Background/Aims: A clinical unmet need persists for medications capable of modulating the progression of primary sclerosing cholangitis (PSC). This study aimed to assess the clinical feasibility of HK-660S (beta-lapachone) in PSC. Methods: In this multicenter, randomized, double-blind, placebo-controlled, parallel-group phase 2 trial, participants were assigned in a 2:1 ratio to receive either 100 mg of HK-660S or a placebo twice daily for 12 weeks. The primary outcomes were the reduction in serum alkaline phosphatase (ALP) levels and the percentage of participants showing improvements in PSC severity, as determined by magnetic resonance cholangiopancreatography with the Anali score. Secondary endpoints included changes in liver stiffness and adverse events. Results: The analysis included 21 patients, 15 receiving HK-660S, and six receiving a placebo. Improvements in the Anali score were observed in 13.3% of the HK-660S group, with no improvements in the placebo group. HK-660S treatment resulted in a 15.2% reduction in mean ALP levels, compared to a 6.6% reduction in the placebo group. A stratified ad-hoc analysis based on baseline ALP levels showed a statistically significant response in the HK-660S group among those with ALP levels greater than twice the upper limit of normal, with a 50% responder rate (p=0.05). Additionally, 26.7% of the HK-660S group showed improvements in the enhanced liver fibrosis score, with no improvements in the placebo group. HK-660S was generally well tolerated. Conclusions HK-660S is well tolerated among patients with PSC and may improve bile duct strictures, decrease serum ALP levels, and reduce liver fibrosis (cris.nih.go.kr, Number KCT0006590).

Systemic sclerosis (SSc), or scleroderma, is a complex autoimmune connective tissue disease characterized by autoimmunity, vasculopathy, and progressive organ fibrosis, leading to severe organ dysfunction. The disease begins with a vascular injury triggered by autoimmune responses and environmental factors against a backdrop of genetic predisposition. This injury impairs angiogenesis and vasculogenesis, resulting in capillary loss and arteriolar constriction, which promotes immune cell infiltration and sustained inflammation within affected tissues. These vascular anomalies cause severe complications, including pulmonary artery hypertension, scleroderma renal crisis, and skin ulcers. Chronic inflammation fosters persistent fibroblast activation, resulting in extensive fibrosis that defines SSc. This review synthesizes the latest research on pathogenesis of SSc, highlighting the shift from fundamental research to a precision therapeutic approach. It explores the potential of technologies like flow cytometry and singlecell RNA sequencing to investigate pathogenic cell subtypes. These platforms integrate transcriptomic, genomic, proteomic, and epigenomic data to uncover insights into the underlying mechanisms of SSc pathogenesis. This review advocates for a multidisciplinary, patient-centric approach that harnesses recent scientific advances, directing future SSc research toward personalized and precise interventions.

Background: and Purpose Previous research on patients with acute ischemic stroke (AIS) has shown a 0.5% incidence of major gastrointestinal bleeding (GIB) requiring blood transfusion during hospitalization. The existing literature has insufficiently explored the long-term incidence in this population despite the decremental impact of GIB on stroke outcomes. Methods: We analyzed the data from a cohort of patients with AIS admitted to 14 hospitals as part of a nationwide multicenter prospective stroke registry between 2011 and 2013. These patients were followed up for up to 6 years. The occurrence of major GIB events, defined as GIB necessitating at least two units of blood transfusion, was tracked using the National Health Insurance Service claims data. Results: Among 10,818 patients with AIS (male, 59%; mean age, 68±13 years), 947 (8.8%) experienced 1,224 episodes of major GIB over a median follow-up duration of 3.1 years. Remarkably, 20% of 947 patients experienced multiple episodes of major GIB. The incidence peaked in the first month after AIS, reaching 19.2 per 100 person-years, and gradually decreased to approximately one-sixth of this rate by the 2nd year with subsequent stabilization. Multivariable analysis identified the following predictors of major GIB: anemia, estimated glomerular filtration rate <60 mL/min/1.73 m2 , and a 3-month modified Rankin Scale score of ≥4. Conclusion Patients with AIS are susceptible to major GIB, particularly in the first month after the onset of AIS, with the risk decreasing thereafter. Implementing preventive strategies may be important, especially for patients with anemia and impaired renal function at stroke onset and those with a disabling stroke.

Objective: To assess the feasibility of ultrafast brain magnetic resonance imaging (MRI) in pediatric patients. Materials and Methods: We retrospectively reviewed 194 pediatric patients aged 0 to 19 years (median 10.2 years) who underwent both ultrafast and conventional brain MRI between May 2019 and August 2020. Ultrafast MRI sequences included T1 and T2-weighted images (T1WI and T2WI), fluid-attenuated inversion recovery (FLAIR), T2*-weighted image (T2*WI), and diffusion-weighted image (DWI). Qualitative image quality and lesion evaluations were conducted on 5-point Likert scales by two blinded radiologists, with quantitative assessment of lesion count and size on T1WI, T2WI, and FLAIR sequences for each protocol. Wilcoxon signed-rank tests and intraclass correlation coefficient (ICC) analyses were used for comparison. Results: The total scan times for equivalent image contrasts were 1 minute 44 seconds for ultrafast MRI and 15 minutes 30 seconds for conventional MRI. Overall, image quality was lower in ultrafast MRI than in conventional MRI, with mean quality scores ranging from 2.0 to 4.8 for ultrafast MRI and 4.8 to 5.0 for conventional MRI across sequences (P < 0.001 for T1WI, T2WI, FLAIR, and T2*WI for both readers; P = 0.018 [reader 1] and 0.031 [reader 2] for DWI). Lesion detection rates on ultrafast MRI relative to conventional MRI were as follows: T1WI, 97.1%; T2WI, 99.6%; FLAIR, 92.9%; T2*WI, 74.1%; and DWI, 100%. The ICC (95% confidence interval) for lesion size measurements between ultrafast and conventional MRI was as follows: T1WI, 0.998 (0.996–0.999); T2WI, 0.998 (0.997–0.999); and FLAIR, 0.99 (0.985–0.994). Conclusion Ultrafast MRI significantly reduces scan time and provides acceptable results, albeit with slightly lower image quality than conventional MRI, for evaluating intracranial abnormalities in pediatric patients.

Helicobacter pylori causes gastric cancer and peptic ulcers, and eradication therapy can reduce the incidence of cancer in high-risk groups. In Korea, discrepancies between the reimbursement criteria and clinical guidelines create clinical challenges. This study investigated the perceptions and practices of experts regarding H. pylori testing during upper gastrointestinal endoscopy and any subsequent eradication therapy. An anonymous 8-question survey was conducted among 51 experts attending the 2024 Korean College of Helicobacter and Upper Gastrointestinal Research Summer Workshop. Only 2% of the experts tested all patients. Testing was performed in 54% of patients with a family history of gastric cancer, 32% of those with atrophic gastritis, 42% of those with dyspeptic symptoms, and 62% of those with iron-deficiency anemia. Among patients with suspected infections (based on endoscopic findings) and eligible for selective reimbursement, 82% underwent H. pylori testing. Age did not influence testing decisions for 60% of the experts, and 57% considered factors other than age when deciding on eradication therapy. The practices of the experts varied depending on the patient’s clinical condition and economic burden. Aligning clinical guidelines with the reimbursement criteria is necessary to reduce confusion and ensure appropriate patient care.

Background/Aims: To determine the effectiveness of tyrosine kinase inhibitor (TKI) plus reduced-intensity therapy in adult patients with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-positive ALL), this retrospective study compared treatment outcomes and induction mortality according to backbone regimen intensity. Methods: The data of 132 patients diagnosed with Ph-positive ALL were retrospectively collected from five centers. Patients received imatinib plus intensive chemotherapy (modified VPD, KALLA1407, or hyper-CVAD) or reduced-intensity chemotherapy (EWALL) for curative purposes. This study analyzed 117 patients, of which 35,22,46, and 14 received modified VPD, KALLA1407, hyper-CVAD, and EWALL, respectively. All patients used imatinib as a TKI. Results: The median age of the patients who received reduced-intensity chemotherapy was 64.4 years, while that of the patients with intensive regimens was 47.5 years. There was no induction death in the reduced-intensity group, while nine patients died in the intensive therapy group. Major molecular response achievement tended to be higher in the intensive chemotherapy group than in the reduced-intensity group. More patients in the intensive chemotherapy group received allogeneic stem cell transplantation (allo-SCT). There was no statistically significant difference in long-term survival between the two groups in terms of relapse-free survival and overall survival rates. Conclusions When imatinib plus reduced-intensity therapy was used as a frontline treatment, there was no inferiority in obtaining complete remission compared to imatinib plus intensive chemotherapy or significant difference in long-term survival. Since imatinib plus reduced-intensity therapy has limitations in obtaining a deep molecular response, proceeding to allo-SCT should be considered.

Cynaropicrin, a sesquiterpene lactone found in artichoke leaves exerts diverse pharmacological effects. This study investigated whether cynaropicrin has a paraptosis-like cell death effect in human hepatocellular carcinoma Hep3B cells in addition to the apoptotic effects reported in several cancer cell lines. Cynaropicrin-induced cytotoxicity and cytoplasmic vacuolation, a key characteristic of paraptosis, were not ameliorated by inhibitors of necroptosis, autophagy, or pan caspase inhibitors in Hep3B cells. Our study showed that cynaropicrin-induced cytotoxicity was accompanied by mitochondrial dysfunction and endoplasmic reticulum stress along with increased cellular calcium ion levels. These effects were significantly mitigated by endoplasmic reticulum stress inhibitor or protein synthesis inhibitor. Moreover, cynaropicrin treatment in Hep3B cells increased reactive oxygen species generation and downregulated apoptosis-linked gene 2-interacting protein X (Alix), a protein that inhibits paraptosis. The addition of the reactive oxygen species scavenger N-acetyl-L-cysteine (NAC) neutralized cynaropicrin-induced changes in Alix expression and endoplasmic reticulum stress marker proteins counteracting endoplasmic reticulum stress and mitochondrial impairment. This demonstrates a close relationship between endoplasmic reticulum stress and reactive oxygen species generation. Additionally, cynaropicrin activated p38 mitogen activated protein kinase and a selective p38 mitogen activated protein kinase blocker alleviated the biological phenomena induced by cynaropicrin. NAC pretreatment showed the best reversal of cynaropicrin induced vacuolation and cellular inactivity. Our findings suggest that cynaropicrin induced oxidative stress in Hep3B cells contributes to paraptotic events including endoplasmic reticulum stress and mitochondrial damage.

Objective: To assess the feasibility of ultrafast brain magnetic resonance imaging (MRI) in pediatric patients. Materials and Methods: We retrospectively reviewed 194 pediatric patients aged 0 to 19 years (median 10.2 years) who underwent both ultrafast and conventional brain MRI between May 2019 and August 2020. Ultrafast MRI sequences included T1 and T2-weighted images (T1WI and T2WI), fluid-attenuated inversion recovery (FLAIR), T2*-weighted image (T2*WI), and diffusion-weighted image (DWI). Qualitative image quality and lesion evaluations were conducted on 5-point Likert scales by two blinded radiologists, with quantitative assessment of lesion count and size on T1WI, T2WI, and FLAIR sequences for each protocol. Wilcoxon signed-rank tests and intraclass correlation coefficient (ICC) analyses were used for comparison. Results: The total scan times for equivalent image contrasts were 1 minute 44 seconds for ultrafast MRI and 15 minutes 30 seconds for conventional MRI. Overall, image quality was lower in ultrafast MRI than in conventional MRI, with mean quality scores ranging from 2.0 to 4.8 for ultrafast MRI and 4.8 to 5.0 for conventional MRI across sequences (P < 0.001 for T1WI, T2WI, FLAIR, and T2*WI for both readers; P = 0.018 [reader 1] and 0.031 [reader 2] for DWI). Lesion detection rates on ultrafast MRI relative to conventional MRI were as follows: T1WI, 97.1%; T2WI, 99.6%; FLAIR, 92.9%; T2*WI, 74.1%; and DWI, 100%. The ICC (95% confidence interval) for lesion size measurements between ultrafast and conventional MRI was as follows: T1WI, 0.998 (0.996–0.999); T2WI, 0.998 (0.997–0.999); and FLAIR, 0.99 (0.985–0.994). Conclusion Ultrafast MRI significantly reduces scan time and provides acceptable results, albeit with slightly lower image quality than conventional MRI, for evaluating intracranial abnormalities in pediatric patients.

Helicobacter pylori causes gastric cancer and peptic ulcers, and eradication therapy can reduce the incidence of cancer in high-risk groups. In Korea, discrepancies between the reimbursement criteria and clinical guidelines create clinical challenges. This study investigated the perceptions and practices of experts regarding H. pylori testing during upper gastrointestinal endoscopy and any subsequent eradication therapy. An anonymous 8-question survey was conducted among 51 experts attending the 2024 Korean College of Helicobacter and Upper Gastrointestinal Research Summer Workshop. Only 2% of the experts tested all patients. Testing was performed in 54% of patients with a family history of gastric cancer, 32% of those with atrophic gastritis, 42% of those with dyspeptic symptoms, and 62% of those with iron-deficiency anemia. Among patients with suspected infections (based on endoscopic findings) and eligible for selective reimbursement, 82% underwent H. pylori testing. Age did not influence testing decisions for 60% of the experts, and 57% considered factors other than age when deciding on eradication therapy. The practices of the experts varied depending on the patient’s clinical condition and economic burden. Aligning clinical guidelines with the reimbursement criteria is necessary to reduce confusion and ensure appropriate patient care.