Translation and Cross-Cultural Adaptation of the Test of Infant Motor Performance to Colombian Spanish / Traducción y adaptación transcultural del Test of Infant Motor Performance al español de Colombia / Tradução e adaptação transcultural do Test of Infant Motor Performance para o espanhol colombiano

Introduction: There has been growing interest in recent years in the cross-cultural adaptation of mea-suring instruments for various conditions treated by physiotherapy. Validation of an instrument within a target language and culture creates a final version that is conceptually and linguistically adapted to the context but remains valid and reliable. This paper describes the process of translation and cross-cul-tural adaptation of the Test of Infant Motor Performance (timp) from us English to Colombian Spanish. This was performed in accordance with international methodological guidelines. Materials and meth-ods: A group of trained translators and field experts participated in the five stages presented herein. These stages were translation and adaptation of the instrument to Colombian Spanish, validation of its content and appearance, back-translation, revision by the original author, and, finally, a pilot test.Results: The existence of two intralingual translated and revised versions of this instrument led to a more appropriate preliminary version from conceptual, discursive, and terminological perspectives. Therefore, the adjustments made in the first stage were primarily semantic. During the second stage, field experts positively assessed the translated version and suggested adjustments to grammar, spell-ing, and word choices. There were no significant discursive problems during the back-translation stage so conceptual and terminological adjustments were minor. The revision stage and the pilot test were satisfactory. Conclusion: This translation and cross-cultural adaptation was successful. The Colombian Spanish version of the measure was culturally relevant and used appropriate language, yet remained a valid and reliable tool

Introducción: la adaptación transcultural de distintos instrumentos de medición, y para diferentes tipos de condiciones en el campo de la fisioterapia, ha sido un tema de interés en los últimos años. La validación lingüística de un instrumento a una lengua y cultura meta implica que la versión final es adaptada conceptual y lingüísticamente al contexto meta. El objetivo de este artículo es describir el proceso de traducción y adaptación transcultural al español de Colombia del Test of Infant Motor Performace(timp) siguiendo los lineamientos metodológicos internacionales. Materiales y método: se conformó un grupo de traductores calificados y de expertos que participaron en cinco fases: traducción y adaptación al español de Colombia, validez de contenido y apariencia, retrotraducción, revisión por autora original y prueba piloto. Resultados: la posibilidad de contar con dos versiones intralinguales revisadas llevó a una versión preliminar más adecuada desde las perspectivas conceptual, discursiva y terminológica. Por lo tanto, los ajustes en esta fase se realizaron principalmente desde una perspectiva semántica. En cuanto a la segunda fase, los expertos validaron positivamente dicha versión y sugirieron cambiar algunas palabras y cuestiones ortográficas. La fase de retrotraducción y la validación no presentaron problemas discursivos, así que las adecuaciones conceptuales y terminológicas fueron mínimas. La fase de revisión y la prueba piloto fueron satisfactorias. Conclusión: este proceso de traducción y adaptación transcultural fue exitoso. La versión al español de Colombia fue apropiada culturalmente, además de ser una herramienta válida y confiable

Introdução: a adaptação transcultural de diferentes instrumentos de medida e para diferentes tipos de condições no campo da fisioterapia tem sido um tema de interesse nos últimos anos. A validação linguís-tica de um instrumento para uma língua e cultura alvo implica que a versão final seja conceitual e lin-guisticamente adaptada ao contexto alvo. O objetivo deste artigo é descrever o processo de tradução e adaptação transcultural para o espanhol colombiano do Test of Infant Motor Performace (timp) de acordo com as diretrizes metodológicas internacionais. Materiais e métodos: foi conformado um grupo de tradu-tores qualificados e especialistas que participaram em cinco fases: tradução e adaptação para o espanhol colombiano, validade de conteúdo e aparência, retrotradução, revisão pelo autor original e teste piloto. Resultados: a possibilidade de haver duas versões intralinguais revisadas levou a uma versão preliminar mais adequada do ponto de vista conceitual, discursivo e terminológico, portanto, os ajustes nesta fase foram feitos principalmente do ponto de vista semântico. Já na segunda fase, os especialistas validaram positivamente essa versão e sugeriram alterações em algumas palavras e problemas ortográficos. A fase de retrotradução e a validação não apresentaram problemas discursivos, portanto as adaptações conceituais e terminológicas foram mínimas. A fase de revisão e o teste pilotoforam bem-sucedidos. Conclusão: este processo de tradução e adaptação transcultural foi favorável do ponto de vista de validade e aparência para o contexto colombiano

Tumor genetic alterations and features of the immune microenvironment drive myelodysplastic syndrome escape and progression.

The transformation and progression of myelodysplastic syndromes (MDS) to secondary acute myeloid leukemia (sAML) involve genetic, epigenetic, and microenvironmental factors. Driver mutations have emerged as valuable markers for defining risk groups and as candidates for targeted treatment approaches in MDS. It is also evident that the risk of transformation to sAML is increased by evasion of adaptive immune surveillance. This study was designed to explore the immune microenvironment, immunogenic tumor-intrinsic mechanisms (HLA and PD-L1 expression), and tumor genetic features (somatic mutations and altered karyotypes) in MDS patients and to determine their influence on the progression of the disease. We detected major alterations of the immune microenvironment in MDS patients, with a reduced count of CD4+ T cells, a more frequent presence of markers related to T cell exhaustion, a more frequent presence of myeloid-derived suppressor cells (MDSCs), and changes in the functional phenotype of NK cells. HLA Class I (HLA-I) expression was normally expressed in CD34+ blasts and during myeloid differentiation. Only two out of thirty-six patients with homozygosity for HLA-C groups acquired complete copy-neutral loss of heterozygosity in the HLA region. PD-L1 expression on the leukemic clone was also increased in MDS patients. Finally, no interplay was observed between the anti-tumor immune microenvironment and mutational genomic features. In summary, extrinsic and intrinsic immunological factors might severely impair immune surveillance and contribute to clonal immune escape. Genomic alterations appear to make an independent contribution to the clonal evolution and progression of MDS.

Aplicación de terapia de restricción del lado sano para el tratamiento de la mano espástica del adulto con hemiplejía. Revisión sistemática / Constraint induced movement therapy to the treatment of the spastic hand with hemiplegia. Systematic review

RESUMEN Objetivo: Realizar una revisión sistemática de la literatura que permita evaluar la efectividad del uso de la terapia de restricción del lado sano (CIMT) para la recuperación de la función motora de la mano espástica del adulto con hemiplejía entre los 18 y 85 años de edad. Materiales y métodos: Se llevó a cabo una revisión sistemática de ensayos clínicos publicados en diferentes bases de datos, tales como Pubmed, PeDro, OTseeker, así como en bibliotecas virtuales como, por ejemplo, Science Direct, ProQuest y Ebsco, con los términos de búsqueda "constraint induced movement therapy" y "stroke", entre enero y diciembre del 2016. Se buscaron artículos sin límites de publicación ni restricción de idioma, cuya elegibilidad se realizó mediante la estrategia Consort y la evaluación de la calidad metodológica aplicando la escala de PEDro. Se incluyeron 29 estudios que cumplieron con los criterios de inclusión, en los que 648 personas fueron asignadas al grupo experimental y 650 al grupo control. Resultados: El grupo de terapia de restricción del lado sano mostro tiempos de intervención que oscilaban entre 45 minutos a seis horas, dependiendo el protocolo de atención. En la síntesis cualitativa se presentaron resultados positivos a nivel de función motora, destreza manual e incorporación al entorno normal en relación con otro tipo de intervención, aunque los efectos no fueron estadísticamente significativos debido a muestras pequeñas incluidas en los estudios, los protocolos de aplicación y la variedad en el tipo de restricción. Conclusión: La CIMT es una alternativa de intervención que puede implementarse en personas con deficiencias funcionales por accidente cerebrovascular (ACV) en cualquier etapa con un compromiso leve a moderado, presentando como condición inicial la capacidad de extender dedos a los 10° y la muñeca a los 30° del lado con la paresia.

ABSTRACT Objective: This study was a systematic review on the effectiveness of the use of the constraint induced movement therapy (CIMT) for the recovery of the motor function hand of the adult with spastic hemiplegia adult between 18 and 85 years of age. Materials and methods: We conducted a systematic review of published clinical trials in different data bases: Pubmed, PeDro, OTseeker, virtual libraries and Science Direct, ProQuest, and Ebsco, with the search terms "constraint induced movement therapy" and "stroke", between January to December of 2016, without limits of publication or restriction of language, whose eligibility is conducted through the strategy Consort and the assessment of the methodological quality using the PEDro scale. A total of 29 clinical trial were included, where 648 people were assigned to the experimental group and 650 in the control group. Results: The group of therapy of CIMT side showed intervention times ranging from 45 minutes to 6 hours depending on the protocol of attention in the qualitative synthesis were presented positive results at the level of motor function, manual dexterity and incorporation into the normal environment in relation with another type of intervention, although not all with homogeneous results and statistically significant effects. This is due to small samples included in the studies, two protocols of perform, the use of restrictions as gloves, cast, sling plus glove. Conclusion: The CIMT is an alternative intervention that can be implemented in people with sequels of stroke with low or moderate compromise, presenting as an initial condition the capacity of extend the fingers to 10° and the wrist to 30° of side with paresia; could be used in people at any stage of stroke.

HLA class I loss and PD-L1 expression in lung cancer: impact on T-cell infiltration and immune escape.

Immune-checkpoint inhibitors show encouraging results in cancer treatment, but the clinical benefit is limited exclusively to a subset of patients. We analyzed the density and composition of tumor T-cell infiltration in non-small-cell lung carcinoma (NSCLC) in relation to PD-L1 and HLA class I (HLA-I) expression. We found that positive HLA-I expression, independently on PD-L1 status, is the key factor determining the increased density of the immune infiltrate. When both markers were analyzed simultaneously, we identified four phenotypes of HLA-I and PD-L1 co-expression. They demonstrated different patterns of tumor infiltration and clinicopathologic characteristics, including the tumor size and lymphatic spread. All HLA-I+/PD-L1+ tumors had a high degree of intratumoral infiltration with CD8+T-lymphocytes, whereas HLA-I loss was associated with a significantly reduced number of tumor infiltrating T-lymphocytes mostly restrained in the stroma surrounding the tumor nest. HLA-I-negative/PD-L1-positive tumors had bigger size (T) and lower grade of infiltration with CD8+T-cells. It represents a cancer immune escape phenotype that combines two independent mechanisms of immune evasion: loss of HLA-I and upregulation of PD-L1. Using GCH-array analysis of human lung cancer cell lines we found that the loss of heterozygosity (LOH) with complete or partial deletion of HLA-I genes is the principal mechanism of HLA-I alterations. This irreversible defect, which could potentially decrease the clinical efficacy of lung cancer immunotherapy, appears to be underestimated. In conclusion, our results suggest that the analysis of HLA-I is very important for the selection of potential responders to cancer immunotherapy.

Neurofibroma of the Nasal Ala: Pediatric Nasal Reconstruction.

Benign tumors of the nasal cavity originating from a peripheral nerve sheath are rare. The authors present a case of a 3-month-old boy with a mass in the left nasal vestibule. The surgical resection was complicated by full-thickness necrosis of more than 50% of the nasal ala. The tumor was diagnosed histopathologically as a neurofibroma with glial heterotopia. The details of the nasal reconstruction with a paramedian forehead flap in 3 stages and postoperative results are provided with satisfactory cosmetic and functional results.

Genomic loss of HLA alleles may affect the clinical outcome in low-risk myelodysplastic syndrome patients.

The Revised International Prognostic Score and some somatic mutations in myelodysplastic syndrome (MDS) are independently associated with transformation to acute myeloid leukemia (AML). Immunity has also been implicated in the pathogenesis of MDS, although the underlying mechanism remains unclear. We performed a SNP array on chromosome 6 in CD34+ purified blasts from 19 patients diagnosed with advanced MDS and 8 patients with other myeloid malignancies to evaluate the presence of loss of heterozygosity (LOH) in HLA and its impact on disease progression. Three patients had acquired copy-neutral LOH (CN-LOH) on 6p arms, which may disrupt antigen presentation and act as a mechanism for immune system evasion. Interestingly, these patients had previously been classified at low risk of AML progression, and the poor outcome cannot be explained by the acquisition of adverse mutations. LOH HLA was not detected in the remaining 24 patients, who all had adverse risk factors. In summary, the clinical outcome of patients with advanced MDS might be influenced by HLA allelic loss, wich allows subclonal expansions to evade cytotoxic-T and NK cell attack. CN-LOH HLA may therefore be a factor favoring MDS progression to AML independently of the somatic tumor mutation load.

Terapia de restricción del lado sano como opción de manejo de personas con secuelas de enfermedad cerebrovascular / Constraint induced movement therapy in people with stroke

La terapia de restricción del lado sano se considera una de las alternativas actuales en neurorehabilitación, en esta se realiza un bloqueo del lado no afectado, propiciando así el desarrollo de habilidades en el lado hemipléjico, a partir de la práctica de actividades sucesivas y tareas adaptadas. Objetivo: determinar los efectos a nivel de función de la mano espástica en adultos con hemiplejia a partir de un proceso de revisión de literatura contenida en diferentes bases de datos. Métodos: se realizó una búsqueda de literatura en diferentes bases de datos como Pubmed, PeDro, OtSeeker, Scient Direct, usando como término de búsqueda "stroke" and "constraint induced movement therapy; se recopiló la información que tratara acerca de la técnica y su aplicación en personas hemipléjicas adultas. Conclusiones: la literatura revisada muestra que la terapia de restricción del lado sano genera múltiples beneficios en cuanto a función del brazo y de mano específicamente, para la función motora de miembro superior (agarres, alcances) y por ende en independencia funcional. Se recomienda la aplicación de los protocolos más difundidos en población latinoamericana al igual que establecer costo efectividad y la adopción de esta estrategia en planes de intervención clínicos...(AU)

Constraint induced movement therapy is considered a current alternatives in neurorehabilitation, in this is a lock on the unaffected side, facilitating the development of skills in the hemiplegic side, from the practice of successive task and shaping. Objective: the effects at the level of hand function in adults with spastic hemiplegia from a process of review of the literature contained in different databases. Methods: we performed a literature search in different databases such as Pubmed, PeDro, OtSeeker, Scient Direct, using as a search term "stroke" and "constraint induced movement therapy; the information was collected which will deal about the technique and its application in patients hemiplegics adults. Conclusions: the reviewed literature shows that the therapy of restriction of the healthy side generates multiple benefits in terms of arm function and specifically, to the motor function of upper limb (grips, scope), and therefore in functional independence. It is recommended that the implementation of the most widespread protocols in Latin American population as well as to establish cost-effectiveness and the adoption of this strategy in clinical intervention plans...(AU)

The Escape of Cancer from T Cell-Mediated Immune Surveillance: HLA Class I Loss and Tumor Tissue Architecture.

Tumor immune escape is associated with the loss of tumor HLA class I (HLA-I) expression commonly found in malignant cells. Accumulating evidence suggests that the efficacy of immunotherapy depends on the expression levels of HLA class I molecules on tumors cells. It also depends on the molecular mechanism underlying the loss of HLA expression, which could be reversible/"soft" or irreversible/"hard" due to genetic alterations in HLA, ß2-microglobulin or IFN genes. Immune selection of HLA-I negative tumor cells harboring structural/irreversible alterations has been demonstrated after immunotherapy in cancer patients and in experimental cancer models. Here, we summarize recent findings indicating that tumor HLA-I loss also correlates with a reduced intra-tumor T cell infiltration and with a specific reorganization of tumor tissue. T cell immune selection of HLA-I negative tumors results in a clear separation between the stroma and the tumor parenchyma with leucocytes, macrophages and other mononuclear cells restrained outside the tumor mass. Better understanding of the structural and functional changes taking place in the tumor microenvironment may help to overcome cancer immune escape and improve the efficacy of different immunotherapeutic strategies. We also underline the urgent need for designing strategies to enhance tumor HLA class I expression that could improve tumor rejection by cytotoxic T-lymphocytes (CTL).

The absence of HLA class I expression in non-small cell lung cancer correlates with the tumor tissue structure and the pattern of T cell infiltration.

We wanted to analyze whether tumor HLA class I (HLA-I) expression influences the pattern of the immune cell infiltration and stromal cell reaction in the tumor microenvironment. Tumor tissues obtained from 57 patients diagnosed with lung carcinomas were analyzed for HLA expression and leukocyte infiltration. 28 patients out of the 57 were completely negative for HLA-I expression (49.1%) or showed a selective HLA-A locus downregulation (three patients, 5.2%). In 26 out of 57 tumors (47.8%) we detected a positive HLA-I expression but with a percentage of HLA-I negative cells between 10 and 25%. The HLA-I negative phenotype was produced by a combination of HLA haplotype loss and a transcriptional downregulation of ß2-microglobulin (ß2-m) and LMP2 and LMP7 antigen presentation machinery genes. The analysis and localization of different immune cell populations revealed the presence of two major and reproducible patterns. One pattern, which we designated "immune-permissive tumor microenvironment (TME)," was characterized by positive tumor HLA-I expression, intratumoral infiltration with cytotoxic T-CD8+ cells, M1-inflammatory type macrophages, and a diffuse pattern of FAP+ cancer-associated fibroblasts. In contrast, another pattern defined as "non-immune-permissive TME" was found in HLA-I negative tumors with strong stromal-matrix interaction, T-CD8+ cells surrounding tumor nests, a dense layer of FAP+ fibroblasts and M2/repair-type macrophages. In conclusion, this study revealed marked differences between HLA class I-positive and negative tumors related to tissue structure, the composition of leukocyte infiltration and stromal response in the tumor microenvironment.

Linfoma cutáneo primario de células B, tipo pierna: reporte de un caso / Primary cutaneous B-cell lymphoma, leg type: report of a case

Los linfomas cutáneos de células B son un grupo heterogéneo de linfomas que se presentan en piel sin evidencia de compromiso extracutáneo al momento del diagnóstico y corresponden entre 20% al 25% de los linfomas cutáneos primarios. Presentamos un caso de un linfoma primario cutáneo difuso de células B grandes, tipo pierna en una anciana, con mala respuesta al tratamiento (AU)

Primary cutaneous B-cell lymphomas are a heterogeneous group of lymphomas occurring in the skin without extracutaneous involvement at time of diagnosis and constitute about 20-25% of primary lymphomas. A case of primary cutaneous diffuse large B-cell lymphoma, leg type, in an elderly woman with a poor response to treatment is reported (AU)

Evaluación como una primera aproximación al manejo fisioterapeutico de la persona quemada: Revisión de literatura / Evaluation as first approach to physiotherapymanagement of burned person: literature review

El propósito de este artículo es generar una propuesta de evaluación de la persona quemada en sus tres fases de recuperación, proceso que ha surgido a partir de la construcción del referente concep-tual de una investigación realizada en el grupo de investigación cuerpo movimiento de la Univer-sidad Autónoma de Manizales en torno al manejo fisioterapéutico del dolor en personas quema-das; donde la evaluación, desempeña un rol fundamental. El objetivo fue identificar las diferentes categorías para la evaluación de la persona quemada, a través del análisis de literatura científica, que brinde fundamentos y herramientas al fisioterapeuta para la construcción de una propuesta de evaluación y toma de decisiones clínicas para manejo del dolor. Se realizaron búsquedas electróni-cas en las bases de datos PubMed, Biblioteca Cochrane, LILACS, Scielo, en las bibliotecas virtuales Hinari, EBSCO, Ovid, ScienceDirect, Proquest con el fin de hallar la mejor evidencia disponible que permitiera la construcción del referente teórico de evaluación fisioterapéutica de las personas quemadas en sus tres fases de recuperación. La búsqueda en bases de datos y el análisis de literatura sirvió como insumo para la construcción del referente propuesto sobre evaluación de personas que-madas en sus tres fases de recuperación. El abordaje integral en el proceso de evaluación guiará al fisioterapeuta al establecimiento de juicios clínicos, para la formulación de objetivos terapéuticos y a la toma de decisiones acordes con los requerimientos particulares de cada usuario, que redunden en beneficio de este y favorezcan la potencialización de su capacidad funcional

Introduction: The purpose of this article is to generate a proposal for evaluation of burned peo-ple in three stages of recovery, a process that has emerged from the construction of the con-ceptual reference of a research performed by the group "Cuerpo Movimiento" from Autónoma de Manizales University, around physiotherapy pain handling in burned victims; where evaluation has an essential role. Objective: To identify the different categories for evaluating of the bur-ned person, through the analysis of scientific literature, that provides tools and fundamentals to physiotherapist for the construction of a proposal for evaluation and clinical decision making for pain handling. Method: Some electronic search was performed on the PubMed databases, Cochrane Library, LILACS, Scielo, in virtual libraries Hinari, EBSCO, Ovid, ScienceDirect, Pro-Quest, among others; in order to find the best evidence that would allow the construction of theoretical benchmark physiotherapy assessment of burned people in their three phases of re-covery. Results: The search on databases and analysis of literature was helpful as input for the construction of theoretical reference of assessment concerning burned people in three phases of recovery. Conclusions: the integrated approach in the assessment process will guide the phy-siotherapist to the establishment of clinical judgments for the formulation of therapeutic goals and decision making, according to the particular requirements of each user, for its benefit and encourages the empowerment of its functional capacity

Pliegue diagonal del lóbulo auricular (de Frank) y su relación con enfermedad coronaria / Diagonal earlobe crease (Frank's sign) and its relationship with coronary artery disease (CAD)

La presencia de pliegue diagonal auricular debe alertar al médico para entender su asociación con la enfermedad cardíaca coronaria y la enfermedad isquémica del corazón, especialmente en aquellos pacientes asintomáticos o pacientes con factores de riesgo tradicionales y no tradicionales. Por lo tanto, esta anormalidad puede ser interpretada como un "marcador cutáneo" de la enfermedad cardíaca coronaria. Este signo también podría servir para identificar mejor a los grupos de alto riesgo cardiovascular y para comenzar con la implementación de las medidas de las estrategias de prevención. Hay otros signos clínicos, además del pliegue de la oreja, que pueden reflejar el envejecimiento arterial y aterosclerosis, independientemente del número, duración o alcance de los factores de riesgo cardiovascular tradicionales. El hallazgo de pliegue auricular no debe sustituir a una historia clínica completa, la aplicación de métodos detallados, exámenes de laboratorio y físicos utilizados con excelente rendimiento en el diagnóstico de la enfermedad coronaria en la actualidad.

A diagonal earlobe crease (ELC) should alert doctors to its association with coronary artery disease (CAD) (also known as ischemic heart disease or atherosclerotic heart disease), especially in asymptomatic patients or patients having non-traditional and traditional risk factors. Such abnormality may be interpreted as a skin marker for CAD and this sign may also be used for identifying groups at high cardiovascular risk and indicate when to begin prevention strategy measures. Other clinical signs (apart from ELC) may reflect arterial aging and atherosclerosis, regardless of traditional cardiovascular risk factors' number, duration and/or scope. A finding of ELC should not replace a full medical history being compiled, complemented by the excellent detailed methods and physical and laboratory tests used today for providing a reliable diagnosis regarding coronary disease.

Implication of the ß2-microglobulin gene in the generation of tumor escape phenotypes.

Classical MHC molecules present processed peptides from endogenous protein antigens on the cell surface, which allows CD8(+) cytotoxic T lymphocytes (CTLs) to recognize and respond to the abnormal antigen repertoire of hazardous cells, including tumor cells. The light chain, ß2-microglobulin (ß2m), is an essential constant component of all trimeric MHC class I molecules. There is convincing evidence that ß2m deficiency generates immune escape phenotypes in different tumor entities, with an exceptionally high frequency in colorectal carcinoma (CRC) and melanoma. Damage of a single ß2m gene by LOH on chromosome 15 may be sufficient to generate a tumor cell precommitted to escape. In addition, this genetic lesion is followed in some tumors by a mutation of the second gene (point mutation or insertion/deletion), which produces a tumor cell unable to express any HLA class I molecule. The pattern of mutations found in microsatellite unstable colorectal carcinoma (MSI-H CRC) and melanoma showed a striking similarity, namely the predominance of frameshift mutations in repetitive CT elements. This review emphasizes common but also distinct molecular mechanisms of ß2m loss in both tumor types. It also summarizes recent studies that point to an acquired ß2m deficiency in response to cancer immunotherapy, a barrier to successful vaccination or adoptive cellular therapy.

Primary bone marrow lymphoma: an uncommon extranodal presentation of aggressive non-hodgkin lymphomas.

Bone marrow involvement by lymphoma is considered a systemic dissemination of the disease arising elsewhere, although some tumors may arise primarily in the bone marrow microenvironment. Primary bone marrow lymphoma (PBML) is a rare entity whose real boundaries and clinicobiological significance are not well defined. Criteria to diagnose PBML encompass isolated bone marrow infiltration, with no evidence of nodal or extranodal involvement, including the bone, and the exclusion of leukemia/lymphomas that are considered to primarily involve the bone marrow. Twenty-one out of 40 lymphomas retrospectively reviewed by the International Extranodal Lymphoma Study Group from 12 institutions in 7 different countries over a 25-year period fulfilled the inclusion criteria. These cases comprised 4 follicular lymphomas (FLs), 15 diffuse large B-cell lymphomas (DLBCLs), and 2 peripheral T-cell lymphomas, not otherwise specified. The FL cases showed paratrabecular infiltration, BCL2 protein and CD10 expression, and BCL2 gene rearrangement. DLBCL showed nodular infiltration in 6 cases and was diffuse in 9 cases; it also showed positivity for BCL2 protein (9/10) and IRF4 (6/8). Median age was 65 years with male predominance. All but 3 FL patients were symptomatic. Most cases presented with cytopenias and high lactate dehydrogenase. Four patients (3 FL cases and 1 DLBCL case) had leukemic involvement. Most DLBCL patients received CHOP-like or R-CHOP-like regimens. The outcome was unfavorable, with a median overall survival of 1.8 years. In conclusion, PBML is a very uncommon lymphoma with particular clinical features and heterogenous histology. Its recognition is important to establish accurate diagnosis and adequate therapy.

Genome-wide differential genetic profiling characterizes colorectal cancers with genetic instability and specific routes to HLA class I loss and immune escape.

AIM: We compared the expression of genes related to inflammatory and cytotoxic functions between MSI and MSS (HLA-class I-negative and HLA-class I-positive) colorectal cancers (CRCs), seeking evidence of differences in inflammatory mediators and cytotoxic T-cell responses. Twenty-two CRCs were divided into three study groups as a function of HLA class I expression and MSI phenotype: 8 MSI tumours, 6 MSS/HLA- tumours and 6 MSS/HLA+ tumours (controls). FINDINGS: A first comparison between eight MSI and six MSS/HLA-positive (control) cancers, based on microarray analysis on an Affymetrix(®) HG-U133-Plus-PM plate, identified 1974 differentially expressed genes (P < 0.05). We grouped genes in Gene Ontology functional categories: apoptotic programme (72 genes, P = 5.5·10(-3)), leucocyte activation (43 genes, P = 1.8·10(-5)), T-cell activation (24 genes, P = 6.3·10(-4)), inflammatory response (40 genes, 2.3·10(-2)) and cytokine production (10 genes, P = 1.9·10(-2)). Real-time PCR and immunohistochemical evaluation were used to validate the data, finding that increased mRNA levels of pro-inflammatory cytokines and cytotoxic mediators were associated with greater infiltration by CD8+T lymphocytes in the MSI group (P < 0.001). Finally, HLA-class I-negative tumours were not grouped together but rather in accordance with features of the gene expression profile of MSI or MSS tumours. As expected, genes associated with antigen processing machinery and MHC class I molecules (TAP2, B2m) were downregulated in MSS/HLA-class I-negative CRCs (n = 6) in comparison to controls. CONCLUSIONS: In conclusion, microarray and immunohistochemical data may be useful to comprehensively assess tumour-host interactions and differentiate MSI from MSS cancers. The two types of tumour, MSI/HLA-class I-negative and MSS/HLA-class I-negative, showed marked differences in the composition and intensity of infiltrating leucocytes, suggesting that their immune escape strategies involve distinct pathways.

Leukocyte infiltrate in gastrointestinal adenocarcinomas is strongly associated with tumor microsatellite instability but not with tumor immunogenicity.

PURPOSE: To analyze the correlation of genomic instability with leukocyte infiltrate in gastrointestinal carcinomas (GIACs) and with tumor immunogenicity, e.g., HLA class I cell surface expression defects and galectin-3 and PDL-1 expression. EXPERIMENTAL DESIGN: Lymphocyte and macrophage infiltrations were immunohistochemically studied in HLA class I negative GIACs with sporadic high-level microsatellite instability (MSI-H) or microsatellite stability (MSS). RESULTS: Tumors with MSI-H were associated with the following: dense infiltration (CD45, P < 0.001); cytotoxic CD8-positive lymphocytes (P < 0.001); and a complete absence of HLA class I cell surface expression, due to inactivating ß2-microglobulin (ß2-m) mutation in 50% of cases. In contrast, HLA class I negative tumors with MSS were significantly associated with fewer CD8-positive lymphocytes. There was no association between microsatellite instability and other molecular features of the tumor cells, including expression of galectin-3. Finally, macrophage infiltrate in the tumors was not correlated with microsatellite instability or HLA class I cell surface expression (CD64, P = 0.63; CD163, P = 0.51). CONCLUSIONS: Microsatellite instability appears to be the most important factor determining the composition, density, and localization of leukocyte infiltrate, which is independent of other molecular features such expression of HLA class I cells, galectin-3, or programmed death ligand-1. Accordingly, the strong intratumoral CD8+ T infiltration of MSI-H tumors may be produced by elevated levels of specific inflammatory chemokines in the tumor microenvironment.

Análisis biomecánico (antropométrico y cinemático) en niños con parálisis cerebral espástica / Biomechanical analysis (anthropometric and kinematic) in children with spastic cerebral palsy

La Parálisis Cerebral Infantil involucra una cantidad de síndromes caracterizados por alteraciones del movimiento y de la postura causados por un daño no progresivo en el cerebro inmaduro, es relevante, reconocer e identificar a través de estudios de análisis de movimiento humano con sistemas computarizados, las diferentes alteraciones del control postural y sus implicaciones biomecánicas, como predictores de la función de la extremidad superior, durante la fase de alcance de objetos en la posición sedente en niños con parálisis cerebral. Objetivo. Establecer el análisis biomecánico en los componentes antropométrico y cinemático de los niños entre 5 y 12 años con parálisis cerebral espástica y sanos que realizan el movimiento de alcance de un objeto frontal desde la posición sedente. Sujetos y métodos. Estudio descriptivo, comparativo enmarcado dentro de una investigación de casos con una muestra de 20 niños. Resultados. En el desarrollo de las tres fases del patrón del alcance los ángulos de inclinación pélvica, tronco relativo y la distancia resultante de la mano fueron estadísticamente significativos. Conclusiones. El comportamiento de las 31 variables cinemáticas indica en forma general que para el grupo PC fueron muy heterogéneas en su magnitud en contraste con aquellas del grupo control donde existe una tendencia a ser más homogéneas.

The Infantile Cerebral Paralysis involves an amount of syndromes characterized by alterations of the movement and of the position caused by a nonprogressive damage in the immature brain, he is excellent, to recognize and to identify through studies of analysis of human movement with systems computerized, the different alterations from the postural control and their biomechanic implications, like predicting of the function of the superior extremity, during the phase of reach of objects in the sedente position in children with cerebral paralysis. Objective. To establish the biomechanic analysis in the components anthropometric and kinematic of the children between 5 and 12 years with healthy espástica cerebral paralysis and that makes the movement of reach of a frontal object from the sedente position. Subjects and methods. Descriptive, comparative study framed within an investigation of cases with a sample of 20 children. Results. In the development of the three phases of the pattern of the reach the pelvic rakes, relative trunk and the resulting distance of the hand were statistically significant. Conclusions. The behavior of the 31 variable kinematics indicates in general form that for group PC they are very heterogenous in his magnitude in contrast to those of the group control where exists a tendency to be more homogenous.

Poly(ADP-ribose) polymerase-1 (PARP-1) longer alleles spanning the promoter region may confer protection to bilateral Meniere's disease.

CONCLUSION: The longer alleles (CA)17-20 of the promoter region of PARP-1 gene may confer some protection against bilateral Meniere's disease (BMD). OBJECTIVE: To analyze microsatellite (CA)(n) polymorphisms in the promoter region of PARP-1 gene and seek out risk and protective variants for BMD. SUBJECTS AND METHODS: Eighty patients from two ethnically defined groups with definite BMD, according to the diagnostic scale of the American Academy of Otolaryngology Head and Neck Surgery, were compared with a group of 371 normal controls from the same origin in a prospective multicenter study. We developed a specific amplification protocol to determine the PARP1-promotor CA microsatellite polymorphisms. RESULTS: We found that the longer alleles (CA)17-20 had a very low frequency in BMD (2/160, 1.3%, OR=7.33 (1.77-30.37, 95% CI), corrected p=0.012), suggesting that it may confer some protection against BMD.

Changes in activatory and inhibitory natural killer (NK) receptors may induce progression to multiple myeloma: implications for tumor evasion of T and NK cells.

The molecular basis of monoclonal gammopathy of undetermined significance (MGUS) progression to a malignant monoclonal gammopathy remains poorly understood. It was recently suggested that this process involves the suppression of innate and adaptive immunity. In this study, we examined immunogenic differences in bone marrow plasma cells among individuals without gammopathy (controls) and patients with MGUS, multiple myeloma (MM), and plasma cell leukemia. We detected differences in major histocompatibility complex (MHC) class I expression, MHC class I chain-related molecule A, and CD95 that were more evident between MGUS and MM samples; there appeared to be a critical imbalance between natural killer (NK)-cell activating and inhibitory signals during the transition from MGUS to MM. Our results indicate that the human leukocyte antigen (HLA) class I(bright), MICA(dim/-), and CD95(dim/-) immunophenotype reported in myeloma cells may result from an extensive interaction of malignant cells with cytotoxic T and NK cells and appears to be immunoedited for the evasion of immunosurveillance.