Consenso de expertos sobre recomendaciones basadas en evidencia para el diagnóstico, tratamiento y seguimiento de enfermedad de Fabry en pediatría / Expert Consensus on Evidence-Based Recommendations for the Diagnosis, Treatment, and Follow-Up of Fabry Disease in Pediatric Patients / Consenso de especialistas colombianos sobre recomendações baseadas em evidências para o diagnóstico, tratamento e acompanhamento da doença de Fabry em pediatria

Antecedentes: la enfermedad de Fabry (Ef) es una enfermedad rara ligada a X secundaria al depósito lisosomal de glicoesfingolípidos, debido a la deficiencia de la enzima alfa galactosidasa A (α-Gal A). A pesar de su baja frecuencia, es una condición que afecta la calidad de vida de los pacientes y disminuye su esperanza de vida. Objetivo: generar recomendaciones informadas para el diagnóstico y tratamiento de pacientes pediátricos (menores de 18 años) con Ef. Material y Métodos: revisión de literatura en bases de datos y literatura gris a partir de 2010, incluyendo guías de práctica clínica, revisiones sistemáticas y estudios primarios. La calidad de evidencia se evaluó de acuerdo con el tipo. Las recomendaciones se sometieron a consenso de expertos a través de metodología Delphi modificada. El acuerdo se definió a partir del 80 %. Resultados: A partir del análisis de la evidencia recolectada se formularon un total de 45 recomendaciones para tamización, diagnóstico y tratamiento de paciente pediátrico con Ef. El panel revisor estuvo conformado por once expertos en el tema. Las recomendaciones fueron aprobadas con puntuaciones entre 82.3 % y 100 %. Conclusiones: las recomendaciones resultantes del consenso de expertos permitirán la toma de decisiones clínicas y estandarización de la práctica en la atención de pacientes pediátricos con Ef en el país y la región. El diagnóstico temprano y oportuno garantiza una disminución del impacto en la calidad de vida de los pacientes y sus familiares

Background: Fabry disease (fD) is a rare X-linked disease characterized by the accumulation of glyco- sphingolipids in lysosomes due to the deficiency in the production of alpha-galactosidase A (α-Gal A) enzyme. Despite its low frequency, this disease has a serious impact on the life expectancy and quality. Objective: To make evidence-based recommendations for the diagnosis and treatment of fD in pediatric patients (<18 years of age). Materials and Methods: A study of databases and gray literature was conducted in 2010, including clinical practice guidelines, systematic reviews, and primary research. The type of evidence was used to determine the quality of evidence. The recommendations were submitted to an expert consensus using the modified Delphi process. The agreement was set at 80%. Conclusions: The recommendations emerging from this expert consensus will enable the standardization of care provision for pediatric patients with fD in Colombia and Latin America and clinical decision-making for disease management. Notably, making an early diagnosis ensures a reduction in the impact of this disease on the quality of life of patients and their families

Fundamento: a doença de Fabry (Df) é uma rara doença ligada ao cromossomo X secundária à deposi- ção lisossômica de glicoesfingolipídeos devido à deficiência da enzima alfa galactosidase A (α-Gal A). Apesar de sua baixa frequência, é uma condição que afeta a qualidade de vida dos pacientes e diminui sua expectativa de vida. Objetivo: gerar recomendações baseadas em evidências para o diagnóstico e tratamento de pacientes pediátricos (com menos de 8 anos de idade) com Df. Materais e Métodos: foi realizada uma revisão da literatura em bases de dados e literatura cinza a partir de 2010, incluindo diretrizes de prática clínica, revisões sistemáticas e estudos primários. A qualidade da evidência foi avaliada de acordo com o tipo de evidência. As recomendações foram submetidas ao consenso de especialistas usando a metodologia Delphi modificada. A concordância foi definida a partir de 80%. Resultados: com base na análise das evidências coletadas, foram formuladas um total de 45 recomendações para triagem, diagnóstico e tratamento de pacientes pediátricos com doença de Fabry. O painel de revisão foi composto por onze especialistas no assunto. As recomendações foram aprovadas com pontuações entre 82,3% e 100%. Conclusões: as recomendações resultantes do consenso de especialistas permitirão a tomada de decisão clínica e a padronização da prática no cuidado de pacientes pediátricos com Df em nível nacional e regional; o diagnóstico precoce e oportuno garante a redução do impacto na qualidade de vida dos pacientes e seus familiares.

Scrotal flap phalloplasty as temporary neophallus in infants and children with penile agenesis: Multi-institutional experience and long-term follow-up.

INTRODUCTION: Aphallia is a rare congenital disorder pertaining to genotypic males. Early surgical creation of a neophallus is recommended to reinforce the child's male gender-identity, favoring proper psychosexual development. Modern microsurgical techniques used to create a neophallus in adults are not recommended in children due to the invasiveness and complexity of the procedures, along with high complication rates. Scrotal flap phalloplasty is a simple and reproducible technique to create a temporary neophallus in prepubertal boys with aphallia. OBJECTIVE: We present a multi-institutional experience, ten years after the initial description of the scrotal flap phalloplasty (SFP) technique, in which a flap from the well-developed scrotum is used to build a temporary neophallus, without obvious scars in patients with aphallia. STUDY DESIGN: The records of surgical neophalloplasty for aphallia patients from 4 centers between 2011 and 2021 were reviewed. All patients had at least one year follow-up to assess for short and long-term complications. Age at initial operation, associated anomalies, and other related surgical procedures were analyzed. RESULTS: The post-operative aesthetic result in all patients was satisfactory and has been maintained in the long-term follow-up, with all patients presenting a cylindrical structure resembling an uncircumcised penis, without evidence of significant contraction or loss of length. (Summary Figure) DISCUSSION: Non-microsurgical neophalloplasty techniques in patients with penile agenesis are temporary procedures that help to establish the body image and preserve the psychosexual development of the patient with aphallia. These techniques do not involve tissue transplant from a distant region, and are simpler to perform, with less scarring at the donor sites. Due to significant donor scars and considerable morbidity and complexity associated with the definitive phalloplasty techniques, we created a simple, reproducible and straightforward procedure to serve as a temporary neophallus in young boys with aphallia. As affected patients usually have a well-formed scrotum with normal and orthotopic testicles, it is the ideal donor site for a temporary neo-phallus in childhood. Furthermore, other donor sites are preserved for a definitive phalloplasty. There are limitations to this study, as quality of life could not be assessed and psychological or gender-identity investigations have not been carried out. None of these children have reached puberty, and hence decision and outcomes of definitive neophallus reconstruction has not been considered to date. CONCLUSION: Scrotal flap phalloplasty is a minimally invasive, simple and reproducible technique used to create a temporary neophallus in boys with aphallia, while waiting for definitive reconstructive surgery after puberty.

Presurgical orthodontic decompensation with clear aligners.

INTRODUCTION: Orthodontists, surgeons, and patients have taken an interest in using clear aligners in combination with orthognathic surgery. This study aimed to evaluate the accuracy of tooth movements with clear aligners during presurgical orthodontics using novel 3-dimensional superimposition techniques. METHODS: The study sample consisted of 20 patients who have completed presurgical orthodontics using Invisalign clear aligners. Initial (pretreatment) digital dental models, presurgical digital dental models, and ClinCheck prediction models were obtained. Presurgical models were superimposed onto initial ones using stable anatomic landmarks; ClinCheck models were superimposed onto presurgical models using surface best-fit superimposition. Five hundred forty-five teeth were measured for 3 angular movements (buccolingual torque, mesiodistal tip, and rotation) and 4 linear movements (buccolingual, mesiodistal, vertical, and total scalar displacement). The predicted tooth movement was compared with the achieved amount for each movement and tooth, using both percentage accuracy and numerical difference. RESULTS: Average percentage accuracy (63.4% ± 11.5%) was higher than in previously reported literature. The most accurate tooth movements were buccal torque and mesial displacement compared with lingual torque and distal displacement, particularly for mandibular posterior teeth. Clinically significant inaccuracies were found for the buccal displacement of maxillary second molars, lingual displacement of all molars, intrusion of mandibular second molars, the distal tip of molars, second premolars, and mandibular first premolars, buccal torque of maxillary central and lateral incisors, and lingual torque of premolars and molars. CONCLUSIONS: Superimposition techniques used in this study lay the groundwork for future studies to analyze advanced clear aligner patients. Invisalign is a treatment modality that can be considered for presurgical orthodontics-tooth movements involved in arch leveling and decompensation are highly accurate when comparing the simulated and the clinically achieved movements.

Complicaciones cardiovasculares en pacientes COVID-19 hospitalizados en Unidades de Pacientes Críticos en Chile. Registro COVICAR / Cardiovascular complications in COVID-19 patients admitted to intensive care units in Chilean hospitals

BACKGROUND: Patients with a cardiovascular (CV) history may be at greater risk of becoming ill and die due to SARS-CoV-2. AIM: To assess the incidence of CV complications in COVID-19 patients, the type of complication, and their association with CV history. MATERIAL AND METHODS: The clinical course of 1,314 patients with COVID-19 admitted consecutively to critical care units of 10 Chilean hospitals was registered between April and August of 2020. RESULTS: The median age of patients was 59 years and 66% were men. One hundred-four (8%) had a CV history, namely heart failure (HF) in 53 (4.1%), coronary heart disease in 50 (3.8 %), and atrial fibrillation in 36 (2.7 %). There were CV complications in 359 patients (27.3%). The most common were venous thrombosis in 10.7% and arrhythmias in 10.5%, HF in 7.2%, type 2 acute myocardial infarction in 4.2%, arterial thrombosis in 2.0% and acute coronary syndrome (ACS) in 1.6%. When adjusted by age, sex and risk factors, only HF (Odds ratio (OR) = 7.16; 95% confidence intervals (CI), 3.96-12.92) and ACS (OR = 5.44; 95% CI, 1.50-19.82) were significantly associated with CV history. There was no association with arrhythmias, type 2 acute myocardial infarction, arterial or venous thrombosis. CONCLUSIONS: Patients with a history of CV disease are at greater risk of suffering HF and ACS when hospitalized due to COVID-19. Arrhythmias, type 2 AMI, and arterial or venous thrombosis occur with the same frequency in patients with or without CV history, suggesting that these complications depend on inflammatory phenomena related to the infection.

Joint Cardioprotective Effect of Vitamin C and Other Antioxidants against Reperfusion Injury in Patients with Acute Myocardial Infarction Undergoing Percutaneous Coronary Intervention.

Percutaneous coronary intervention (PCI) has long remained the gold standard therapy to restore coronary blood flow after acute myocardial infarction (AMI). However, this procedure leads to the development of increased production of reactive oxygen species (ROS) that can exacerbate the damage caused by AMI, particularly during the reperfusion phase. Numerous attempts based on antioxidant treatments, aimed to reduce the oxidative injury of cardiac tissue, have failed in achieving an effective therapy for these patients. Among these studies, results derived from the use of vitamin C (Vit C) have been inconclusive so far, likely due to suboptimal study designs, misinterpretations, and the erroneous conclusions of clinical trials. Nevertheless, recent clinical trials have shown that the intravenous infusion of Vit C prior to PCI-reduced cardiac injury biomarkers, as well as inflammatory biomarkers and ROS production. In addition, improvements of functional parameters, such as left ventricular ejection fraction (LVEF) and telediastolic left ventricular volume, showed a trend but had an inconclusive association with Vit C. Therefore, it seems reasonable that these beneficial effects could be further enhanced by the association with other antioxidant agents. Indeed, the complexity and the multifactorial nature of the mechanism of injury occurring in AMI demands multitarget agents to reach an enhancement of the expected cardioprotection, a paradigm needing to be demonstrated. The present review provides data supporting the view that an intravenous infusion containing combined safe antioxidants could be a suitable strategy to reduce cardiac injury, thus improving the clinical outcome, life quality, and life expectancy of patients subjected to PCI following AMI.

Ovario histerectomía laparoscópica canina. A propósito de un primer caso informado en Venezuela / Canine laparoscopic ovary hysterectomy. About a first case reported in Venezuela

La ovariohisterectomia (OH) es el procedimiento quirúrgico que con más frecuencia se realiza para la esterilización quirúrgica de los animales. No solo garantiza el control de la población sino también disminuye el riesgo de enfermedades mortales como la piómetra y el cáncer.1 Este procedimiento puede realizarse a través de 2 vías de abordaje, la tradicionalmente conocida por laparotomía y la vía laparoscópica o mínimamente invasiva.Objetivos : A continuación, presentamos el primer caso informado en Venezuela de una perra a quien se le realizó ovario histerectomía laparoscópica (OHL) para la esterilización quirúrgica.Materiales y métodos: Se describe el protocolo quirúrgico practicado en una canina sana sometida a OHL. La descripción incluye la preparación del paciente, el instrumental utilizado, la preparación del área quirúrgica, el posicionamiento del animal, así como las etapas de la técnica quirúrgica laparoscópica.Resultados : La perra evolucionó de manera satisfactoria. Los resultados del seguimiento demostraron que la OHL puede ser realizada con seguridad, con mínimos períodos de recuperación y complicaciones transoperatorias y posoperatorias. La técnica de OHL se convierte en una alternativa para la realización de diferentes procedimientos quirúrgicos en pequeños animales.Conclusión : La OHL es una técnica segura, que incluye dentro de sus beneficios la reducción del dolor posoperatorio, dehiscencia de la herida, así como disminución del riesgo de resección incompleta del tejido ovárico(AU)

Ovariohysterectomy (OH) is the most frequently performed surgical procedure for the surgical sterilization of animals. It not only ensures population control but also reduces the risk of deadly diseases such as pyometra and cancer.1 This procedure can be performed through 2 approaches, the traditionally known as laparotomy and the laparoscopic or minimally invasive route.Objetives : Next, we present the first reported case in Venezuela) who underwent a laparoscopic hysterectomy (OHL) ovary for surgical sterilization.Material and Methods : The surgical protocol practiced in a healthy canine subjected to OHL is described. The description includes the preparation of the patient, the instruments used, the preparation of the surgical area, the positioning of the animal, as well as the stages of the laparoscopic surgical technique.Results : The dog evolved satisfactorily. The results of the follow-up demonstrated that OHL can be performed safely, with minimal recovery periods and intraoperative and postoperative complications.Conclusión : OHL is a safe technique, which includes among its benefits the reduction of postoperative pain, wound dehiscence, as well as reduction of the risk of incomplete resection of ovarian tissue(AU)

The contribution of metabolic parameters of FDG PET/CT prior and during therapy of adult patients with lymphomas.

Lymphomas are the most common hematological malignancies and are further distinguished in Hodgkin lymphoma (HL) and non-Hodgkin (NHL). For staging purposes and for assessing response to treatment, the Lugano classification is currently used, both for HL and NHL patients, whereas for the assessment of prognosis, several prognostic systems exist, such as the international prognostic index (IPI) and revised-IPI for diffuse large B cell lymphomas, follicular lymphoma IPI (FLIPI)-1 and 2 for follicular lymphomas, and the international prognostic score for advanced HL. The aim of this systematic review was to determine the significance of the metabolic FDG PET/CT parameters, such as metabolic tumor volume (MTV) and total lesion glycolysis (TLG), in monitoring therapeutic interventions and prognostic outcome of patients with HL and NHL. We performed a systematic search on the literature and selection of articles concerning treatment evaluation, response and survival in association with MTV and TLG in patients with lymphomas. Our review documented that in most studies, baseline MTV and TLG were predictive of treatment response, progression-free survival (PFS) and overall survival (OS) for both HL and NHL patients. There were conflicting results for the value of interim determination of MTV and TLG. Our conclusion was that combination of baseline MTV and TLG parameters with prognostic scoring systems, such as IPI, or FLIPI-1 and -2, will add additional predictive power for response and prognosis in lymphoma patients.

The effect of the Covid-19 pandemic on pediatric urology

ABSTRACT Medical and surgical priorities have changed dramatically at the time of this pandemic. Scientific societies around the World have provided rapid guidance, underpinned by the best knowledge available, on the adaptation of their guidelines recommendations to the current situation. There are very limited scientific evidence especially in our subspecialty of pediatric urology. We carry out a review of the little scientific evidence based mainly on the few publications available to date and on the recommendations of the main scientific societies regarding which patients should undergo surgery, when surgery should be performed and how patient visits should be organize.

The effect of the Covid-19 Pandemic on pediatric urology.

Medical and surgical priorities have changed dramatically at the time of this pandemic. Scientific societies around the World have provided rapid guidance, underpinned by the best knowledge available, on the adaptation of their guidelines recommendations to the current situation. There are very limited scientific evidence especially in our subspecialty of pediatric urology. We carry out a review of the little scientific evidence based mainly on the few publications available to date and on the recommendations of the main scientific societies regarding which patients should undergo surgery, when surgery should be performed and how patient visits should be organize.

Disorders of sex development: Genetic characterization of a patient cohort.

Disorders of sex development (DSDs) are congenital conditions in which the external appearance of the individual does not coincide with the chromosomal constitution or the gonadal sex. In other words, there is an ambiguous or intermediate condition between the male and female phenotypes of the anatomical sex. These atypical conditions are manifested in several ways, ranging from genital ambiguity to phenotypes that are so attenuated that they can go unnoticed or appear normal. Currently, there is a lack of understanding of the factors responsible for these outcomes; however, they are likely to be conditioned by genetic, hormonal and environmental factors during prenatal and postnatal development. The present study determined the genetic etiology of DSDs in Colombian patients by conventional cytogenetic analysis, FISH and MLPA (for SF1, DAX1, SOX9, SRY and WNT4). A cohort of 43 patients with clinical phenotypes of sex development disorder was used in the present study. Using this multistep experimental approach, a diagnostic percentage of 25.58% was obtained: 17 patients (39.53%) were classified as having gonadal development disorders, the majority of which were ovotesticular disorders with numerical and/or structural alterations of the sex chromosomes, 9 patients (20.93%) were classified as having testicular DSD with a 46,XY karyotype, and 3 patients (6.98%) as having ovarian DSD with a 46,XX karyotype. The remaining 14 patients (32.56%) were classified as 'other' since they could not be grouped into a specific class of gonadal development, corresponding to hypospadias and multiple congenital anomalies. These findings highlight the importance of histological and cytogenetic studies in a gonadal biopsy. In 11/43 cases, the multistep experimental protocol presented in the present study yielded etiological or histological findings that could be used to define the medical management of patients with DSDs. In conclusion, for the etiological diagnosis of DSDs, a broad­spectrum approach that includes endocrinological tests, conventional karyotyping, molecular karyotyping by FISH and, molecular tests is required, in addition to gonadal tissue analyses, to identify genetic alterations.

Gene dosage of DAX-1, determining in sexual differentiation: duplication of DAX-1 in two sisters with gonadal dysgenesis.

Two sisters phenotypically normal females, presenting with tumor abdominal mass with histopathological findings of teratoma and gonadoblastoma associated to 46,XY male-to-female sex reversal syndrome, secondary to a duplication in DAX-1, possibly inherited of maternal gonadal mosaicism. Copy number variation and functional effects of the duplication were done by MLPA multiplex ligation-dependent probe amplification and real time PCR. DAX-1, also known as dosage sensitive sex reversal gene (DSS), is considered the most likely candidate gene involved in XY gonadal dysgenesis when overexpressed. The excess of DAX-1 gene disturbs testicular development by down regulation of SF-1, WT1, and SOX9. This is the first report of 46,XY sex reversal in two siblings who have a maternally inherited duplication of DAX-1 associated with reduced levels of expression of downstream genes as SOX9-SF1.

Challenges in measuring angles between craniofacial structures

Abstract Objective: Three-dimensional (3D) angular measurements between craniofacial planes pose challenges to quantify maxillary and mandibular skeletal discrepancies in surgical treatment planning. This study aims to compare the reproducibility and reliability of two modules to measure angles between planes or lines in 3D virtual surface models. Methodology: Twenty oriented 3D virtual surface models de-identified and constructed from CBCT scans were randomly selected. Three observers placed landmarks and oriented planes to determine angular measurements of pitch, roll and yaw using (1) 3D pre-existing planes, (2) 3D planes created from landmarks and (3) lines created from landmarks. Inter- and intra-observer reproducibility and repeatability were examined using the Intra-Class Correlation (ICC) test. One observer repeated the measurements with an interval of 15 days. ANOVA was applied to compare the 3 methods. Results: The three methods tested provided statistically similar, reproducible and reliable angular measurements of the facial structures. A strong ICC varying from 0.92 to 1.00 was found for the intra-observer agreement. The inter-observer ICC varied from 0.84 to 1.00. Conclusion: Measurements of 3D angles between facial planes in a common coordinate system are reproducible and repeatable either using 3D pre-existing planes, created based on landmarks or angles between lines created from landmarks.

Antinociception induced by rosuvastatin in murine neuropathic pain.

BACKGROUND: Neuropathic pain, and subsequent hypernociception, can be induced in mice by paclitaxel (PTX) administration and partial sciatic nerve ligation (PSNL). Its pharmacotherapy has been a clinical challenge, due to a lack of effective treatment. In two models of mouse neuropathic pain (PTX and PSNL) the antinociception induced by rosuvastatin and the participation of proinflammatory biomarkers, interleukin (IL)- 1ß, TBARS and glutathione were evaluated. METHODS: A dose-response curve for rosuvastatin ip was obtained on cold plate, hot plate and Von Frey assays. Changes on spinal cord levels of IL-1ß, glutathione and lipid peroxidation were measured at 7 and 14days in PTX and PSNL murine models. RESULTS: PTX or PSNL were able to induce in mice peripheral neuropathy with hypernociception, either to 7 and 14days. Rosuvastatin induced a dose dependent antinociception in hot plate, cold plate and Von Frey assays. The increased levels of IL-1ß or TBARS induced by pretreatment with PTX or PSNL were reduced by rosuvastatin. The reduction of spinal cord glutathione, by PTX or PSNL, expressed as the ratio GSH/GSSG, were increased significantly in animals pretreated with rosuvastatin. The anti-inflammatory properties of statins could underlie their beneficial effects on neuropathic pain by reduction of proinflammatory biomarkers and activation of glia. CONCLUSION: The findings of this study suggest a potential usefulness of rosuvastatin in the treatment of neuropathic pain.

Caracterización fenotípica y molecular de una familia colombiana con fenilcetonuria / Phenotypic and molecular characterization of a Colombian family with phenylketonuria

Introducción. La fenilcetonuria es un trastorno metabólico caracterizado por un compromiso neurológico grave y por alteraciones del comportamiento. Su diagnóstico temprano permite establecer un tratamiento efectivo que evita las secuelas y modifica el pronóstico. Objetivo. Caracterizar a una familia con fenilcetonuria en Colombia, a nivel clínico, bioquímico y molecular. Materiales y métodos. Se estudió una población de siete individuos de una familia consanguínea en la que cuatro hijos presentaban signos clínicos sugestivos de fenilcetonuria. Una vez firmado el consentimiento informado, se tomaron muestras de sangre y orina para las pruebas colorimétricas, la cromatografía de capa fina y la cromatografía líquida de alta eficacia. Se extrajo el ADN y se secuenciaron los 13 exones del gen PAH de todos los sujetos estudiados. Se diseñaron iniciadores para cada exón con el programa Primer 3; la secuenciación automática se hizo con el equipo Abiprism 3100 Avant y, el análisis de las secuencias, con el programa SeqScape v2.0. Resultados. Se describieron las características clínicas y moleculares de una familia colombiana con fenilcetonuria en la que se identificó la mutación c.398_401delATCA; se presentó una correlación fenotipo-genotipo con una interesante variabilidad clínica entre los afectados, a pesar de tener la misma mutación. Conclusiones. Es importante el reconocimiento temprano de esta enfermedad para evitar sus secuelas neurológicas y psicológicas, pues los pacientes llegan a edades avanzadas sin diagnóstico ni tratamiento adecuados.

Introduction: Phenylketonuria is a metabolic disorder characterized by severe neurological involvement and behavioral disorder, whose early diagnosis enables an effective treatment to avoid disease sequelae, thus changing the prognosis. Objective: To characterize a family with phenylketonuria in Colombia at clinical, biochemical and molecular levels. Materials and methods: The population consisted of seven individuals of a consanguineous family with four children with suggestive symptoms of phenylketonuria. After signing an informed consent, blood and urine samples were taken for colorimetric tests and high performance liquid and thin layer chromatographies. DNA extraction and sequencing of the 13 exons of the PAH gene were performed in all subjects. We designed primers for each exon with the Primer 3 software using automatic sequencing equipment Abiprism 3100 Avant. Sequences were analyzed using the SeqScape, v2.0, software. Results: We described the clinical and molecular characteristics of a Colombian family with phenylketonuria and confirmed the presence of the mutation c.398_401delATCA. We established a genotype-phenotype correlation, highlighting the interesting clinical variability found among the affected patients despite having the same mutation in all of them. Conclusions: Early recognition of this disease is very important to prevent its neurological and psychological sequelae, given that patients reach old age without diagnosis or proper management.

[Characteristics, management, and outcomes of illicit drug consumers with acute myocardial infarction]. / Características, manejo y evolución intrahospitalaria de usuarios de drogas ilícitas con infarto agudo del miocardio.

BACKGROUND: Consumption of illicit drugs (ID) has been associated with an increased risk of acute myocardial infarction (AMI). There is limited national evidence about the impact of substance use over the clinical presentation, management and outcomes of AMI patients. AIM: To describe the prevalence of ID consumption in patients within the Chilean Registry of Myocardial Infarction (GEMI), comparing clinical characteristics, management and outcome according to consumption status. MATERIAL AND METHODS: We reviewed data from the GEMI registry between 2001 and 2013, identifying 18,048 patients with AMI. The sample was stratified according to presence or absence of previous ID consumption, comparing different demographic and clinical variables between groups. RESULTS: Two hundred eighty five patients (1.6%) had history of ID consumption (cocaine in 66%, cannabis in 35% and central nervous system stimulants in 24.0%). Compared with non-users, ID consumers were younger, predominantly male and had a lower prevalence of cardiovascular risk factors, except for tobacco smoking (86.3% and 42.5% respectively, p < 0.01). Among consumers, there was a higher percentage of ST segment elevation (85.2% and 67.8% respectively, p < 0.01) and anterior wall AMI (59.9 and 49.5% respectively, p = 0.01). Additionally, they had a higher rate of primary angioplasty (48.8% and 25.5% respectively, p < 0.01). There was no difference in hospital mortality between groups when stratified by age. CONCLUSIONS: A low percentage of patients with AMI had a previous history of ID consumption in our national setting. These patients were younger and had a greater frequency of ST segment elevation AMI, which probably determined a more invasive management.

Características, manejo y evolución intrahospitalaria de usuarios de drogas ilícitas con infarto agudo del miocardio / Characteristics, management, and outcomes of illicit drug consumers with acute myocardial infarction

Background: Consumption of illicit drugs (ID) has been associated with an increased risk of acute myocardial infarction (AMI). There is limited national evidence about the impact of substance use over the clinical presentation, management and outcomes of AMI patients. Aim: To describe the prevalence of ID consumption in patients within the Chilean Registry of Myocardial Infarction (GEMI), comparing clinical characteristics, management and outcome according to consumption status. Material and Methods: We reviewed data from the GEMI registry between 2001 and 2013, identifying 18,048 patients with AMI. The sample was stratified according to presence or absence of previous ID consumption, comparing different demographic and clinical variables between groups. Results: Two hundred eighty five patients (1.6%) had history of ID consumption (cocaine in 66%, cannabis in 35% and central nervous system stimulants in 24.0%). Compared with non-users, ID consumers were younger, predominantly male and had a lower prevalence of cardiovascular risk factors, except for tobacco smoking (86.3% and 42.5% respectively, p < 0.01). Among consumers, there was a higher percentage of ST segment elevation (85.2% and 67.8% respectively, p < 0.01) and anterior wall AMI (59.9 and 49.5% respectively, p = 0.01). Additionally, they had a higher rate of primary angioplasty (48.8% and 25.5% respectively, p < 0.01). There was no difference in hospital mortality between groups when stratified by age. Conclusions: A low percentage of patients with AMI had a previous history of ID consumption in our national setting. These patients were younger and had a greater frequency of ST segment elevation AMI, which probably determined a more invasive management.

Identification of mutations in Colombian patients affected with Fabry disease.

Fabry Disease (FD) is an X-linked inborn error of glycosphingolipid catabolism, caused by a deficiency of the lisosomal α-galactosidase A (AGAL). The disorder leads to a vascular disease secondary to the involvement of kidney, heart and the central nervous system. The mutation analysis is a valuable tool for diagnosis and genetic counseling. Although more than 600 mutations have been identified, most mutations are private. Our objective was to describe the analysis of nine Colombian patients with Fabry disease by automated sequencing of the seven exons of the GLA gene. Two novel mutations were identified in two patients affected with the classical subtype of FD, in addition to other 6 mutations previously reported. The present study confirms the heterogeneity of mutations in Fabry disease and the importance of molecular analysis for genetic counseling, female heterozygotes detection as well as therapeutic decisions.

Caracterización clínica de pacientes con infarto agudo al miocardio sin lesiones coronarias significativas: estudio GEMI 2011-2013 / Clinical characteristics of patients with acute myocardial Infarction and no significant coronary artery lesions: GEMI study (2011-1013)

Antecedentes: El infarto agudo del miocardio (IAM) es consecuencia de la disrupción del endotelio vascular que lleva a oclusión del vaso coronario por un trombo. En la coronariografía de algunos de estos pacientes es posible encontrar arterias coronarias sin lesiones significativas. Objetivo: Comparar características basales, presentación clínica, tratamiento y mortalidad intrahospitalaria de pacientes con IAM, con y sin lesiones significativas. Métodos: Se incluyeron 3.194 pacientes registrados en la ficha electrónica GEMI que además del diagnóstico de IAM, hubiesen sido sometidos a estudio coronariográfico. Se consideró "sin lesiones significativas" si ninguna estenosis era > al 50 por ciento. Resultados: El grupo sin lesiones significativas correspondió a 116 pacientes (3,6 por ciento). La edad promedio en este grupo fue menor (60+/-14 años vs 62+/-12 años, p<0,024) y con una mayor proporción de mujeres. En este grupo se observó menor prevalencia de dislipidemia (30,2 por ciento vs 42,8 por ciento, p<0.007), diabetes mellitus (14,7 por ciento vs 28,9 por ciento, p<0.001) y tabaquismo (40,5 por ciento vs 61,3 por ciento, p<0.0001). En el ECG de ingreso predominó el IAM sin SDST y menor elevación de CK y CK-MB, junto a una mejor fracción de eyección. Durante la hospitalización se utilizó menos aspirina, clopidogrel, betabloqueadores, heparina ev y HBPM. Existió un mayor uso de antagonistas de Calcio. Conclusiones: Los pacientes con IAM sin lesiones significativas tienen una menor carga de factores de riesgo coronario, es más frecuente encontrar al ingreso ECG SSDST, menor grado de daño miocárdico y mejor fracción de eyección. Además, se observan diferencias en el tratamiento farmacológico en este grupo de pacientes.

Background: Acute myocardial infarction (AMI) is a consequence of disruption of coronary artery lesions leading to intracoronary thrombosis. Some patients with AMI show no significant lesions in a coronary angiography. Aim: To compare clinical characteristics, treatment and intrahospital mortality in patients with AMI with or without coronary artery lesions. Methods: 3194 patients from a clinical registry of AMI (GEMI) were included. AMI with no significant coronary artery lesions was defined as the abscense of any lesion >50 percent. Results: 116 patients (3.6 percent) had no significant coronary lesions (NSL). Compared to the group with significant lesions (SL), they were younger (60+/-14 years vs 62+/-12 years, p<0,024) and the proportion of women was higher. NSL patients lower prevalence of hyperlipidemia (30,2 percent vs 42,8 percent, p<0.007), diabetes mellitus (14,7 percent vs 28,9 percent, p<0.001) and smoking habit (40,5 percent vs 61,3 percent, p<0.0001). NSL patients had a higher prevalence of non ST elevation AMI and lower levels of CK and CK-MB, as well as a lower ejection fraction. During hospitalization, NSL patients received aspirin, clopidogrel, betablockers, iv heparin and LMW heparin, less frequently tan SL patients. In contrast, they received calcium antagonists more frequently. Conclusion: Patients with AMI and no significant coronary lesions have a lower prevalence of coronary artery disease risk factors. A greater frequency of non ST elevation AMI, lower indices of myocardial necrosis and better EF was also observed. The intensity of pharmacologic therapy was lower.

Thrombin-receptor antagonist vorapaxar in acute coronary syndromes.

BACKGROUND: Vorapaxar is a new oral protease-activated-receptor 1 (PAR-1) antagonist that inhibits thrombin-induced platelet activation. METHODS: In this multinational, double-blind, randomized trial, we compared vorapaxar with placebo in 12,944 patients who had acute coronary syndromes without ST-segment elevation. The primary end point was a composite of death from cardiovascular causes, myocardial infarction, stroke, recurrent ischemia with rehospitalization, or urgent coronary revascularization. RESULTS: Follow-up in the trial was terminated early after a safety review. After a median follow-up of 502 days (interquartile range, 349 to 667), the primary end point occurred in 1031 of 6473 patients receiving vorapaxar versus 1102 of 6471 patients receiving placebo (Kaplan-Meier 2-year rate, 18.5% vs. 19.9%; hazard ratio, 0.92; 95% confidence interval [CI], 0.85 to 1.01; P=0.07). A composite of death from cardiovascular causes, myocardial infarction, or stroke occurred in 822 patients in the vorapaxar group versus 910 in the placebo group (14.7% and 16.4%, respectively; hazard ratio, 0.89; 95% CI, 0.81 to 0.98; P=0.02). Rates of moderate and severe bleeding were 7.2% in the vorapaxar group and 5.2% in the placebo group (hazard ratio, 1.35; 95% CI, 1.16 to 1.58; P<0.001). Intracranial hemorrhage rates were 1.1% and 0.2%, respectively (hazard ratio, 3.39; 95% CI, 1.78 to 6.45; P<0.001). Rates of nonhemorrhagic adverse events were similar in the two groups. CONCLUSIONS: In patients with acute coronary syndromes, the addition of vorapaxar to standard therapy did not significantly reduce the primary composite end point but significantly increased the risk of major bleeding, including intracranial hemorrhage. (Funded by Merck; TRACER ClinicalTrials.gov number, NCT00527943.).

Mortalidad intrahospitalaria en hombres y mujeres según terapias de reperfusión en infarto agudo del miocardio con supradesnivel del ST / ln-hospital mortality after ST-segment elevation myocardial infarction according to reperiusion therapy

Primary angioplasty is considered the best reperiusion therapy in the treatment of ST-segment elevation myocardial infarction (STEMI). However, thrombolysis is the reperiusion method most commonly used, due to its wide availability, reduced costs and ease of administration. Aim: To compare inhospital mortality in STEMI patients according to reperiusion therapy. Material and Methods: Patients admitted to Chilean hospitals participating in the GEMI network, from 2001 to 2005, with STEMI were included. They were divided in three groups: a) treated with thrombolytics, b) treated with primary angioplasty, c) without reperiusion procedure. Inhospital mortality according to gender, was analized in each group, using a logistic regression method, to assess risk factors associated with mortality. Results: We included 3,255 patients. Global mortality was 9.9 percent (7.5 percent in men and 16.7 percent in women, p <0.001). Mortality in patients treated with thrombolytics, was 10.2 percent (7.6 percent in men and 18.7 percent in women, p <0.01). The figure for patients treated with primary angioplasty, was 4.7 percent (2.5 percent in men and 13 percent in women, p <0.01), and in patients without reperiusion, was 11.6 percent (9.8 percent in men and in 15.4 percent women, p <0.01). In each group women were older, had a higher prevalence of hypertension and a higher percentage of Killip 3-4 infarctions. Logistic regression showed that angioplasty, compared with no reperiusion, was associated with a reduced mortality only in men. The use oí thrombolytics in women was associated with a higher mortality. Conclusions: Primary angioplasty was the reperiusion therapy associated to the lower mortality in STEMI. Use of thrombolytics in women was associated with a higher mortality rate than in non reperfused women.