations of Tromethamine-Diflunisal were designed, optimized and docked to the crystal structures of COX-1 (PDB ID: 6Y3C) and COX-2 (PDB ID: 5IKR) enzymes, using PyRx software. The combinations with lower COX-1 and COX-2 binding energies relative to Diflunisal were noted. It was analysed if the combinations of Diflunisal, Tromethamine and pyrrole lowers drug-properties or induce toxicities. Pyrrole substitution at position R4 was not found favourable for COX binding. Among the favourable combinations, DF19 is the Diflunisal-Pyrrole-Tromethamine combination, equally favourable for binding to COX targets.

Designing of promising Tromethamine-Diflunisal-Pyrrole combinations based on COX binding, drug-properties and safety-Supplementary Data

Gastric issues that accompany the use of NSAIDs (Non-steroid anti-inflammatory drugs) are always a serious global concern. The inhibition of the Cycloxygenase enzyme (COX) limits the prostaglandin synthesis and thereby facilitates the control of pains, inflammation etc. But this creates gastric issues due to the reduction of mucin formation in the stomach. The present work was performed to create a modification in the structure of NSAID drug Diflunisal, to reduce the gastric effect of acidic moiety in the structure and elevate the overall biological properties. The drug Tromethamine, a base used in acidosis treatment was substituted to reduce the acidic issues. The heterocyclic compound pyrrole was substituted to elevate the properties. Neutral, salt, amide and ester combinations of Tromethamine-Diflunisal were designed, optimized and docked to the crystal structures of COX-1 (PDB ID: 6Y3C) and COX-2 (PDB ID: 5IKR) enzymes, using PyRx software. The combinations with lower COX-1 and COX-2 binding energies relative to Diflunisal were noted. It was analysed if the combinations of Diflunisal, Tromethamine and pyrrole lowers drug-properties or induce toxicities. Pyrrole substitution at position R4 was not found favourable for COX binding. Among the favourable combinations, DF19 is the Diflunisal-Pyrrole-Tromethamine combination, equally favourable for binding to COX targets.

Designing of promising Tromethamine-Diflunisal-Pyrrole combinations based on COX binding, drug-properties and safety

Gastric issues that accompany the use of NSAIDs (Non-steroid anti-inflammatory drugs) are always a serious global concern. The inhibition of the Cycloxygenase enzyme (COX) limits the prostaglandin synthesis and thereby facilitates the control of pains, inflammation etc. But this creates gastric issues due to the reduction of mucin formation in the stomach. The present work was performed to create a modification in the structure of NSAID drug Diflunisal, to reduce the gastric effect of acidic moiety in the structure and elevate the overall biological properties. The drug Tromethamine, a base used in acidosis treatment was substituted to reduce the acidic issues. The heterocyclic compound pyrrole was substituted to elevate the properties. Neutral, salt, amide and ester combinations of Tromethamine-Diflunisal were designed, optimized and docked to the crystal structures of COX-1 (PDB ID: 6Y3C) and COX-2 (PDB ID: 5IKR) enzymes, using PyRx software. The combinations with lower COX-1 and COX-2 binding energies relative to Diflunisal were noted. It was analysed if the combinations of Diflunisal, Tromethamine and pyrrole lowers drug-properties or induce toxicities. Pyrrole substitution at position R4 was not found favourable for COX binding. Among the favourable combinations, DF19 is the Diflunisal-Pyrrole-Tromethamine combination, equally favourable for binding to COX targets.

Late Onset Subacute Profound Biotinidase Deficiency Caused by a Novel Homozygous Variant c.466-3T>G in the BTD Gene

Biotinidase defciency (BD) is an autosomal recessive disorder caused by bi-allelic mutation in the BTD gene. Clinical manifestations in BD mainly depends on residual biotinidase enzyme activity, although there are some exceptions. Broadly BD disorders are classifed as profound BD and partial BD. Further profound BD can be early onset, late onset, and sometimes may be asymptomatic. Clinically late-onset profound BD can present with spectrum of manifestations ranging from single organ to multiple organ involvement, typically afecting function of brain, eye, ear, and skin. Here, a frst-born child to consanguineous parents with late-onset profound BD presenting with hyperventilation secondary to lactic acidosis, hypotonia, evolving spasticity, and abnormal neuroimaging fndings caused by novel homozygous variant, c.466-3T>G in the BTD gene is reported.

Alteraciones del estado ácido básico en pacientes adultos con insuficiencia renal crónica / Acid-base status alterations in adult patients with chronic renal failure

RESUMEN Introducción: el portador de insuficiencia renal crónica puede presentar diversas alteraciones del estado ácido básico, siendo la acidosis metabólica la más frecuente. Objetivos: describir las características demográficas y clínicas y las alteraciones del estado ácido básico de pacientes adultos que ingresan con insuficiencia renal crónica en dos centros hospitalarios del Paraguay. Metodología: se aplicó un diseño observacional, descriptivo, transversal. Se incluyó a sujetos adultos de ambos sexos, portadores de insuficiencia renal crónica, que acudieron al Hospital Nacional (Itauguá) y Hospital Militar (Asunción) entre abril y noviembre del 2021. Se midieron variables antropométricas, clínicas y laboratoriales al ingreso. Los datos se sometieron a estadística descriptiva con el programa Epi Info 7™. El estudio contó con la aprobación del Comité de Ética de la Universidad Privada del Este, Paraguay. Resultados: se incluyó a 148 sujetos, siendo 78 (52,7 %) varones con edad media 58 ± 16 años y 70 (47,3 %) mujeres con edad media 54 ± 17 años. Las etiologías más frecuentes de la insuficiencia renal crónica fueron la diabetes mellitus e hipertensión arterial (44,5 %). Se detectó 12 sujetos (8,1 %) con gasometría normal. La alteración del estado ácido básico más frecuente fue la acidosis metabólica (87,2 %), predominando en este grupo los casos con brecha aniónica normal. Conclusiones: las alteraciones del estado ácido básico predominantes en pacientes con insuficiencia renal crónica fue la acidosis metabólica con brecha aniónica normal. Se sugiere aplicar los cálculos de los mecanismos compensadores para llegar al diagnóstico certero de estas alteraciones metabólicas.

ABSTRACT Introduction: the carrier of chronic renal failure can present various alterations of the basic acid state, being the metabolic acidosis the most frequent. Objectives: to describe the demographic and clinical characteristics and alterations in the acid-base status of adult patients admitted with chronic renal failure in two hospitals in Paraguay. Methodology: an observational, descriptive, cross-sectional design was applied. Adult subjects of both sexes, carriers of chronic renal failure, who attended the National Hospital (Itauguá) and the Military Hospital (Asunción) between April and November 2021 were included. Anthropometric, clinical and laboratory variables were measured at admission. The data was submitted to descriptive statistics with the Epi Info 7™ program. The study was approved by the Ethics Committee of the Universidad Privada del Este, Paraguay. Results: 148 subjects were included, being 78 (52.7 %) men with a mean age of 58 ± 16 years and 70 (47.3 %) women with a mean age of 54 ± 17 years. The most frequent etiologies of chronic renal failure were diabetes mellitus and arterial hypertension (44.5 %). 12 subjects (8.1 %) with normal blood gases were detected. The most frequent alteration of the acid-base status was metabolic acidosis (87.2 %), with cases with normal anion gap predominating in this group. Conclusions: the predominant acid-base status alterations in patients with chronic renal failure was metabolic acidosis with normal anion gap. It is suggested to apply the calculations of the compensatory mechanisms to arrive at the accurate diagnosis of these metabolic alterations.

Lethargy and hypotonia in a preterm neonate: Usual symptom with unusual diagnosis of mitochondrial trifunctional protein deficiency

Methodical evaluation of a neonate with common clinical findings (hypotonia and lethargy) is important whenever it cannot be attributed to the frequent causes. This case report is on a preterm neonate with persistent hypotonia and metabolic acidosis who was evaluated and diagnosed with mitochondrial trifunctional protein deficiency. A preterm male baby, second born to second degree consanguineous parents, was found to have persistent lethargy and hypotonia with severe metabolic acidosis despite the shock being corrected. Strong clinical suspicion for inborn errors of metabolism (IEM) was considered despite negative reports of first tier investigations for IEM. He was started on carnitine and biotin. Whole exome sequencing of the baby and Sanger sequencing of mother revealed mutation in HADHA gene suggesting mitochondrial trifunctional protein (MTFP) deficiency. He was started on special infant formula containing medium chain triglycerides along with breastfeeding. When common causes cannot be attributed to the clinical picture, evaluation for uncommon aetiologies should be strongly considered. In case of IEMs, early diagnosis and appropriate therapeutic measures can have satisfactory growth and development in the child

Hypokalemic paralysis due to distal renal tubular acidosistype 1 in patient of mucormycosison amphotericin B: a case report

A 42-year-old male patient who is a known case of DM and mucormycosison treatment presented with sudden onset difficulty in moving all 4 limbs followed by decreased depth of respiration for 4 hours. The patient was known case of DM for 10 years and was on OHA for the same, he had history of biopsy diagnosed rhino mucormycosis 4 months ago and was on treatment for the same. On initial examination the tone was hypotonic in all4 limbs along with power of 3+, respiration was shallow and patient was bedridden unable to stand on his own, he was ambulatory 6 days before presentingto hospital. Potassium-1.7 mEq/l, ABGA pH-7.18, HCO3-10 Meq/l, urine osmolality 220 mOsm/l, urine pH-7.0, potassium-to-creatinine rstio (K/Cr)-3.9 mEq/ml, urine K-22 mEq/ml. Distal RTA (dRTA) is the classical form of RTA, being the first described. DistalRTA is characterized by a failure of H+ secretion into lumen of nephron by the alpha intercalatedcellsof themedullary collecting ductof thedistalnephron.This failure of acid secretion may be due to a number of causes, and it leads to an inability to acidify the urine to apHof less than 5.3.This case study enumerates the potentially dangerous side effects of amphotericin B in patients which canprecipitate RTA type 1 leading to severe hypokalaemia and acidosis, thus all patients receiving amphotericin B should be cautiously warned regarding side effect of hypokalaemia and prophylactic potassium syrup supplementation may be given in predisposed patients.