El difícil camino al diagnóstico del paciente con atrofia muscular espinal / The difficult path to diagnosis of the patient with spinal muscular atrophy

Introducción. Con las nuevas terapias, el diagnóstico temprano de la atrofia muscular espinal (AME) es esencial. El objetivo de este estudio es analizar los distintos componentes que influyen en el retraso diagnóstico. Población y métodos. Se incluyeron pacientes con un diagnóstico molecular de AME tipo I, II y III. Se estudiaron varios parámetros, como la edad al momento de la aparición del primer signo, qué signo fue y el intervalo entre este y el diagnóstico confirmado. Neurólogos especialistas realizaron entrevistas que se complementaron con la revisión de historias clínicas cuando fue necesario. Resultados. Se entrevistaron 112 pacientes. AME I n = 40, AME II n = 48, AME III n = 24. La mediana de edad en meses al momento del reporte del primer signo fue AME I: 1,5 (R 0-7), AME II: 9 (R 2-20), AME III: 18 (R 8-180). Los primeros signos fueron reconocidos por los padres en el 75 % al 85 % de las veces en todos los subtipos. La mediana del tiempo transcurrido entre el primer signo y la primera consulta médica fue menor a un mes en los tres tipos. La mediana de tiempo transcurrido en meses entre el primer signo y el diagnóstico molecular confirmado fue en AME I: 2 (R 0-11), en AME II: 10 (3-46) y en AME III: 31,5 (R 4-288). Conclusiones. Existe un significativo retraso en el diagnóstico de la AME relacionado fundamentalmente a la falta de sospecha clínica. La demora es menor en AME I y mayor en AME III. Otros factores incluyen deficiencias en el sistema de salud.

Introduction. News treatments, make early diagnosis of spinal muscular atrophy (SMA) critical. The objective of this study is to analyze the different factors that influence delay in diagnosis. Population and methods. Patients with a molecular diagnosis of types I, II, and III SMA were included. Several parameters were studied, such as age at onset of first sign, what sign it was, and the time from recognition of first sign to confirmed diagnosis. Neurologists specialized in SMA conducted interviews, supported by the review of medical records when deemed necessary. Results. A total of 112 patients were interviewed. SMA I n = 40, SMA II n = 48, SMA III n = 24. The median age in months at the time of reporting the first sign was SMA I: 1.5 (R: 0­7), SMA II: 9 (R: 2­20), SMA III: 18 (R: 8­180). In all subtypes, first signs were identified by parents from 75% to 85% of the times. The median time from first sign to first medical consultation was less than a month in all 3 types. The median time in months, from first sign to confirmed molecular diagnosis in SMA I was: 2 (R: 0­11), in SMA II: 10 (R: 3­46), in SMA III: 31.5 (R: 4­288). Conclusions. There is a significant delay in SMA diagnosis mainly related to the absence of clinical suspicion. The delay is shorter in SMA I and longer in SMA III. Other factors include deficiencies in the health care system.

Enfermedades crónicas degenerativas como factor de riesgo de letalidad por COVID-19 en México / Chronic degenerative conditions as risk factors for lethal COVID-19 / Doenças crônicas degenerativas como fator de risco para letalidade por COVID-19

RESUMEN Objetivo. Determinar el riesgo de letalidad de las enfermedades crónicas degenerativas en pacientes con COVID-19. Métodos. Se realizo un estudio de cohorte, en expedientes clínicos electrónicos de pacientes con RT-PCR positiva para COVID-19 en atención ambulatoria o intrahospitalaria en una Institución de Seguridad Social de marzo 2020 a marzo 2021. Se integraron 2 grupos de estudio, el grupo expuesto se dividió en cuatro subgrupos, cada uno con diagnóstico único y exclusivo de una patología crónica (diabetes, hipertensión, obesidad o enfermedad renal crónica); el grupo no expuesto lo integraron expedientes de pacientes sin comorbilidades. Se revisaron 1 114 expedientes en total utilizando técnica muestral aleatoria simple, una vez obtenido el tamaño mínimo de muestra se calculó el riesgo relativo para cada enfermedad crónica, se realizaron combinaciones de 2, 3 y 4, con cada uno de ellos se realizó el análisis. Resultados. En ausencia de enfermedad crónica degenerativa la prevalencia de letalidad en COVID-19 es 3,8%; en presencia de diabetes mellitus tipo 2 la letalidad es 15,8; en hipertensión arterial de 15,6%; y en obesidad 15,0%. Cuando se combinan diabetes e hipertensión la letalidad es 54,1%; en diabetes y obesidad 36,8%; y en obesidad e hipertensión 28,1%. Conclusiones. En pacientes con COVID-19 el riesgo relativo para letalidad de letalidad en diabetes es 4,17; en hipertensión 4,13; y en obesidad 3,96. Cuando se combinan dos enfermedades crónicas el riesgo relativo se duplica o triplica, para diabetes e hipertensión el riesgo relativo para letalidad es 14,2; para diabetes y obesidad 9,73; y para obesidad e hipertensión 7,43. Es verdad que las enfermedades crónicas no se presentan solas, generalmente se encuentra asociadas, y desde esa perspectiva los riesgos relativos para letalidad ofrecidos en este artículo adquieren relevancia.

ABSTRACT Objective. To determine the relative risk of a lethal outcome associated with chronic degenerative conditions in patients with COVID-19. Methods. A cohort study was conducted using electronic medical records belonging to patients who tested positive for COVID-19 on RT-PCR while receiving care as outpatients or inpatients in a social security system facility between March 2020 and March 2021. Two study groups were formed. The exposed group was divided into four subgroups, each of which was diagnosed with one and only one chronic condition (diabetes, hypertension, obesity, or chronic kidney disease); the unexposed group was obtained from the medical records of patients without comorbidities. A total of 1 114 medical records were examined using simple random sampling. Once the minimum sample size was reached, the relative risk was calculated for each chronic condition. Combinations of two, three, and four conditions were created, and each of them was included in the analysis. Results. In the absence of a chronic degenerative condition, the prevalence of a lethal outcome from COVID-19 is 3.8%; in the presence of type 2 diabetes mellitus, 15.8%; in the presence of arterial hypertension, 15.6%; and in the presence of obesity, 15.0%. For diabetes and hypertension combined, the prevalence of a lethal outcome is 54.1%; for diabetes and obesity combined, 36.8%, and for obesity and hypertension combined, 28.1%. Conclusion. In patients with COVID-19, the relative risk of a lethal outcome is 4.17 for those with diabetes, 4.13 for those with hypertension, and 3.96 for those with obesity. For two chronic conditions combined, the relative risk doubles or triples. The relative risk of a lethal outcome is 14.27 for diabetes plus hypertension; 9.73 for diabetes plus obesity, and 7.43 for obesity plus hypertension. Chronic conditions do not present alone; they generally occur together, hence the significance of the relative risks for lethal outcomes presented in this paper.

RESUMO Objetivo. Determinar o risco de letalidade conferido por doenças crônicas degenerativas em pacientes com COVID-19. Métodos. Foi realizado um estudo de coorte em prontuários eletrônicos de pacientes com RT-PCR positivo para COVID-19 em atendimento ambulatorial ou hospitalar em uma instituição de previdência social, no período de março de 2020 a março de 2021. Foram constituídos dois grupos de estudo. O grupo exposto foi dividido em quatro subgrupos, cada um com diagnóstico único e exclusivo de uma doença crônica (diabetes, hipertensão, obesidade ou doença renal crônica). O grupo não exposto foi constituído por prontuários de pacientes sem comorbidades. Foram revisados 1.114 prontuários no total, utilizando técnica de amostragem aleatória simples. Uma vez obtido o tamanho mínimo da amostra, foi calculado o risco relativo para cada doença crônica. Foram realizadas combinações de 2, 3 e 4, tendo sido feita a análise com cada uma delas. Resultados. Na ausência de doença crônica degenerativa, a prevalência de letalidade na COVID-19 é de 3,8%; na presença de diabetes mellitus tipo 2, a letalidade é de 15,8%; na presença de hipertensão arterial, 15,6%; e na presença de obesidade, 15%. Quando tanto diabetes como hipertensão estão presentes, a letalidade é de 54,1%; com diabetes e obesidade, 36,8%; e obesidade com hipertensão, 28,1%. Conclusões. Em pacientes com COVID-19, o risco relativo de letalidade é de 4,17 naqueles com diabetes; 4,13 naqueles com hipertensão; e 3,96 naqueles com obesidade. Quando duas doenças crônicas são combinadas, o risco relativo dobra ou triplica. Para diabetes e hipertensão, o risco relativo de letalidade é 14,27; para diabetes e obesidade, 9,73; e para obesidade e hipertensão, 7,43. As doenças crônicas não ocorrem sozinhas (geralmente estão associadas), e nessa perspectiva os riscos relativos de letalidade apresentados neste artigo tornam-se relevantes.

Relaxant effect of 7-ethoxy-4-methyl-2H-chromen-2-one by calcium channel blockade: computational and ex vivo studies.

Current work was conducted in order to determine the underlying mode of relaxant action of 7-ethoxy-4-methyl- 2H-chromen-2-one (1), a coumarin obtained by semisynthesis from umbelliferone (2), with significant relaxant effect in a concentration-dependent manner on tracheal rat rings pre-contracted with carbachol (1 μM). In a previous study it was demonstrated that compound 1 and 2 showed significant relaxant effect, being 1 the most active compound (Emax= 100% and EC50= 83 μM) even more active than theophylline an unspecific phosphodiesterases (PDE’s) inhibitor used as positive control. Moreover, pretreatment with 1 significantly shifted to the right the carbachol-induced contraction. On the other hand, compound 1 (83 μM) produces significant (100%) relaxant effect on the contraction induced by KCl (80 mM) and the CaCl2-induced contraction was significantly reduced by the coumarin 1 as nifedipine does (a L-type calcium channel blocker), used as positive control. Indomethacin (10 μM, unspecific COX inhibitor) significantly reduced 1-relaxation. Meanwhile, in the presence of isoproterenol (a  -adrenergic agonist), and K+ channel blockers glibenclamide (10 μM) and 2- AP (100 μM) the relaxant curve was not modified. Compound 1 was docked on an outer cavity located on the extracellular side of the human L-type calcium channel model (affinity energy -6.8 kcal/mol). However, compound 1 was also found on the same location as nifedipine with the same affinity energy (-6.3 kcal/mol) as previously described. Both conformations were stabilized by aliphatic interactions on both binding sites, primordially by a π-π interaction between FIVS6.7 and aromatic rings from compound 1. In conclusion, 7-ethoxy-4- methyl-2H-chromen-2-one (1) induces a significant relaxant action on rat trachea rings, through L-type calcium channel blockade and, as a second mechanism of action, by a possible intracellular cyclic AMP increasing.

Ventana aortopulmonar: reporte de 4 casos / Aortopulmonary window: report of four cases

La ventana aortopulmonar es una malformación congénita rara en la cual la aorta y la arteria pulmonar están comunicados por un orificio de diámetro variable. En forma retrospectiva revisamos el cuadro clínico , diagnóstico, lesiones asociadas y tratamiento en cuatro casos con esta malformación, manejados en nuestro servicio en el período comprendido entre 1980 y 1990. Dos pacientes tenían una ventana aortopulmonar de tipo distal, y dos de las del tipo proximal. Existió lesión asociada en tres pacientes: interrupción del arco aórtico tipo A, estenosis subvalcular aórtica, persistencia del conducto arteriosos y comunicación interventricular. Todos los pacientes fueron tratados quirúrgicamente encontrándose un orificio de comunicación con un diámetro entre 12 y 15 mm. Se presentó una sola reapertura que se cerró en forma satisfactoria en un segundo tiempo. Se discuten los problemas de diagnóstico y tratamiento que planea esta malformación