Songhwa Choi

Background/Objectives: Short bowel syndrome (SBS) is the leading cause of intestinal failure (IF) that often requires long-term parenteral nutrition (PN). Extended PN results in severe complications and reduced quality of life (QoL). This study aimed to evaluate the QoL utility weights associated with PN duration using vignettes. Methods: We developed detailed scenarios and descriptions to represent eight hypothetical health states, reflecting variations in PN frequency in both pediatric and adult patients. A cross-sectional survey was conducted among 359 Korean adults (aged 19–59 years) from the general population, assigned to evaluate adult (n = 179) or pediatric (n = 180) vignette groups. Health utility was measured using the EuroQol 5-Dimension (EQ-5D), visual analog scale (VAS), and time trade-off (TTO) methods. Multivariable regression analysis using a mixed-effects model was employed to manage repeated measures and control for sociodemographic variables. Results: Utility scores measured using the EQ-5D, VAS, and TTO were negatively correlated with increasing PN days in both adult and pediatric patients with SBS-IF. The highest mean utility values were “0 days on PN” (adults: EQ-5D 0.808, VAS 0.689, TTO 0.874; pediatric: EQ-5D 0.804, VAS 0.680, TTO 0.883), while the lowest were “7 days on PN” (adults: EQ-5D 0.117, VAS 0.180, TTO 0.272; pediatric: EQ-5D 0.070, VAS 0.178, TTO 0.291). These trends remained significant after covariate adjustment (p < 0.001). Conclusions: The study revealed a steady decline in utility values with an increasing number of PN days. These findings highlight the importance of enhancing the QoL in patients with SBS-IF by supporting intestinal adaptation and reducing PN dependency.

Fabry disease (FD) is a lysosomal storage disorder caused by pathogenic variants in the gene encoding alpha-galactosidase A (GLA). Deficiency of GLA results in the progressive accumulation of glycosphingolipids in virtually all organs, resulting in a progressive multisystem disease. Due to multi-organ involvement in FD, a comprehensive, multidisciplinary approach to diagnosis and treatment with regular follow-ups is essential. The Pusan National University Yangsan Hospital (PNUYH) multidisciplinary care model of FD aims to provide detailed practice guidelines and evidence-based recommendations for the diagnosis, screening, and treatment of FD according to specialty. This guideline focuses on the “quarterback” type of multidisciplinary team (MDT) operation and is limited in its applicability to the Korean insurance system. However, it reflects our team’s extensive experience and insights into optimizing MDT operations within these constraints and is expected to be highly beneficial for centers initiating MDTs for the effective treatment of FD.

BackgroundNonpersistence in anticoagulation therapy is common and associated with undesirable clinical outcomes in patients with venous thromboembolism (VTE).MethodsWe investigated preceding clinical events of treatment nonpersistence (e.g., switching, discontinuing, or restarting) in VTE patients with and without active cancer using Korean claims database.ResultsClinically significant events including thromboembolic events, hepatic function change and surgery preceded treatment nonpersistence, but heterogeneous distributions of clinical events were observed in the presence of active cancer. Patients with active cancer had a low rate of clinical events preceding treatment nonpersistence, and new active cancer diagnosis in the nonactive cancer group was most common before the switch to parenteral anticoagulants from warfarin or non-vitamin K antagonist oral anticoagulants (NOACs).ConclusionThese findings suggest that clinically significant events can precede treatment nonpersistence and largely paralleled current guidelines for patients with VTE, whereas heterogeneous distributions of clinical events were observed in the presence of active cancer.

Sungwon Roh, Kang Soo Lee, Songhwa Choi, Jae-Min Kim. Clin Psychopharmacol Neurosci 2022;20:548-59. https://doi.org/10.9758/cpn.2022.20.3.548

Hypovitaminosis D is prevalent worldwide. It is more prevalent in Eastern Asia region, including Korea. In addition to various environmental factors that influence serum 25-hydroxyvitamin D (25(OH)D) concentration, genetic influence also plays a significant role based on studies estimating the heritability of 25(OH)D in non-Asian populations. The objective of this study was to determine the genetic influence on serum 25(OH)D concentration in Korean men using the twin and family data. A total of 1126 Korean male adult twins and family members from the Healthy Twin Study with serum 25(OH)D measurement were included in this cross-sectional study. Intraclass correlation coefficients (ICCs) and heritability were calculated by mixed linear regression analysis and quantitative genetic analysis after adjusting for environmental and lifestyle factors. Mean (± standard deviation; SD) of serum 25(OH)D concentration was 15.34 ± 6.18 ng/ml. The prevalence of vitamin D insufficiency was 19.8% and that of vitamin D deficiency was 77.9%. After adjusting for age, the highest ICC (0.61) was observed for monozygotic twin pairs while the lowest ICC (0.31) was found for father-son pairs. Age-adjusted heritability was estimated to be 58%. When physical activity, multivitamin intake and season of blood sampling were further considered, the ICC and heritability did not materially change. In the sensitivity analysis after excluding known multivitamin users, age-adjusted heritability was reduced to 44%. In our study of Korean male twins and family members, heritability of 25(OH)D was moderately high. This supports the finding that genetic factors have significant influence on vitamin D status.

Saturated fatty acids (SFAs) have been shown to induce endoplasmic reticulum (ER) stress and chronic inflammatory responses, as well as alter sphingolipid metabolism. Disruptions in ER stress and sphingolipid metabolism have also been implicated in intestinal inflammation. Therefore, to elucidate the roles of SFAs in ER stress and inflammation in intestinal epithelial cells, we examined myristate (C14:0) and palmitate (C16:0). My‐ ristate, but not palmitate, induced ER stress signaling, including activation of inositol‐requiring enzyme 1 (IRE1) and X‐box binding protein 1 (XBP1) signaling. Myristate significantly increased C14‐ceramide levels, whereas palmitate increased several long‐chain ceramides. To define the role of ceramide synthases (CerSs) in myristate‐induced ER stress, we used the pharmacologic inhibitor, fumonisin B1 (FB1), and small interfering RNA (siRNA) for CerS5 and 6, the primary isoforms that are involved in C14‐ceramide generation. FB1 and siRNA for CerS5 or 6 suppressed myristate‐induced C14‐ceramide generation and XBP1 splicing (XBP1s). Moreover, increased XBP1s induced the downstream expression of IL‐6 in a CerS5/6‐dependent manner. In addition, a myristate‐enriched milk fat‐ based diet, but not a lard‐ based diet, increased C14‐ ceramide, XBP1s, and IL‐ 6 expression in vivo. Taken together, our data suggest that myristate modulates ER stress and cytokine production in the intestinal epithelium via CerS5/6 and C14‐ ceramide generation.—Choi, S., Snider, J. M., Olakkengil, N., Lambert, J. M., Anderson, A. K., Ross‐Evans, J. S., Cowart, L. A., Snider, A. J. Myristate‐induced endoplasmic reticulum stress requires ceramide synthases 5/6 and generation of C14‐ceramide in intestinal epithelial cells. FASEB J. 32, 5724–5736 (2018). www.fasebj.org