A20 (TNFAIP3) Deletion in Epstein-Barr Virus-Associated Lymphoproliferative Disorders/Lymphomas

A negative regulator of the nuclear factor (NF)-kappa B pathway, A20 (TNFAIP3), is inactivated in several types of lymphomas; particularly in diffuse large B-cell lymphoma (DLBCL), classical Hodgkin's lymphoma, and extranodal marginal zone lymphoma of the mucosa-associated lymphoid tissue. These findings suggest that the NF-kappa B activation is related to A20 inactivation. Recently, A20 inactivation has also been observed in Epstein-Barr virus (EBV)-related lymphomas; however, this occurrence has not been well investigated. Moreover, NF-kappa B is a key molecule in activated B-cell-like (ABC)-type DLBCL; EBV-associated DLBCL is of the ABC type. Therefore, we focused on A20 deletions in EBV-associated lymphoproliferative disorders/lymphomas. Using fluorescent in situ hybridization analysis, A20 deletions were identified in 4 of 13 samples from patients with pyothorax-associated lymphoma (PAL) (31%), 3 of 20 samples from nasal-type NK/T cell lymphomas (NKTLs) (15%), 1 of 8 samples of EBV-positive DLBCL of the elderly (DLBCL-e) (13%), but not in any of the 11 samples from individuals with methotrexate-related lymphoproliferative disorder (MTX-LPD) (0%). Among the samples with A20 deletions, EBV latent membrane protein 1 (LMP-1) expression was detected in all 4 of the PAL samples with A20 deletions and in the DLBCL-e sample with an A20 deletion, but not in any of the 3 NKTL samples. This finding indicated that A20 deletions were not directly related to the EBV latency pattern of lymphomas, although such deletions might be related to the diagnostic category. Immunohistologically, the A20 protein was absent in 2 (15%) of the13 PAL samples, 1 (9%) of 11 MTX-LPD samples, and in none of the 20 NKTL (0%) or 8 DLBCL-e samples. In conclusion, A20 deletion and/or dysfunctional expression are frequently associated with PALs, and A20 abnormalities may be related to the pathogenesis of PAL

Socioeconomic Impact of HIV/AIDS on Household under Free Antiretroviral Therapy in Preah Sihanouk Province, Cambodia

Objectives: The aim of this study was to compare the economic status of HIV-affected households with nonaffected households and explore the economic impact of HIV/AIDS on HIV-affected households under high coverage of free antiretroviral therapies (ART). Design and methods: We conducted a cross-sectional study in Preah Sihanouk Province, Cambodia in February and March 2008. We recruited HIV-positive participants (n=285) from a referral hospital and five health centers, and other 285 HIV-negative participants. We interviewed them using a questionnaire and compared the differences of economic status such as household income, expenditure, assets as well as medical cost, education cost, transportation cost for health services and funeral cost between the households of HIV-positive participants (HIV-positive households) and the households of HIV-negative participants (HIV-negative households). Results: Compared to the negative households, the HIV-positive households were more likely to have lower household income (p\u3c0.001), household expenditure (p\u3c0.001), assets (p\u3c0.001), education cost (p=0.001) and medical cost (p\u3c0.001). Among the HIV-positive households, the proportion of medical cost to the household expenditure was 1.3%, which was lower than that of the HIV-negative households. On the contrary, the economic burden for transportations for medical service and funeral cost was much higher among the HIV-positive households compared to the HIV-negative households. Conclusions: The HIV-positive households had worse economic status compared to the negative households. Though medical cost was lower than that of the negative households under high coverage of free ART, the HIV positives were still suffering from high economic burden in non health related living cost. From the results of our study, we suggest that the government and global agencies should support their living beyond health

Gene Expression Profile Signature of Aggressive Waldenström Macroglobulinemia with Chromosome 6q Deletion

Background. Waldenström macroglobulinemia (WM) is a rare, indolent B-cell lymphoma. Clinically, chromosome 6q deletion (6q del) including loss of the B lymphocyte-induced maturation protein 1 gene (BLIMP-1) is reported to be associated with poor prognosis. However, it remains unclear how the underlying biological mechanism contributes to the aggressiveness of WM with 6q del. Methods. Here, we conducted oligonucleotide microarray analysis to clarify the differences in gene expression between WM with and without 6q del. Gene ontology (GO) analysis was performed to identify the main pathways underlying differences in gene expression. Eight bone marrow formalin-fixed paraffin-embedded samples of WM were processed for interphase fluorescence in situ hybridization analysis, and three were shown to have 6q del. Results. GO analysis revealed significant terms including “lymphocyte activation” (corrected p value=6.68E-11), which included 31 probes. Moreover, IL21R and JAK3 expression upregulation and activation of the B-cell receptor signaling (BCR) pathway including CD79a, SYK, BLNK, PLCγ2, and CARD11 were detected in WM with 6q del compared with WM without 6q del. Conclusion. The present study suggested that the BCR signaling pathway and IL21R expression are activated in WM with 6q del. Moreover, FOXP1 and CBLB appear to act as positive regulators of the BCR signaling pathway. These findings might be attributed to the aggressiveness of the WM with 6q del expression signature

Accuracy of the Simplified Nutritional Appetite Questionnaire for Malnutrition and Sarcopenia Screening among Older Patients Requiring Rehabilitation

This cross-sectional study aimed to examine the accuracy of the Simplified Nutritional Appetite Questionnaire (SNAQ) and the SNAQ for Japanese Elderly (SNAQ-JE) for the Global Leadership Initiative on Malnutrition (GLIM)-defined malnutrition and sarcopenia screening in older persons. We included 380 inpatients aged ≥65 years (mean age, 79.3 ± 7.9; 60.0% women) and admitted to rehabilitation units. Undernutrition and sarcopenia were diagnosed based on GLIM criteria and the Asian Working Group for Sarcopenia, respectively, using bioimpedance analysis. Poor appetite was defined as an SNAQ score of <14 points and an SNAQ-JE score of ≤14 points. The sensitivity, specificity, and accuracy of these tools for detecting poor appetite for GLIM-defined malnutrition and sarcopenia were assessed. The rates of GLIM-defined malnutrition and sarcopenia were 56.8% and 59.2%, respectively. The number of patients with poor appetite was 94 (24.7%) for the SNAQ and 234 (61.6%) for the SNAQ-JE. The sensitivity and specificity of the SNAQ measured against GLIM-defined malnutrition were 32.9% and 73.1%, respectively, and against sarcopenia were 29.8% and 70.2%, respectively. The sensitivity and specificity of the SNAQ-JE measured against GLIM-defined malnutrition were 82.6% and 51.0%, respectively, and against sarcopenia were 86.0% and 53.7%, respectively. The SNAQ-JE showed fair accuracy for GLIM-defined malnutrition and sarcopenia in older patients admitted to rehabilitation units