Objectives: Currently available interferon (IFN)-g-release assays (IGRA) cannot discriminate active tuberculosis (TB) from latent TB infection (LTBI), and so have limited clinical utility for diagnosing active TB. Since numbers of tumour necrosis factor (TNF)-a-producing T cells are highly correlated with active TB, we hypothesized that detecting IFN-g-and/or TNF-a-producing T cells would overcome this limitation of IGRA. This study evaluated the diagnostic performances of the IFN-g and TNF-a dual release fluorospot assay for active TB. Methods: Adult patients with suspected TB including recent TB exposers were prospectively enrolled over a 28-month period. In addition to the conventional IGRA test (i.e. QuantiFERON-In-Tube), a fluorospot assay for detecting IFN-g-and TNF-a-producing T cells was performed. The final diagnoses were classified by clinical category. Patients with confirmed or probable TB were regarded as active TB, and patients with not active TB were further classified as having not active TB with and without LTBI, based on the QuantiFERON-In-Tube results. Results: A total of 153 patients including 45 with active TB and 108 with not active TB (38 LTBI vs. 70 not LTBI) were finally analysed. The sensitivity and specificity of the QuantiFERON-In-Tube assay for active TB were 84% (95% confidence interval (CI), 70e93) and 70% (95% CI 61e79), respectively. The IFN-g/TNF-a dual release assay by fluorospot had substantially higher diagnostic specificity (94%) for diagnosing active TB than the IFN-g single release assay (72%, p < 0.001), without compromising sensitivity (84% vs. 89%, p 0.79). Conclusions: The fluorospot-based IFN-g/TNF-a dual release assay appears to be a simple and useful test for diagnosing active TB.

Healthcare providers should test the psychometric properties of tools for screening accuracy, clinical decision-making, and understanding of a phenomenon within different cultural settings.

Recent studies identified germline HAVCR2 (TIM-3) mutations as the specific genetic predisposition to subcutaneous panniculitis-like T-cell lymphoma (SPTCL). However, distinction between HAVCR2-mutated and HAVCR2-wildtype SPTCLs remains elusive. We studied the prevalence of HAVCR2 mutation in a nation-wide cohort of SPTCL and investigated clinical and molecular distinction between HAVCR2-mutated and HAVCR2-wild-type SPTCLs. A multicenter nationwide cohort of 53 SPTCL cases was established; patients were diagnosed at seven Korean institutions between 2003 and 2020. Histologic features were reviewed by experienced hematopathologists and clinical features were retrospectively reviewed. Whole-exome sequencing (WES) and RNA-seq were performed using formalin-fixed, paraffin-embedded (FFPE) samples of 8 patients diagnosed in Seoul National University Hospital (SNUH), with matched non-neoplastic tissue samples from two patients. Direct sequencing of HAVCR2 exon 2 was successfully carried out using FFPE samples from 33 of the remaining 45 patients. Among 41 patients with available HAVCR2 mutation status, 28 (68.3%) were women, and the median age at diagnosis was 30 years (range 11–74). Ten patients (10/40; 25.0%) suffered hemophagocytic syndrome (HPS) or HPS-like systemic illness during the clinical course, and 14 patients (14/40; 35.0%) progressed during the follow-up. Six patients (6/41; 14.6%) died of disease progression or HPS. We found 18 patients (18/41; 43.9%) with HAVCR2 mutation; 15 patients harbored biallelic HAVCR2 Y82C mutation and 3 patients were noted for heterozygous HAVCR2 Y82C mutation. HAVCR2-mutated SPTCLs occurred in younger patients (median age 26.5 versus 37; Mann-Whitney p-value = 0.003), and were more often complicated by HPS or HPS-like systemic illness (10/18 versus 0/22; Fisher's exact p-value &lt; 0.001), compared to HAVCR2-wild-type SPTCLs. Survival analysis using log-rank test revealed that HAVCR2-mutated SPTCLs had shorter progression-free survival, though statistical significance was not achieved (p-value = 0.081) WES results did not show recurrent genetic alteration other than HAVCR2 Y82C in 4 out of 8 patients. Mutations in genes involved in T/NK cell-associated inflammation (PVRL1, PVRL2, TICAM1, GZMA), epigenetic modification (BAZ2A, KMT2C, KMT2D, SETD1A), JAK-STAT signaling (IFNL2, PIAS3), and NF-kB pathway (PDCD11) were observed in individual cases. Gene set enrichment analyses (GSEA) using RNA-seq results showed significant enrichment of pathways involving TNF-alpha signaling via NF-kB (FDR q-value = 0.008), hypoxia (FDR q-value = 0.009), IL6-JAK-STAT3 signaling (FDR q-value = 0.026), apoptosis (FDR q-value = 0.121), and MTORC1 signaling (FDR q-value = 0.188) in HAVCR2-mutated SPTCLs. HAVCR2 Y82C hotspot mutation frequently occurs in Korean patients with SPTCL, which was characterized by unique clinicopathologic features. SPTCL with HAVCR2 Y82C was enriched with distinct cellular pathways, which remains to be further validated. Citation Format: Jiwon Koh, Insoon Jang, Seungchan Mun, Cheol Lee, Hee-Jung Cha, Young Ha Oh, Jin Man Kim, Young Hyeh Ko, Jae Ho Han, Heounjeong Go, Jooryung Huh, Kwangsoo Kim, Yoon Kyung Jeon. Subcutaneous panniculitis-like T-cell lymphoma with HAVCR2 mutation shows unique clinicopathologic features and gene expression profile [abstract]. In: Proceedings of the AACR Virtual Meeting: Advances in Malignant Lymphoma; 2020 Aug 17-19. Philadelphia (PA): AACR; Blood Cancer Discov 2020;1(3_Suppl):Abstract nr PO-34.

PURPOSE: Sodium meta-arsenite is an orally bioavailable arsenic compound that currently undergoing clinical evaluation. The sodium meta-arsenite leads to blood vessel congestion, the selective destruction of the vasculature, and extensive necrosis in experimental tumors. The aim of this study is to assess the ability of dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) to measure the antivascular effects of sodium meta-arsenite in colon cancer allograft model. MATERIALS AND METHODS: Mice CT26 colon cell carcinoma allografts were treated with sodium meta-arsenite or saline. Changes in tumor vascularity were assessed by DCE-MRI. DCE-MRI data were analyzed calculating the k(ep). For histologic analysis, liver, spleen and tumor tissues were taken at 8, 24 and 48 hours after sodium meta-arsenite injection from CT26 tumor allograft models. RESULTS: DCE-MRI results showed comparison between pre-treatment and 24 hr post-treatment Gd-DTPA contrast enhancement T1-weighted MR image. Enhancement has been significantly decreased in sodium meta-arsenite treated group than sham injection group. We also showed extensive central necrosis of tumor by 24 h after treated with sodium meta-arsenite (10 mg/kg, i.p.). CONCLUSION: These results suggest that DCE-MRI could quantitatively visualized the perfusion efficacy of the sodium meta-arsenite acting as a VDA in colon caner allograft model Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2435. doi:1538-7445.AM2012-2435

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