Surfactant therapy using vibrating-mesh nebulizers in adults with COVID-19-induced ARDS: A case series.

Coronavirus adult respiratory distress syndrome, characterized by decreased surfactant due to lysis of type II pneumocytes and hyaline membrane formation, contributes to severe hypoxemia. The administration of surfactant via high-flow nasal cannula (HFNC) may positively affect lung structure and function in this context. In this study, we report on five clinical cases, encompassing patients aged 40-60 years of both sexes, who tested positive for coronavirus disease 2019 via real-time polymerase chain reaction and exhibited significant pulmonary compromise with elevated inflammatory biomarkers. These patients were treated with aerosol therapy using surfactant delivered through vibrating-mesh nebulizers alongside HFNC. Of these patients, four demonstrated positive responses to the treatment, suggesting that aerosol therapy with surfactant through vibrating-mesh nebulizers could be a viable rescue therapy in adults receiving HFNC oxygen therapy for hypoxemic respiratory failure caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Unfortunately, one patient had a negative outcome and succumbed. The findings from these cases indicate that the use of aerosol therapy with vibrating-mesh nebulizers as rescue therapy might offer an alternative approach for managing adults with hypoxemic respiratory failure due to SARS-CoV-2, as evidenced by the positive outcomes in four out of the five cases presented.

An Unusual Case of Severe Pneumonia Caused Due Candida Tropicalis With a Favorable Clinical Response to Antifungals in a Nonimmunocompromised Patient From the Community.

Severe pneumonia due to Candida tropicalis infection mainly occurs in immunosuppressed patients or those currently receiving broad-spectrum antibiotics. Herein, we report a case of severe pneumonia caused due to C tropicalis in an elderly patient. A 72-year-old man with a previous history of hypertension, ischemic stroke, and facial paralysis sequelae treated with the botulinic toxin, was admitted to the hospital for dyspnea. Severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection was negative. Computed tomography of the chest revealed bilateral consolidation with left predominance. A bronchoalveolar lavage sample was sent to molecular biology, but no microorganisms were detected using a FilmArray respiratory panel. However, mamanocandidas test for candida was 166 pg/mL (positive), and fungal structures were identified by the MALDI-TOF Biotyper mass spectrometry and attributed to C tropicalis. Antifungal therapy was started using caspofungin 75 mg as the initial dose followed by 50 mg daily. After 10 days of treatment, ventilatory weaning was achieved. By day 14, the patient was decannulated from the tracheostomy. Oral antifungal treatment with voriconazole was continued, and he was discharged from intensive care in good clinical condition. Severe pneumonia due to C tropicalis might occur in specific cases, especially in those patients with risk factors, and must thus be considered when approaching such cases.

A 71-Year-Old Man From Ecuador With a History of Type 2 Diabetes Mellitus and Severe COVID-19 Pneumonia and Lung Cavitation Associated With Triple Infection With Trichosporon Asahii, Klebsiella Pneumoniae, and Pseudomonas Aeruginosa.

Unvaccinated patients with comorbidities that impair the immune function, such as type 2 diabetes mellitus, are more likely to develop severe COVID-19. The COVID-19-associated acute respiratory distress syndrome has raised new concerns in intensive care units globally owing to the presence of secondary fungal infections. We report the case of a 71-year-old man from Ecuador with a history of type 2 diabetes mellitus, severe COVID-19 pneumonia, and lung cavitation associated with triple infections with Trichosporon asahii, Klebsiella pneumoniae, and Pseudomonas aeruginosa. The patient with a history of high blood pressure and type 2 diabetes was admitted to our hospital from a private care center with a diagnosis of COVID-19-associated acute respiratory distress syndrome. On arrival, the patient presented with signs of hypoxemic respiratory failure. During his stay at another hospital, he had received tocilizumab and corticosteroid therapy. Therefore, intubation was performed and mechanical ventilation was initiated. The patient developed a septic shock and renal failure with a glomerular filtration rate of 27.5 mL/min/1.73 m2; therefore, two hemodiafiltration sessions were started. The bronchoalveolar lavage revealed erythematous lesions in the bronchial tree and abundant purulent secretions and erosions in the bronchial mucosa, with a cavitary lesion in the right bronchial tree. The bronchoalveolar lavage samples were used to isolate Trichosporon asahii, Klebsiella pneumoniae, and Pseudomonas aeruginosa carbapenemase class A. Matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) Biotyper mass spectrometry and polymerase chain reaction (PCR) molecular identification were performed. This case report suggested that patients with severe COVID-19 pneumonia, with or without comorbidities, are more susceptible to opportunistic infections.

Management of COVID-19 at the pandemic's first wave in Ecuador.

During March and April 2020, Ecuador was the country with the highest death toll in Latin America due to the coronavirus disease 2019 pandemic. Simultaneously, research was being developed and published globally, and to a certain extent, guided therapeutic approaches in real time, mostly in under-resourced settings. We present the case of a 59-year-old male physician residing in Guayaquil, who presented with severe coronavirus disease 2019, in which mechanical ventilation, prone position, and pulmonary protective ventilatory strategy were used. We discuss the clinical management of the first reported case in the literature of a physician in Ecuador who survived severe acute respiratory syndrome coronavirus 2 infection, as well as the topic of self-medication within health professionals, the management approach that was emerging at the moment in scientific publications and guiding treatment, the role of responsible research and its worldwide impact, and the emotional burdens of the care team who had to make very difficult decisions in extremely adverse circumstances.

CYP3A5 and UGT1A9 Polymorphisms Influence Immunosuppressive Therapy in Pediatric Kidney Transplant Recipients.

Background: Tacrolimus (TAC) and mycophenolic acid (MPA) are the main immunosuppressive drugs used in pediatric kidney transplantation. Single nucleotide polymorphisms (SNPs) in metabolizing enzymes and transporters might influence plasma levels of these drugs. Herein, we sought to determine the influence of SNPs on CYP3A5, MRP2 and UGT1A9 genes in Chilean pediatric kidney recipients using TAC and MPA. Patients and Methods: A prospective study was performed on 104 pediatric kidney recipients that used TAC and MPA for immunosuppression. The median age at the time of transplantation was 8.1 years [Q1-Q3 4.5-11.6 years] and the main clinical diagnosis was a structural anomaly. In a subgroup of patients, a complete steroid withdrawal was made at day 7. The CYP3A5 polymorphism (ancestral allele *1; variant allele *3) was determined in the entire cohort, while MRP2 -24G > A, UGT1A9 -275T > A, and UGT1A9 -2152C > T polymorphisms were determined in 53 patients. Genotypes were associated with trough drug concentrations (C0), dose requirements normalized by weight (TAC-D mg/kg) or body surface (MPA-D mg/m2), trough levels normalized by dose requirements (C0/D), and area under the curve in 12 h normalized by dose requirements (AUC0-12h/D). Results: The frequencies of the variant alleles CYP3A5*3, MRP2-24A, UGT1A9-275A, and UGT1A9-2152T were 76.9, 22.1, 6.6, and 2.9%, respectively. AUC0-12h/TAC-D were 1.6-fold higher in CYP3A5*3/*3 patients than in CYP3A5*1 carriers (CYP3A5*1/*3 and CYP3A5*1/*1). When analyzing patients with steroid withdrawal, CYP3A5*3/*3 patients had 1.7-fold higher AUC0-12h/TAC-D than the other genotypes. Patients carrying the CYP3A5*3/*3 genotype had higher TAC-C0, lower TAC-D and higher TAC-C0/D, consistently in a 6-months follow-up. Creatinine clearance was stable during the follow-up, regardless of the genotype. No significant differences between MRP2 and UGT1A9 genotypes were observed in MPA-C0, MPA-D or MPA-C0/D. However, patients carrying the UGT1A9-275A allele had lower AUC0-12h/MPA-D than those carrying the UGT1A9-275T ancestral allele. Conclusions: These results support that CYP3A5 and UGT1A9 genotyping in pediatric recipients might be useful and advisable to guide TAC and MPA dosing and monitoring in children that undergo kidney transplantation.

Garantía de calidad en nutrición parenteral: Implementación de control de calidad químico y microbiológico / Quality guarantee in parenteral nutrition: Implementation of chemical and microbiological quality controls

La elaboración de una nutrición parenteral (NP) no está exenta de riesgos debido a su compleja composición y fabricación, susceptible de errores en adición u omisión de nutrientes (composición química) o ruptura de la técnica aséptica estricta (contaminación microbiológica).La farmacopea y legislación nacional vigente sólo sugiere controles básicos, algunos no cuantitativos, además de la supervisión del personal y áreas de trabajo. Considerando la importancia de la composición y esterilidad de una NP, se analizaron controles de calidad analíticos y microbiológicos que den cuenta del proceso de preparación, así como de estabilidad química y esterilidad, previo a la administración considerando un almacenamiento de 5 días.Como control de calidad químico se cuantificó: glucosa, sodio, calcio, magnesio, fósforo, potasio y cloro en 40 muestras en los equipos Cobas®B221 y Vitros®4600. Los controles microbiológicos (agar sangre) se realizaron posterior a la preparación y a los 5 días de almacenamiento, previo a la administración. Los resultados de día 0, muestran que para glucosa, sodio y calcio las concentraciones se correlacionan con la concentración teórica, mientras que para el día 5 post almacenamiento; glucosa, sodio, calcio, magnesio, fósforo, potasio y cloro se correlacionan con la concentración teórica del día 0. En ninguna muestra se observó crecimiento de microorganismos.De acuerdo a los resultados se establece como control de preparación de NP: glucosa, sodio y calcio, como controles de estabilidad química: glucosa, sodio, calcio, magnesio, fósforo, potasio y cloro, además se asegura la esterilidad a los 5 días de almacenamiento. (AU)

The elaboration of a parenteral nutrition (NP) is not exempt of risks due to its complex composition and manufacture, susceptible to errors in addition or omission of nutrients (chemical composition) or rupture of the strict aseptic technique (microbiological contamination).The current pharmacopoeia and national legislation only suggests basic controls, some not quantitative, in addition to the supervision of personnel and work areas. Considering the importance of the composition and sterility of a NP, analytical and microbiological quality controls that account for the preparation process, as well as chemical stability and sterility, were analyzed prior to administration considering a 5-day storage.As chemical quality control, glucose, sodium, calcium, magnesium, phosphorous, potassium and chlorine were quantified in 40 samples in the Cobas®B221 and Vitros®4600 kits. Microbiological controls (blood agar) were performed after preparation and at 5 days of storage, prior to administration.The results from day 0 show that for glucose, sodium and calcium the concentrations correlate with the theoretical concentration, while for day 5 post storage; glucose, sodium, calcium, magnesium, phosphorus, potassium and chlorine are correlated with the theoretical concentration on day 0. In no sample was growth of microorganisms observed.According to the results, it is established as control of NP preparation: glucose, sodium and calcium, as chemical stability controls: glucose, sodium, calcium, magnesium, phosphorus, potassium and chlorine, and sterility is ensured 5 days after storage. (AU)

Optimizing RT-PCR detection of SARS-CoV-2 for developing countries using pool testing.

The global shortage of reagents and kits for nucleic acid extraction and molecular detection of SARS-CoV-2 requires new cost-effective strategies for the diagnosis of suspected COVID-19 cases, especially in countries that need to increase detection capacity. Pooled nucleic acid testing has been extensively used as a cost-effective strategy for HIV, HepB, HepC and influenza. Also, protocols dispensing of RNA extraction appears as an attractive option for detection of SARS-CoV-2. In this study, we found that pooling of 5 samples showed that CT variations were in the range of 1.0-4,5 units, with less likelihood of a false negative result. Results of the sample without nucleic acid ex-traction, was unsatisfactory, with a significant increase in CT values, and thus for risk of a false negative result. In conclusion, pooling nasopharyngeal samples with both automated and manual extraction proved reliable, and thus a potential efficient alternative for the diagnosis of suspected COVID-19 in developing countries.

Optimizing RT-PCR detection of SARS-CoV-2 for developing countries using pool testing / Optimización de la detección de SARS-CoV-2 mediante el análisis de muestras agrupadas

Abstract The global shortage of reagents and kits for nucleic acid extraction and molecular detection of SARS-CoV-2 requires new cost-effective strategies for the diagnosis of suspected COVID-19 cases, especially in countries that need to increase detection capacity. Pooled nucleic acid testing has been extensively used as a cost-effective strategy for HIV, HepB, HepC and influenza. Also, protocols dispensing of RNA extraction appears as an attractive option for detection of SARS-CoV-2. In this study, we found that pooling of 5 samples showed that CT variations were in the range of 1.0-4,5 units, with less likelihood of a false negative result. Results of the sample without nucleic acid ex-traction, was unsatisfactory, with a significant increase in CT values, and thus for risk of a false negative result. In conclusion, pooling nasopharyngeal samples with both automated and manual extraction proved reliable, and thus a potential efficient alternative for the diagnosis of suspected COVID-19 in developing countries.

Resumen La escasez mundial de reactivos para la extracción de ácidos nucleicos y la detección molecular de SARS-CoV-2 requiere de nuevas estrategias de mayor rendimiento para el diagnóstico de casos sospechosos de COVID-19, especialmente en países que necesitan aumentar su capacidad diagnóstica. La detección de ácidos nucleicos en muestras agrupadas o pool testing se ha utilizado ampliamente como una estrategia costo-efectiva para el VIH, hepatitis B, hepatitis C e influenza. Adicionalmente, los protocolos que no requieren extracción de ARN aparecen como una opción para la detección de SARS-CoV-2. En este trabajo, presentamos los resultados de una estrategia detección de SARS-CoV-2 en muestras agrupadas, que incluye diferentes métodos de extracción de ARN que puede ser una estrategia atractiva para los países en desarrollo. La agrupación de 5 muestras mostró variaciones CT en el rango de 1,0 a 4,5 unidades, con una baja probabilidad de obtener falsos negativos, a diferencias de los resultados agregando muestras agrupadas directamente en la reacción de amplificación de SARS-CoV-2. En conclusión, la agrupación de muestras nasofaríngeas, demostró ser un método confiable y, por lo tanto, una alternativa para aumentar el rendimiento en el diagnóstico de COVID-19 para países en desarrollo.

Anquilosis de la articulación temporomandibular / Ankylosis of the temporomandibular joint

Introducción: resulta de interés para médicos y especialistas el conocimiento sobre la incapacidad de la apertura de la cavidad oral debido a coaliciones entre los elementos óseos y fibrosos en la región glenoidea. Objetivo: revisar la literatura sobre las características de esta patología. Desarrollo: en el primer trimestre del año 2006, a fin de realizar una revisión bibliográfica no exhaustiva para localizar la información disponible sobre la anquilosis de la articulación temporomandibular, se realizó una búsqueda bibliográfica en Scielo, Medline, Isi Web of Knowlegde y Dialnet, buscando como palabras clave: anquilosis (ankylosis) y articulación temporomandibular (temporomandibular joint). Además de la búsqueda computarizada se realizó una búsqueda manual entre las referencias de los estudios seleccionados. Conclusiones: la anquilosis temporomandibular resulta una entidad clínica compleja, usualmente molesta para los pacientes dada la imposibilidad de alimentarse y nutrirse adecuadamente, además de las deformidades que desde el punto de vista estético afecta la esfera psicológica de las personas aquejadas. Su tratamiento es difícil, no obstante, una atención adecuada minimiza las consecuencias de las complicaciones que pueden aparecer como resultado de la técnica quirúrgica u otros factores no relacionados con ella. Se reconoce que una identificación y tratamiento oportuno del problema puede favorecer los buenos resultados de la conducta médica y la rápida integración del paciente a la sociedad(AU)

Introduction: it is of interest for physicians and specialist's knowledge about the inability of the opening of the oral cavity due to coalitions between the bone and fibrous elements in the glenoid region. Objective: to review the literature on the characteristics of this pathology. Development: in the first quarter of 2006, in order to perform a non-exhaustive literature review to locate the available information on ankylosis of the temporomandibular joint, a literature search was carried out in Scielo, Medline, Isi Web of Knowlegde and Dialnet, searching as key words: ankylosis (ankylosis) and temporomandibular joint (temporomandibular joint). In addition to the computerized search, a manual search was made among the references of the selected studies. Conclusions: the temporomandibular ankylosis is a complex clinical entity, usually annoying for patients given the impossibility of feeding and nourishing adequately, in addition to the deformities that from the aesthetic point of view affects the psychological sphere of the people afflicted. Its treatment is difficult, nevertheless, an adequate attention minimizes the consequences of the complications that can appear as a result of the surgical technique or other factors not related to it. It is recognized that an identification and timely treatment of the problem can favor the good results of medical behavior and the rapid integration of the patient into society(AU)

Mental disorders and drug use in victims of the armed conflict in three cities in Colombia

Introduction: Violence in its different forms increases the risk of mental disorders and the use of drugs. Objectives: To assess the prevalence of mental disorders, and the use and abuse of drugs, as well as associated factors in victims of forced displacement in three cities in Colombia. Materials and methods: We conducted a prevalence study with 1.026 participants between 13 and 65 years old. Participants completed four surveys: the World Health Organization World Mental Composite International Diagnostic Interview, the World Health Organization Alcohol Use and Disorders Identification Test, a survey on drug use based on the Inter-American System of Uniform Drug-Use Data under the Inter-American Drug Abuse Commission of the Organization of American States, and a survey on aspects related to forced displacement. Data were analyzed using the SPSS™, version 21, software. Results: Lifetime prevalence of mental disorders was 17.7% for specific phobia, 16.4% for major depression, 9.9% for post-traumatic stress disorder, 8.9% for oppositional defiant disorder, 7.2% for separation anxiety disorder, 5.8% for conduct disorder, and 5.6% for attention deficit disorder. The lifetime prevalence of alcohol use was 68.7%; 31,3% for tobacco; 11,2% for marihuana; 3.5% for cocaine; 2.0% for coca paste (basuco); 2.5% for non-prescription anxiolytic drugs, 2.3% for inhalants, and 0.7% of participants had injected drugs. Presenting any mental disorder was associated with being female (OR=1,61 IC95%: 1,21-2,14) and experiencing more than one forced displacement (OR=1,47 IC95%: 1,05-2,05). The use of any drug was associated with being male (OR=5,38 IC95%: 2,35-12,34). Conclusions: Compared to the general population, our study population exhibited high prevalence of mental disorders and drug use, emerging as a public health issue that calls for the design of plans and the implementation of programs aimed at recovering the mental health and well-being of this population.

Trastornos mentales y consumo de drogas en la población víctima del conflicto armado en tres ciudades de Colombia / Mental disorders and drug use in victims of the armed conflict in three cities in Colombia

Resumen Introducción. La violencia en sus diferentes modalidades incrementa el riesgo de trastornos mentales y de consumo de drogas. Objetivos. Estimar la prevalencia de los trastornos mentales, del uso y abuso de drogas, así como los factores asociados en víctimas de desplazamiento forzado en tres ciudades colombianas. Materiales y métodos. Se hizo un estudio de prevalencia en una muestrade 1.026 personas entre los 13 y los 65 años de edad, a quienes se entrevistó utilizando el instrumento Composite International Diagnostic Interview y el Alcohol Use Disorders Identification Test de la Organización Mundial de la Salud, así como un cuestionario sobre el consumo de drogas modificado a partir de la encuesta del Sistema Interamericano de Datos Uniformes sobre Drogas de la Comisión Interamericana para el Control del Abuso de Drogas de la Organización de Estados Americanos, y otro sobre aspectos relacionados con el desplazamiento forzado. El análisis se hizo mediante el programa estadístico SPSS™, versión 21. Resultados. La prevalencia de vida de los trastornos mentales fue la siguiente: fobia específica, 17,7 %; depresión mayor, 16,4 %; estrés postraumático, 9,9 %; trastorno oposicionista desafiante, 8,9 %; ansiedad por separación, 7,2 %; trastornos de conducta, 5,8 %, y déficit de atención, 5,6 %. La prevalencia de vida del consumo de alcohol fue de 68,7 %; de tabaco, 31,3 %, de marihuana, 11,2 %, de cocaína, 3,5 %, de basuco, 2,0 %, de inhalables, 2,3 %, y de medicamentos ansiolíticos sin receta, 2,5 %, en tanto que 0,7 % de los entrevistados se había inyectado drogas. Elpresentar cualquiera de los trastornos mentales se asoció con el sexo femenino (odds ratio, OR=1,61; IC95% 1,21-2,14), así como el haber sido sometido a más de un desplazamiento forzado (OR=1,47; IC951,05-2,05). El consumo de cualquiera de las drogas se asoció con ser hombre (OR=5,38; IC95% 2,35-12,34). Conclusiones. La alta prevalencia de trastornos mentales y de consumo de drogas en la población estudiada, comparada con la población general, constituye un problema de salud pública que justifica el diseño de planes y la implementación de programas orientados a la recuperación de su bienestar y salud mental.

Abstract Introduction: Violence in its different forms increases the risk of mental disorders and the use of drugs. Objectives: To assess the prevalence of mental disorders, and the use and abuse of drugs, as well as associated factors in victims of forced displacement in three cities in Colombia. Materials and methods: We conducted a prevalence study with 1.026 participants between 13 and 65 years old. Participants completed four surveys: the World Health Organization World Mental Composite International Diagnostic Interview, the World Health Organization Alcohol Use and Disorders Identification Test, a survey on drug use based on the Inter-American System of Uniform Drug-Use Data under the Inter-American Drug Abuse Commission of the Organization of American States, and a survey on aspects related to forced displacement. Data were analyzed using the SPSS™, version 21, software. Results: Lifetime prevalence of mental disorders was 17.7% for specific phobia, 16.4% for major depression, 9.9% for post-traumatic stress disorder, 8.9% for oppositional defiant disorder, 7.2% for separation anxiety disorder, 5.8% for conduct disorder, and 5.6% for attention deficit disorder. The lifetime prevalence of alcohol use was 68.7%; 31,3% for tobacco; 11,2% for marihuana; 3.5% for cocaine; 2.0% for coca paste (basuco); 2.5% for non-prescription anxiolytic drugs, 2.3% for inhalants, and 0.7% of participants had injected drugs. Presenting any mental disorder was associated with being female (OR=1,61 IC95%: 1,21-2,14) and experiencing more than one forced displacement (OR=1,47 IC95%: 1,05-2,05). The use of any drug was associated with being male (OR=5,38 IC95%: 2,35-12,34). Conclusions: Compared to the general population, our study population exhibited high prevalence of mental disorders and drug use, emerging as a public health issue that calls for the design of plans and the implementation of programs aimed at recovering the mental health and well-being of this population.

[Drug interaction of voriconazole-cyclosporine in children undergoing hematopoietic stem cell transplantation (2013-2014)]. / Evaluación de interacción medicamentosa de voriconazol-ciclosporina en pacientes pediátricos que reciben trasplante de precursores hematopoyéticos (2013-2014).

BACKGROUND: Drug interactions (DI) in patients receiving hematopoietic stem cell transplantation (HSCT) are common and clinically significant, highlighting: anticonvulsants, voriconazole (VCZ) and cyclosporine (CsA), which require monitoring. OBJECTIVE: To describe the interactions between CsA-VCZ in children undergoing HSCT. METHODS: Retrospective, descriptive study in immunocompromised children hospitalized since January 2013 to December 2014 at Bone Marrow Transplant Unit, Hospital Dr. Luis Calvo Mackenna, who received CsA and VCZ. RESULTS: The median age was 5 years (3-6) and the median weight was 20 kg (17-30). Sixtythree baseline drug levels were analyzed, of those, 27 were CsA drug levels obtained previous to using VCZ and 36 were CsA drug levels collected concomitantly with VCZ. In the group CsA previous to VCZ, the CsA dose was 4.6 ± 2.6 (mg/ kg/ day) and the CsA average level was 188.8 ± 84.1 (µg/ml). In the group of CsA concomitantly with VCZ, the dose of CsA was 5.5 ± 3.0 (mg/ kg/day) (p = 0.07) and CsA average level was significantly higher: 232.5 ± 106.7 (µg/ml) (p = 0.04). CONCLUSION: This study shows an increased level of CsA when it is used together with VCZ. Therapeutic drug monitoring could improve the management of the DI and optimize the co-administration of CsA and VCZ.

Evaluación de interacción medicamentosa de voriconazol-ciclosporina en pacientes pediátricos que reciben trasplante de precursores hematopoyéticos (2013-2014) / Drug interaction of voriconazole-cyclosporine in children undergoing hematopoietic stem cell transplantation (2013-2014)

Background: Drug interactions (DI) in patients receiving hematopoietic stem cell transplantation (HSCT) are common and clinically significant, highlighting: anticonvulsants, voriconazole (VCZ) and cyclosporine (CsA), which require monitoring. Objective: To describe the interactions between CsA-VCZ in children undergoing HSCT. Methods: Retrospective, descriptive study in immunocompromised children hospitalized since January 2013 to December 2014 at Bone Marrow Transplant Unit, Hospital Dr. Luis Calvo Mackenna, who received CsA and VCZ. Results: The median age was 5 years (3-6) and the median weight was 20 kg (17-30). Sixtythree baseline drug levels were analyzed, of those, 27 were CsA drug levels obtained previous to using VCZ and 36 were CsA drug levels collected concomitantly with VCZ. In the group CsA previous to VCZ, the CsA dose was 4.6 ± 2.6 (mg/ kg/ day) and the CsA average level was 188.8 ± 84.1 (μg/ml). In the group of CsA concomitantly with VCZ, the dose of CsA was 5.5 ± 3.0 (mg/ kg/day) (p = 0.07) and CsA average level was significantly higher: 232.5 ± 106.7 (μg/ml) (p = 0.04). Conclusion: This study shows an increased level of CsA when it is used together with VCZ. Therapeutic drug monitoring could improve the management of the DI and optimize the co-administration of CsA and VCZ.

Introducción: Las interacciones medicamentosas (IM) en el trasplante de progenitores hematopoyéticos (TPH) son comunes y clínicamente significativas, especialmente en: anticonvulsivantes, voriconazol (VCZ) y ciclosporina (CsA). Objetivo: Describir las interacciones de CsA-VCZ en pacientes con TPH. Métodos: Estudio descriptivo, retrospectivo, en pacientes receptores de TPH entre enero de 2013 y diciembre de 2014 en la Unidad de Trasplante de Médula Ósea del Hospital Dr. Luis Calvo Mackenna, que recibieran CsA y VCZ. Resultados: Edad media: 5 años (3-6), peso promedio: 20 kg (17-30). Se analizaron 63 concentraciones plasmáticas de CsA, 27 eran concentraciones de CsA previas al uso de VCZ y 36 concentraciones plasmáticas de CsA concomitantes con VCZ. En el grupo de CsA previo a VCZ, la dosis de CsA fue 4,6 ± 2,6 (mg/kg/día) y la concentración media de CsA 188,8 ± 84,1 (μg/ml). En el grupo de CsA en forma concomitante con VCZ, la dosis de CsA fue de 5,5 ± 3,0 (mg/kg/día) (p 0,07) y la concentración media de CsA fue: 232,5 ± 106,7 (μg/ml) (p = 0,04). Conclusión: Se demostró un aumento de las concentraciones plasmáticas de CsA en IM con VCZ. La monitorización terapéutica podría mejorar el manejo de la IM y optimizar la coadministración de CsA y VCZ.

Resultado de estudio prenatal invasivo para el diagnóstico de aneuploidía en el Hospital Sótero del Río / Results of an invasive prenatal study for the diagnosis of aneuploidy at Hospital Sótero del Río

ANTECEDENTES: Las aneuploidías y malformaciones congénitas son causa importante de morbi-mortalidad perinatal e infantil en Chile. OBJETIVO: Evaluar la realidad local del diagnóstico genético antenatal para mejorar el resultado perinatal. MÉTODOS: Estudio retrospectivo y descriptivo. Se realizó amniocentesis a embarazadas con indicación de estudio genético prenatal por sospecha ecográfica de alteraciones cromo-sómicas, entre octubre de 2010 y marzo de 2015, en el Hospital Sótero del Río. RESULTADOS: Los hallazgos ecográficos más frecuentes fueron: cardiopatías congénitas, malformaciones del sistema nervioso central y restricción de crecimiento fetal precoz. 164 pacientes aceptaron el estudio invasivo antenatal, obteniéndose resultados de 154. El promedio de edad materna y edad gestacional del examen fueron 30 años y 27+3 semanas, respectivamente. En embarazos con trisomía 21 y 13, el 71% de las pacientes tenía sobre 35 años. Un 31% de las muestras presentaron cariotipo anormal, siendo la más frecuente la trisomía 21 (14%), trisomía 18 (9%), monosomía X (4,5%) y trisomía 13 (2,6%). CONCLUSIÓN: El diagnóstico genético prenatal permite un adecuado manejo perinatal, coordinación apropiada entre las unidades de Obstetricia y Neonatología, y la preparación de las pacientes y sus familias para un pronóstico perinatal adverso.

BACKGROUND: Malformations and aneuploidy are a major cause of perinatal morbidity and mortality in Chile. Invasive techniques are offered to determine the fetal karyotype, when there is an abnormal finding in the ultrasound. AIMS: To assess the local situation of prenatal genetic diagnosis to improve the management of this population. METHODS: This is a retrospective and descriptive study of patients from october 2010 to march 2015, who had an amniocentesis for genetic testing due suspected fetal malformations or aneu-ploidy. RESULTS: The sonographic findings most frequently found were: congenital heart disease, malformations of the central nervous system and early growth restrictions. 164 patients agree to perform invasive prenatal genetic, obtaining 154 results. The average maternal age was 30 years and the mean gestational age at amniocentesis was 27+3 weeks. In trisomy 21 pregnancies, 71% of patients were higher than 35 years. 31% of the samples had abnormal karyotype: trisomy 21 (14%), trisomy 18 (9%), Turner's syndrome (4.5%) and trisomy 13 (3%). CONCLUSIONS: Prenatal genetic diagnosis allows appropriate perinatal management and contributes to prepare the patient and their families for an adverse perinatal outcome.

Prevalence of TPMT and ITPA gene polymorphisms and effect on mercaptopurine dosage in Chilean children with acute lymphoblastic leukemia.

BACKGROUND: Mercaptopurine (6-MP) plays a pivotal role in treatment of childhood acute lymphoblastic leukemia (ALL); however, interindividual variability in toxicity of this drug due to genetic polymorphism in 6-MP metabolizing enzymes has been described. We determined the prevalence of the major genetic polymorphisms in 6-MP metabolizing enzymes in Chilean children with ALL. METHODS: 103 Chilean pediatric patients with a confirmed diagnosis of ALL were enrolled. DNA was isolated from whole blood and genetic polymorphism in thiopurine S-methyltransferase (TPMT) and inosine triphosphate pyrophosphatase (ITPA) coding genes were detected by polymorphism chain reaction-restriction fragment length (PCR-RFLP) assay. RESULTS: The total frequency of variant TPMT alleles was 8%. TPMT*2, TPMT*3A and TPMT*3B alleles were found in 0%, 7%, and 1% of patients, respectively. For ITPA, the frequency of P32T allele was 3%. We did not observe any homozygous variant for TPMT and ITPA alleles. We also analyzed a subgroup of 40 patients who completed the maintenance phase of ALL treatment, and we found that patients carrying a TPMT gene variant allele required a significantly lower median cumulative dosage and median daily dosage of 6-MP than patients carrying wild type alleles. CONCLUSION: TMPT genotyping appears an important tool to further optimize 6-MP treatment design in Chilean patients with ALL.

Evaluación de la eficacia de drogas antihelmínticas para el control de Trichuris trichiura y otras helmintiasis en el estado Aragua, Venezuela / Evaluation of the efficacy of antihelmintic drugs for the control of Trichuris trichiura and other helminthic diseases in the state of Aragua, Venezuela

Un ensayo clínico de cuatro brazos fue llevado a cabo en 14 comunidades del estado Aragua para evaluar cuatro esquemas de tratamientos antihelmínticos para geohelmintos: Mebendazol y albendazol como monoterapias y cada una de estas drogas en combinación con ivermectina como terapias combinadas. Los tratamientos fueron administrados posteriormente a un examen coproparsitoscópico inicial, con reevaluaciones a los 7 y 21 días. Quedó en evidencia que las tasas de curación observadas a los 7 días posteriores al tratamiento, a favor de los esquemas combinados, particularmente la combinación albendazol + ivermectina (χ2 = 10,85; P < 0,0009), pero no se reflejaron a los 21 días después de la administración de los tratamientos y ningún esquema demostró una eficacia superior. Trichuris trichiura aún responde satisfactoriamente a los tratamientos convencionales. A pesar de la similitud en la eficacia de las monoterapias y terapias combinadas, el porcentaje de pacientes curados con T. trichiura solo o con infecciones mixtas fue elevada (> 93%). Las uncinarias fueron curadas en 100% (cero huevos en heces), seguido de A. lumbricoides (98,2%) y las infecciones mixtas de T. trichiura + A. lumbricoides + uncinarias (100%). La reducción porcentual de huevos por gramo de heces fue de 100% para las uncinarias, 89,3% para A. lumbricoides y 81,7% para T. trichiura. Las tasas de fracasos fueron bajas para los cuatro esquemas terapéuticos: mebendazol (5,14%), albendazol (6,20%), albendazol + ivermectina (2,02%) y mebendazol + ivermectina (2,22%). El grupo de edad de 0 a 9 años registró el mayor número de fracasos terapéuticos (n = 13). Quizás convendría emplear esquemas combinados en casos de fracasos terapéuticos. Pero, surge la duda si se está evidenciando la posibilidad de resistencia a estos medicamentos, dado que la mayoría de los fracasos terapéuticos se observaron en pacientes con bajas cargas parasitarias que bien podrían revertirse en el tiempo.

A four-arm clinical trial was carried out in 14 communities in the State of Aragua to evaluate four antihelminthics treatments, as monotherapy and combined treatments for soil-transmitted helminthiasis: Mebendazole, albendazole and each of these drugs in combination with ivermectin. Treatments were given after an initial stool specimens were obtained for examination, with two sequential stool reevaluations on days 7 and 21. Cure rates (zero eggs in stools) at day 7 after treatments were favourable for combined treatments, specially albendazole + ivermectin (χ2 = 10.85; P < 0.0009), which was not reflected by day 21 since no treatment showed any superior efficacy. Trichuris trichiura still responds satisfactorily to conventional treatments offered by the national Programme for the Fight against Anclyostomiasis and other Intestinal Parasites. Notwithstanding the similarities of monotherapy and combined treatments efficacy, the percentage of patients cured with T. trichiura solely or with mixed infections was high (> 93%). Hookworm infections were cured a 100% (zero eggs found in feces), followed by A. lumbricoides (98.2%) and mixed infections by T. trichiura + A. lumbricoides + hookworms (100%). However, the mean egg reduction percent was also a 100% for hookworms, 89.3% for A. lumbricoides and 81.7% for T. trichiura. The rates of treatment failure were limited, albendazole 6.20%, mebendazole 5.14%, for the combination of albendazole + ivermectin 2.02% and for mebendazole + ivermectine 2.22%. The majority of treatment failures were seen in the 0-9 age group. It is perhaps convenient to use combined schemes in cases of treatment failure. But, there is doubt as to whether there is the possibility of resistance to these drugs given that the majority of treatment failures observed in patients with low intensity infections which might be subdued in time.

[Child and adolescent abuse recorded at a national referral hospital, 2006 - 2011]. / Maltrato infantil y del adolescente registrado en un hospital de referencia nacional, 2006 - 2011.

OBJECTIVES: To describe the records of child and adolescent abuse of the Instituto Nacional de Salud del Niño (INSN) from January 2006 to September 2011, characterizing the victim and perpetrator. MATERIALS AND METHODS: A secondary sources analysis was performed, based on the domestic violence and child abuse records, from froms administered by Child Abuse and Adolescent Health Unit (MAMIS) at the INSN. The records include data of the victim, offender and characteristics of the aggression. Types of aggression were categorized as: sexual, physical, psychological or neglection. Frequencies and percentages are presented. RESULTS: A total of 1798 records were included. From them 63.9% were girls, and 39.9% were adolescents. Males accounted for 60.6% of the offenders, and 65.8% of assaults occurred at home. Sexual assault was recorded in 48.6%, with more frequency among girls (73.2%) and adolescents (44.4%); and intercourse occurred in 9.6% of the cases. CONCLUSIONS: From the INSN MAMIS records, aggressions to girls was the most frequent type of report, the aggressor was often a male and most of the attacks occurred in the child's home. Sexual assault accounted for almost half of the series.

Maltrato infantil y del adolescente registrado en un Hospital de referencia nacional, 2006 2011 / Child and adolescent abuse recorded at a national referral hospital, 2006 - 2011

Objetivos. Realizar una descripción de los registros del Instituto Nacional de Salud del Niño (INSN), desde enero de 2006 hasta septiembre de 2011, sobre maltrato infantil y del adolescente, lo cual permite la caracterización del agredido y del agresor. Materiales y métodos. Se realizó un análisis de fuentes secundarias, basado en registros de la “Ficha de evaluación de violencia familiar y maltrato infantil”, aplicada por el Módulo de Atención al Maltrato Infantil y del Adolescente en Salud (MAMIS) del INSN. La ficha incluye datos del agredido, del agresor y las características de la agresión. Se diferenció el tipo de agresión como: sexual, física, psicológica o por abandono. Se muestran los resultados en frecuencias y porcentajes. Resultados. Se incluyeron 1798 registros. El 63,9 por ciento eran niñas y el 39,9 por ciento fueron adolescentes. El 60,6 por ciento de los agresores fueron varones y el 65,8 por ciento de las agresiones ocurrieron en casa. El 48,6 por ciento fueron registros de agresión sexual, que fue más frecuente en niñas (73,2por ciento) y adolescentes (44,4 por ciento); en el 9,6 por ciento de los casos existió coito. Conclusiones. En los registros del MAMIS del INSN, la agresión en niñas fue la más frecuente; el agresor con frecuencia era un varón y la mayoría de las agresiones ocurrieron en el domicilio del menor. La agresión sexual fue casi la mitad de la serie.(AU)

Maltrato infantil y del adolescente registrado en un hospital de referencia nacional, 2006 - 2011 / Child and adolescent abuse recorded at a national referral hospital, 2006 - 2011

Objetivos. Realizar una descripción de los registros del Instituto Nacional de Salud del Niño (INSN), desde enero de 2006 hasta septiembre de 2011, sobre maltrato infantil y del adolescente, lo cual permite la caracterización del agredido y del agresor. Materiales y métodos. Se realizó un análisis de fuentes secundarias, basado en registros de la "Ficha de evaluación de violencia familiar y maltrato infantil", aplicada por el Módulo de Atención al Maltrato Infantil y del Adolescente en Salud (MAMIS) del INSN. La ficha incluye datos del agredido, del agresor y las características de la agresión. Se diferenció el tipo de agresión como: sexual, física, psicológica o por abandono. Se muestran los resultados en frecuencias y porcentajes. Resultados. Se incluyeron 1798 registros. El 63,9% eran niñas y el 39,9% fueron adolescentes. El 60,6% de los agresores fueron varones y el 65,8% de las agresiones ocurrieron en casa. El 48,6% fueron registros de agresión sexual, que fue más frecuente en niñas (73,2%) y adolescentes (44,4%); en el 9,6% de los casos existió coito. Conclusiones. En los registros del MAMIS del INSN, la agresión en niñas fue la más frecuente; el agresor con frecuencia era un varón y la mayoría de las agresiones ocurrieron en el domicilio del menor. La agresión sexual fue casi la mitad de la serie.

Objectives. To describe the records of child and adolescent abuse of the Instituto Nacional de Salud del Niño (INSN) from January 2006 to September 2011, characterizing the victim and perpetrator. Materials and methods. A secondary sources analysis was performed, based on the domestic violence and child abuse records, from froms administered by Child Abuse and Adolescent Health Unit (MAMIS) at the INSN. The records include data of the victim, offender and characteristics of the aggression. Types of aggression were categorized as: sexual, physical, psychological or neglection. Frequencies and percentages are presented. Results. A total of 1798 records were included. From them 63.9% were girls, and 39.9% were adolescents. Males accounted for 60.6% of the offenders, and 65.8% of assaults occurred at home. Sexual assault was recorded in 48.6%, with more frequency among girls (73.2%) and adolescents (44.4%); and intercourse occurred in 9.6% of the cases. Conclusions. From the INSN MAMIS records, aggressions to girls was the most frequent type of report, the aggressor was often a male and most of the attacks occurred in the child’s home. Sexual assault accounted for almost half of the series.

Caracterización de la violencia en niños y adolescentes en el Instituto Nacional de Salud del Niño 2000-2010 / Characterization of the violence in children and teenagers in the National Institute of Health of the Child 2000-2010

Objetivos: describir las características del agresor, de la víctima y según tipo de violencia en niños y basado en la ficha multisectorial de violencia familiar que es conducida por el MAMIS (Módulo de Atención al Maltrato Infantil en Salud) del Instituto Nacional de Salud del Niño (INSN) en el periodo 2006-2011. Metodología: estudio descriptivo observacional retrospectivo análitico retrsopectivo basado en la ficha multisectorial de violencia familiar que es conducida por la MAMIS (Módulo de Atención al Maltrato Infantil en Salud)del Instituto Nacional de Salud del Niño (INSN) en el periodo 2006-2011. La ficha recolecta datos de filiación del agredido, del agresor, del lugar de la agresión las medidas que se tomarán y el seguimiento y es aplicada a niñas y niños de 0 a 18 años atendidos o referidos al INSN por sospecha del maltrato infantil. Análisis de datos usando el programa estadístico SPSS V.18 se aplica Chi cuadrado para las variables cualitativas...