Linfoma hepático primario no Hodgkin de células T y B asociado a VEB: un reporte de caso

El linfoma hepático primario (LHP) es una forma rara de linfoma no Hodgkin que suele manifestarse clínicamente con dolor abdominal, pérdida de peso, hepatomegalia e ictericia, sin presencia de adenomegalias o invasión extrahepática. De todos lo linfomas este presenta una prevalencia 0.016%. La etiología no se encuentra bien definida, sin embargo, el LHP se ha reportado estar asociado al virus Epstein-Barr (VEB), el cual posee la capacidad promover el crecimiento de los linfocitos, mediante los mecanismos de expresión del antígeno nuclear de Epstein-Barr 1 (EBNA1), la proteína de membrana latente 1 (LMP1) y LMP2 que producen la proliferación de células B. Mientras que, la activación de citocinas proinflamatorias y expresión de genes latentes, conducen a la proliferación de células T. Presentamos el caso de una paciente de 68 años que acude por presentar pérdida de peso de 10 kg en un periodo de 3 meses, malestar general, dolor abdominal tipo cólico localizado en epigastrio y sensación de llenura precoz asociado a fiebre no cuantificada, episodios de náuseas, diarrea en múltiples ocasiones e ictericia en escleras en los últimos 5 días. Mediante biopsia, se identifica Linfoma no Hodgkin inmunofenotipo T y B.Primary liver lymphoma (LHP) is a rare form of non-Hodgkin lymphoma that usually manifests clinically with abdominal pain, weight loss, hepatomegaly and jaundice, without the presence of adenomegalies or extrahepatic invasion. Of all lymphomas, this has a prevalence of 0.016%. The etiology is not well defined, however LHP has been reported to be associated with the Epstein-Barr virus (EBV), which has the ability to promote lymphocyte growth, by means of the Epstein-Barr nuclear antigen expression mechanisms. 1 (EBNA1), the latent membrane protein 1 (LMP1) and LMP2 that produce B-cell proliferation. While, the activation of proinflammatory cytokines and latent gene expression, lead to the proliferation of T-cells. We present the case of a 68-year-old patient who presented with a 10 kg weight loss over a period of 3 months, malaise, abdominal cramps in the epigastrium and a feeling of early fullness associated with unquantified fever, nausea episodes, multiple diarrhea occasions and jaundice in scleras in the last 5 days. By biopsy, non-Hodgkin lymphoma immunophenotype T and B is identified

Early progression to active tuberculosis is a highly heritable trait driven by 3q23 in Peruvians

Abstract: Of the 1.8 billion people worldwide infected with Mycobacterium tuberculosis, 5–15% will develop active tuberculosis (TB). Approximately half will progress to active TB within the first 18 months after infection, presumably because they fail to mount an effective initial immune response. Here, in a genome-wide genetic study of early TB progression, we genotype 4002 active TB cases and their household contacts in Peru. We quantify genetic heritability (hg2) of early TB progression to be 21.2% (standard error 0.08). This suggests TB progression has a strong genetic basis, and is comparable to traits with well-established genetic bases. We identify a novel association between early TB progression and variants located in a putative enhancer region on chromosome 3q23 (rs73226617, OR = 1.18; P = 3.93 × 10−8). With in silico and in vitro analyses we identify rs73226617 or rs148722713 as the likely functional variant and ATP1B3 as a potential causal target gene with monocyte specific function

Dise?o y construcci?n de la habilitaci?n urbano industrial del Complejo Maderero de Pucallpa

El proyecto denominado ?Dise?o y construcci?n de la habilitaci?n urbano industrial del Complejo Maderero de Pucallpa, responde a atender la necesidad de contar con infraestructura para el uso de lotes industriales que impulsen la cadena de valor de la transformaci?n de la madera en la Regi?n Ucayali. Para el desarrollo del presente Proyecto se ha aplicado las buenas pr?cticas del PMBOOK 6ta. Edici?n, siendo el alcance del Proyecto desde la elaboraci?n de estudios previos, el desarrollo del dise?o de Habilitaci?n Urbana, la elaboraci?n del expediente t?cnico, gesti?n y tramitaci?n de certificados y licencia, hasta la procura y ejecuci?n de las obras de habilitaci?n urbana industrial que albergue 134 lotes industriales en 17 manzanas, distribuidos en 04 sectores, con cerco perimetral y p?rtico de ingreso, as? como la construcci?n de un edificio administrativo de dos pisos. EL plazo de ejecuci?n es de veintiocho (28) meses, con un monto de inversi?n de US 25,148,000, desarroll?ndose dentro de un terreno con un ?rea de 51 has, activo de propiedad del principal stakeholder la Asociaci?n de Madereros de Pucallpa. Cuenta con un plan de acci?n de mitigaci?n y reserva de contingencia, basado en la identificaci?n de los riesgos principales del proyecto

Blood pressure variability and closed-loop baroreflex assessment in adolescent chronic fatigue syndrome during supine rest and orthostatic stress

Hemodynamic abnormalities have been documented in the chronic fatigue syndrome (CFS), indicating functional disturbances of the autonomic nervous system responsible for cardiovascular regulation. The aim of this study was to explore blood pressure variability and closed-loop baroreflex function at rest and during mild orthostatic stress in adolescents with CFS. We included a consecutive sample of 14 adolescents 12–18 years old with CFS diagnosed according to a thorough and standardized set of investigations and 56 healthy control subjects of equal sex and age distribution. Heart rate and blood pressure were recorded continuously and non-invasively during supine rest and during lower body negative pressure (LBNP) of –20 mmHg to simulate mild orthostatic stress. Indices of blood pressure variability and baroreflex function (α-gain) were computed from monovariate and bivariate spectra in the low-frequency (LF) band (0.04–0.15 Hz) and the high–frequency (HF) band (0.15–0.50 Hz), using an autoregressive algorithm. Variability of systolic blood pressure in the HF range was lower among CFS patients as compared to controls both at rest and during LBNP. During LBNP, compared to controls, α-gain HF decreased more, and α-gain LF and the ratio of α-gain LF/α-gain HF increased more in CFS patients, all suggesting greater shift from parasympathetic to sympathetic baroreflex control. CFS in adolescents is characterized by reduced systolic blood pressure variability and a sympathetic predominance of baroreflex heart rate control during orthostatic stress. These findings may have implications for the pathophysiology of CFS in adolescents

Heart Rate Variability Characteristics in Sedentary Postmenopausal Women Following Six Months of Exercise Training: The DREW Study

Article on heart rate variability characteristics in sedentary postmenopausal women following six months of exercise training

Abamectin and emamectin in grapes of Vitis vinifera L. from a district of the Valley of Ica-Peru

Context: In 14 districts of the valley of Ica-Peru, Vitis vinifera L. plants are cultivated that produce grapes for consumption as table grapes and raisins (dried grapes); at the same time, for the production of wines and Piscos. Aims: To determine the levels of abamectin and emamectin in grapes of Vitis vinifera L from a district of the Valley of Ica-Peru. Methods: 30 lots (30 kg) of Moscatel grape variety V. vinifera L. were collected from six countryside (artisanal and organic cultivation) of the San Juan Bautista district. The extraction of abamectin (ABM) and emamectin benzoate (EMB) from the grapes was carried out with acetonitrile; it was quantified by means of Liquid Chromatography coupled to Mass Spectrometry (HPLC-MS). The maximum permissible limit values (MRL) were established at 0.010 ppm for both insecticides. Results: The determined levels of abamectin and emamectin in grapes were 0.0012-0.015 ppm and 0.0013-0.013 ppm, respectively. Values higher than the maximum permissible limits of abamectin were found in batches A2 (0.0102 ppm), C1 (0.015 ppm), C5 (0.0113 ppm), and F2 (0.012 ppm); emamectin benzoate in lots B1 (0.0113 ppm), B4 (0.013 ppm) and C4 (0.012 ppm). Using the Shapiro-Wilk, Anderson Darling and Student’s t tests, it was found that the global means of the values of the two insecticides in grapes are lower than the MRL. According to the global analysis of variance, the means of the concentrations of both insecticides were not different between the six sampling zones (countryside). Conclusions: The insecticides abamectin and emamectin are below the maximum permissible limit values (0.010 ppm) in Moscatel grapes of Vitis vinifera L., so the residual effect would not have implications for human health

Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial

Background Non-alcoholic steatohepatitis (NASH) is a common type of chronic liver disease that can lead to cirrhosis. Obeticholic acid, a farnesoid X receptor agonist, has been shown to improve the histological features of NASH. Here we report results from a planned interim analysis of an ongoing, phase 3 study of obeticholic acid for NASH. Methods In this multicentre, randomised, double-blind, placebo-controlled study, adult patients with definite NASH,non-alcoholic fatty liver disease (NAFLD) activity score of at least 4, and fibrosis stages F2–F3, or F1 with at least oneaccompanying comorbidity, were randomly assigned using an interactive web response system in a 1:1:1 ratio to receive oral placebo, obeticholic acid 10 mg, or obeticholic acid 25 mg daily. Patients were excluded if cirrhosis, other chronic liver disease, elevated alcohol consumption, or confounding conditions were present. The primary endpointsfor the month-18 interim analysis were fibrosis improvement (≥1 stage) with no worsening of NASH, or NASH resolution with no worsening of fibrosis, with the study considered successful if either primary endpoint was met. Primary analyses were done by intention to treat, in patients with fibrosis stage F2–F3 who received at least one dose of treatment and reached, or would have reached, the month 18 visit by the prespecified interim analysis cutoff date. The study also evaluated other histological and biochemical markers of NASH and fibrosis, and safety. This study is ongoing, and registered with ClinicalTrials.gov, NCT02548351, and EudraCT, 20150-025601-6. Findings Between Dec 9, 2015, and Oct 26, 2018, 1968 patients with stage F1–F3 fibrosis were enrolled and received at least one dose of study treatment; 931 patients with stage F2–F3 fibrosis were included in the primary analysis (311 in the placebo group, 312 in the obeticholic acid 10 mg group, and 308 in the obeticholic acid 25 mg group). The fibrosis improvement endpoint was achieved by 37 (12%) patients in the placebo group, 55 (18%) in the obeticholic acid 10 mg group (p=0·045), and 71 (23%) in the obeticholic acid 25 mg group (p=0·0002). The NASH resolution endpoint was not met (25 [8%] patients in the placebo group, 35 [11%] in the obeticholic acid 10 mg group [p=0·18], and 36 [12%] in the obeticholic acid 25 mg group [p=0·13]). In the safety population (1968 patients with fibrosis stages F1–F3), the most common adverse event was pruritus (123 [19%] in the placebo group, 183 [28%] in the obeticholic acid 10 mg group, and 336 [51%] in the obeticholic acid 25 mg group); incidence was generally mild to moderate in severity. The overall safety profile was similar to that in previous studies, and incidence of serious adverse events was similar across treatment groups (75 [11%] patients in the placebo group, 72 [11%] in the obeticholic acid 10 mg group, and 93 [14%] in the obeticholic acid 25 mg group). Interpretation Obeticholic acid 25 mg significantly improved fibrosis and key components of NASH disease activity among patients with NASH. The results from this planned interim analysis show clinically significant histological improvement that is reasonably likely to predict clinical benefit. This study is ongoing to assess clinical outcomes

Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial

BACKGROUND Non-alcoholic steatohepatitis (NASH) is a common type of chronic liver disease that can lead to cirrhosis. Obeticholic acid, a farnesoid X receptor agonist, has been shown to improve the histological features of NASH. Here we report results from a planned interim analysis of an ongoing, phase 3 study of obeticholic acid for NASH. METHODS In this multicentre, randomised, double-blind, placebo-controlled study, adult patients with definite NASH, non-alcoholic fatty liver disease (NAFLD) activity score of at least 4, and fibrosis stages F2-F3, or F1 with at least one accompanying comorbidity, were randomly assigned using an interactive web response system in a 1:1:1 ratio to receive oral placebo, obeticholic acid 10 mg, or obeticholic acid 25 mg daily. Patients were excluded if cirrhosis, other chronic liver disease, elevated alcohol consumption, or confounding conditions were present. The primary endpoints for the month-18 interim analysis were fibrosis improvement (≥1 stage) with no worsening of NASH, or NASH resolution with no worsening of fibrosis, with the study considered successful if either primary endpoint was met. Primary analyses were done by intention to treat, in patients with fibrosis stage F2-F3 who received at least one dose of treatment and reached, or would have reached, the month 18 visit by the prespecified interim analysis cutoff date. The study also evaluated other histological and biochemical markers of NASH and fibrosis, and safety. This study is ongoing, and registered with ClinicalTrials.gov, NCT02548351, and EudraCT, 20150-025601-6. FINDINGS Between Dec 9, 2015, and Oct 26, 2018, 1968 patients with stage F1-F3 fibrosis were enrolled and received at least one dose of study treatment; 931 patients with stage F2-F3 fibrosis were included in the primary analysis (311 in the placebo group, 312 in the obeticholic acid 10 mg group, and 308 in the obeticholic acid 25 mg group). The fibrosis improvement endpoint was achieved by 37 (12%) patients in the placebo group, 55 (18%) in the obeticholic acid 10 mg group (p=0·045), and 71 (23%) in the obeticholic acid 25 mg group (p=0·0002). The NASH resolution endpoint was not met (25 [8%] patients in the placebo group, 35 [11%] in the obeticholic acid 10 mg group [p=0·18], and 36 [12%] in the obeticholic acid 25 mg group [p=0·13]). In the safety population (1968 patients with fibrosis stages F1-F3), the most common adverse event was pruritus (123 [19%] in the placebo group, 183 [28%] in the obeticholic acid 10 mg group, and 336 [51%] in the obeticholic acid 25 mg group); incidence was generally mild to moderate in severity. The overall safety profile was similar to that in previous studies, and incidence of serious adverse events was similar across treatment groups (75 [11%] patients in the placebo group, 72 [11%] in the obeticholic acid 10 mg group, and 93 [14%] in the obeticholic acid 25 mg group). INTERPRETATION Obeticholic acid 25 mg significantly improved fibrosis and key components of NASH disease activity among patients with NASH. The results from this planned interim analysis show clinically significant histological improvement that is reasonably likely to predict clinical benefit. This study is ongoing to assess clinical outcomes. FUNDING Intercept Pharmaceuticals