Severe Aortic Stenosis and Myocardial Function: Diagnostic and Prognostic Usefulness of Ultrasonic Integrated Backscatter Analysis

Background— The aim of this study was to assess the myocardial reflectivity pattern in severe aortic valve stenosis through the use of integrated backscatter (IBS) analysis. Patients with aortic stenosis (AS) were carefully selected in the Department of Cardiology. Methods and Results— Thirty-five subjects (AS: valve orifice ≤1 cm2; 12 female; mean age, 71.8±6.2 years) and 25 healthy subjects were studied. All subjects of the study had conventional 2D-Doppler echocardiography and IBS. Backscatter signal was sampled at the septum and posterior wall levels. Patients with AS were divided into 2 groups: 16 patients with initial signs of congestive heart failure and a depressed left ventricular systolic function (DSF) (ejection fraction [EF] range, 35% to 50%) and 19 asymptomatic patients with normal left ventricular systolic function (NSF) (EF >50%). Myocardial echo intensity (pericardium related) was significantly higher at the septum and posterior wall levels in DSF than in NSF and in control subjects. IBS variation, as an expression of variation of the signal, appeared to be significantly lower in AS with DSF than in NSF and in control subjects, at both the septum and posterior wall levels. Patients with DSF underwent aortic valve replacement, and, during surgical intervention, a septal myocardial biopsy was made for evaluation of myocardium/fibrosis ratio. Abnormally increased echo intensity was detected in left ventricular pressure overload by severe aortic stenosis and correlated with increase of myocardial collagen content (operating biopsy). Conclusions— One year after aortic valve replacement, we observed a significant reduction of left ventricular mass, and, only if pericardial indexed IBS value (reduction of interstitial fibrosis) decreased, it was possible to observe an improvement of EF and of IBS variation

Desarrollo de un modelo de simulación para terminales terrestres. Caso: Mejoramiento o reubicación de los terminales terrestres nacional e internacional de la ciudad de Arica

El presente trabajo de investigación tiene por objetivo principal determinar si las actuales instalaciones de los terminales terrestres nacional e internacional de la ciudad de Arica debe mejorarse, conservando su ubicación actual o deben ser reubicados. Para el logro de este objetivo se desarrolla un modelo de simulación que representa, bajo algunos supuestos, el funcionamiento de los terminales terrestres de la ciudad de Arica, de modo tal que permita analizar sus comportamientos frente a distintas condiciones de operación.En primer lugar, se examinan los síntomas y problemas que dan origen al trabajo de investigación. Luego se analiza el marco teórico, el cual proporciona las definiciones y teorías sobre sistemas, simulación, números y variables aleatorias y líneas de espera. Por otro lado, se realiza una descripción física y operacional de los terminales terrestres de la ciudad de Arica, base teórica en la que se fundamenta el modelo de simulación.El modelo de simulación se desarrolla formulando, en primer lugar, el sistema que se desea simular, e identificando la información necesaria para poder formular el modelo matemático. Luego se evalúan las características de la información procesada identificando su distribución de probabilidad. Posteriormente, se elabora un diagrama de flujo que representa en forma secuencial las actividades del modelo ejecutadas en un programa computacional desarrollado en lenguaje Visual Basic para Aplicaciones. Los datos entregados por este programa que corresponden a la simulación de los terminales terrestres son validados para verificar su semejanza con la realidad.Se realizan cuatro experimentos de simulación, para observar el funcionamiento de los terminales terrestres en periodos futuros, encontrar problemas operacionales o de congestionamiento e identificar el momento en que estos ocurren.Finalmente se exponen las conclusiones y recomendaciones para la solución de los problemas operativos identificados en el desarrollo de la investigación

Risk factors associated to hospital mortality in patients with acute kidney injury on hemodialysis.

INTRODUCTION: The worldwide incidence of acute kidney injury is 18% and the overall hospital mortality can rise above 50%. In Peru, there are few series about mortality of acute kidney injury in hemodialysis patients. OBJECTIVES: To identify risk factors associated to hospital mortality of acute kidney injury in hemodialysis patients. METHODS: This is a retrospective cohort of patients with acute kidney injury in hemodialysis of Hospital Nacional Edgardo Rebagliati Martins gathered between January 2013 and December 2015. The sample size was 154 patients which allowed a power of 80% and a CI of 95%. ICD-10 codes were used to identify medical records of patients with acute kidney injury (N.17) and hemodialysis (Z.49). The independent variable was oliguria, and the primary outcome was hospital mortality. Poisson regression was used for multivariate analysis. RESULTS: We identified a total of 285 patients; 212 medical records were analyzed and 44 were excluded. Out of the 168 medical records, 129 belonged to living patients and 39 to deceased ones. The overall mortality incidence was 17.2%. The principal etiologies of acute kidney injury while in hemodialysis were sepsis (39.2%), and severe dehydration (10.8%). In the adjusted model, the risk factors associated to hospital mortality of acute kidney injury while in hemodialysis were elevated serum lactate (RR 1.09), elevated serum potassium (RR 0.93), and mean arterial pressure (RR 0.97). CONCLUSIONS: Lactate is an objective parameter that can predict prognosis and contributes to a better management of acute kidney injury in hemodialysis patients. INTRODUCCIÓN: La incidencia de insuficiencia renal aguda a nivel mundial es 18% y la mortalidad intrahospitalaria puede alcanzar más del 50%. En Perú, existen escasos estudios acerca de la mortalidad en pacientes con insuficiencia renal aguda en hemodiálisis. OBJETIVOS: Identificar los factores de riesgo asociados a mortalidad intrahospitalaria en pacientes con insuficiencia renal aguda en hemodiálisis. MÉTODOS: Es una cohorte retrospectiva, en la cual se estudió a los pacientes con insuficiencia renal aguda en hemodiálisis en el Hospital Nacional Edgardo Rebagliati Martins entre enero de 2013 y diciembre de 2015. Se halló un tamaño de muestra de 154 pacientes con una potencia de 80%, y un intervalo de confianza de 95%. Se utilizaron los códigos de la Clasificación Internacional de Enfermedades-10 para identificar las historias clínicas de pacientes con insuficiencia renal aguda (N.17) y hemodiálisis (Z.49). La variable independiente fue oliguria y la variable dependiente fue mortalidad intrahospitalaria. Para el análisis multivariado, se utilizó regresión de Poisson. RESULTADOS: El universo fue de 285 pacientes. Se revisaron 212 historias clínicas y se excluyeron 44. De las 168 historias clínicas estudiadas, 129 pertenecían a pacientes vivos y 39 a fallecidos. La incidencia de mortalidad fue de 17,2%. Las principales causas de insuficiencia renal aguda en hemodiálisis fueron sepsis (39,2%) y deshidratación severa (10,8%). En el modelo ajustado, los factores de riesgo asociados a mortalidad intrahospitalaria de insuficiencia renal aguda en hemodiálisis fueron lactato (riesgo relativo 1,09), potasio (riesgo relativo 0,93), y presión arterial media (riesgo relativo 0,97). CONCLUSIONES: El lactato es un parámetro objetivo que permite predecir el pronóstico y contribuye a un mejor manejo de los pacientes con insuficiencia renal aguda en hemodiálisis.Revisión por paresRevisión por pare

Different somatic alterations of the HRPT2 gene in a patient with recurrent sporadic primary hyperparathyroidism carrying an HRPT2 germline mutation

Early onset of primary hyperparathyroidism (PHPT) and multiglandular involvement suggest a familial form in which germline mutation of a PHPT-related gene(s) and a somatic event at the same locus can be often demonstrated. We investigated the involvement of multiple endocrine neoplasia type 1 (MEN1) and HRPT2 genes in a 39-year-old man with recurrent PHPT. PHPT was firstly diagnosed at the age of 21 and the patient had two recurrences separated by extended periods of normocalcemia. This unusual history prompted us to investigate other family members and study the MEN1 and HRPT2 genes. An HRPT2 germline missense mutation in exon 3 (R91P) was found in the index case, which was associated with different HRPT2 somatic alterations in each of the three examined parathyroid tumors. These findings are consistent with Knudson's 'two hit' concept of biallelic inactivation of classical tumor suppressor genes. Screening of 15 asymptomatic relatives was negative for the R91P germline mutation. All the three abnormal parathyroid specimens showed cystic features at histology and were negative for parafibromin immunostaining. In one specimen, diffuse parafibromin staining was evident in a rim of normal parathyroid tissue surrounding the adenomatous lesion. Our study shows that different somatic genetic events at the HRPT2 locus are responsible for the asynchronous occurrence of multiple adenomas in a patient carrying an HRPT2 germline mutation. The finding of diffuse parafibromin staining in a rim of normal parathyroid tissue, but not in the contiguous adenomatous lesion, reinforces the concept that loss of parafibromin expression is responsible for the development of parathyroid tumors in this setting

Neonates and Infants with Left Heart Obstruction and Borderline Left Ventricle Undergoing Biventricular Repair: What Do We Know about Long-Term Outcomes? A Critical Review

Background: The decision to perform biventricular repair (BVR) in neonates and infants presenting with either single or multiple left ventricle outflow obstructions (LVOTOs) and a borderline left ventricle (BLV) is subject to extensive discussion, and limited information is known regarding the long-term outcomes. As a result, the objective of this study is to critically assess and summarize the available data regarding the prognosis of neonates and infants with LVOTO and BLV who underwent BVR. Methods: In February 2023, we conducted a review study with three different medical search engines (the National Library of Medicine, Science Direct, and Cochrane Library) for Medical Subject Headings and free text terms including “congenital heart disease”, “outcome”, and “borderline left ventricle”. The search was refined by adding keywords for “Shone’s complex”, “complex LVOT obstruction”, “hypoplastic left heart syndrome/complex”, and “critical aortic stenosis”. Results: Out of a total of 51 studies, 15 studies were included in the final analysis. The authors utilized heterogeneous definitions to characterize BLV, resulting in considerable variation in inclusion criteria among studies. Three distinct categories of studies were identified, encompassing those specifically designed to evaluate BLV, those focused on Shone’s complex, and finally those on aortic stenosis. Despite the challenges associated with comparing data originating from slightly different cardiac defects and from different eras, our results indicate a favorable survival rate and clinical outcome following BVR. However, the incidence of reintervention remains high, and concerns persist regarding residual pulmonary hypertension, which has been inadequately investigated. Conclusions: The available data concerning neonates and infants with LVOTO and BLV who undergo BVR are inadequate and fragmented. Consequently, large-scale studies are necessary to fully ascertain the long-term outcome of these complex defects

Contextual and individual factors associated with dental services utilisation by Brazilian adults: A multilevel analysis

BACKGROUND: Inequalities in the utilisation of dental services in Brazil are remarkable. The aim of this study was to evaluate the association of contextual and individual factors with the utilisation of dental services by Brazilian adults using the Andersen's behavioural model. METHODS: Individual-level data from 27,017 adults residents in the State capitals who were interviewed in the 2013 Brazilian National Health Survey were pooled with contextual city-level data. The outcomes were non-utilisation of dental services and last dental visit over 12 months ago. Individual predisposing variables were age, sex, race/skin colour, schooling and social network. Individual enabling variables included income, health insurance and registration in primary health care. Individual need variables were self-perceived dental health and self-reported missing teeth. Multilevel logistic regression models were performed to estimate odds ratio (OR) and 95% confidence intervals (95% CIs) of the association of contextual and individual predisposing, enabling and need-related variables with dental services outcomes. RESULTS: Predisposing (OR = 0.89; 95% CI 0.81-0.97) and enabling (OR = 0.90; 95% CI 0.85-0.96) contextual factors were associated with non-utilisation of dental services. Individual predisposing (sex, race/skin colour, schooling), enabling (income, health insurance) and need (self-perceived oral health, missing teeth) were associated with non-utilisation of dental services and last dental visit over 12 months ago. The latter was also associated with other individual predisposing (age, social network) and need (eating difficulties due to oral problems) characteristics. CONCLUSIONS: Individual and contextual determinants influenced dental services utilisation in Brazilian adults. These factors should be on the policy agenda and considered in the organisation of health services aiming to reduce oral health inequalities related to access and utilisation of dental services

Antiangiogenic and anticolorectal cancer effects of metronomic irinotecan chemotherapy alone and in combination with semaxinib

Metronomic chemotherapy refers to the administration of chemotherapy at low, nontoxic doses on a frequent schedule with no prolonged breaks. The aim of the study is to rationally develop a CPT-11 metronomic regimen in preclinical settings of colon cancer. In vitro cell proliferation, apoptosis and thrombospondin-1/vascular endothelial growth factor (TSP-1/VEGF) expression analyses were performed on endothelial (HUVEC, HMVEC-d) and colorectal cancer (HT-29, SW620) cells exposed for 144 h to metronomic concentrations of SN-38, the active metabolite of CPT-11. HT-29 human colorectal cancer xenograft model was used, and tumour growth, microvessel density and VEGF/TSP-1 quantification was performed in tumours. In vitro and in vivo combination studies with the tyrosine inhibitor semaxinib were also performed. SN-38 preferentially inhibited endothelial cell proliferation alone and interacted synergistically with semaxinib; it induced apoptosis and increased the expression and secretion of TSP-1. Metronomic CPT-11 alone and combined with semaxinib significantly inhibits tumour growth in the absence of toxicity, which was accompanied by decreases in microvessel density and increases in TSP-1 gene expression in tumour tissues. In vitro results show the antiangiogenic properties of low-concentration SN-38, suggesting a key role of TSP-1 in this effect. In vivo, the CPT-11 metronomic schedule is effective against tumour and microvessel growth without toxic effect on mice