First report of KPC variants conferring ceftazidime-avibactam resistance in Colombia: introducing KPC-197.

Resistance to ceftazidime-avibactam (CZA) due to Klebsiella pneumoniae carbapenemase (KPC) variants is increasing worldwide. We characterized two CZA-resistant clinical Klebsiella pneumoniae strains by antimicrobial susceptibility test, conjugation assays, and WGS. Isolates belonged to ST258 and ST45, and produced a KPC-31 and a novel variant KPC-197, respectively. The novel KPC variant presents a deletion of two amino acids on the Ω-loop (del_168-169_EL) and an insertion of two amino acids in position 274 (Ins_274_DS). Continued surveillance of KPC variants conferring CZA resistance in Colombia is warranted. IMPORTANCE: Latin America and the Caribbean is an endemic region for carbapenemases. Increasingly high rates of Klebsiella pneumoniae carbapenemase (KPC) have established ceftazidime-avibactam (CZA) as an essential antimicrobial for the treatment of infections due to MDR Gram-negative pathogens. Although other countries in the region have reported the emergence of CZA-resistant KPC variants, this is the first description of such enzymes in Colombia. This finding warrants active surveillance, as dissemination of these variants could have devastating public health consequences.

SNUPN deficiency causes a recessive muscular dystrophy due to RNA mis-splicing and ECM dysregulation.

SNURPORTIN-1, encoded by SNUPN, plays a central role in the nuclear import of spliceosomal small nuclear ribonucleoproteins. However, its physiological function remains unexplored. In this study, we investigate 18 children from 15 unrelated families who present with atypical muscular dystrophy and neurological defects. Nine hypomorphic SNUPN biallelic variants, predominantly clustered in the last coding exon, are ascertained to segregate with the disease. We demonstrate that mutant SPN1 failed to oligomerize leading to cytoplasmic aggregation in patients' primary fibroblasts and CRISPR/Cas9-mediated mutant cell lines. Additionally, mutant nuclei exhibit defective spliceosomal maturation and breakdown of Cajal bodies. Transcriptome analyses reveal splicing and mRNA expression dysregulation, particularly in sarcolemmal components, causing disruption of cytoskeletal organization in mutant cells and patient muscle tissues. Our findings establish SNUPN deficiency as the genetic etiology of a previously unrecognized subtype of muscular dystrophy and provide robust evidence of the role of SPN1 for muscle homeostasis.

Supervivencia global y libre de enfermedad en mujeres con sobrepeso/obesidad al diagnóstico de cáncer de mama: Un estudio observa-cional de centro único / Overall and disease-free survival in women being over-weight/obesityat the diagnosis of breast cancer. A single-center observationalstudy

Introducción:El objetivo del presente estudio fue evaluar las características clínicas, patológi-cas e histológicas tumorales y su asociación con la recurrencia, metástasis y pronóstico en términos de supervivencia global y libre de enfermedad, de las pacientes que padecen sobre-peso u obesidad al momento del diagnóstico de cáncer de mama.Materiales y métodos:Se condujo un estudio descriptivo,longitudinal,retrospectivo, en un centro oncológico de referencia de Medellín. Se recolectó información de pacientes mayores de 18 años, con cáncer de mama infiltrante temprano y avanzado, entre los años 2012 ­2017, quienes presentaran IMC ≥ 25 kg/m2 al momento del diagnóstico. Las medianas de supervi-vencia se calcularon a través de curvas de Kaplan Meier y las diferencias mediante Log Rank Test.Resultados:Se analizó información de 1.349 pacientes. La mortalidad por todas las causas fue de 13.6% y aumentó proporcionalmente con el IMC (HR = 1.03, IC 1.0-1.05). Se identifica-ron 12.6% de recurrencias y el riesgo con el aumento de IMC no fue estadísticamente signifi-cativo (HR =1.02, IC 0.99 -1.05). Características como mala diferenciación tumoral, invasión linfovascular y estadio tumoral se asociaron de forma univariada con mayor mortalidad.Conclusión:Se demostró una asociación positiva e independiente entre el IMC elevado, la mortalidad y el riesgo de recurrencia en pacientes con cáncer de mama. Así como una aso-ciación con fenotipos tumorales agresivos y características de peor pronóstico. Se sugiere considerar modificaciones en el estilo de vida y un manejo multidisciplinario, como estrate-gias que posiblemente impacten en estos desenlaces

Introduction:The objective of the present study was to evaluate the clinical, pathological, and histological characteristics of tumors and their associations with recurrence, metastasis,and prognosis in terms of overall and disease-free survival inoverweight or obese patients at the time of diagnosis.Materials and methods: A descriptive, longitudinal, retrospective study was conducted at a reference cancer center in Medellin. Information was collected from patients older than 18 years of age with early or advanced infiltrating breast cancer between 2012 and 2017 who had a BMI ≥ 25 kg/m2 at the time of diagnosis. Median survival rates were calculated using Kaplan­Meier curves, and differences were determined using the log-rank test.Results: Information from 1,349 patients was analyzed. All-cause mortality was 13.6% and increased proportionally with BMI (HR = 1.03, CI 1.0-1.05). A total of 12.6% of the recurrences were identified,and the risk with increasing BMI was not significantly different(HR =1.02, CI 0.99 -1.05). Patient characteristicssuch as poor tumor differentiation, lymphovascular inva-sion, and tumor stage were univariately associated with increasedmortality.Conclusion: Positiveand independent associations weredemonstrated between high BMI and mortality and between high BMI and the risk of recurrence in patients with breast cancer. In addition, there wasan association betweenaggressive tumor phenotypes and worse prog-nostic characteristics. Lifestylemodifications and multidisciplinary management should be considered strategies for impactingthese outcomes

New spinocerebellar ataxia subtype caused by SAMD9L mutation triggering mitochondrial dysregulation (SCA49).

Spinocerebellar ataxias consist of a highly heterogeneous group of inherited movement disorders clinically characterized by progressive cerebellar ataxia variably associated with additional distinctive clinical signs. The genetic heterogeneity is evidenced by the myriad of associated genes and underlying genetic defects identified. In this study, we describe a new spinocerebellar ataxia subtype in nine members of a Spanish five-generation family from Menorca with affected individuals variably presenting with ataxia, nystagmus, dysarthria, polyneuropathy, pyramidal signs, cerebellar atrophy and distinctive cerebral demyelination. Affected individuals presented with horizontal and vertical gaze-evoked nystagmus and hyperreflexia as initial clinical signs, and a variable age of onset ranging from 12 to 60 years. Neurophysiological studies showed moderate axonal sensory polyneuropathy with altered sympathetic skin response predominantly in the lower limbs. We identified the c.1877C > T (p.Ser626Leu) pathogenic variant within the SAMD9L gene as the disease causative genetic defect with a significant log-odds score (Z max = 3.43; θ = 0.00; P < 3.53 × 10-5). We demonstrate the mitochondrial location of human SAMD9L protein, and its decreased levels in patients' fibroblasts in addition to mitochondrial perturbations. Furthermore, mutant SAMD9L in zebrafish impaired mobility and vestibular/sensory functions. This study describes a novel spinocerebellar ataxia subtype caused by SAMD9L mutation, SCA49, which triggers mitochondrial alterations pointing to a role of SAMD9L in neurological motor and sensory functions.

Recommendations for the diagnosis and management of persons with suspected vaccine-induced immune thrombotic thrombocytopenia (VITT) / Recomendaciones para diagnostico y manejo de personas con trombocitopenia trombotica inmune inducida por vacunas (VITT)

Abstract In recent months, rare cases of thrombosis at unusual sites associated with thrombocytopenia, occurring within a typical risk window (i.e., 4-28 days) after receiving SARS CoV2 vaccines, have been reported. Healthcare professionals should be prepared to detect these cases on time. The Expert Panel of the Knowledge Management and Transfer Network conducted a free search of the related literature. With the available information and the clinical expertise of the working group, we formulated, reviewed, and endorsed recommendations for the timely suspicion, diagnosis (case definitions, the use of initial laboratory and imaging tests, specific tests), and management of these thrombotic conditions. This document is considered a living document that will be updated as new evidence emerges, and recommendations may change over time.

Resumen En meses recientes se han reportado casos raros de trombocitopenia y trombosis en sitios inusuales, que ocurren dentro de una ventana de riesgo típica ( por ejemplo de 4 a 28 días) luego de recibir vacunas de SARS CoV 2. Los profesionales de la salud deben estar preparados para detectar estos casos a tiempo. Un panel de expertos y una red de transferencia de conocimiento realizó una búsqueda libre de literatura seleccionada. Con la información disponible y la experticia clínica del grupo de trabajo revisamos y dimos recomendaciones para la sospecha temprana, el diagnostico (definición de caso, el uso de pruebas de laboratorio especificas y de imágenes diagnósticas) para le manejo de estas condiciones tromboticas. Este documento es considerado un documento vivo que debe ser actualizado a medida que surja nueva evidencia y las recomendaciones vayan cambiando con el tiempo

Training primary health care providers in Colombia, Mexico and Peru to increase alcohol screening: Mixed-methods process evaluation of implementation strategy.

Background: Initial results from the SCALA study demonstrated that training primary health care providers is an effective implementation strategy to increase alcohol screening in Colombia, Mexico and Peru, but did not show evidence of superior performance for the standard compared to the shorter training arm. This paper elaborates on those outcomes by examining the relationship of training-related process evaluation indicators with the alcohol screening practice. Methods: A mix of convergent and exploratory mixed-methods design was employed. Data sources included training documentation, post-training questionnaires, observation forms, self-report forms and interviews. Available quantitative data were compared on outcome measure - providers' alcohol screening. Results: Training reach was high: three hundred fifty-two providers (72.3% of all eligible) participated in one or more training or booster sessions. Country differences in session length reflected adaptation to previous topic knowledge and experience of the providers. Overall, 49% of attendees conducted alcohol screening in practice. A higher dose received was positively associated with screening, but there was no difference between standard and short training arms. Although the training sessions were well received by participants, satisfaction with training and perceived utility for practice were not associated with screening. Profession, but not age or gender, was associated with screening: in Colombia and Mexico, doctors and psychologists were more likely to screen (although the latter represented only a small proportion of the sample) and in Peru, only psychologists. Conclusions: The SCALA training programme was well received by the participants and led to half of the participating providers conducting alcohol screening in their primary health care practice. The dose received and the professional role were the key factors associated with conducting the alcohol screening in practice.Plain Language Summary: Primary health care providers can play an important role in detecting heavy drinkers among their consulting patients, and training can be an effective implementation strategy to increase alcohol screening and detection. Existing training literature predominantly focuses on evaluating trainings in high-income countries, or evaluating their effectiveness rather than implementation. As part of SCALA (Scale-up of Prevention and Management of Alcohol Use Disorders in Latin America) study, we evaluated training as implementation strategy to increase alcohol screening in primary health care in a middle-income context. Overall, 72.3% of eligible providers attended the training and 49% of training attendees conducted alcohol screening in practice after attending the training. Our process evaluation suggests that simple intervention with sufficient time to practice, adapted to limited provider availability, is optimal to balance training feasibility and effectiveness; that booster sessions are especially important in context with lower organizational or structural support; and that ongoing training refinement during the implementation period is necessary.

Prevalence of caregiver burden syndrome in formal caregivers of institutionalised patients with psychiatric illness.

INTRODUCTION: Caregiver burden syndrome has been highlighted as a neglected problem, in which a dependent person's caregiver must change their lifestyle while facing a range of stressors which they cannot always overcome. This leads to a state of physical and mental exhaustion, hindering the caregiver's performance at their work environment. OBJECTIVE: To define the caregiver burden syndrome prevalence among formal caregivers of mentally-ill dependent patients at Clínica del Oriente in the period 2016 II (July-December) and 2017 I (January-June). MATERIALS AND METHODS: A descriptive cross-sectional observational study was carried out in a population of formal caregivers of with mental illness institutionalised at either of the two facilities of Clínica del Oriente, La Ceja and El Carmen de Viboral. We used a survey with sociodemographic, clinical and work-related variables, and the Zarit Burden Interview. RESULTS: 53 caregivers were analysed; 11 had the syndrome (20.8%), 17% had mild burden and 3.8% severe burden. CONCLUSION: The prevalence of caregiver burden syndrome in formal caregivers was lower than found in studies on informal caregivers.

Prevalencia del Síndrome de Carga del Cuidador en cuidadores formales de pacientes con enfermedad psiquiátrica institucionalizados / Prevalence of caregiver burden syndrome in formal caregivers of institutionalised patients with psychiatric illness

RESUMEN Introducción: El síndrome de carga del cuidador se ha destacado a través del tiempo como una problemática ignorada, en la que el cuidador de una persona dependiente debe permutar su estilo de vida y enfrentarse a diferentes factores estresores que, en ocasiones, no alcanza a controlar, lo que desencadena un estado de agotamiento físico y mental, obstaculizando su desenvolvimiento en el entorno laboral. Objetivo: Definir la prevalencia de síndrome de carga del cuidador en cuidadores formales de paciente dependiente con enfermedad psiquiátrica en la Clínica del Oriente para el semestre 2016 II (julio-diciembre) y 2017 I (enero-junio). Materiales y métodos: Se ejecutó un estudio observacional descriptivo de corte transversal en una población de cuidadores formales de pacientes con enfermedad psiquiátrica institucionalizados en la Clínica del Oriente, la cual tiene 2 sedes, ubicadas en La Ceja y en El Carmen de Viboral. La investigación se realizó por medio de una encuesta con variables sociodemográficas, clínicas y laborales, y la escala de sobrecarga de Zarit y Zarit. Resultados: Se analizó a 53 cuidadores, 11 cuidadores presentaron el síndrome (20,8%), el 17% presentaba sobrecarga leve y el 3,8% sobrecarga intensa. Conclusión: La prevalencia del síndrome de carga del cuidador en cuidadores formales fue menor a lo encontrado en estudios sobre cuidadores informales.

ABSTRACT Introduction: Caregiver burden syndrome has been highlighted as a neglected problem, in which a dependent person's caregiver must change their lifestyle while facing a range of stressors which they cannot always overcome. This leads to a state of physical and mental exhaustion, hindering the caregiver's performance at their work environment. Objective: To define the caregiver burden syndrome prevalence among formal caregivers of mentally-ill dependent patients at Clínica del Oriente in the period 2016 II (July-December) and 2017 I (January-June). Materials and methods: A descriptive cross-sectional observational study was carried out in a population of formal caregivers of with mental illness institutionalised at either of the two facilities of Clínica del Oriente, La Ceja and El Carmen de Viboral. We used a survey with sociodemographic, clinical and work-related variables, and the Zarit Burden Interview. Results: 53 caregivers were analysed; 11 had the syndrome (20.8%), 17% had mild burden and 3.8% severe burden. Conclusion: The prevalence of caregiver burden syndrome in formal caregivers was lower than found in studies on informal caregivers.

Percepción estudiantil sobre el modelo educativo basado en la simulación / Student perception of the educational model based on simulation

Objetivo: evaluar la percepción de los estudiantes sobre un modelo educativo basado en simulación, en una escuela de medicina privada ubicada en Medellín, Colombia, respecto a su capacidad para desempeñarse en escenarios clínicos reales. Materiales y métodos: estudio transversal. La muestra fueron estudiantes de medicina del IV al XIII período académico. Los datos se recolectaron en fuentes primarias, mediante el diseño y aplicación de un cuestionario. Resultados: la muestra incluyó 300 estudiantes durante sus prácticas clínicas y pasantías y la edad promedio fue de 21,9 años. El 68,3% (n = 205) de la muestra eran mujeres. Se evaluó el nivel de satisfacción con la experiencia de usar simulación clínica; el 65,3% (n = 196) describió la experiencia como satisfactoria, el 2% (n = 6) y el 23% (n = 69) como insatisfactoria y moderadamente satisfactoria respectivamente; los participantes restantes 9,7% (n = 29) describieron la experiencia como totalmente satisfactoria. En cuanto a la percepción de las competencias desarrolladas bajo el modelo educativo se destacan el razonamiento clínico, 98% (n = 294) y la toma de decisiones, 95% (n = 285). Conclusión: los estudiantes encuestados percibieron que la simulación facilita el aprendizaje al posibilitar el desarrollo de habilidades como el trabajo en equipo y la comunicación, lo que genera un alto grado de satisfacción en los estudiantes con respecto a su proceso de formación..(Au)

Objective: to assess perception of the students on a simulation-based educational model, in a private medical school located at the municipality of Medellín, Colombia, regarding with their ability to perform in real clinical scenarios. Materials and methods: a cross sectional study. Sample were medical students from IV to the XIII academic period. Data was collected from primary sources, through the design and application of a questionnaire. Results: the sample included were 300 students during their clinical practices and clerkship, the mean age was 21.9 years. 68.3% (205) of the sample were female. We assess the level of satisfaction with the experience of using clinical simulation; 65.3% (n=196) described the experience as satisfactory, 2% (n=6) and 23% (n=69) as unsatisfactory and moderately satisfactory respectively; remaining participants described the experience as full satisfactory. Regarding the perception of the competences developed under the simulation-based education model, the main ones were 98% (n=294) clinical reasoning and 95% (n=285) decision making. Conclusion: surveyed students perceived that simulation facilitates learning by making possible the development of skills such as teamwork and communication, which generates a high degree of satisfaction in students regarding their training process..(Au)

Prevalence of caregiver burden syndrome in formal caregivers of institutionalised patients with psychiatric illness. / Prevalencia del Síndrome de Carga del Cuidador en cuidadores formales de pacientes con enfermedad psiquiátrica institucionalizados.

INTRODUCTION: Caregiver burden syndrome has been highlighted as a neglected problem, in which a dependent person's caregiver must change their lifestyle while facing a range of stressors which they cannot always overcome. This leads to a state of physical and mental exhaustion, hindering the caregiver's performance at their work environment. OBJECTIVE: To define the caregiver burden syndrome prevalence among formal caregivers of mentally-ill dependent patients at Clínica del Oriente in the period 2016 II (July-December) and 2017 I (January-June). MATERIALS AND METHODS: A descriptive cross-sectional observational study was carried out in a population of formal caregivers of with mental illness institutionalised at either of the two facilities of Clínica del Oriente, La Ceja and El Carmen de Viboral. We used a survey with sociodemographic, clinical and work-related variables, and the Zarit Burden Interview. RESULTS: 53 caregivers were analysed; 11 had the syndrome (20.8%), 17% had mild burden and 3.8% severe burden. CONCLUSION: The prevalence of caregiver burden syndrome in formal caregivers was lower than found in studies on informal caregivers.

Comparing lung oscillometry with a novel, portable flow interrupter device to measure lung mechanics.

In the community setting, assessing spirometry in school-aged children is often limited by the unavailability of respirology technicians at the point-of-care. We developed a new technique called the Rapid Expiratory Occlusion Method (REOM) that measures respiratory resistance during normal breathing, without specialized training. The aim was to examine the concordance between respiratory resistance measured with the REOM and respiratory resistance measured by oscillometry on the tremoflo. Children aged 6-17 yr, with or without asthma, received respiratory resistance testing on the tremoflo, then on the REOM. Three to five replicates with a coefficient of variation ≤15% were obtained on each instrument; the primary outcome was the concordance between the average respiratory resistance on the REOM and that measured at 5 Hz (R5) on the tremoflo. Thirty-two children (11 girls; 21 boys) were enrolled with a mean age of 11.2 (range 6-17) yr; after excluding two children not meeting reproducibility criteria, 9 healthy controls, 15 controlled asthmatics, and 6 poorly controlled asthmatics were included. Resistance measured on the REOM showed a strong correlation with R5 measured on the tremoflo (P < 0.0001) with no significant differences on the Bland-Altman analyses. Children and their parents found the REOM easy to use and would consider for home use if recommended by their doctor. With the high concordance between resistance values measured on the REOM and that on the tremoflo combined with perceived ease of use, the REOM appears as a promising means for measuring lung function, thus supporting further testing of other psychometric properties.NEW & NOTEWORTHY We have developed a novel version of the interrupter technique to measure respiratory resistance. The Rapid Expiratory Occlusion Method (REOM) is a small handheld device that measures respiratory resistance and demonstrates excellent correlation with airway oscillometry. With its ease of use, REOM may be promising for use in community practice, patient's homes, and, if paired with a telemedicine application, could enable the healthcare provider to monitor patients in their homes.

Hematopoietic Stem Cell Transplantation in Children with Inborn Errors of Immunity: a Multi-center Experience in Colombia.

PURPOSE: To characterize the pediatric population with inborn errors of immunity (IEI) that was treated with hematopoietic stem cell transplantation (HSCT) in three reference centers in Colombia. What have been the characteristics and outcomes of hematopoietic stem cell transplantation in pediatric patients with inborn errors of immunity in three reference care centers in Colombia between 2007 and 2018? METHODS: We conducted an observational, retrospective cohort study in children with a diagnosis of IEI who underwent HSCT between 2007 and 2018. RESULTS: Forty-seven patients were identified, and 5 were re-transplanted. Sixty-eight percent were male. The median age at diagnosis was 0.6 years, and for HSCT was 1.4 years. The most common diseases were chronic granulomatous disease (38%) followed by severe combined immune deficiencies (19%) and hemophagocytic lymphohistiocytosis (15%). Cord blood donors were the most used source of HSCT (44%). T cell-replete grafts from haploidentical donors using post-transplantation cyclophosphamide represent 37% of the cohort. All patients received conditioning, 62% with a non-myeloablative regimen. Calcineurin inhibitors were the main graft-versus-host disease prophylaxis (63.8%). Acute graft-versus-host disease developed in 35% of the total patients. The most frequent post-transplant infections were viral and fungal infections. The 1-year overall survival rates for the patients who received HSCT from identical, haploidentical, and cord sources were 80%, 72%, and 63%, respectively. The 5-year overall survival was 63%. CONCLUSIONS: HSCT is a curative treatment option for some IEI and can be performed with any donor type. Early and timely treatment in referral centers can improve survival.

Rasgo falciforme e infarto esplénico: una entidad no ajena en población antioqueña / Sickle trait and splenic infarction, a non-foreign entity in Antioquia population

Resumen Generalmente, los pacientes con rasgo falciforme sufren pocas manifestaciones del espectro de la anemia de células falciformes. El infarto esplénico es raro, pero es una complicación documentada del rasgo falciforme y, usualmente, se presenta en condiciones de disminución de la presión parcial de oxígeno, como ocurre en grandes alturas. Se presenta el caso de un joven sin antecedentes, quien presentó dolor súbito en hipocondrio izquierdo luego de viaje a zona de gran altura y en quien se documentó infarto esplénico y posteriormente se confirmó como etiología del cuadro, rasgo falciforme mediante electroforesis de hemoglobina. La mayoría de los pacientes desconocen su rasgo falciforme, lo que hace desafiante su enfoque, retrasa el diagnóstico y resulta en manejos inadecuados que pueden aumentar la extensión del infarto esplénico y requerir finalmente esplenectomía.

Abstract Generally, patients with sickle cell trait have few manifestations of the sickle cell spectrum. Splenic infarction is rare, but is a documented complication of sickle cell trait and usually occurs under conditions of decreased partial pressure of oxygen, such as at high altitudes. We present the case of a young man with no previous history who presented sudden pain in the left hypochondrium after traveling to a high-altitude area. Splenic infarction was documented and sickle cell trait was later confirmed with hemoglobin electrophoresis as the etiology of the condition. Most patients remain ignorant of their sickle cell trait, which makes their approach challenging, delays diagnosis, and results in inappropriate management that may increase the extent of splenic infarction and eventually require splenectomy.

Deficiencia de fenilalanina hidroxilasa: espectro clínico y estado actual del diagnóstico en colombia / Phenylalanine hydroxylase deficiency: clinical spectrum and current diagnosis in colombia

RESUMEN Las mutaciones del gen PAH generan deficiencia de la enzima fenilalanina hidroxilasa. Su actividad final varía desde una actividad casi nula o indetectable en la fenilcetonuria clásica hasta una actividad residual del 10 al 35% de la normal. Esta alteración corresponde al error innato del metabolismo de los aminoácidos más frecuente, afectando a 1 de cada 10.000 personas. Las diferentes cantidades de fenilalanina en sangre se traducen en un espectro amplio de manifestaciones clínicas que incluyen retraso global del desarrollo, discapacidad intelectual, convulsiones, rasgos autistas y comportamiento agresivo en los casos más graves. El diagnóstico temprano a través de los programas de tamizaje neonatal se considera prioritario pues las intervenciones oportunas evitan el daño del sistema nervioso central. Conclusiones: El diagnóstico en Colombia es tardío, las intervenciones realizadas a partir de ese momento son fútiles pues el deterioro cognitivo es irreparable, por lo tanto es imperativa la realización de pruebas diagnósticas tempranas cuando aún las intervenciones médicas pueden impactar la mejoría clínica del paciente con disminución importante de la morbilidad propia de esta patología, convirtiéndose en una necesidad la ampliación del programa de tamizaje neonatal, el cual estaría amparado bajo la ley colombiana de enfermedades huérfanas.

ABSTRACT Mutations in the PAH gene generate phenylalanine hydroxylase enzyme deficiency. Its final activity varies from almost null or undetectable in classical phenylketonuria to a residual activity of 10 to 35% of normal activity. This alteration corresponds to the innate more frequent error of the metabolism of the amino acids, affecting 1 of every 10,000 people. Different amounts of phenylalanine in blood translate into a broad spectrum of clinical manifestations including global developmental delay, intellectual disability, seizures, autistic traits, and aggressive behavior in the most severe cases. Early diagnosis through neonatal screening programs is considered a priority because timely interventions avoid damage to the central nervous system. Conclusions: The diagnosis in Colombia is belated, the interventions made from that moment are futile because the cognitive deterioration is irreparable. Therefore, it is imperative to carry out early diagnostic tests when medical interventions can still impact the clinical improvement of the patient with an important decrease of the morbidity characteristic of this pathology, making it necessary to expand the neonatal screening program which would be protected under the Colombian law of orphan diseases.

Paciente con hipertensión arterial y deterioro de su clase funcional secundarios al síndrome de taquicardia postural ortostática / Patient with arterial hypertension and functional class deterioration secondary to postural orthostatic tachycardia syndrome

Resumen La hipertensión ortostática ha sido un diagnóstico elusivo en la práctica clínica por la falta de estudio respecto a su fisiopatología y epidemiología. De esa manera, el abordaje clínico no ha sido expedito para su diagnóstico y tratamiento, así que las causas primarias pueden pasar inadvertidas y sin tratamiento. Se expone el caso clínico de una paciente latina, con hipertensión arterial sumada a deterioro de su clase funcional, a quien se le descartaron otras causas secundarias de hipertensión, y se diagnosticó, mediante estudio hemodinámico y autonómico, síndrome de taquicardia ortostática postural y compromiso del retorno venoso como causa primaria. Este reporte de caso pretende ilustrar respecto a esta causa infrecuente de hipertensión secundaria.

Abstract Orthostatic hypertension has been an elusive diagnosis in clinical practice due to the lack of research with regards to its pathophysiology and aetiology. Thus, clinical approach has not been unobstructed for its diagnosis and treatment, so the primary causes may go unnoticed and remain untreated. The clinical case of a Latin American patient with arterial hypertension associated to a deterioration of her functional class is reported. Secondary causes for hypertension were ruled out and, by means of a hemodynamic and autonomic study, she was diagnosed with postural orthostatic tachycardia syndrome and reduced venous return as the primary cause. This case report pretends to illustrate this rare case of secondary hypertension.

Preservación de biopsias obtenidas por colonoscopia en pacientes con cáncer colorrectal para análisis moleculares / Preservation of obtained biopsies by colonoscopy in patients with colorectal cancer for molecular analysis

Introducción: los estudios relacionados con el análisis del ADN han marcado una pauta para los avances en las ciencias básicas y uno de los requisitos para la obtención de buenos resultados es la calidad del material genético extraído, en conjunto con el método empleado para la preservación de las muestras. Objetivo: comparar tres métodos de preservación de biopsias obtenidas por colonoscopia en pacientes con cáncer colorrectal con fines de uso en estudios de biología molecular. Materiales y métodos: se tomaron biopsias por colonoscopia a nueve pacientes con diagnóstico clínico de cáncer de colon, las cuales se preservaron en solución salina y dos solventes estabilizadores de ácidos nucleicos, RNAlater® y LifeGuard™ Soil Preservation Solution; se realizó extracción del ADN total a las nueve muestras y se verificó la concentración y la calidad del ADN extraído. Resultados: la extracción del ADN a las 24 horas, ocho días, quince días, un mes, seis meses, uno y dos años después de la toma de la muestra, mostró que el ADN de las biopsias preservadas en solución salina se presentaba con baja concentración y degradado a los ocho días, mientras que el preservado en soluciones comerciales estabilizadoras presentó una buena calidad y alta concentración. Por otro lado, la calidad del ADN fue verificada mediante la amplificación por reacción en cadena de la polimerasa (PCR) de un fragmento de ADN asociado al gen APC. Conclusiones: las soluciones LifeGuard™ y RNAlater® pueden ser usadas durante el transporte y conservación de tejidos humanos, y pueden ser recomendados para aquellos laboratorios que deseen preservar muestras con métodos diferentes al embebido de muestras en parafina o que no cuentan con métodos de conservación altamente eficientes como la criogénesis. (AU)

Introduction: Studies related to DNA analysis have set a standard for development in the basic sciences, and one of the requirements for obtaining good results is the quality of the genetic material extracted, together with the method used for the samples preservation. Objective: To compare three methods of preserving biopsies obtained by colonoscopy in patients with colorectal cancer, for purposes of use in molecular biology studies. Materials and methods: Biopsies by colonoscopy from nine patients with clinical diagnosis of colon cancer were taken and preserved in saline solution and two nucleic acids stabilizing solvents, RNAlater® y LifeGuard™ Soil Preservation Solution. The extraction of total DNA was carried out to the nine samples and the concentration and quality of the extracted DNA was verified. Results: DNA extraction at 24 hours, eight days, 15 days, one month, six months, one year and two years after sampling showed that the DNA from biopsies preserved in saline solution had low concentration and degraded at eight days. DNA from samples preserved in commercial stabilizing solutions had high concentration and good quality. This last one was verified by amplification of a DNA fragment associated to the APC gene by polymerase chain reaction. Conclusions: The LifeGuard™ solution as well as the RNAlater® can be used in transport and conservation of human tissues, and may be recommended for laboratories wishing to preserve specimens with different methods to paraffin-embedded specimen or that do not have highly efficient conservation methods such as cryogenics. (AU)

Development of a Dynamic and Adaptive Simulator for Health.

One of the ways to develop health simulations is through the use of computers. This paper presents the use of Intelligent Computer-aided Instruction (ICAI) for the development of an interactive simulator for learning Cardio Pulmonary Resucitation (CPR) which incorporates online tutorials, training and evaluation.

Rapid diagnosis of pulmonary tuberculosis.

INTRODUCTION: World Health Organization had estimated 9.4 million tuberculosis cases on 2009, with 1.7 million of deaths as consequence of treatment and diagnosis failures. Improving diagnostic methods for the rapid and timely detection of tuberculosis patients is critical to control the disease. The aim of this study was evaluating the accuracy of the cord factor detection on the solid medium Middlebrook 7H11 thin layer agar compared to the Lowenstein Jensen medium for the rapid tuberculosis diagnosis. METHODS: Patients with suspected tuberculosis were enrolled and their sputum samples were processed for direct smear and culture on Lowenstein Jensen and BACTEC MGIT 960, from which positive tubes were subcultured on Middlebrook 7H11 thin layer agar. Statistical analysis was performed comparing culture results from Lowenstein Jensen and the thin layer agar, and their corresponding average times for detecting Mycobacterium tuberculosis. The performance of cord factor detection was evaluated determining its sensitivity, specificity, positive and negative predictive value. RESULTS: 111 out of 260 patients were positive for M. tuberculosis by Lowenstein Jensen medium with an average time ± standard deviation for its detection of 22.3 ± 8.5 days. 115 patients were positive by the MGIT system identifying the cord factor by the Middlebrook 7H11 thin layer agar which average time ± standard deviation was 5.5 ± 2.6 days. CONCLUSION: The cord factor detection by Middlebrook 7H11 thin layer agar allows early and accurate tuberculosis diagnosis during an average time of 5 days, making this rapid diagnosis particularly important in patients with negative sputum smear.

Cancer colorrectal: una mirada clínica, genética y molecular / Colorectal cancer: clinical, molecular and genetics view

El cáncer Colorrectal ocupa la cuarta causa de muerte por cáncer en Estados Unidosde América y la quinta causa de muerte por cáncer en Colombia y de esta forma se convierte en un problema de salud pública. El 98% de los cánceres Colorrectales son adenocarcinomas y el otro 2% corresponden a linfomas, carcinoides y tumores estromales gastrointestinales. Las manifestaciones clínicas se relacionan con el tamaño y la localización de la lesión, el 80% de los casos reportados de CCR no presentan un componente hereditario convirtiéndolos en CCR esporádicos. El CCR está asociado con la acumulación de mutaciones en genes supresores de tumores (p53, APC, SMAD,SCC, NM23), oncogenes (MYC y RAS) y genes reparadores del ADN (MSH1, MSH6 y MLH2) estas alteraciones genéticas hacen de este tipo de cáncer un desorden poligenético,convirtiéndolo en un modelo clásico para estudiar las bases genéticas del cáncer.

Post-ablation prolongation of atrioventricular nodal refractory period is correlated with long-term success of cryoablation for atrioventricular nodal reentrant tachycardia in the case of the persistence of a residual jump.

PURPOSE: A residual slow pathway after successful cryoablation for atrioventricular nodal reentrant tachycardia (AVNRT) is correlated with a higher recurrence rate. We described determinants of recurrence in subjects with a residual jump. METHODS: We analyzed the data of subjects with acute successful slow pathway cryoablation for AVNRT using a 6-mm-tip cryocatheter. Success was defined as AVNRT non-inducibility. Patients with no baseline elicitable jump, no inducible AVNRT, and transient first atrioventricular (AV) block at the last site were excluded. RESULTS: From 371 patients who underwent cryoablation from May 2002 to March 2011, 303 fulfilled the entry criteria (mean age, 41 ± 16; 222 women). Baseline AV nodal effective refractory period (ERP) was 272 ± 57 ms, postprocedural 331 ± 64 (P < 0.001), and the mean of the difference (Δ ERP) 60 ± 41. At the end of the procedure, 64 patients (21 %) had a residual jump, of whom 22 with a single echo. At 12 months follow-up, the actuarial recurrence-free rate was 70.3 % in patients with a residual jump and 86 % in those without (P = 0.01). In patients with a jump, only Δ AV nodal ERP was correlated with recurrence (37 ± 41 vs. 68 ± 47 ms; P < 0.04) while a single echo was not. The actuarial rate of recurrence was 60.8 % in patients with a Δ AV nodal ERP ≤ 30 ms and 18.8 % in those with a Δ AV nodal ERP >30 ms (P < 0.01). CONCLUSIONS: Suppression of slow pathway conduction is the optimal endpoint for AVNRT cryoablation. A residual jump can be tolerated if AV nodal ERP postcryoablation is prolonged >30 ms.