Mexican consensus on Hodgkin's lymphoma.

El linfoma de Hodgkin (LH) se debe a la transformación clonal de células originadas en los linfocitos B, lo que genera las células binucleadas patognomónicas de Reed-Sternberg. El LH es una enfermedad de células B con una distribución bimodal, con mayor incidencia en la adolescencia y la tercera década de la vida y un segundo pico en personas mayores de 55 años. Las células del LH clásico habitualmente sufren una reprogramación de la expresión génica, ya que pierden la expresión de la mayoría de los genes típicos de las células B y han adquirido la expresión de múltiples genes que son típicos de otros tipos de células del sistema inmunitario. El algoritmo de tratamiento dependerá si se trata de LH clásico o de predominio linfocítico, si es un estadio temprano con marcadores de pronóstico desfavorables o no, el esquema inicial de manejo y si existe enfermedad voluminosa, entre las variables más relevantes.Hodgkin's lymphoma (HL) is due to the clonal transformation of cells originating from B lymphocytes, generating the pathognomonic binucleate Reed-Sternberg cells. HL is a B cell disease with a bimodal distribution, with higher incidence in adolescence and the third decade of life, showing a second peak in people over 55 years of age. Classic Hodgkin lymphoma cells routinely undergo gene expression reprogramming, as they lose the expression of most of the typical B-cell genes and acquire the expression of multiple genes that are typical of other types of cells in the immune system. The treatment algorithm will depend on whether it is classic or predominantly lymphocytic HL, if it is early stage with unfavorable prognostic markers or not, the initial management regimen, and whether there is bulky disease, among the most relevant variables.

Mexican Consensus on Hodgkin's Lymphoma.

Hodgkin's lymphoma is due to the clonal transformation of cells originating from B lymphocytes, generating the pathognomonic binucleate Reed-Sternberg cells. Hodgkin's lymphoma is a B cell disease with a bimodal distribution, with higher incidence in adolescence and the third decade of life, showing a second peak in people over 55 years of age. Classic Hodgkin lymphoma cells routinely undergo gene expression reprogramming, as they lose the expression of most of the typical B-cell genes and acquire the expression of multiple genes that are typical of other types of cells in the immune system. The treatment algorithm will depend on whether it is classic or predominantly lymphocytic HL, if it is early stage with unfavorable prognostic markers or not, the initial management regimen, and whether there is bulky disease, among the most relevant variables.

El linfoma de Hodgkin (LH) se debe a la transformación clonal de células originadas en los linfocitos B, lo que genera las células binucleadas patognomónicas de Reed-Sternberg. El LH es una enfermedad de células B con una distribución bimodal, con mayor incidencia en la adolescencia y la tercera década de la vida y un segundo pico en personas mayores de 55 años. Las células del LH clásico habitualmente sufren una reprogramación de la expresión génica, ya que pierden la expresión de la mayoría de los genes típicos de las células B y han adquirido la expresión de múltiples genes que son típicos de otros tipos de células del sistema inmunitario. El algoritmo de tratamiento dependerá si se trata de LH clásico o de predominio linfocítico, si es un estadio temprano con marcadores de pronóstico desfavorables o no, el esquema inicial de manejo y si existe enfermedad voluminosa, entre las variables más relevantes.

Consenso mexicano de linfoma de Hodgkin / Mexican Consensus on Hodgkin's Lymphoma

Resumen El linfoma de Hodgkin (LH) se debe a la transformación clonal de células originadas en los linfocitos B, lo que genera las células binucleadas patognomónicas de Reed-Sternberg. El LH es una enfermedad de células B con una distribución bimodal, con mayor incidencia en la adolescencia y la tercera década de la vida y un segundo pico en personas mayores de 55 años. Las células del LH clásico habitualmente sufren una reprogramación de la expresión génica, ya que pierden la expresión de la mayoría de los genes típicos de las células B y han adquirido la expresión de múltiples genes que son típicos de otros tipos de células del sistema inmunitario. El algoritmo de tratamiento dependerá si se trata de LH clásico o de predominio linfocítico, si es un estadio temprano con marcadores de pronóstico desfavorables o no, el esquema inicial de manejo y si existe enfermedad voluminosa, entre las variables más relevantes.

Abstract Hodgkin's lymphoma is due to the clonal transformation of cells originating from B lymphocytes, generating the pathognomonic binucleate Reed-Sternberg cells. Hodgkin's lymphoma is a B cell disease with a bimodal distribution, with higher incidence in adolescence and the third decade of life, showing a second peak in people over 55 years of age. Classic Hodgkin lymphoma cells routinely undergo gene expression reprogramming, as they lose the expression of most of the typical B-cell genes and acquire the expression of multiple genes that are typical of other types of cells in the immune system. The treatment algorithm will depend on whether it is classic or predominantly lymphocytic HL, if it is early stage with unfavorable prognostic markers or not, the initial management regimen, and whether there is bulky disease, among the most relevant variables.

Mexican Concensus of Multiple Myeloma.

To identify this increasingly common pathology, known as multiple myeloma (MM), it is necessary to refer to the specific factors that characterize it; to this end, the classic criteria known as CRAB (hyperkalemia, renal failure, anemia, and lytic lesions) are available, in which renal failure is one of the most frequent complications. Recently, three indisputable biomarkers have been described for the diagnostic support for MM, which are: more than 10% of clonal plasma cells in bone marrow or, a biopsy that corroborates the presence of a plasmacytoma, light chain ratio ≥ 100 mg/dL and more than one focal lesion on magnetic resonance imaging. A differential diagnosis for plasma cell leukemia, solitary bone plasmacytoma, and extramedullary plasmacytoma should always be considered. Being this an incurable disease, a lot of research has been done regarding its therapeutic management, whose main objective is the disappearance of plasma cells and the patient clinical improvement. Melphalan was the first drug that showed a benefit in 1958 and afterward, with the addition of a steroid as a second drug, it was possible to improve response rates. Subsequently, different molecules were studied, forming multiple combinations, and achieving better rates of overall survival and progression-free survival. Years later, with the arrival of proteasome inhibitors such as bortezomib, and immunomodulators such as thalidomide and lenalidomide, an important turnaround in the disease has been seen, as deeper responses, more prolonged remissions, and improvement in the quality of life of patients have been achieved. This consensus has the purpose of integrating a group of Mexican specialists and promoting the updating of this pathology.

Para identificar una patología cada vez más común, conocida como mieloma múltiple, es necesario hacer alusión de los factores específicos que la caracterizan. Para ello existen los clásicos criterios conocidos como CRAB (hipercalcemia, insuficiencia renal, anemia y lesiones líticas), siendo la insuficiencia renal una de sus complicaciones más frecuentes. Recientemente se han descrito tres biomarcadores indiscutibles para el apoyo diagnóstico del mieloma múltiple, que son: más del 10% de células plasmáticas clonales en medula ósea o biopsia que corrobora la presencia de un plasmocitoma, relación de cadenas ligeras ≥ 100 mg/dl y más de una lesión focal en resonancia magnética. Se debe tomar siempre en cuenta el diagnóstico diferencial con leucemia de células plasmáticas, plasmocitoma óseo solitario y plasmocitoma extramedular. Al ser una enfermedad incurable, se ha investigado mucho en cuanto al manejo terapéutico, el cual tiene como objetivo principal la desaparición de las células plasmáticas y la mejoría clínica del paciente. El primer fármaco que demostró algún beneficio fue el melfalán en el año 1958 y posteriormente al adicionar un esteroide como segundo fármaco se logró mejorar las tasas de respuesta. Después se fueron estudiando diferentes moléculas, con las que se han realizado múltiples combinaciones, alcanzando mejores tasas de supervivencia global y supervivencia libre de progresión. Años más tarde, con la llegada de los inhibidores de proteosoma como el bortezomib, así como de los agentes inmunomoduladores como la talidomida y la lenalidomida, se presenta un giro importante en la enfermedad, ya que se logran respuestas más profundas, periodo de remisiones más prolongadas y mejoría en la calidad de vida de los pacientes. Este consenso tiene la finalidad de integrar a un grupo de especialistas mexicanos y promover la actualización de esta patología.

Plasmablastic Lymphomas: Characterization of Tumor Microenvironment Using CD163 and PD-1 Immunohistochemistry.

This study aims to characterize the tumor microenvironment of plasmablastic lymphoma (PBL) in regard to the quantities of CD163(+) tumor associated macrophages (TAM) and PD1(+) tumor infiltrating lymphocytes (TIL). This article also reviews the existing knowledge of the role of PD-1/PD-L1 pathway in the tumor microenvironment of hematopoietic neoplasms, discusses potential mechanisms to explain our findings, and outlines areas for future studies. We performed CD163 and PD1 immunohistochemical studies in 11 cases classified as plasmablastic lymphoma, and recorded the percentages of positive TAMs and TILs. Based on previous studies, cut off values of ≥30% and >5% were used to classify the cases into high TAMs and TILs, respectively. We determined that the majority of cases (8 of 11, or 73%) had high percentage of TAMs, while only a minority had high percentage of TILs (3 of 11, or 27%). Our data shows a trend towards a negative correlation between TAMs and TILs (p=0.08), and a predominance of the pattern TAMhigh/TILlow (7 of 11, or 63%) compared to other patterns. The microenvironment of plasma-blastic lymphoma tends to show high percentage of TAMs (≥30%) combined with low percentage of TILs (≤5%). Additional studies are needed to determine the clinical significance of TILs and the influence of EBV and HIV infections on numbers of TILs in PBL. As high microenvironment TAMs have been associated with high microenvironment PD-L1 in other hematopoietic malignancies, our data supports the need for future studies on the expression of PD-L1 in PBL.

Utilidad del strain bidimensional longitudinal por speckle tracking en pacientes con enfermedad de Chagas-Mazza sin cardiopatía demostrada / Usefulness of two-dimensional longitudinal strain by speckle tracking in patients with Chagas disease without evident heart disease / Utilidade de strain bidimensional longitudinal por speckle tracking em pacientes com doença de Chagas sem evidência de doença cardíaca

Introducción. La enfermedad de Chagas es una causa importante de insuficiencia cardíaca y su identificación precoz puede ayudar a identificar pacientes en riesgo de progresión de la enfermedad. El strain bidimensional longitudinal (Str2D) podría ser una herramienta útil para detectar disfunción ventricular izquierda incipiente. Objetivos. Analizar si el strain puede detectar alteraciones en pacientes asintomáticos y sin patología demostrable por los métodos convencionales en la enfermedad de Chagas. Materiales y métodos. Estudio transversal de 45 pacientes menores de 65 años de zona rural con enfermedad de Chagas, sin patología demostrada frente a 33 individuos sanos (controles). En todos realizamos serología por dos métodos, examen clínico, electrocardiograma y eco-Doppler cardíaco: diámetro diastólico del ventrículo izquierdo (DDVI), área auricular izquierda (AI), fracción de eyección del ventrículo izquierdo (Fey) por Simpson, excursión sistólica del plano del anillo tricuspídeo (TAPSE), E/A mitral (E/A), E/e', S tisular (S´) de ventrículo izquierdo (VI) y ventrículo derecho (VD), Str2D de cada segmento del VI y strain global. Estadística: variables cuantitativas de distribución normal se compararon mediante test de t y cualitativas con test de chi cuadrado. Variabilidad intra e interobservador por r de Pearson y coeficiente de correlación intraclase.Resultados. Edad, sexo y eco-Doppler convencional (DDVI, Fey, AI, TAPSE, E/A, E/e') no mostraron diferencias estadísticamente significativas. El strain global y el strain de los segmentos apicales del VI evidenciaron diferencias significativas entre pacientes con enfermedad de Chagas sin cardiopatía demostrada (SCD) y controles, aunque dichos valores se encuadran dentro de rangos considerados fisiológicos. Variabilidad intraobservador del strain global (r de Pearson: 0,93 y CCI: 0,93) e interobservador (coeficiente r de Pearson 0,89 y un CCI: 0,88). Conclusiones. Los hallazgos del estudio muestran reducción significativa del strain longitudinal global y distal, compatible con un daño miocárdico incipiente en los pacientes con serología positiva para enfermedad de Chagas sin cardiopatía demostrada, hipótesis de trabajo que sólo el tiempo y un prolijo seguimiento podrán confirmar.

Introduction. Chagas disease is a major cause of heart failure and early identification may help identify patients at risk for disease progression. The two-dimensional longitudinal strain (Str2D) could be a useful tool for detecting incipient left ventricular dysfunction. Objectives. Analyze whether longitudinal dimensional strain can detect abnormalities in asymptomatic patients without demonstrable pathology by conventional methods in Chagas disease. Materials and Methods. Cross-sectional study of 45 patients under age 65 years in an endemic rural area with Chagas disease without proven pathology (non evident cardiopathy: NEC) versus 33 control patients. In all patients study was made by two serologic methods, clinical examination, electrocardiogram and Doppler ultrasound of the heart: diastolic diameter of the left ventricle (LVDD), left atrial area (LAA), left ventricle ejection fraction (Fey) by Simpson, excursion of tricuspid ring (TAPSE), E/A mitral ratio (E/A), E/e' ratio, S tissue (S') of left ventricular (LV) and right ventricular (RV), Str2D of each segment LV and global strain. Statistics: Normal distribution quantitative variables were compared using t test and qualitative variables with chi square test. Intra- and inter-observer variability for r Pearson and intra-class correlation coefficient (ICC). Results. Age, sex and conventional Doppler echocardiography (LVDD, Fey, LAA, TAPSE, E/A, E/e') showed no statistically significant differences. Global strain and strain of the apical LV segments showed significant differences between patients with Chagas disease without proven disease and their controls, although these values fall within ranges considered physiological. Intraobserver variability of global strain (Pearson's r 0.93 and ICC: 0.93) and interobserver (Pearson coefficient r of 0.89 and an ICC: 0.88). Conclusions. In a group of asymptomatic patients with Chagas disease without apparent cardiac involvement (NEC stage), the Str2D was lower compared with healthy individuals, suggesting the existence of subtle myocardial damage in these patients. Hypotheses that only time can confirm and track.

Introdução. A doença de Chagas é uma das principais causas de insuficiência cardíaca e sua identificação precoce pode ajudar a identificar pacientes com risco de progressão da doença. Strain longitudinal bidimensional (Str2D) poderia ser uma ferramenta útil para a detecção de disfunção ventricular esquerda incipiente. Objetivos. Analise se strain longitudinal dimensional pode detectar anormalidades em pacientes assintomáticos, sem patologia demonstrável por métodos convencionais na doença de Chagas. Materiais e métodos. Estudo transversal de 45 pacientes com idade inferior a 65 anos em uma área rural endêmica de doença de Chagas sem comprovada patologia (cardiopatia não evidente: CNE) versus 33 pacientes do grupo controle. Em todos os pacientes do estudo foi feita por dois métodos sorológicos, exame clínico, eletrocardiograma e ultrasom Doppler do coração: diâmetro diastólico do ventrículo esquerdo (DDVE), área do átrio esquerdo (AE), fração de ejeção do ventrículo esquerdo (Fey) por Simpson, excursão de anel tricúspide (TAPSE), relação E/A mitral (E/A), E/e' ratio, S tecido (S') do ventrículo esquerdo (VE) e do ventrículo direito (VD), Str2D de cada segmento VI e strain geral. Estatística: variáveis quantitativas de distribuição normal foram comparadas pelo teste t e qualitativa com o teste qui-quadrado. Variabilidade intra e interobservador para r Pearson e coeficiente de correlação intraclasse (CCI). Resultados. Idade, sexo e ecocardiograma Doppler convencional (DDVI, Fey, AE, TAPSE, E/A, E/e') não mostraram diferenças estatisticamente significativas. Strain global e strain dos segmentos do VE apicais apresentaram diferenças significativas entre os pacientes com doença de Chagas sem doença comprovada e seus controles; embora estes valores caem dentro da faixa considerada fisiológica. Variabilidade intra-observador da strain global (r de Pearson: 0,93 e CCI: 0,93) e inter-observador (coeficiente r de Pearson 0,89 e um CCI: 0,88). Conclusões. Os resultados deste estudo poderiam mostrar uma lesão miocárdica incipiente em pacientes com sorologia positiva para doença de Chagas sem cardiopatia demonstrada. A hipótese de trabalho de que só o tempo e um longo seguimento irão confirmar.

CXCL17 is a major chemotactic factor for lung macrophages.

Chemokines are a superfamily of chemotactic cytokines that direct the movement of cells throughout the body under homeostatic and inflammatory conditions. The mucosal chemokine CXCL17 was the last ligand of this superfamily to be characterized. Several recent studies have provided greater insight into the basic biology of this chemokine and have implicated CXCL17 in several human diseases. We sought to better characterize CXCL17's activity in vivo. To this end, we analyzed its chemoattractant properties in vivo and characterized a Cxcl17 (-/-) mouse. This mouse has a significantly reduced number of macrophages in its lungs compared with wild-type mice. In addition, we observed a concurrent increase in a new population of macrophage-like cells that are F4/80(+)CDllc(mid). These results indicate that CXCL17 is a novel macrophage chemoattractant that operates in mucosal tissues. Given the importance of macrophages in inflammation, these observations strongly suggest that CXCL17 is a major regulator of mucosal inflammatory responses.

Adipokines in a group of Mexican patients with nonalcoholic steatohepatitis.

INTRODUCTION: Leptin has been implicated in the pathogenesis of nonalcoholic steatohepatitis. It has also been suggested that adiponectin plays an important role in the transition from fatty liver disease to nonalcoholic steatohepatitis. OBJECTIVE: To evaluate whether leptin and adiponectin levels are related to the degree of necroinflammatory activity and fibrosis in patients with nonalcoholic steatohepatitis. METHODS: Leptin and adiponectin levels were determined in 52 patients with nonalcoholic steatohepatitis and in 49 controls by enzyme-linked immunosorbent analysis. RESULTS: Median (interquartile range) leptin levels were higher in patients with nonalcoholic steatohepatitis than in the controls (5.75 (12.3) ng mL-1 and 2.80 (2.40) ng mL-1, respectively; P = 0.0035). Adiponectin levels were lower in patients with nonalcoholic steatohepatitis than in the controls (6.55 (5.05) mg mL-1 and 9.30 (6.70) mg mL-1, respectively; P = 0.0218). Leptin levels were lower in overweight patients than in obese patients (2.25 (6.73) and 8.0 (16.0) ng mL-1, respectively; P = 0.0025). The amount of necroinflammatory activity observed in liver biopsies correlated positively with the amount of fibrosis (P < 0.0001). Increased lactate dehydrogenase correlated with increased fibrosis in patients with nonalcoholic steatohepatitis (P = 0.0012). Necroinflammatory activity correlated with adiponectin, g-glutamyltranspeptidase, the quantitative insulin-sensitivity check index, and ferritin (P < 0.05). Risk factors for nonalcoholic steatohepatitis in the logistic regression analysis were leptin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and g-glutamyltranspeptidase (P < 0.0001). Only lactate dehydrogenase (P = 0.0012) was significantly associated with advanced fibrosis on logistic regression analysis. CONCLUSIONS: Lactate dehydrogenase was associated with fibrosis and advanced fibrosis. Leptin was associated with nonalcoholic steatohepatitis but not with fibrosis or necroinflammatory activity. Adiponectin was related to necroinflammatory activity. Risk factors for nonalcoholic steatohepatitis were leptin and liver enzymes (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and gama-glutamyltranspeptidase).

Prevalence and risk factors of hepatitis C virus, hepatitis B virus, and human immunodeficiency virus in multiply transfused recipients in Mexico.

BACKGROUND: Transfusion-transmitted viral infection (TTI) is a major problem in patients receiving blood products. Monitoring high-risk patients is essential for assessing the epidemiology of blood-borne infections. STUDY DESIGN AND METHODS: A 1-year, cross-sectional seroprevalence study in patients with a history of multiple transfusions was conducted. Peripheral blood samples were titered to detect serologic markers of human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV). The presence of these viruses and demographic, behavioral, and medical traits were assessed. RESULTS: A total of 300 male and female multiply transfused patients with a mean age of 30.7 (+/-17.5) years were studied. The prevalence was 13.7% for HCV, 7% for HBV, and 1.7% for HIV. Patients with hemophilia had the highest prevalence for HCV and HIV infections, and hemodialyzed patients, for HBV infection. The risk factors related to acquired HCV were hemophilia (odds ratio [OR], 5.6; 95% confidence interval [CI], 2.5-12.6), more than five hospitalizations (OR, 3.8; 95% CI, 1.6-8.9), and having received a transfusion before mandatory screening in 1993 (OR, 8.4; 95% CI, 2.0-34.6), and for HIV, having received a transfusion before 1987 (OR, 19.0; 95% CI, 2.0-177.7). The main risk factors for HBV were having end-stage renal disease and being treated with hemodialysis (OR, 3.7; 95% CI, 1.4-9.9) and transplantation (OR, 4.2; 95% CI, 1.4-12.1). CONCLUSIONS: This study showed that HCV infection was more frequently identified than HBV and HIV infections in multiply transfused Mexican patients. Additionally, several risk factors are associated with TTI such as mandatory screenings before 1987 and 1993, which were the most important for HIV and HCV infections but not for HBV.