Background: Despite widespread vaccination efforts against severe acute respiratory syndrome coronavirus 2, variants with increased transmissibility or immune evasion continue to emerge, posing a considerable challenge. Understanding the immunological factors associated with coronavirus disease (COVID-19) progression is essential for improving patient management and treatment strategies. We explored the dynamic changes in the peripheral white blood cell (WBC) profile, including T lymphocyte subsets, to assess their potential as predictors of disease severity and progression. Methods: Two hundred fifty-eight patients hospitalized for confirmed COVID-19 were classified into four sub-cohorts based on changes in disease severity over 7 days. WBC parameters, including absolute neutrophil, total lymphocyte, and T cell subset counts, and the neutrophil-to-lymphocyte ratio (NLR) were assessed at admission and after 7 days. Results: Patients with persistent mild-to-moderate illness exhibited a marked increase in the lymphocyte count and a decrease in the NLR over time. In contrast, patients with sustained severe-to-critical illness showed an increasing WBC count without a corresponding increase in the lymphocyte count, in addition to a marked elevation in the NLR. Patients whose condition improved from severe-to-critical to mild-to-moderate illness showed increased cluster of differentiation (CD)3+ and CD4+ T cell counts and an elevated CD4/CD8 ratio, whereas the NLR did not significantly change. Conclusions The early-phase dynamics of T cell subsets may serve as a useful biomarker of disease severity and recovery in patients with COVID-19. Monitoring these immunological changes may help support clinical decision-making and inform the timing of therapeutic interventions.

X-linked ichthyosis (XLI) is an inherited disorder of keratinization resulting from a deficiency of steroid sulfatase (STS), for which no effective therapy is currently available. E-cadherin, a key upstream regulator of keratinocyte differentiation, has been found to be markedly overexpressed in STS-deficient HaCaT cells, suggesting its potential as a therapeutic target in XLI. To investigate the functional role of E-cadherin and explore its therapeutic potential, we introduced mutations into the N-terminal region of Ecadherin and examined the resulting effects on keratinocyte differentiation. In addition, a microRNA (miR-6766) and a rationally designed gapmer antisense oligonucleotide (gASO) targeting the same E-cadherin mRNA sequence were employed to modulate E-cadherin expression in HaCaT cells. Mutations within the N-terminal region of E-cadherin significantly reduced keratin 1 expression, underscoring the critical role of this domain in regulating keratinocyte differentiation. Treatment with miR-6766 led todownregulation of both early and terminal differentiation markers. Building on this, the gASO modified with 2′-O-methoxyethyl andphosphorothioate linkages exhibited enhanced potency and stability, resulting in stronger suppression of E-cadherin and keratin 1 expression compared with miR-6766 (maintained 37.7% greater inhibition of E-cadherin at 96 h and 35.7% greater inhibition of keratin 1 at 96 h). Furthermore, gASO treatment induced a concentration-dependent reduction in early (keratin 1 and keratin 10) and terminal (transglutaminase 1, involucrin, and loricrin) differentiation markers. These findings demonstrate that an E-cadherin– targeting gASO effectively suppresses abnormal keratinocyte differentiation and may serve as a promising therapeutic strategy for X-linked ichthyosis.

Background: and Purpose Although gastrointestinal (GI) surgery can affect drug efficacy, its impact on oral anticoagulants (OACs) remains unclear. This study investigated the impact of GI surgery on the comparative effectiveness and safety of direct oral anticoagulants (DOACs) versus warfarin in atrial fibrillation (AF). Methods: Using a nationwide South Korean claims database, AF patients prescribed OACs between 2015 and 2021 were analyzed. The primary outcome was ischemic stroke, and secondary outcomes were major bleeding, all-cause death, and composite outcome (ischemic stroke, major bleeding, all-cause death). Outcomes were compared by OAC type (DOAC vs. warfarin) and GI surgery status using inverse probability of treatment weighting and a Fine–Gray subdistribution hazard model with time-varying covariates. Results: Among 388,214 AF patients (mean age, 71.9 yr; 42.7% male), 6,907 (1.8%) underwent GI surgery. The effect of GI surgery differed between warfarin and DOACs for ischemic stroke (Pint= 0.018), with increased risk for warfarin (adjusted HR [aHR]: 2.32; 95% confidence interval [CI] 1.17–4.62), but not for DOACs (aHR: 0.97 [95% CI 0.77–1.22]) after surgery. Effects of surgery on major bleeding, all-cause death, and composite outcome did not differ. In post–GI surgery setting, DOACs demonstrated lower ischemic stroke risk (aHR: 0.35 [95% CI 0.17–0.72]) and comparable risks for other outcomes. Exploratory analyses by surgery location suggested a more favorable profile of DOACs after upper GI surgery. Conclusions In AF patients, GI surgery significantly increased ischemic stroke risk among warfarin users, but not among DOAC users. DOACs showed generally favorable profiles after GI surgery and may remain a reasonable anticoagulant, with potentially more favorable profile after upper GI surgery.

Non-Down syndrome pediatric acute megakaryoblastic leukemia (AMKL) may be classified according to the presence of recurrent genetic abnormalities with prognostic relevance. In this case study, we report on a girl with AMKL, 32 months old at the time of diagnosis, in whom we confirmed the presence of the cryptic, poor prognosis NUP98::KDM5A fusion. The patient achieved complete remission (CR) with the first course of chemotherapy, underwent haploidentical family donor hematopoietic stem cell transplantation (HSCT) without event, but relapsed 5 months after HSCT. Through this case report, we emphasize the good initial response to chemotherapy, and the early relapse despite undergoing HSCT in first CR. We review the limited literature on NUP98::KDM5A (+) pediatric AML, and underscore the need for further study to improve the outcome of patients with this rare AML subtype.

Non-Down syndrome pediatric acute megakaryoblastic leukemia (AMKL) may be classified according to the presence of recurrent genetic abnormalities with prognostic relevance. In this case study, we report on a girl with AMKL, 32 months old at the time of diagnosis, in whom we confirmed the presence of the cryptic, poor prognosis NUP98::KDM5A fusion. The patient achieved complete remission (CR) with the first course of chemotherapy, underwent haploidentical family donor hematopoietic stem cell transplantation (HSCT) without event, but relapsed 5 months after HSCT. Through this case report, we emphasize the good initial response to chemotherapy, and the early relapse despite undergoing HSCT in first CR. We review the limited literature on NUP98::KDM5A (+) pediatric AML, and underscore the need for further study to improve the outcome of patients with this rare AML subtype.

Non-Down syndrome pediatric acute megakaryoblastic leukemia (AMKL) may be classified according to the presence of recurrent genetic abnormalities with prognostic relevance. In this case study, we report on a girl with AMKL, 32 months old at the time of diagnosis, in whom we confirmed the presence of the cryptic, poor prognosis NUP98::KDM5A fusion. The patient achieved complete remission (CR) with the first course of chemotherapy, underwent haploidentical family donor hematopoietic stem cell transplantation (HSCT) without event, but relapsed 5 months after HSCT. Through this case report, we emphasize the good initial response to chemotherapy, and the early relapse despite undergoing HSCT in first CR. We review the limited literature on NUP98::KDM5A (+) pediatric AML, and underscore the need for further study to improve the outcome of patients with this rare AML subtype.

Non-Down syndrome pediatric acute megakaryoblastic leukemia (AMKL) may be classified according to the presence of recurrent genetic abnormalities with prognostic relevance. In this case study, we report on a girl with AMKL, 32 months old at the time of diagnosis, in whom we confirmed the presence of the cryptic, poor prognosis NUP98::KDM5A fusion. The patient achieved complete remission (CR) with the first course of chemotherapy, underwent haploidentical family donor hematopoietic stem cell transplantation (HSCT) without event, but relapsed 5 months after HSCT. Through this case report, we emphasize the good initial response to chemotherapy, and the early relapse despite undergoing HSCT in first CR. We review the limited literature on NUP98::KDM5A (+) pediatric AML, and underscore the need for further study to improve the outcome of patients with this rare AML subtype.

Background/Aims: Cholangiocarcinoma frequently recurs even after curative resection. Expression levels of proteins such as epidermal growth factor receptor (EGFR), Snail, epithelial cadherin (E-cadherin), and interleukin-6 (IL-6) examined by immunohistochemistry have been studied as potential prognostic factors for cholangiocarcinoma. The aim of this study was to investigate significant factors affecting the prognosis of resectable cholangiocarcinoma. Methods: Ninety-one patients who underwent surgical resection at Samsung Medical Center for cholangiocarcinoma from 1995 to 2013 were included in this study. Expression levels of Ecadherin, Snail, IL-6, membranous EGFR, and cytoplasmic EGFR were analyzed by immunohistochemistry using tissue microarray blocks made from surgical specimens. Results: Patients with high levels of membranous EGFR in tissue microarrays had significantly shorter overall survival (OS) and disease-free survival (DFS): high membranous EGFR (score 0–2) 38.0 months versus low membranous EGFR (score 3) 14.4 months (p=0.008) and high membranous EGFR (score 0–2) 23.2 months versus low membranous EGFR (score 3) 6.1 months (p=0.004), respectively. On the other hand, E-cadherin, Snail, cytoplasmic EGFR, and IL-6 did not show significant association with OS or DFS. Patients with distant metastasis had significantly higher IL-6 levels than those with locoregional recurrence (p=0.01). Conclusions This study showed that overexpression of membranous EGFR was significantly associated with shorter OS and DFS in surgically resected bile duct cancer patients. In addition, higher IL-6 expression was a predictive marker for recurrence in cholangiocarcinoma patients with distant organ metastasis after surgical resection.

Background: This study aimed to evaluate whether fluvoxamine reduces clinical deterioration in adult patients with mild to moderate coronavirus disease 2019 (COVID-19), and to identify risk factors for clinical deterioration in patients admitted to a community treatment center (CTC). Materials and Methods: A randomized, placebo-controlled trial was conducted in a CTC, in Seoul, Korea from January 15, 2021, to February 19, 2021. Symptomatic adult patients with positive results of severe acute respiratory syndrome coronavirus 2 real timepolymerase chain reaction within 3 days of randomization were assigned at random to receive 100 mg of fluvoxamine or placebo twice daily for 10 days. The primary outcome was clinical deterioration defined by any of the following criteria: oxygen requirement to keep oxygen saturation over 94.0%, aggravation of pneumonia with dyspnea, or World Health Organization clinical progression scale 4 or greater. Results: Of 52 randomized participants [median (interquartile range) age, 53.5 (43.3 - 60.0) years; 31 (60.0%) men], 44 (85.0%) completed the trial. Clinical deterioration occurred in 2 of 26 patients in each group (P >0.99). There were no serious adverse events in either group. Clinical deterioration occurred in 15 (6.0%) of 271 patients admitted to the CTC, and all of them were transferred to a hospital. In multivariate analysis, age between 55 and 64, fever and pneumonia at admission were independent risk factors for clinical deterioration. Conclusion In this study of adult patients with symptomatic COVID-19 who were admitted to the CTC, there was no significant differences in clinical deterioration between patients treated with fluvoxamine and placebo (ClinicalTrials.gov Identifier: NCT04711863).

Multisystem inflammatory disease in children is a Kawasaki disease like illness occurring after severe acute respiratory syndrome coronavirus 2 infection in children. As the pandemic progresses, similar syndromes were also reported in adult with a decreased incidence.Multisystem inflammatory syndrome in adults (MIS-A) can be characterized with shock, heart failure, and gastrointestinal symptoms with elevated inflammatory markers after coronavirus disease 2019 (COVID-19) infection. Herein, we describe the first case of MIS-A in South Korea. A 38-year-old man presented to our hospital with a 5-day history of abdominal pain and fever. He had been treated with antibiotics for 5 days at the previous hospital, but symptoms had worsened and he had developed orthopnea on the day of presentation.He suffered COVID-19 six weeks ago. Laboratory data revealed elevated white blood cell counts with neutrophil dominance, C-reactive protein, and B-type natriuretic peptide. Chest X-ray showed normal lung parenchyme and echocardiography showed severe biventricular failure with normal chamber size. We diagnosed him as MIS-A and treated with intravenous immunoglobulin and steroid.