Search

Contains fulltext : 294569.pdf (Publisher’s version ) (Open Access), AIMS: Subclassification of large B cell lymphoma (LBCL) is challenging due to the overlap in histopathological, immunophenotypical and genetic data. In particular, the criteria to separate diffuse large B cell lymphoma (DLBCL) and high-grade B cell lymphoma (HGBL) are difficult to apply in practice. The Lunenburg Lymphoma Biomarker Consortium previously reported a cohort of over 5000 LBCL that included fluorescence in-situ hybridisation (FISH) data. This cohort contained 209 cases with MYC rearrangement that were available for a validation study by a panel of eight expert haematopathologists of how various histopathological features are used. METHODS AND RESULTS: Digital whole slide images of haematoxylin and eosin-stained sections allowed the pathologists to visually score cases independently as well as participate in virtual joint review conferences. Standardised consensus guidelines were formulated for scoring histopathological features and included overall architecture/growth pattern, presence or absence of a starry-sky pattern, cell size, nuclear pleomorphism, nucleolar prominence and a range of cytological characteristics. Despite the use of consensus guidelines, the results show a high degree of discordance among the eight expert pathologists. Approximately 50% of the cases lacked a majority score, and this discordance spanned all six histopathological features. Moreover, none of the histological variables aided in prediction of MYC single versus double/triple-hit or immunoglobulin-partner FISH-based designations or clinical outcome measures. CONCLUSIONS: Our findings indicate that there are no specific conventional morphological parameters that help to subclassify MYC-rearranged LBCL or select cases for FISH analysis, and that incorporation of FISH data is essential for accurate classification and prognostication.

Contains fulltext : 294352.pdf (Publisher’s version ) (Open Access), Deleterious variants in N-acetylneuraminate pyruvate lyase (NPL) cause skeletal myopathy and cardiac edema in humans and zebrafish, but its physiological role remains unknown. We report generation of mouse models of the disease: Npl(R63C), carrying the human p.Arg63Cys variant, and Npl(del116) with a 116-bp exonic deletion. In both strains, NPL deficiency causes drastic increase in free sialic acid levels, reduction of skeletal muscle force and endurance, slower healing and smaller size of newly formed myofibers after cardiotoxin-induced muscle injury, increased glycolysis, partially impaired mitochondrial function, and aberrant sialylation of dystroglycan and mitochondrial LRP130 protein. NPL-catalyzed degradation of sialic acid in the muscle increases after fasting and injury and in human patient and mouse models with genetic muscle dystrophy, demonstrating that NPL is essential for muscle function and regeneration and serves as a general marker of muscle damage. Oral administration of N-acetylmannosamine rescues skeletal myopathy, as well as mitochondrial and structural abnormalities in Npl(R63C) mice, suggesting a potential treatment for human patients.

AIMS: Trimethylamine N-oxide (TMAO), choline and betaine serum levels have been associated with metabolic diseases including type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD). These associations could be mediated by insulin resistance. However, the relationships among these metabolites, insulin resistance and NAFLD have not been thoroughly investigated. Moreover, it has recently been suggested that TMAO could play a role in NAFLD by altering bile acid metabolism. We examined the association between circulating TMAO, choline and betaine levels and NAFLD in obese subjects. METHODS: Serum TMAO, choline, betaine and bile acid levels were measured in 357 Mexican obese patients with different grades of NAFLD as determined by liver histology. Associations of NAFLD with TMAO, choline and betaine levels were tested. Moreover, association of TMAO levels with non-alcoholic steatohepatitis (NASH) was tested separately in patients with and without T2D. RESULTS: TMAO and choline levels were significantly associated with NAFLD histologic features and NASH risk. While increased serum TMAO levels were significantly associated with NASH in patients with T2D, in non-T2D subjects this association lost significance after adjusting for sex, BMI and HOMA2-IR. Moreover, circulating secondary bile acids were associated both with increased TMAO levels and NASH. CONCLUSIONS: In obese patients, circulating TMAO levels were associated with NASH mainly in the presence of T2D. Functional studies are required to evaluate the role of insulin resistance and T2D in this association, both highly prevalent in NASH patients.

This study explores the activities, projects and lines of action of twenty-four media labs of Higher Education Institutions, chosen from a non-probabilistic system. A qualitative content analysis is applied on it to map the characteristics of the laboratories. Following an inductive process of categorization, the study identifies as outstanding work axes initiatives that materialize the principles of collective intelligence, encourage the transformation of teaching and learning systems, and promote the use of multimedia and audiovisual languages ?inside and outside the classroom. The results underline the teaching patterns that strengthen the links of Institutions with their social environments. The projects and initiatives found show how media labs facilitate new ways of reaching knowledge in areas as varied as art, design, journalism or engineering through the use of technologies. © 2020, Universidad Complutense de Madrid. All rights reserved.

© 2020 John Wiley & Sons, Ltd. Distributed slack bus (DSB) models for the resolution of power flow problems are a more realistic approach than the classical single slack bus concept. DSB models have been widely implemented in iterative approaches such as in Newton-Raphson power flow methods. However, iterative algorithms may lead to incorrect solutions or may fail to reach convergence under inappropriate initial estimations. The holomorphic embedding load-flow method (HELM) deals with the solution of the nonlinear power flow equations by means of complex analysis techniques, resulting in a deterministic and noniterative method, which is independent of initial estimations. As such, this paper proposes, from two different methodologies, a novel formulation and implementation of the DSB model for the HELM, which overcomes in that way the disadvantages of iterative methods and also incorporates the inherent advantages of DSB models. Moreover, this paper performs convergence and speed capability tests of the two proposed methodologies using two real-size benchmark systems.

[ES] Introducción El objetivo de este trabajo fue evaluar la utilidad del implante de semillas radiactivas (RSL) para la localización de la recurrencia cervical del cáncer de tiroides. Material y método Diez pacientes con cáncer de tiroides y compromiso ganglionar (4 de nuevo diagnóstico y 6 reoperados por recurrencia cervical) confirmados por ultrasonido y citología/Tg-PAAF fueron seleccionados para este procedimiento. Se introdujo una semilla 125I en la lesión metastásica mediante una aguja guiada por ecografía. Durante la cirugía se utilizó una sonda/gammacámara portátil para la localización de la lesión. Después de la cirugía se verificó que la semilla estaba incluida en el tejido extirpado. Se analizaron la duración de la intervención quirúrgica, la actividad de la semilla, los niveles de tiroglobulina, la dosis efectiva de radiación, las complicaciones y el grado de resección quirúrgica. Resultados Todos los ganglios marcados fueron positivos en histología. La duración media del procedimiento ecográfico fue de 11,4 ± 3,4 minutos. La semilla permaneció dentro del paciente, una media de 4 días (1-7) y el tiempo quirúrgico medio fue de 44,7 ± 29,1 minutos. Encontramos 21 especímenes metastásicos con un diámetro medio de 13,9 ± 6,3 mm. La actividad media de la semilla implantada fue de 71,27 ± 21,6 MBq (42,8-105). En el grupo reoperado, el nivel de tiroglobulina fue de 2,08 ± 1,56 ng/dl y tras la cirugía 0,13 ± 0,12 ng/dl, p < 0,01. Registramos un caso de hipoparatiroidismo transitorio en el grupo total. Conclusiones La introducción de RSL en nuestra unidad ha mostrado beneficios para el paciente y el equipo médico, siendo un procedimiento seguro y efectivo que también mejora la programación quirúrgica., [EN] Introduction The aim of this work is the evaluation of usefulness of radioactive seed localization (RSL) for the detection of cervical recurrence of thyroid cancer in order to improve the surgical outcome. Material and method Ten patients with thyroid cancer and lymph node involvement (4 naive and 6 with cervical recurrence) evidenced by ultrasound, cytology/Tg-FNAB (reoperated group) were selected for this procedure. A 125I seed was placed in the metastatic lesion using a needle guided by ultrasound. During surgery, a handheld gamma probe/portable gammacamera were used for lesion localization and excision. After removing the target tissue, it was verified that the seed was included in the excised tissue. Surgical intervention duration, lesion location, seed activity, thyroglobulin level, effective radiation dose, complications and the degree of surgical resection were analyzed. Results All the marked nodes were positive in histology. The mean duration of the ultrasound procedure was 11.4 ± 3.4 minutes. Seed was kept inside the patient, in average, during 4 days (1-7) and the average surgical time was 44.7 ± 29.1 minutes. We found 21 metastatic specimens with an average diameter 13.9 ± 6.3 mm. The mean activity of the implanted seed was 71.27 ± 21.6 MBq (42.8-105) In the reoperated group, thyroglobulin level was 2.08 ± 1.56 ng/dl and decreased after surgery to 0.13 ± 0.12 ng/dl, P < .01. Only one case of transient hypoparathyroidism was found in the total group. Conclusions The introduction of RSL in our unit has shown benefits for the patient and medical team, being a safe and effective procedure that also improves surgical programming.

© 2020 John Wiley & Sons, Ltd. Distributed slack bus (DSB) models for the resolution of power flow problems are a more realistic approach than the classical single slack bus concept. DSB models have been widely implemented in iterative approaches such as in Newton-Raphson power flow methods. However, iterative algorithms may lead to incorrect solutions or may fail to reach convergence under inappropriate initial estimations. The holomorphic embedding load-flow method (HELM) deals with the solution of the nonlinear power flow equations by means of complex analysis techniques, resulting in a deterministic and noniterative method, which is independent of initial estimations. As such, this paper proposes, from two different methodologies, a novel formulation and implementation of the DSB model for the HELM, which overcomes in that way the disadvantages of iterative methods and also incorporates the inherent advantages of DSB models. Moreover, this paper performs convergence and speed capability tests of the two proposed methodologies using two real-size benchmark systems.

© 2020 John Wiley & Sons, Ltd. Distributed slack bus (DSB) models for the resolution of power flow problems are a more realistic approach than the classical single slack bus concept. DSB models have been widely implemented in iterative approaches such as in Newton-Raphson power flow methods. However, iterative algorithms may lead to incorrect solutions or may fail to reach convergence under inappropriate initial estimations. The holomorphic embedding load-flow method (HELM) deals with the solution of the nonlinear power flow equations by means of complex analysis techniques, resulting in a deterministic and noniterative method, which is independent of initial estimations. As such, this paper proposes, from two different methodologies, a novel formulation and implementation of the DSB model for the HELM, which overcomes in that way the disadvantages of iterative methods and also incorporates the inherent advantages of DSB models. Moreover, this paper performs convergence and speed capability tests of the two proposed methodologies using two real-size benchmark systems.

BACKGROUND: Our aim was to evaluate whether the cell of origin (COO) as defined by the Hans algorithm and MYC/BCL2 coexpression, which are the two main biological risk factors in elderly patients treated with rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisolone (R-CHOP), maintain their prognostic value in a large prospective clinical trial. PATIENTS AND METHODS: We evaluated 285 paraffin-embedded samples from patients (60-80 years of age) enrolled in the Lymphoma Study Association trial LNH03-6B who were treated with R-CHOP. We correlated the COO defined by the transcriptome according to the Wright algorithm with that defined by the Hans algorithm in a subset of 62 tumors with available frozen tissue samples. RESULTS: The non-germinal center B-cell-like phenotype according to the Hans algorithm and BCL2 expression (but not MYC and BCL2 coexpression) predicted worse progression-free survival [hazard ratio (HR)=1.78, P = 0.003 and HR = 1.79, P = 0.003, respectively] and overall survival (HR = 1.85, P = 0.005 and HR = 1.67, P = 0.02, respectively) independently of the International Prognostic Index. The correlation between the Hans algorithm and the Wright algorithm was 91%, with an almost perfect concordance according to a kappa test (0.81). CONCLUSIONS: Our results suggest that immunohistochemically defined COO remains a useful tool for predicting prognosis in diffuse large B-cell lymphoma when performed under optimized standardized conditions and that BCL2 expression may help to identify elderly patients at risk for relapse and who could potentially respond to anti-BCL2 targeted agents. In this prospective phase III trial, the coexpression of MYC and BCL2 does not appear to predict worse survival. CLINICAL TRIAL NUMBER: NCT00144755.

Background Diffuse large B-cell lymphomas (DLBCLs) arising in specific extranodal sites have peculiar clinicopathologic features. Patients and methods We analyzed a cohort of 187 primary Waldeyer's ring (WR) DLBCLs retrieved from GELA protocols using anthracyclin-based polychemotherapy. Results Most patients (92%) had stage I-II disease. A germinal center B-cell-like (GCB) immunophenotype was observed in 61%, and BCL2 expression in 55%, of WR DLBCLs. BCL2, BCL6, IRF4 and MYC breakpoints were observed in, respectively, 3 of 42 (7%), 9 of 36 (25%), 2 of 26 (8%) and 4 of 40 (10%) contributive cases. A variable follicular pattern was evidenced in 30 of 68 (44%) large biopsy specimens. The 5-year progression-free survival (PFS) and the overall survival (OS) of 153 WR DLBCL patients with survival information were 69.5% and 77.8%, respectively. The GCB immunophenotype correlated with a better OS (P=0.0015), while BCL2 expression predicted a worse OS (P=0.037), an effect overcome by the GCB/non-GCB classification. Compared with matched nodal DLBCLs, WR DLBCLs with no age-adjusted international prognostic index factor disclosed a better 5-year PFS rate (77.5% versus 70.7%; P=0.03). Conclusions WR DLBCLs display distinct clinicopathologic features compared with conventional DLBCLs, with usual localized-stage disease, common follicular features and a high frequency of GCB immunophenotype contrasting with a low rate of BCL2 rearrangements. In addition, they seem to be associated with a better outcome than their nodal counterpart

Health Technologies Assessment is a practice that enablesthe evaluation of the consequences of the use of a technology. However, the lack of standardization and methodologies that guide the process remains a challenge. This paper presents the development and validation of a Health Technology Assessment tool which process was carried out in three phases. First, the tool was developed to assess the acquisition process of medical equipment, after which a discussion group was formed to obtain different perceptions regarding the tool. Finally,was the implementation through case studies, evaluating its real use and applying an evaluation survey to measure its usefulness in the processes of acquisition of medical equipment. The importance of each type of technology assessment was weighed and modules for technical, clinical, economic, ethical, social and organizational evaluation were developed. In addition, validation with experts demonstrated the usefulness of the tool in the selection and acquisition processes of medical equipment in a way that will reduce costs and enable better investments., A Avaliação de Tecnologias em Saúde é uma prática que permite às Instituições de Saúde valorizar de forma integral as consequências do uso de uma tecnologia, no entanto, a falta de estandardização e de metodologias que guiem o processo segue sendo um desafio por superar. Este trabalho apresenta o desenvolvimento e a validação de uma ferramenta de Avaliação de Tecnologias em Saúde a qual se realizou em três fases: primeiro desenvolveu-se a ferramenta que permite valorizar o processo de aquisição de equipamentos biomédicos, depois se conformou um grupo de discussão para obter diferentes percepções em frente à metodologia empregada, o desenho e desenvolvimento da ferramenta para finalmente implementá-la mediante casos de estudo avaliando seu uso real e aplicando uma pesquisa que permitiu valorizar sua utilidade nos processos de aquisição de equipamentos biomédicos. Ponderou-se a importância de cada tipo de avaliação de tecnologias selecionadas e desenvolveram-se os módulos para as avaliações técnica, clínica, económica, ética, social e organizacional. Por sua vez, a validação com experientes demonstrou a utilidade da ferramenta nos processos de seleção e aquisição de equipamentos biomédicos de maneira que se diminuam custos e se realizem melhores investimentos., La Evaluación de Tecnologías en Salud es una práctica que permite a las Instituciones de Salud valorar de forma integral las consecuencias del uso de una tecnología, sin embargo, la falta de estandarización y de metodologías que guíen el proceso sigue siendo un reto por superar. Este trabajo presenta el desarrollo y la validación de una herramienta de Evaluación de Tecnologías en Salud la cual se realizó en tres fases: primero se desarrolló la herramienta que permite valorar el proceso de adquisición de equipos biomédicos, después se conformó un grupo de discusión para obtener diferentes percepciones frente a la metodología empleada, el diseño y desarrollo de la herramienta para finalmente implementarla mediante casos de estudio evaluando su uso real y aplicando una encuesta que permitió valorar su utilidad en los procesos de adquisición de equipos biomédicos. Se ponderó la importancia de cada tipo de evaluación de tecnologías seleccionada y se desarrollaron los módulos para las evaluaciones técnica, clínica, económica y ética, social y organizacional. Por su parte, la validación con expertos demostró la utilidad de la herramienta en los procesos de selección y adquisición de equipos biomédicos de manera que se disminuyan costos y se realicen mejores inversiones.

[EN] Atmospheric plasma spraying (APS) is an interesting technique to obtain nanostructured coatings due to its versatility, simplicity and relatively low cost. However, nanometric powders cannot be fed into the plume using conventional feeding systems, due to their low mass and poor flowability, and must be adequately reconstituted into sprayable micrometric agglomerates. In this work, Al2O3–13 wt.%TiO2 nanostructured and submicron-nanostructured powders were deposited using APS. The feedstocks were obtained by spray drying from two starting suspensions, prepared by mixing two commercial nanosuspensions of Al2O3 and TiO2, or by adding nanosized TiO2 and submicron-sized Al2O3 powders to water. The spray-dried granules were heat-treated to reduce their porosity and the resultant powders were fully characterized. Optimization of the deposition conditions enabled the reconstituted powders to be successfully deposited, yielding coatings that were well bonded to the substrate. The coating microstructure, characterized by SEM, was formed by semi-molten feedstock agglomerates surrounded by fully molten particles that act as a binder. Moreover, microhardness, adhesion, and tribological behavior were determined, and the impact of the granule characteristics on these properties was studied. It was found that changing the feedstock characteristics allowed controlling the coating quality and properties.

[EN] Atmospheric plasma spraying (APS) is an interesting technique to obtain nanostructured coatings due to its versatility, simplicity and relatively low cost. However, nanometric powders cannot be fed into the plume using conventional feeding systems, due to their low mass and poor flowability, and must be adequately reconstituted into sprayable micrometric agglomerates. In this work, Al2O3–13 wt.%TiO2 nanostructured and submicron-nanostructured powders were deposited using APS. The feedstocks were obtained by spray drying from two starting suspensions, prepared by mixing two commercial nanosuspensions of Al2O3 and TiO2, or by adding nanosized TiO2 and submicron-sized Al2O3 powders to water. The spray-dried granules were heat-treated to reduce their porosity and the resultant powders were fully characterized. Optimization of the deposition conditions enabled the reconstituted powders to be successfully deposited, yielding coatings that were well bonded to the substrate. The coating microstructure, characterized by SEM, was formed by semi-molten feedstock agglomerates surrounded by fully molten particles that act as a binder. Moreover, microhardness, adhesion, and tribological behavior were determined, and the impact of the granule characteristics on these properties was studied. It was found that changing the feedstock characteristics allowed controlling the coating quality and properties.

http://archive.org/details/numericalelectro1094522386, NA, NA

Item does not contain fulltext, The Lunenburg Lymphoma Biomarker Consortium (LLBC) evaluated the prognostic value of IHC biomarkers in a large series of patients with diffuse large B-cell lymphoma (DLBCL). Clinical data and tumor samples were retrieved from 12 studies from Europe and North America, with patients treated before or after the rituximab era. Using tissue microarrays from 1514 patients, IHC for BCL2, BCL6, CD5, CD10, MUM1, Ki67, and HLA-DR was performed and scored according to previously validated protocols. Optimal cut points predicting overall survival of patients treated in the rituximab era could only be determined for CD5 (P = .003) and Ki67 (P = .02), whereas such cut points for BCL2, BCL6, HLA-DR, and MUM1 could only be defined in patients not receiving rituximab. A prognostic model for patients treated in the rituximab era identified 4 risk groups using BCL2, Ki67, and International Prognostic Index (IPI) with improved discrimination of low-risk patients. Newly recognized correlations between specific biomarkers and IPI highlight the importance of carefully controlling for clinical and biologic factors in prognostic models. These data demonstrate that the IPI remains the best available index in patients with DLBCL treated with rituximab and chemotherapy.

Item does not contain fulltext, The Lunenburg Lymphoma Biomarker Consortium (LLBC) evaluated the prognostic value of IHC biomarkers in a large series of patients with diffuse large B-cell lymphoma (DLBCL). Clinical data and tumor samples were retrieved from 12 studies from Europe and North America, with patients treated before or after the rituximab era. Using tissue microarrays from 1514 patients, IHC for BCL2, BCL6, CD5, CD10, MUM1, Ki67, and HLA-DR was performed and scored according to previously validated protocols. Optimal cut points predicting overall survival of patients treated in the rituximab era could only be determined for CD5 (P = .003) and Ki67 (P = .02), whereas such cut points for BCL2, BCL6, HLA-DR, and MUM1 could only be defined in patients not receiving rituximab. A prognostic model for patients treated in the rituximab era identified 4 risk groups using BCL2, Ki67, and International Prognostic Index (IPI) with improved discrimination of low-risk patients. Newly recognized correlations between specific biomarkers and IPI highlight the importance of carefully controlling for clinical and biologic factors in prognostic models. These data demonstrate that the IPI remains the best available index in patients with DLBCL treated with rituximab and chemotherapy.

Item does not contain fulltext, The Lunenburg Lymphoma Biomarker Consortium (LLBC) evaluated the prognostic value of IHC biomarkers in a large series of patients with diffuse large B-cell lymphoma (DLBCL). Clinical data and tumor samples were retrieved from 12 studies from Europe and North America, with patients treated before or after the rituximab era. Using tissue microarrays from 1514 patients, IHC for BCL2, BCL6, CD5, CD10, MUM1, Ki67, and HLA-DR was performed and scored according to previously validated protocols. Optimal cut points predicting overall survival of patients treated in the rituximab era could only be determined for CD5 (P = .003) and Ki67 (P = .02), whereas such cut points for BCL2, BCL6, HLA-DR, and MUM1 could only be defined in patients not receiving rituximab. A prognostic model for patients treated in the rituximab era identified 4 risk groups using BCL2, Ki67, and International Prognostic Index (IPI) with improved discrimination of low-risk patients. Newly recognized correlations between specific biomarkers and IPI highlight the importance of carefully controlling for clinical and biologic factors in prognostic models. These data demonstrate that the IPI remains the best available index in patients with DLBCL treated with rituximab and chemotherapy.

Item does not contain fulltext, BACKGROUND AND AIMS: The results of class prediction and the determination of prognostic markers in diffuse large B-cell lymphoma (DLBCL) have been variably reported. Apart from biological variations, this may be caused by differences in laboratory techniques, scoring definitions and inter- and intra-observer variation. In this study, an international collaboration of clinical lymphoma research groups has concentrated on validation and standardisation of immunohistochemistry of the currently potentially interesting prognostic markers in DLBCL. METHODS: Sections of a tissue microarray with 36 cases of DLBCL were stained in eight laboratories with antibodies to CD20, CD5, bcl-2, bcl-6, CD10, HLA-DR, MUM-1 and Ki-67 according to local methods. The study was performed in two rounds, firstly focused on the evaluation of laboratory staining variation, and secondly on the scoring variation. RESULTS: Different techniques resulted in highly variable results and poor reproducibility for almost all markers. Reproducibility of the nuclear markers was highly sensitive to technical variations, including immunological enhancement techniques (agreements 34%). With elimination of variation due to staining and uniformly agreed on scoring criteria, significant improvement was seen; however less so for bcl-6 and Ki-67 (agreement 53-58%). Absence of internal controls that preclude scoring, significantly influenced the results for CD10 and bcl-6. CONCLUSION: Semi-quantitative immunohistochemistry for subclassification of DLBCL is feasible, but with varying rates of concordance for different markers and only using optimised techniques and strict scoring criteria. These findings may explain the wide variation in prognostic impact reported in the literature. Harmonisation of techniques and centralised consensus review appears mandatory when using immunohistochemical biomarkers for treatment stratification.

Item does not contain fulltext, BACKGROUND AND AIMS: The results of class prediction and the determination of prognostic markers in diffuse large B-cell lymphoma (DLBCL) have been variably reported. Apart from biological variations, this may be caused by differences in laboratory techniques, scoring definitions and inter- and intra-observer variation. In this study, an international collaboration of clinical lymphoma research groups has concentrated on validation and standardisation of immunohistochemistry of the currently potentially interesting prognostic markers in DLBCL. METHODS: Sections of a tissue microarray with 36 cases of DLBCL were stained in eight laboratories with antibodies to CD20, CD5, bcl-2, bcl-6, CD10, HLA-DR, MUM-1 and Ki-67 according to local methods. The study was performed in two rounds, firstly focused on the evaluation of laboratory staining variation, and secondly on the scoring variation. RESULTS: Different techniques resulted in highly variable results and poor reproducibility for almost all markers. Reproducibility of the nuclear markers was highly sensitive to technical variations, including immunological enhancement techniques (agreements 34%). With elimination of variation due to staining and uniformly agreed on scoring criteria, significant improvement was seen; however less so for bcl-6 and Ki-67 (agreement 53-58%). Absence of internal controls that preclude scoring, significantly influenced the results for CD10 and bcl-6. CONCLUSION: Semi-quantitative immunohistochemistry for subclassification of DLBCL is feasible, but with varying rates of concordance for different markers and only using optimised techniques and strict scoring criteria. These findings may explain the wide variation in prognostic impact reported in the literature. Harmonisation of techniques and centralised consensus review appears mandatory when using immunohistochemical biomarkers for treatment stratification.

Item does not contain fulltext, BACKGROUND AND AIMS: The results of class prediction and the determination of prognostic markers in diffuse large B-cell lymphoma (DLBCL) have been variably reported. Apart from biological variations, this may be caused by differences in laboratory techniques, scoring definitions and inter- and intra-observer variation. In this study, an international collaboration of clinical lymphoma research groups has concentrated on validation and standardisation of immunohistochemistry of the currently potentially interesting prognostic markers in DLBCL. METHODS: Sections of a tissue microarray with 36 cases of DLBCL were stained in eight laboratories with antibodies to CD20, CD5, bcl-2, bcl-6, CD10, HLA-DR, MUM-1 and Ki-67 according to local methods. The study was performed in two rounds, firstly focused on the evaluation of laboratory staining variation, and secondly on the scoring variation. RESULTS: Different techniques resulted in highly variable results and poor reproducibility for almost all markers. Reproducibility of the nuclear markers was highly sensitive to technical variations, including immunological enhancement techniques (agreements 34%). With elimination of variation due to staining and uniformly agreed on scoring criteria, significant improvement was seen; however less so for bcl-6 and Ki-67 (agreement 53-58%). Absence of internal controls that preclude scoring, significantly influenced the results for CD10 and bcl-6. CONCLUSION: Semi-quantitative immunohistochemistry for subclassification of DLBCL is feasible, but with varying rates of concordance for different markers and only using optimised techniques and strict scoring criteria. These findings may explain the wide variation in prognostic impact reported in the literature. Harmonisation of techniques and centralised consensus review appears mandatory when using immunohistochemical biomarkers for treatment stratification.

Item does not contain fulltext, PURPOSE: The results of immunohistochemical class prediction and prognostic stratification of diffuse large B-cell lymphoma (DLBCL) have been remarkably various thus far. Apart from biologic variations, this may be caused by differences in laboratory techniques, scoring definitions, and inter- and intraobserver variations. In this study, an international collaboration of clinical lymphoma research groups from Europe, United States, and Canada concentrated on validation and standardization of immunohistochemistry of the currently potentially interesting prognostic markers in DLBCL. PATIENTS AND METHODS: Sections of a tissue microarray from 36 patients with DLBCL were stained in eight laboratories with antibodies to CD20, CD5, bcl-2, bcl-6, CD10, HLA-DR, MUM1, and MIB-1 according to local methods. The study was performed in two rounds firstly focused on the evaluation of laboratory staining variation and secondly on the scoring variation. RESULTS: Different laboratory staining techniques resulted in unexpectedly highly variable results and very poor reproducibility in scoring for almost all markers. No single laboratory stood out as uniformly poor or excellent. With elimination of variation due to staining, high agreement was found for CD20, HLA-DR, and CD10. Poor agreement was found for bcl-6 and Ki-67. Optimization of techniques and uniformly agreed on scoring criteria improved reproducibility. CONCLUSION: This study shows that semiquantitative immunohistochemistry for subclassification of DLBCL is feasible and reproducible, but exhibits varying rates of concordance for different markers. These findings may explain the wide variation of biomarker prognostic impact reported in the literature. Harmonization of techniques and centralized consensus review appears mandatory when using immunohistochemical biomarkers for treatment stratification.

Item does not contain fulltext, PURPOSE: The results of immunohistochemical class prediction and prognostic stratification of diffuse large B-cell lymphoma (DLBCL) have been remarkably various thus far. Apart from biologic variations, this may be caused by differences in laboratory techniques, scoring definitions, and inter- and intraobserver variations. In this study, an international collaboration of clinical lymphoma research groups from Europe, United States, and Canada concentrated on validation and standardization of immunohistochemistry of the currently potentially interesting prognostic markers in DLBCL. PATIENTS AND METHODS: Sections of a tissue microarray from 36 patients with DLBCL were stained in eight laboratories with antibodies to CD20, CD5, bcl-2, bcl-6, CD10, HLA-DR, MUM1, and MIB-1 according to local methods. The study was performed in two rounds firstly focused on the evaluation of laboratory staining variation and secondly on the scoring variation. RESULTS: Different laboratory staining techniques resulted in unexpectedly highly variable results and very poor reproducibility in scoring for almost all markers. No single laboratory stood out as uniformly poor or excellent. With elimination of variation due to staining, high agreement was found for CD20, HLA-DR, and CD10. Poor agreement was found for bcl-6 and Ki-67. Optimization of techniques and uniformly agreed on scoring criteria improved reproducibility. CONCLUSION: This study shows that semiquantitative immunohistochemistry for subclassification of DLBCL is feasible and reproducible, but exhibits varying rates of concordance for different markers. These findings may explain the wide variation of biomarker prognostic impact reported in the literature. Harmonization of techniques and centralized consensus review appears mandatory when using immunohistochemical biomarkers for treatment stratification.

Purpose: Because it is unclear whether T-cell/histiocyte-rich large B-cell lymphomas (H/TCRBCL) should be considered as a true clinicopathologic entity, we conducted a matched-control analysis comparing patients with H/TCRBCL and patients with diffuse large-B cell lymphoma (B-DLCL). Patients and Methods: More than 4,500 patients were enrolled onto non-Hodgkin's lymphoma trials conducted by the Groupe d'Etude des Lymphomes de l'Adulte. After histologic review, 50 patients were subclassified as H/TCRBCL. They were matched to 150 patients with B-DLCL for each of the factors of the International Prognostic Index (IPI). Results: Clinical characteristics of H/TCRBCL patients showed a male predominance and a median age of 47 years. Performance status was normal in 89% of patients, whereas lactate dehydrogenase level was increased in 60% of patients. The disease was disseminated in 81% of patients, and 48% had two or more involved extranodal sites. The IPI score was greater than or equal to 2 in 53% of patients. The complete response rote to chemotherapy was 63%, and 5-year overall survival (OS) and event-free survival (EFS) rates (mean +/- SD) were 58% +/- 18% and 53% +/- 16%, respectively. The matched-control analysis showed a trend toward a better response to chemotherapy for patients with B-DLCL (P = .06), whereas no difference was observed in OS (P = .9) and EFS (P = .8). Conclusion: H/TCRBCL is an aggressive disease that often presents with adverse prognostic factors. However, when treatment is adapted to the disease risk, outcome is equivalent to that observed in patients with B-DLCL. Thus H/TCRBCL should be considered a pathologic variant that belongs to the B-DLCL category. (C) 2003 by American Society of Clinical Oncology.

A new anaerobic reactor called the Sludge Central Fixed Bed Reactor (SCFBR) was built and evaluated for the treatment of liquid residue from the pig farms. The SCFBR has three main parts. The lower area is for sludge, the middle part consists of a concentrically packed zone and an upper area for the separation of solids, liquids and gases. The 28.51 SCFBR reactor was evaluated over a period of 210 days, using three organic loads of 0.548,0.421 and 1.239 g COD/1 day. Initially, the reactor was fed non-continuously using 10 and 10.7 days Hydraulic Retention Times (HRT). The HRT was later decreased to 3.87 days using continuous feeding. For the three 0.548, 0.421 and 1.239 g COD/1 day organic loads, Chemical Oxygen Demand (COD) removal was 68%, 81% and 73% respectively and Volatile Solids (VS) removal was 53.5%, 55.8% and 50.1% respectively. The SCFBR performed well, as shown by the removal efficiency and stability obtained. A microphotograph of sludge from the lower zone is presented, showing high Methanosaeta (Methanothrix) presence., Un nuevo reactor anaeróbico denominado Sludge Central Fixed Bed Reactor (SCFBR) fue construido y evaluado para tratar los residuos líquidos de las granjas porcícolas. El SCFBR está constituido por tres zonas principales. Una zona inferior de lodos, seguida por un módulo empacado ubicado en forma concéntrica y, en la parte superior, una zona de separación sólido, líquido y gas. El reactor de 28,5 1 de volumen de reacción fue evaluado durante 210 días para tres cargas orgánicas de 0,548, 0,421 y 1,239 g DQO/ 1 día. El SCFBR fue alimentado inicialmente en forma discontinua con tiempos de retención hidráulicos (TRH) de 10 y 10,7 días. Posteriormente el TRH fue disminuido a 3,87 días con una alimentación en continuo. Para las tres cargas orgánicas de 0,548, 0,421 y 1,239 g DQO/1 día se obtuvieron remociones en la demanda química de oxígeno (DQO) de 68%, 81% y 73% y en los sólidos volátiles (SV), de 53,5%, 55,8% y 50,1%, respectivamente. El SCFBR presentó un buen desempeño, re-presentado en las eficiencias de remoción y en la estabilidad observada. Se presenta una microfotografía tomada de una muestra de lodo de la zona inferior del SCFBR, observándose una gran presencia de microorganismos del género Methanosaeta (Methanothrix).

A new anaerobic reactor called the Sludge Central Fixed Bed Reactor (SCFBR) was built and evaluated for the treatment of liquid residue from the pig farms. The SCFBR has three main parts. The lower area is for sludge, the middle part consists of a concentrically packed zone and an upper area for the separation of solids, liquids and gases. The 28.51 SCFBR reactor was evaluated over a period of 210 days, using three organic loads of 0.548,0.421 and 1.239 g COD/1 day. Initially, the reactor was fed non-continuously using 10 and 10.7 days Hydraulic Retention Times (HRT). The HRT was later decreased to 3.87 days using continuous feeding. For the three 0.548, 0.421 and 1.239 g COD/1 day organic loads, Chemical Oxygen Demand (COD) removal was 68%, 81% and 73% respectively and Volatile Solids (VS) removal was 53.5%, 55.8% and 50.1% respectively. The SCFBR performed well, as shown by the removal efficiency and stability obtained. A microphotograph of sludge from the lower zone is presented, showing high Methanosaeta (Methanothrix) presence., Un nuevo reactor anaeróbico denominado Sludge Central Fixed Bed Reactor (SCFBR) fue construido y evaluado para tratar los residuos líquidos de las granjas porcícolas. El SCFBR está constituido por tres zonas principales. Una zona inferior de lodos, seguida por un módulo empacado ubicado en forma concéntrica y, en la parte superior, una zona de separación sólido, líquido y gas. El reactor de 28,5 1 de volumen de reacción fue evaluado durante 210 días para tres cargas orgánicas de 0,548, 0,421 y 1,239 g DQO/ 1 día. El SCFBR fue alimentado inicialmente en forma discontinua con tiempos de retención hidráulicos (TRH) de 10 y 10,7 días. Posteriormente el TRH fue disminuido a 3,87 días con una alimentación en continuo. Para las tres cargas orgánicas de 0,548, 0,421 y 1,239 g DQO/1 día se obtuvieron remociones en la demanda química de oxígeno (DQO) de 68%, 81% y 73% y en los sólidos volátiles (SV), de 53,5%, 55,8% y 50,1%, respectivamente. El SCFBR presentó un buen desempeño, re-presentado en las eficiencias de remoción y en la estabilidad observada. Se presenta una microfotografía tomada de una muestra de lodo de la zona inferior del SCFBR, observándose una gran presencia de microorganismos del género Methanosaeta (Methanothrix).

A new anaerobic reactor called the Sludge Central Fixed Bed Reactor (SCFBR) was built and evaluated for the treatment of liquid residue from the pig farms. The SCFBR has three main parts. The lower area is for sludge, the middle part consists of a concentrically packed zone and an upper area for the separation of solids, liquids and gases. The 28.51 SCFBR reactor was evaluated over a period of 210 days, using three organic loads of 0.548,0.421 and 1.239 g COD/1 day. Initially, the reactor was fed non-continuously using 10 and 10.7 days Hydraulic Retention Times (HRT). The HRT was later decreased to 3.87 days using continuous feeding. For the three 0.548, 0.421 and 1.239 g COD/1 day organic loads, Chemical Oxygen Demand (COD) removal was 68%, 81% and 73% respectively and Volatile Solids (VS) removal was 53.5%, 55.8% and 50.1% respectively. The SCFBR performed well, as shown by the removal efficiency and stability obtained. A microphotograph of sludge from the lower zone is presented, showing high Methanosaeta (Methanothrix) presence., Un nuevo reactor anaeróbico denominado Sludge Central Fixed Bed Reactor (SCFBR) fue construido y evaluado para tratar los residuos líquidos de las granjas porcícolas. El SCFBR está constituido por tres zonas principales. Una zona inferior de lodos, seguida por un módulo empacado ubicado en forma concéntrica y, en la parte superior, una zona de separación sólido, líquido y gas. El reactor de 28,5 1 de volumen de reacción fue evaluado durante 210 días para tres cargas orgánicas de 0,548, 0,421 y 1,239 g DQO/ 1 día. El SCFBR fue alimentado inicialmente en forma discontinua con tiempos de retención hidráulicos (TRH) de 10 y 10,7 días. Posteriormente el TRH fue disminuido a 3,87 días con una alimentación en continuo. Para las tres cargas orgánicas de 0,548, 0,421 y 1,239 g DQO/1 día se obtuvieron remociones en la demanda química de oxígeno (DQO) de 68%, 81% y 73% y en los sólidos volátiles (SV), de 53,5%, 55,8% y 50,1%, respectivamente. El SCFBR presentó un buen desempeño, re-presentado en las eficiencias de remoción y en la estabilidad observada. Se presenta una microfotografía tomada de una muestra de lodo de la zona inferior del SCFBR, observándose una gran presencia de microorganismos del género Methanosaeta (Methanothrix).

A new anaerobic reactor called the Sludge Central Fixed Bed Reactor (SCFBR) was built and evaluated for the treatment of liquid residue from the pig farms. The SCFBR has three main parts. The lower area is for sludge, the middle part consists of a concentrically packed zone and an upper area for the separation of solids, liquids and gases. The 28.51 SCFBR reactor was evaluated over a period of 210 days, using three organic loads of 0.548,0.421 and 1.239 g COD/1 day. Initially, the reactor was fed non-continuously using 10 and 10.7 days Hydraulic Retention Times (HRT). The HRT was later decreased to 3.87 days using continuous feeding. For the three 0.548, 0.421 and 1.239 g COD/1 day organic loads, Chemical Oxygen Demand (COD) removal was 68%, 81% and 73% respectively and Volatile Solids (VS) removal was 53.5%, 55.8% and 50.1% respectively. The SCFBR performed well, as shown by the removal efficiency and stability obtained. A microphotograph of sludge from the lower zone is presented, showing high Methanosaeta (Methanothrix) presence., Un nuevo reactor anaeróbico denominado Sludge Central Fixed Bed Reactor (SCFBR) fue construido y evaluado para tratar los residuos líquidos de las granjas porcícolas. El SCFBR está constituido por tres zonas principales. Una zona inferior de lodos, seguida por un módulo empacado ubicado en forma concéntrica y, en la parte superior, una zona de separación sólido, líquido y gas. El reactor de 28,5 1 de volumen de reacción fue evaluado durante 210 días para tres cargas orgánicas de 0,548, 0,421 y 1,239 g DQO/ 1 día. El SCFBR fue alimentado inicialmente en forma discontinua con tiempos de retención hidráulicos (TRH) de 10 y 10,7 días. Posteriormente el TRH fue disminuido a 3,87 días con una alimentación en continuo. Para las tres cargas orgánicas de 0,548, 0,421 y 1,239 g DQO/1 día se obtuvieron remociones en la demanda química de oxígeno (DQO) de 68%, 81% y 73% y en los sólidos volátiles (SV), de 53,5%, 55,8% y 50,1%, respectivamente. El SCFBR presentó un buen desempeño, re-presentado en las eficiencias de remoción y en la estabilidad observada. Se presenta una microfotografía tomada de una muestra de lodo de la zona inferior del SCFBR, observándose una gran presencia de microorganismos del género Methanosaeta (Methanothrix).

A new anaerobic reactor called the Sludge Central Fixed Bed Reactor (SCFBR) was built and evaluated for the treatment of liquid residue from the pig farms. The SCFBR has three main parts. The lower area is for sludge, the middle part consists of a concentrically packed zone and an upper area for the separation of solids, liquids and gases. The 28.51 SCFBR reactor was evaluated over a period of 210 days, using three organic loads of 0.548,0.421 and 1.239 g COD/1 day. Initially, the reactor was fed non-continuously using 10 and 10.7 days Hydraulic Retention Times (HRT). The HRT was later decreased to 3.87 days using continuous feeding. For the three 0.548, 0.421 and 1.239 g COD/1 day organic loads, Chemical Oxygen Demand (COD) removal was 68%, 81% and 73% respectively and Volatile Solids (VS) removal was 53.5%, 55.8% and 50.1% respectively. The SCFBR performed well, as shown by the removal efficiency and stability obtained. A microphotograph of sludge from the lower zone is presented, showing high Methanosaeta (Methanothrix) presence., Un nuevo reactor anaeróbico denominado Sludge Central Fixed Bed Reactor (SCFBR) fue construido y evaluado para tratar los residuos líquidos de las granjas porcícolas. El SCFBR está constituido por tres zonas principales. Una zona inferior de lodos, seguida por un módulo empacado ubicado en forma concéntrica y, en la parte superior, una zona de separación sólido, líquido y gas. El reactor de 28,5 1 de volumen de reacción fue evaluado durante 210 días para tres cargas orgánicas de 0,548, 0,421 y 1,239 g DQO/ 1 día. El SCFBR fue alimentado inicialmente en forma discontinua con tiempos de retención hidráulicos (TRH) de 10 y 10,7 días. Posteriormente el TRH fue disminuido a 3,87 días con una alimentación en continuo. Para las tres cargas orgánicas de 0,548, 0,421 y 1,239 g DQO/1 día se obtuvieron remociones en la demanda química de oxígeno (DQO) de 68%, 81% y 73% y en los sólidos volátiles (SV), de 53,5%, 55,8% y 50,1%, respectivamente. El SCFBR presentó un buen desempeño, re-presentado en las eficiencias de remoción y en la estabilidad observada. Se presenta una microfotografía tomada de una muestra de lodo de la zona inferior del SCFBR, observándose una gran presencia de microorganismos del género Methanosaeta (Methanothrix).

The objectives of this study were to evaluate the outcome after polychemotherapy for patients with primary cutaneous large-cell lymphomas (PCLL) and to validate the recently proposed immunohistologic classification of cutaneous lymphomas. Among 140 patients with positive skin biopsies included in the LNH87 protocol (for treatment of aggressive lymphomas), 49 patients met the criteria of ROLL, Characteristics were: sex ratio M/F, 2.3; age 18 to 83 years (median, 52), peripheral lymph nodes, n = 22; diffuse disease, n = 12; median tumor size, 4.5cm; elevated lactate dehydrogenase, n = 9; ECOG: 0/1, n = 49. Histology was: follicular center B cell, n = 23; B-lymphoblastic, n = 1; anaplastic large-cell lymphoma, n = 14 (T cell phenotype n = 8); CD30(-) T cell lymphoma, n = 11. All patients received polychemotherapy: under 70 years, ACVBP (three to four cycles and consolidation for 6 months) n = 25; mBACOD (eight cycles) n = 16; over 70 years, C(T)VP (six cycles) n = 8, Radiation therapy was not included in the protocol, With a median follow-up of 5 years, 24/49 patients had relapsed, with 20 skin relapses. Event-free (EFS) and overall survival (OS) at 5 years were, respectively, 50 and 77%, Significant adverse prognostic factors were: histology (CD30(-) T cell lymphoma) and diffuse cutaneous disease (>10% of skin), The presence of nodal involvement was only significant for EFS. When compared to 140 non-cutaneous lymphoma patients included in the same trial and fully matched for the main clinical characteristics, OS was similar, In conclusion, PCLL behaves like other localized B or T cell extranodal lymphomas with the same prognostic factors (LDH, ECOG, age) except for CD30(+) PCLL which have a very good prognosis.

Se evalúa la efectividad de la alimentación complementaria (convenio Ministerio de Salud - OFASA) en desnutridos menores de 6 años controlados ambulatoriamente en consultorios dependientes del Hospital de Coronel, en los períodos junio-diciembre 1977 y junio-diciembre 1978. Este estudio demuestra que la alimentación complementaria permite disminuir significativamente la desnutrición infantil.

Background Diffuse large B-cell lymphomas (DLBCLs) arising in specific extranodal sites have peculiar clinicopathologic features. Patients and methods We analyzed a cohort of 187 primary Waldeyer's ring (WR) DLBCLs retrieved from GELA protocols using anthracyclin-based polychemotherapy. Results Most patients (92%) had stage I-II disease. A germinal center B-cell-like (GCB) immunophenotype was observed in 61%, and BCL2 expression in 55%, of WR DLBCLs. BCL2, BCL6, IRF4 and MYC breakpoints were observed in, respectively, 3 of 42 (7%), 9 of 36 (25%), 2 of 26 (8%) and 4 of 40 (10%) contributive cases. A variable follicular pattern was evidenced in 30 of 68 (44%) large biopsy specimens. The 5-year progression-free survival (PFS) and the overall survival (OS) of 153 WR DLBCL patients with survival information were 69.5% and 77.8%, respectively. The GCB immunophenotype correlated with a better OS (P=0.0015), while BCL2 expression predicted a worse OS (P=0.037), an effect overcome by the GCB/non-GCB classification. Compared with matched nodal DLBCLs, WR DLBCLs with no age-adjusted international prognostic index factor disclosed a better 5-year PFS rate (77.5% versus 70.7%; P=0.03). Conclusions WR DLBCLs display distinct clinicopathologic features compared with conventional DLBCLs, with usual localized-stage disease, common follicular features and a high frequency of GCB immunophenotype contrasting with a low rate of BCL2 rearrangements. In addition, they seem to be associated with a better outcome than their nodal counterpart