Consenso chileno para la atención integral de niños y adultos con fibrosis quística

Resumen La Fibrosis Quística (FQ) es la enfermedad hereditaria de pronóstico reservado más frecuente en raza blanca. Desde el año 2003, Chile inicia un Programa Nacional de Fibrosis Quística, de carácter integral, dirigido por la Unidad de Salud Respiratoria del Ministerio de Salud. Hasta la fecha, los principales resultados del Programa registran una significativa mayor sobrevida (promedio 27 años) y una significativa reducción en la edad de diagnóstico de los pacientes ingresados desde 2006 en adelante. El acceso a la canasta GES (Garantías Explícitas en Salud), la implementación del tamizaje neonatal en algunas regiones del país, la organización y la constitución de equipos entrenados en FQ de diversas especialidades, ha contribuido a mejorar los resultados. Si bien las principales manifestaciones son del aparato respiratorio y digestivo, el carácter multisistémico de la FQ obliga a conocer los distintos aspectos involucrados en su manejo, a fin de optimizar los resultados del tratamiento y los recursos invertidos, tanto en el sector público como privado. Este documento es una revisión y actualización sobre los principales aspectos del diagnóstico, seguimiento y tratamiento de las manifestaciones respiratorias y no respiratorias de la FQ.

Cystic Fibrosis (CF) is the most frequent hereditary disease in whites, with a reserved prognosis. Since 2003, Chile began a comprehensive National Cystic Fibrosis Program, directed by the Respiratory Health Unit of the Ministry of Health. To date, the main results of the Program record a significantly longer survival (average 27 years) and a significant reduction in the age of diagnosis of patients admitted from 2006 onwards. Access to Chilean Explicit Health Guarantees, the implementation of neonatal screening in some regions of the country, the organization and setting up of CF-trained teams of various specialties, has contributed to improving results. Although the main manifestations are of the respiratory and digestive system, the multisystemic nature of CF makes it necessary to know the different aspects involved in its management, in order to optimize the results of the treatment and the resources invested, both in the public and private sectors. This document is a review and an update on the main aspects of the diagnosis, monitoring and treatment of the respiratory and non-respiratory manifestations of CF.

Consenso chileno para la atención integral de niños y adultos con fibrosis quística / Chilean consensus for the integral care of children and adults with cystic fibrosis

Cystic Fibrosis (CF) is the most frequent hereditary disease in whites, with a reserved prognosis. Since 2003, Chile began a comprehensive National Cystic Fibrosis Program, directed by the Respiratory Health Unit of the Ministry of Health. To date, the main results of the Program record a significantly longer survival (average 27 years) and a significant reduction in the age of diagnosis of patients admitted from 2006 onwards. Access to Chilean Explicit Health Guarantees, the implementation of neonatal screening in some regions of the country, the organization and setting up of CF-trained teams of various specialties, has contributed to improving results. Although the main manifestations are of the respiratory and digestive system, the multisystemic nature of CF makes it necessary to know the different aspects involved in its management, in order to optimize the results of the treatment and the resources invested, both in the public and private sectors. This document is a review and an update on the main aspects of the diagnosis, monitoring and treatment of the respiratory and non-respiratory manifestations of CF.

La Fibrosis Quística (FQ) es la enfermedad hereditaria de pronóstico reservado más frecuente en raza blanca. Desde el año 2003, Chile inicia un Programa Nacional de Fibrosis Quística, de carácter integral, dirigido por la Unidad de Salud Respiratoria del Ministerio de Salud. Hasta la fecha, los principales resultados del Programa registran una significativa mayor sobrevida (promedio 27 años) y una significativa reducción en la edad de diagnóstico de los pacientes ingresados desde 2006 en adelante. El acceso a la canasta GES (Garantías Explícitas en Salud), la implementación del tamizaje neonatal en algunas regiones del país, la organización y la constitución de equipos entrenados en FQ de diversas especialidades, ha contribuido a mejorar los resultados. Si bien las principales manifestaciones son del aparato respiratorio y digestivo, el carácter multisistémico de la FQ obliga a conocer los distintos aspectos involucrados en su manejo, a fin de optimizar los resultados del tratamiento y los recursos invertidos, tanto en el sector público como privado. Este documento es una revisión y actualización sobre los principales aspectos del diagnóstico, seguimiento y tratamiento de las manifestaciones respiratorias y no respiratorias de la FQ.

Modulation of cell function by electric field: a high-resolution analysis.

Regulation of cell function by a non-thermal, physiological-level electromagnetic field has potential for vascular tissue healing therapies and advancing hybrid bioelectronic technology. We have recently demonstrated that a physiological electric field (EF) applied wirelessly can regulate intracellular signalling and cell function in a frequency-dependent manner. However, the mechanism for such regulation is not well understood. Here, we present a systematic numerical study of a cell-field interaction following cell exposure to the external EF. We use a realistic experimental environment that also recapitulates the absence of a direct electric contact between the field-sourcing electrodes and the cells or the culture medium. We identify characteristic regimes and present their classification with respect to frequency, location, and the electrical properties of the model components. The results show a striking difference in the frequency dependence of EF penetration and cell response between cells suspended in an electrolyte and cells attached to a substrate. The EF structure in the cell is strongly inhomogeneous and is sensitive to the physical properties of the cell and its environment. These findings provide insight into the mechanisms for frequency-dependent cell responses to EF that regulate cell function, which may have important implications for EF-based therapies and biotechnology development.

Neumonía grave por Streptococcus pyogenes: presentación de un caso y revisión de la literatura / Streptococcus pyogenes severe pneumonia: case report and review of the literature

Serious infections caused by Streptococcus pyogenes can encompass a wide spectrum of disease entities including cellulitis, necrotizing fasciitis, arthritis, puerperal fever, septicemia, streptococcal toxic shock syndrome and pulmonary conditions such as pneumonia, empyema and abscesses, which lead to an increased lethality. In this article we describe a school age child with S. pyogenes pneumonia who subsequently presents multisystem involvement. We review the current literature with respect to this pathogen.

Las infecciones graves por Streptococcus pyogenes pueden abarcar un amplio espectro de entidades nosológicas que incluyen celulitis, fascitis necrotizante, artritis, fiebre puerperal, septicemia, síndrome de shock tóxico estreptocócico y afecciones pulmonares tales como: neumonías, empiemas y abscesos, los cuales conllevan a un aumento en la letalidad por este agente. En el presente artículo se revisa el caso clínico de un escolar que inicia un cuadro de neumonía por Streptococcus pyogenes y que posteriormente evoluciona con compromiso multisistémico. Además se revisa la literatura actual con respecto a este patógeno.

Macrosomic newborns of non-diabetic mothers: anthropometric measurements and neonatal complications.

OBJECTIVE: To assess the association of anthropometric measurements with neonatal complications in macrosomic newborns of non-diabetic mothers. DESIGN: Retrospective cohort study. PATIENTS: All liveborn, singleton, full term newborns with birth weight ≥4000 g born to non-diabetic mothers at a tertiary medical centre in 1995-2005 (n=2766, study group) were matched to the next born, healthy, full term infant with a birth weight of 3000-4000 g (control group). Exclusion criteria were multiple birth, congenital infection, major malformations and pregnancy complications. INTERVENTION: Data collection by file review. OUTCOME MEASURES: Complication rates were compared between study and control groups and between symmetric and asymmetric macrosomic newborns, defined by weight/length ratio (WLR), Body Mass Index and Ponderal Index. RESULTS: The 2766 non-diabetic macrosomic infants identified were matched to 2766 control infants. The macrosomic group had higher rates of hypoglycaemia (1.2% vs 0.5%, p=0.008), transient tachypnoea of the newborn (1.5% vs 0.5%, p<0.001), hyperthermia (0.6% vs 0.1%, p=0.012), and birth trauma (2% vs 0.7%, p<0.001), with no cases of symptomatic polycythaemia, and only one case of hypoglycaemia. Hypoglycaemia was positively associated with birth weight. It was significantly higher in the asymmetric than the symmetric macrosomic newborns, defined by WLR (1.7% vs 0.3%, p<0.001). CONCLUSIONS: Macrosomic infants of non-diabetic mothers are at increased risk of neonatal complications. However, routine measurements of haematocrit and calcium may not be necessary. Symmetric macrosomic infants (by WLR) have a similar rate of hypoglycaemia as normal-weight infants. Thus, repeat glucose measurements in symmetric macrosomic infants are not justified.

Adult respiratory distress syndrome following cardiac surgery.

BACKGROUND: Severe lung injury with the development of acute respiratory distress syndrome (ARDS) is a serious complication of cardiac surgery. The aim of this study was to determine the incidence, risk factors, and mortality of ARDS following cardiac surgery. METHODS: We retrospectively analyze data in the period between January 2005 and March 2013. RESULTS: Of 6069 patients who underwent cardiac surgery during the study period, 37 patients developed ARDS during the postoperative period. The incidence of ARDS was 0.61%, with a mortality of 40.5% (15 patients). Multivariate regression analysis identified previous cardiac surgery, complex cardiac surgery, and more than three transfusions with packed red blood cells (PRBC) were independent predictors for developing ARDS. CONCLUSIONS: ARDS remains a serious, but very rare complication associated with significant mortality. In our study, previous cardiac surgery, complex cardiac surgery, and more than three transfusions of PRBC were independent predictors for the development of ARDS.

Citomegalovirus: modalidades broncopulmonares de presentación / Cytomegalovirus: detailed respiratory presentation

Citomegalovirus (CMV), a herpesviridae, due to its high transmission rate, is endemic, with wide world distribution, especially in underdeveloped countries. CMV is an important pathogen agent during embryological period, being the commonest cause of TORCH syndrome. Due to its capability of infecting different organs, it can have a variety of clinical presentations. The more frequent and severe forms affect the respiratory, gastrointestinal, central nervous system and the retina. At the respiratory system CMV manifests in different ways, depending on age and immunological state of the patient. It produces interstitial pneumonias in immunocompromised host; but occasionally affects immunocompetent patients as a first trimester pneumonia, whooping cough like syndrome or chronic interstitial lung disease. The diagnostic method in use, the shell vial accelerated cultivation of samples obtain by bronchoalveolar lavage is both highly sensitive and specific. Treatment with ganciclovir has improved prognosis. The objective of this article is to show the different clinical presentations of CMV infection of the respiratory system in pediatric patients and the response to treatment.

Citomegalovirus (CMV) es un herpesviridae, endémico de amplia distribución mundial, debido a su alta tasa de transmisión, especialmente en países de bajo nivel socioeconómico. CMV es un importante agente patógeno en el período embrionario-fetal, siendo el principal agente etiológico del síndrome de TORCH. Por su capacidad de infectar diferentes órganos puede producir una variedad de cuadros clínicos, las formas más graves y frecuentes afectan al aparato respiratorio, gastrointestinal, sistema nervioso central y la retina. En el aparato respiratorio CMV se manifiesta de diversas maneras, dependiendo de la edad y del estado inmunológico del huésped. En inmunodeprimidos produce neumonías intersticiales graves; sin embargo, ocasionalmente afecta a individuos inmunocompetentes manifestándose como neumonía del primer trimestre, síndrome coqueluchoídeo o enfermedad pulmonar intersticial crónica. En la actualidad el método diagnóstico de elección es el cultivo acelerado de shell vial de muestra obtenida mediante lavado broncoalveolar, presenta alta sensibilidad y especificidad. El tratamiento con ganciclovir ha mejorado el pronóstico. El objetivo de este artículo es mostrar las diferentes formas de presentación clínica del CMV en el aparato respiratorio en pediatría y la respuesta al tratamiento utilizado.

Is gender an independent risk factor for coronary bypass grafting?

BACKGROUND: Postoperative mortality after coronary artery bypass grafting (CABG) surgery is traditionally considered to be influenced by gender. However, the data are conflicting and it is not clear whether gender is a true independent risk factor for death in this setting. We analyzed our database to determine whether gender is an independent risk factor for death after CABG. PATIENTS AND DESIGN: A retrospective analysis of 1 758 isolated first-time coronary artery bypass graft patients treated between 2003 and 2005 was conducted in the Department of Cardiothoracic Surgery of Rabin Medical Center, a major tertiary facility in Israel. RESULTS: The female patients had a distinctly different pre- and intraoperative profile compared with the male patients, and significantly higher postoperative mortality (p < 0.05). On a propensity scoring of 359 matched pairs, the risk factors for death were found to be severe left ventricular dysfunction, chronic obstructive pulmonary disease, and use of an intra-aortic balloon pump (p < 0.05). The addition of intraoperative data to the model yielded only cardiopulmonary bypass time and use of an intra-aortic balloon pump as risk factors for death (p < 0.05). Validation with the bootstrap technique revealed that strong predictors of death (> 50 % of the sample) were cardiopulmonary bypass time, use of an intra-aortic balloon pump, and, to a lesser extent, chronic obstructive pulmonary disease. Female gender was not found to be an independent risk factor for death after coronary artery bypass graft. CONCLUSIONS: Female gender is apparently not an independent risk factor for coronary artery bypass graft mortality in this patient group.

Cardiac surgery in patients on chronic hemodialysis: short and long-term survival.

OBJECTIVE: Open-heart surgery carries a high risk for hemodialysis patients. This study focuses on the short and long-term outcomes of hemodialysis patients undergoing heart surgery. DESIGN: The study was carried out as a retrospective analysis in the Department of Cardiothoracic Surgery in a large university-affiliated hospital. PATIENTS: 115 hemodialysis patients underwent cardiac surgery in our department between 1 July 1996 and 31 July 2006. 67.5 % (77 patients) underwent isolated coronary artery bypass grafting (CABG), 13.2 % (15 patients) underwent isolated aortic valve replacement (AVR) and 20.2 % (23 patients) underwent mitral valve surgery or combined valve and coronary artery bypass grafting or multiple valve surgery. METHODS: The relationship between several variables (age, sex, hypertension, diabetes, and previous myocardial infarction, type of disease, preoperative ejection fraction, and congestive heart failure) and operative (30 days) mortality and late survival was analyzed. RESULTS: The overall 30-day mortality was 18.3 % (21 patients). It was 13 % (10/77 patients) for the isolated CABG group and 13.3 % (2/15) for the isolated AVR group. Patients undergoing combined valve and coronary surgery or multiple valve surgery had a higher perioperative mortality of 39.1 % (9/23) compared to the isolated CABG and isolated AVR patients. Perioperative death was also higher in patients with moderate and severe LV dysfunction, and in patients with diabetes. The duration of dialysis periods was not related to perioperative death. Mean follow-up was 26.4 +/- 29.7 months (0.1 to 104 months). Actuarial survival at 1 year and 5 years was 76 % and 55 % for isolated CABG, 59 % and 21 % for isolated AVR, and 44 % and 33 % for all other cases, respectively (log rank P = 0.001). CONCLUSION: Patients on dialysis have a high risk of perioperative mortality and poor long-term survival rates. Mortality is higher and survival is worse after combined CABG and valve-related procedures or multiple valve surgery than after isolated CABG and AVR.

[Utility of chest x-ray like approach to etiology of community acquired pneumonia in children]. / Utilidad de la radiografía de tórax en niños como aproximación a la etiología de neumonía adquirida en la comunidad.

INTRODUCTION: Chest X-ray (CR) utility to predict etiology in community-acquired pneumonia (CAP), in children has been controversial. Nevertheless, some authors propose the use of well standardized radiological patterns. OBJECTIVE: To evaluate usefulness of modified Swischuk's radiological patterns (RaP) to determine probable etiology in children hospitalized with CAP. PATIENTS AND METHODS: Eighty children were studied using 6 standardized RaP. The RaP were blindly and individually analyzed by 9 pneumologists, who registered the results (stage 1). Thereafter, (stage 2) a second evaluation adding clinical information was performed. Then, the patients complementary examinations and clinical evolution were included (stage 3). The reference standard (RS) was generated from a blind consensus. Every result was compared with the RS using Student test. RESULTS: According to RS, children were classified as having a virus-like pneumonia in 63% of cases, bacterial in 13%, mixed in 16%, atypical in 5% and ADV in 3%. The agreement of stage 1 and 2 with RS was 64 and 77%, respectively. Virus and bacterial RaP agreement increased from 66 to 82 % (p < 0.001) and from 82 to 90% (p < 0.05), respectively after incorporating clinical parameters. CONCLUSION: Modified Swischuk's RaP used in association with clinical elements allows a quite satisfactory approach to etiologic diagnosis of CAP.

Utilidad de la radiografía de tórax en niños como aproximación a la etiología de neumonía adquirida en la comunidad / Utility of chest x-ray like approach to etiology of community acquired pneumonia in children

Introduction: Chest X-ray (CR) utility to predict etiology in community-acquired pneumonia (CAP), in children has been controversial. Nevertheless, some authors propose the use of well standardized radiological patterns. Objective: To evaluate usefulness of modified Swischuk's radiological patterns (RaP) to determine probable etiology in children hospitalized with CAP. Patients and Methods: Eighty children were studied using 6 standardized RaP. The RaP were blindly and individually analyzed by 9 pneumologists, who registered the results (stage 1). Thereafter, (stage 2) a second evaluation adding clinical information was performed. Then, the patients complementary examinations and clinical evolution were included (stage 3). The reference standard (RS) was generated from a blind consensus. Every result was compared with the RS using Student test. Results: According to RS, children were classified as having a virus-like pneumonia in 63 percent of cases, bacterial in 13 percent, mixed in 16 percent, atypical in 5 percent and ADV in 3 percent. The agreement of stage 1 and 2 with RS was 64 and 77 percent, respectively. Virus and bacterial RaP agreement increased from 66 to 82 percent (p < 0.001) and from 82 to 90 percent (p < 0.05), respectively after incorporating clinical parameters. Conclusion: Modified Swischuk's RaP used in association with clinical elements allows a quite satisfactory approach to etiologic diagnosis of CAP.

Introducción: La utilidad de la radiografía de tórax.(RT) para establecer etiología en niños con neumonía adquirida en la comunidad (NAC) es cuestionada. Objetivo: Evaluar la utilidad de los patrones radiológicos (PRa) de Swischuk modificados para determinar la probable etiología en niños hospitalizados con NAC. Pacientes y Método: Se estudió 80 niños mediante el uso de seis PRa estandarizados. Se procedió al análisis secuencial por nueve neumólogos; individualmente de manera ciega (etapa 1), se registró el PRa. Posteriormente (etapa 2) se agregó información clínica. En seguida se incluyó exámenes complementarios y la evolución de cada niño (etapa 3). El estándar de referencia (ER) fue generado mediante consenso ciego. Se comparó cada resultado con el ER mediante t de Student. Resultados: Según el ER, las etiologías identificadas fueron: viral (63 por ciento), bacteriana (13 por ciento), mixta (16 por ciento), atípica (5 por ciento) y ADV (3 por ciento). El rendimiento de la etapa 1 y 2 fue 64 y 77 por ciento>, respectivamente. El PRa viral y bacteriano aumentó de 66 a 82 por ciento> (p < 0,001) y de 82 a 90 por ciento (p < 0,05), respectivamente, luego de incorporar elementos clínicos. Conclusión: La utilización de PRa de Swischuk modificados, asociados a elementos clínicos, permitió un adecuado rendimiento como aproximación del diagnóstico etiológico en NAC

Comparison of soluble and placental transferrin receptors as standards for the determination of soluble transferrin receptor in humans.

Transferrin receptor is a transmembrane protein that mediates iron transport from blood into cells. The extracellular part of this receptor circulates in blood as soluble transferrin receptor (sTfR) and the immunological determination of this parameter is widely used in clinical practice. This study aimed at comparing the properties of sTfR and placental TfR (pTfR) and to evaluate the validity of pTfR as a standard for the determination of sTfR in human serum. sTfR and pTfR were studied by immunofluorescent assay and fast protein liquid chromatography (FPLC) gel filtration. Serum sTfR levels were calculated using sTfR or pTfR as a standard. The immunological activity of pTfR was lower than that of sTfR in all anti-TfR monoclonal antibody pairs. Upon FPLC gel filtration, pTfR eluted in a void volume of the column as a protein with a molecular weight (MW) of >1500 kDa, whereas the MW of sTfR corresponded to 237 kDa. This could be a result of micelle formation by pTfR because of its hydrophobic intracellular part. The serum sTfR levels calculated against sTfR were 2.5 times lower than those calculated against pTfR. Serum sTfR levels are overestimated when pTfR is used as the standard.

Seguimiento clínico y factores de riesgo en niños con enfermedades respiratorias por adenovirus / Clinical evaluation and risk factors analysis in children with adenovirus respiratory infections

Introducción: El adenovirus es un importante agente etiológico en infecciones respiratorias en niños, que en ocasiones puede producir una gran morbimortalidad. Objetivo: Describir las características clínicas y epidemiológicas de las infecciones respiratorias por ADV e identificar posibles factores de riesgo asociados a gravedad, mortalidad y secuelas broncopulmonares. Pacientes y Metodos: Se revisaron las fichas clínicas de los pacientes con diagnóstico de infección respiratoria por adenovirus mediante IFI durante 2004; se registraron datos epidemiológicos y clínicos; se evaluaron factores de riesgo y se calculó la tasa de ataque. Resultados: Se incluyeron 57 niños, 68,4 por ciento varones, mediana de edad de 10 meses, 67 por ciento menores de 1 año. 89,5 por ciento fueron hospitalizados; 26,3 por ciento evolucionó grave, 8,8 por ciento falleció y 47,3 por ciento presentó secuelas broncopulmonares. En este período se produjeron 2 brotes intrahospitalarios, con una tasa de ataque de 16,5 por ciento. Se identificaron como factores de riesgo para enfermedad grave: edad entre 4 y 10 meses y adquirir el ADV durante un brote intrahospitalario; para mortalidad el antecedente de enfermedad subyacente, y para secuelas pulmonares la edad entre 4 y 10 meses. Conclusiones: Los factores de riesgo identificados deben llamar nuestra atención en niños hospitalizados con diagnóstico de adenovirus ya que pueden predecir una evolución desfavorable.

Immunological study of complex formation between soluble transferrin receptor and transferrin.

Transferrin receptor (TfR) is a dimeric transmembrane protein that provides iron transport from plasma to cells by binding and internalization of iron-loaded transferrin (Tf). Soluble transferrin receptor (sTfR) is an extracellular part of the TfR molecule that is truncated from the cell surface and released into the blood stream. Using monoclonal antibodies (HyTest Ltd., Turku, Finland), immunofluorescent methods for sTfR and sTfR-Tf complex determination were developed. Soluble TfR was isolated from human plasma, and complex formation between sTfR and Tf was studied by stepwise complex construction and by FPLC gel filtration. It was found that sTfR could bind two Tf molecules step by step when the sTfR-Tf complex is constructed in the plate wells. FPLC gel filtration of sTfR-Tf mixtures and analysis of sTfR and sTfR-Tf immunological activities in collected fractions showed that sTfR can form different complexes with TF depending upon the ratios between them: a 291-kDa compound is assumed to be a 2:1 sTfR/Tf complex, and a 345-kDa compound is assumed to be a 2:2 sTfR/Tf complex. Isolated sTfR eluted as a 237-kDa protein. FPLC gel filtration of serum revealed that all sTfR in serum is bound to Tf in a 2:2 complex, and no isolated sTfR can be found in serum. This raises the question as to the nature of the bonds that hold two molecules of sTfR together to form a dimer.

Measurements of Kondo and spin splitting in single-electron transistors.

We measure the spin splitting in a magnetic field B of localized states in single-electron transistors using a new method, inelastic spin-flip cotunneling. Because it involves only internal excitations, this technique gives the most precise value of the Zeeman energy Delta=/g/mu(B)B. In the same devices we also measure the splitting with B of the Kondo peak in differential conductance. The Kondo splitting appears only above a threshold field as predicted by theory. However, the magnitude of the Kondo splitting at high fields exceeds 2/g/mu(B)B in disagreement with theory.

Recombinant factor VIIa use in cardiac surgery--expanding the arsenal therapy for intractable bleeding?

A 72-year-old patient was admitted for mitral valve replacement because of infective endocarditis. Severe intractable bleeding in the early postoperative period was successfully treated with recombinant activated factor VII (rFVIIa). Thereafter, recovery was uneventful, and the patient was discharged on postoperative day 16. The current clinical aspects and experience of rFVIIa use in cardiac surgery are discussed.