Proteomic profiling of HTLV-1 carriers and ATL patients reveals sTNFR2 as a novel diagnostic biomarker for acute ATL

Adult T-cell leukemia/lymphoma (ATL) is a human T-cell leukemia virus type 1 (HTLV-1)–associated T-cell malignancy with generally poor prognosis. Although only ∼5% of HTLV-1 carriers progress to ATL, early diagnosis is challenging because of the lack of ATL biomarkers. In this study, we analyzed blood plasma profiles of asymptomatic HTLV-1 carriers (ACs); untreated ATL patients, including acute, lymphoma, smoldering, and chronic types; and ATL patients in remission. Through SOMAscan, expression levels of 1305 plasma proteins were analyzed in 85 samples (AC, n = 40; ATL, n = 40; remission, n = 5). Using gene set enrichment analysis and gene ontology, overrepresented pathways in ATL vs AC included angiogenesis, inflammation by cytokines and chemokines, interleukin-6 (IL-6)/JAK/STAT3, and notch signaling. In selecting candidate biomarkers, we focused on soluble tumor necrosis factor receptor 2 (sTNFR2) because of its active role in enriched pathways, extreme significance (Welch’s t test P 0.90), and novelty in ATL research. Quantification of sTNFR2 in 102 plasma samples (AC, n = 30; ATL, n = 68; remission, n = 4) using enzyme-linked immunosorbent assay showed remarkable elevations in acute ATL, at least 10 times those of AC samples, and return of sTNFR2 to AC state levels after achieving remission. Flow cytometry and immunostaining validated the expression of TNFR2 in ATL cells. No correlation between sIL-2 and sTNFR2 levels in acute ATL was found, suggesting the possibility of sTNFR2 as an independent biomarker. Our findings represent the first extensive blood-based proteomic analysis of ATL, suggesting the potential clinical utility of sTNFR2 in diagnosing acute ATL

Intestinal helminth infections in HIV-infected patients in Savannakhet after establishment of an HIV registration network in Lao People’s Democratic Republic

Abstract Background In Lao People’s Democratic Republic (PDR), which borders China, Vietnam, Cambodia, Thailand, and Myanmar, the number of HIV-infected patients has increased in recent years. HIV-infected patients diagnosed in Lao PDR are enrolled in a registration network and receive antiretroviral therapy (ART) covered by governmental financial support. Based on the registration network, we investigated intestinal helminth infections and coinfection with HTLV-1 in HIV-infected patients treated with an early intervention using ART in Lao PDR. Methods This cross-sectional study of all 252 HIV-infected patients at Savannakhet Provincial Hospital, located in the southern part of Lao PDR, was conducted between February and March 2018. Socioepidemiological information and clinical information were collected from a registration network database and by questionnaire administered to participants. Microscopic examination of intestinal helminth infections in stool samples and particle agglutination for anti-HTLV-1 antibody in plasma were performed. Results The median age of all 252 participants was 39 years old (range, 18–59). Based on the registration network database, there were 156 (61.9%) HIV-infected patients with a CD4-positive cell count ≥ 200 cells/μL and 146 (57.9%) with an HIV viral load < 250 copies/mL. Among 212 stool samples, 75 (35.4%) were found to contain one or more intestinal helminth species, including Opisthorchis viverrini (16.5%), Strongyloides stercoralis (10.8%), hookworm (10.4%), and Taenia saginata (3.3%). This rate of intestinal helminth infections was lower than that of a previous report conducted before the establishment of the registration network for HIV-infected patients in Lao PDR. There was no significant association between intestinal helminth infections and a lower CD4-positive T cell count or higher HIV viral load. HIV-infected patients with anti-HTLV-1 antibody positivity were not found in this cohort. Conclusion The registration network and an early intervention using ART may provide good medical care and improve the clinical course of HIV-infected patients in Lao PDR. However, the incidence of intestinal helminth infections remains high at 35.4%. The development of a specific medical care system for helminth infection for HIV-infected patients is necessary

Effect of Functional Electrical Stimulation in Convalescent Stroke Patients: A Multicenter, Randomized Controlled Trial

Background: We evaluated whether the Walkaide® device could effectively improve walking ability and lower extremity function in post-stroke patients with foot drop. Patients aged 20–85 years with an initial stroke within ≤6 months and a functional ambulation classification score of 3 or 4 were eligible. Materials and Methods: Patients were randomly allocated to the functional electrical stimulation (FES) or control group at a 1:1 ratio. A 40 min training program using Walkaide was additionally performed by the FES group five times per week for 8 weeks. The control group received the 40 min training program without FES. Results: A total of 203 patients were allocated to the FES (n = 102) or control (n = 101) groups. Patients who did not receive the intervention or whose data were unavailable were excluded. Finally, the primary outcome data of 184 patients (n = 92 in each group) were analyzed. The mean change in the maximum distance during the 6-MWT (primary outcome) was 68.37 ± 62.42 m and 57.50 ± 68.17 m in the FES and control groups (difference: 10.86 m; 95% confidence interval: −8.26 to 29.98, p = 0.26), respectively. Conclusions: In Japanese post-stroke patients with foot drop, FES did not significantly improve the 6 min walk distance during the convalescent phase. The trial was registered at UMIN000020604

Evaluation of two prognostic indices for adult T‐cell leukemia/lymphoma in the subtropical endemic area, Okinawa, Japan

Aggressive adult T‐cell leukemia/lymphoma (ATL) has an extremely poor prognosis and is hyperendemic in Okinawa, Japan. This study evaluated two prognostic indices (PIs) for aggressive ATL, the ATL‐PI and Japan Clinical Oncology Group (JCOG)‐PI, in a cohort from Okinawa. The PIs were originally developed using two different Japanese cohorts that included few patients from Okinawa. The endpoint was overall survival (OS). Multivariable Cox regression analyses in the cohort of 433 patients revealed that all seven factors for calculating each PI were statistically significant prognostic predictors. Three‐year OS rates for ATL‐PI were 35.9% (low‐risk, n = 66), 10.4% (intermediate‐risk, n = 256), and 1.6% (high‐risk, n = 111), and those for JCOG‐PI were 22.4% (moderate‐risk, n = 176) and 5.3% (high‐risk, n = 257). The JCOG‐PI moderate‐risk group included both the ATL‐PI low‐ and intermediate‐risk groups. ATL‐PI more clearly identified the low‐risk patient subgroup than JCOG‐PI. To evaluate the external validity of the two PIs, we also assessed prognostic discriminability among 159 patients who loosely met the eligibility criteria of a previous clinical trial. Three‐year OS rates for ATL‐PI were 34.5% (low‐risk, n = 42), 9.2% (intermediate‐risk, n = 109), and 12.5% (high‐risk, n = 8). Those for JCOG‐PI were 22.4% (moderate‐risk, n = 95) and 7.6% (high‐risk, n = 64). The low‐risk ATL‐PI group had a better prognosis than the JCOG‐PI moderate‐risk group, suggesting that ATL‐PI would be more useful than JCOG‐PI for establishing and examining novel treatment strategies for ATL patients with a better prognosis. In addition, strongyloidiasis, previously suggested to be associated with ATL‐related deaths in Okinawa, was not a prognostic factor in this study