The present study aimed to investigate the prognostic importance of the neutrophil-to-lymphocyte ratio (NLR) in patients with amyotrophic lateral sclerosis (ALS). Among 322 patients diagnosed as having definite, probable, or possible ALS at a single tertiary hospital, 194 patients were included in the final analysis. Patients were divided into three groups (T1, T2, and T3) according to the tertile of their NLR. Survival rate was significantly lower in T3 compared to the other groups (log-rank test; T1 vs. T3, p = 0.009; T2 vs. T3, p = 0.008). Median survival duration was 37.0 (24.0–56.0), 32.5 (19.5–51.2), and 22.0 (17.0–38.0) months in T1, T2, and T3, respectively. In a multivariable Cox proportional hazards regression analysis, the hazard ratio of age at onset, bulbar-onset, and NLR (T3/T1) was 1.04 (1.02–1.06, p < 0.001), 1.68 (1.10–2.57, p = 0.015), and 1.60 (1.01–2.51, p = 0.041), respectively. A high baseline NLR may serve as a useful indicator for short survival duration in patients with ALS.
The prevalence of CT interstitial lung abnormalities (ILAs) in an Asian health screening cohort was approximately 3%, and fibrotic ILA was independently associated with imaging progression, lung ca... Background The association between interstitial lung abnormalities (ILAs) and long-term outcomes has not been reported in Asian health screening populations. Purpose To investigate ILA prevalence i...
The effect of diabetes distress on glycemic control and its association with diabetes complications is still poorly understood. We aimed to study the clinical features of patients with high diabetes distress, focusing on changes in glycemic control and risk of diabetic complications. From the Korean National Diabetes Program data, we investigated 1862 individuals with type 2 diabetes mellitus (T2DM) who completed diabetic complication studies and the Korean version of the Problem Areas in Diabetes Survey (PAID-K). A total score of PAID-K ≥ 40 was considered indicative of high distress. Individuals with high distress (n = 589) had significantly higher levels of glycated hemoglobin than those without distress (7.4% vs. 7.1%, p < 0.001). This trend persisted throughout the 3-year follow-up period. Higher PAID-K scores were associated with younger age, female gender, longer duration of diabetes, and higher carbohydrate intake (all p < 0.05). There was a significant association between high distress and diabetic neuropathy (adjusted odds ratio, 1.63; p = 0.002), but no significant association was found with other complications, including retinopathy, albuminuria, and carotid artery plaque. In conclusion, high diabetes distress was associated with uncontrolled hyperglycemia and higher odds of having diabetic neuropathy.
1 January 2019 in Journal of Korean Medical Science
Acute myeloid leukemia (AML) generally has an unsatisfactory prognosis despite the recent introduction of new regimens, including targeted agents and antibodies. To find a new druggable pathway, we performed integrated bioinformatic pathway screening on large OHSU and MILE AML databases, discovered the SUMOylation pathway, and validated it independently with an external data set (totaling 2959 AML and 642 normal sample data). The clinical relevance of SUMOylation in AML was supported by its core gene expression which is correlated with patient survival, European LeukemiaNet 2017 risk classification, and AML-relevant mutations. TAK-981, a first-in-class SUMOylation inhibitor currently under clinical trials for solid tumors, showed antileukemic effects with apoptosis induction, cell-cycle arrest, and induction of differentiation marker expression in leukemic cells. It exhibited potent nanomolar activity, often stronger than that of cytarabine, which is part of the standard of care. TAK-981’s utility was further demonstrated in in vivo mouse and human leukemia models as well as patient-derived primary AML cells. Our results also indicate direct and cancer cell-inherent anti-AML effects by TAK-981, different from the type 1 interferon and immune-dependent mechanism in a previous solid tumor study. Overall, we provide a proof-of-concept for SUMOylation as a new targetable pathway in AML and propose TAK-981 as a promising direct anti-AML agent. Our data should prompt studies on optimal combination strategies and transitions to clinical trials in AML.