Background: Barriers to treatment with intravenous thrombolysis (IVT) for patients with acute ischemic stroke (AIS) in South Korea remain incompletely characterized. We analyze a nationwide prospective cohort to determine patient-level features associated with delayed presentation and non-treatment of potential IVT-eligible patients. Methods: We identified consecutive patients with AIS from 01/2011 to 08/2023 from a multicenter and prospective acute stroke registry in Korea. Patients were defined as IVT candidates if they presented within 4.5 hours from the last known well, had no lab evidence of coagulopathy, and had National Institute of Health Stroke Scale (NIHSS) ≥ 4. Multivariable generalized linear mixed regression models were used to investigate the associations between their characteristics and the IVT candidates or the use of IVT among the candidates. Results: Among 84,103 AIS patients, 41.0% were female, with a mean age of 69 ± 13 years and presentation NIHSS of 4 [interquartile range, 1–8]. Out of these patients, 13,757 (16.4%) were eligible for IVT, of whom 8,179 (59.5%) received IVT. Female sex (adjusted risk ratio [RR], 0.90; 95% confidence interval [CI], 0.86–0.94) and lower years of education (adjusted RR, 0.90; 95% CI, 0.84–0.97 for 0–3 years, compared to ≥ 13 years) were associated with a decreased likelihood of presenting as eligible for IVT after AIS; meanwhile, young age (adjusted RR, 1.12; 95% CI, 1.01–1.24 for ≤ 44 years, compared to 75–84 years) was associated with an increased likelihood of being an IVT candidate. Among those who were eligible for IVT, only age was significantly associated with the use of IVT (adjusted RR, 1.09; 95% CI, 1.03–1.16 for age 65–74 and adjusted RR, 0.83; 95% CI, 0.76–0.90 for ≥ 85 years, respectively). Conclusion Most patients with AIS present outside IVT eligibility in South Korea, and only 60% of eligible patients were ultimately treated. We identified increased age, female sex and lower education as key features on which to focus interventions for improving IVT utilization.

Background: With growing elderly populations, management of patients with acute stroke is increasingly important. In South Korea, the Acute Stroke Quality Assessment Program (ASQAP) has contributed to improving the quality of stroke care and practice behavior in healthcare institutions. While the mortality of hemorrhagic stroke remains high, there are only a few assessment indices associated with hemorrhagic stroke. Considering the need to develop assessment indices to improve the actual quality of care in the field of acute stroke treatment, this study aims to investigate the current status of human resources and practices related to the treatment of patients with acute stroke through a nationwide survey. Methods: For the healthcare institutions included in the Ninth ASQAP of the Health Insurance Review and Assessment Service (HIRA), data from January 2022 to December 2022 were collected through a survey on the current status and practice of healthcare providers related to the treatment of patients with acute stroke. The questionnaire consisted of 19 items, including six items on healthcare providers involved in stroke care and 10 items on the care of patients with acute stroke. Results: In the treatment of patients with hemorrhagic stroke among patients with acute stroke, neurosurgeons were the most common providers. The contribution of neurosurgeons in the treatment of ischemic stroke has also been found to be equivalent to that of neurologists. However, a number of institutions were found to be devoid of healthcare providers who perform definitive treatments, such as intra-arterial thrombectomy for patients with ischemic stroke or cerebral aneurysm clipping for subarachnoid hemorrhage. The intensity of the workload of healthcare providers involved in the care of patients with acute stroke, especially those involved in definitive treatment, was also found to be quite high. Conclusion Currently, there are almost no assessment indices specific to hemorrhagic stroke in the ASQAP for acute stroke. Furthermore, it does not reflect the reality of the healthcare providers and practices that provide definitive treatment for acute stroke. The findings of this study suggest the need for the development of appropriate assessment indices that reflect the realities of acute stroke care.

Background: Though accumulating evidence suggests an association between childhood trauma and anhedonia, further analysis is needed to consider specific traumatic dimensions, both traits and state anhedonia, and the role of circulating proteins. Therefore, this study investigated the association between different types of childhood traumas and their influence on anhedonia-related symptoms, and to evaluate the influence of anhedonia traits and plasma proteins as mediators. Methods: This study included 170 patients with schizophrenia, bipolar disorder, major depressive disorder, and healthy controls aged 19–65 years. Multiple reaction monitoring was performed to quantify plasma proteins, and 464 proteins were analyzed. The association between childhood trauma dimensions, anhedonic traits, and related symptoms was analyzed with linear regression. A series of mediation analyses was performed to determine whether anhedonic traits and plasma proteins mediated the association between childhood trauma and anhedonia-related symptoms. Results: Childhood emotional neglect was significantly associated with anhedonic traits and anhedonia-related symptoms. Mediation analysis revealed that the indirect effect of anhedonic traits for childhood emotional neglect on anhedonia-related symptoms (effect = 0.037; bias-corrected CI, 0.009 to 0.070) was statistically significant. The indirect effect of plasma TNR5 for anhedonic traits on anhedonia-related symptoms was statistically significant (effect = −0.011; bias-corrected CI, −0.026 to −0.002). Serial mediation analysis revealed that the indirect effect of childhood emotional neglect on anhedonia-related symptoms via anhedonic traits and TNR5 was statistically significant (effect = 0.007; biascorrected CI, 0.001 to 0.017). Conclusion Anhedonic traits and plasma TNR5 protein levels serially mediated the association between childhood emotional neglect and anhedonia-related symptoms.The study highlights the importance of considering both psychopathological traits and biological correlates when investigating the association between childhood trauma and psychopathological symptoms.

Background/Aims: Fexuprazan, a novel potassium-competitive acid blocker, was developed for treating acid-related disorders. Pharmacokinetic and pharmacodynamic properties of fexuprazan, unlike those of proton pump inhibitors, are independent of food effect. This study aims to evaluate differences in efficacy and safety of fexuprazan in patients with erosive esophagitis (EE) according to the timing of dosing. Methods: In this multicenter, open-label noninferiority study, patients who had typical reflux symptoms with endoscopically confirmed EE were randomized 1:1 to receive fexuprazan 40 mg daily 30 minutes before or after meal. Treatment was completed after 2 weeks or 4 weeks when healing was endoscopically confirmed. The primary endpoint was the proportion of patients with healed EE confirmed by endoscopy up to week 4. Safety endpoints included treatment-emergent adverse events (TEAEs). Results: In the prior-to-meal group (n = 89) and after-meal group (n = 86), 4-week EE healing rates were 98.77% and 100.00% (difference, 0.01%; 95% CI, –0.01% to 0.04%) and 2-week EE healing rates were 95.77% and 97.14% (difference, 0.01%; 95% CI, –0.05% to 0.07%), respectively. TEAEs were 9.78% and 8.70% in the prior-to-meal group and the after-meal group, respectively. Conclusions Non-inferiority analysis revealed that taking fexuprazan after meal was non-inferior to taking fexuprazan before meals in patients with EE. The frequency of adverse events was similar between the 2 study groups. The drug is safe and effective for healing EE regardless of the timing of dosing.

Background: Given the association between nonalcoholic fatty liver disease and metabolic risks, a new term, metabolic dysfunction- associated steatotic liver disease (MASLD) has been proposed. We aimed to explore the association between MASLD and all-cause, cause-specific mortalities. Methods: We included individuals with steatotic liver disease (SLD) from the Korean National Health Insurance Service. Moreover, SLD was defined as a fatty liver index ≥30. Furthermore, MASLD, metabolic alcohol-associated liver disease (MetALD), and alcoholic liver disease (ALD) with metabolic dysfunction (MD) were categorized based on alcohol consumption and MD. We also analyzed all-cause, liver-, cancer-, hepatocellular carcinoma (HCC)- and cardiovascular (CV)-related mortalities. Results: This retrospective nationwide cohort study included 1,298,993 individuals aged 40 to 79 years for a mean follow-up duration of 9.04 years. The prevalence of MASLD, MetALD, and ALD with MD was 33.11%, 3.93%, and 1.00%, respectively. Relative to the “no SLD” group, multivariable analysis identified that MASLD (adjusted hazard ratio [aHR], 1.28; 95% confidence interval [CI], 1.26 to 1.31), MetALD (aHR, 1.38; 95% CI, 1.32 to 1.44), and ALD with MD group (aHR, 1.80; 95% CI, 1.68 to 1.93) have a significantly higher risk of all-cause mortality. Furthermore, MASLD, MetALD, ALD with MD groups showed higher liver-, cancer- and HCC-related mortality than “no SLD” group. While all-cause specific mortalities increase from MASLD to MetALD to ALD with MD, the MetALD group shows a lower risk of CV-related mortality compared to MASLD. However, ALD with MD group still have a higher risk of CV-related mortality compared to MASLD. Conclusion SLD is associated with an increased risk of all-cause, liver-, cancer-, HCC-, and CV-related mortalities.

Background: We aimed to investigate the predictive values of plasma C-peptide levels and the continuous glucose monitoring (CGM)-defined coefficient of variation (CV) in risk prediction for hypoglycemia in Korean people with diabetes with normal and impaired kidney function. Methods: We analyzed data from 1,185 participants diagnosed with type 1 and type 2 diabetes who underwent blinded professional CGM between January 2009 and May 2021 at outpatient clinics. We explored correlations among CGM-defined CV, plasma C-peptide levels, and time below range at <70 and 54 mg/dL across different kidney function categories. Results: In patients with chronic kidney disease (CKD) stages 1–2 (n=934), 89.3% who had a random plasma C-peptide level higher than 600 pmol/L exhibited a CV of ≤36%. Among those in CKD stage 3 (n=161) with a random plasma C-peptide level exceeding 600 pmol/L, 66.7% showed a CV of ≤36%. In stages 4–5 of CKD (n=90), the correlation between random C-peptide levels and CV was not significant (r=–0.05, P=0.640), including cases with a CV greater than 36% despite very high random plasma C-peptide levels. Random plasma C-peptide levels and CGM-assessed CV significantly predicted hypoglycemia in CKD stages 1–2 and 1–5, respectively. Conclusion The established C-peptide criteria in Western populations are applicable to Korean people with diabetes for hypoglycemic risk prediction, unless kidney function is impaired equivalent to CKD stage 3–5. The CGM-defined CV is informative for hypoglycemic risk prediction regardless of kidney function.

Purpose: Surgical resection is the primary curative treatment for gastrointestinal (GI) cancer; however, it is associated with high postoperative complication rates and impaired recovery. Frailty, malnutrition, and sarcopenia increase morbidity and mortality, underscoring the need for perioperative rehabilitation programs. Standardized rehabilitation protocols during the perioperative period are currently lacking in Korea. We aimed to develop an evidence-based rehabilitation protocol for GI cancer patients to enhance postoperative outcomes and facilitate clinical implementation. Methods: A multidisciplinary task force team comprising experts in surgery, clinical nutrition, and rehabilitation medicine conducted a systematic literature search and comprehensive review from 2012 to 2022 to develop a standardized pre- and re-habilitation protocol for GI cancer surgery. The protocol underwent external validation and subsequent refinements before being finalized through expert consensus. Results: The protocol development process was organized into four consecutive phases: keyword selection, literature review and case report form development, initial protocol drafting, and external validation leading to the final version of the protocol. The final version of the rehabilitation protocol is presented in the main text and included as Supplements. Conclusion This protocol provides a standardized clinical guideline based on the latest evidence-based pre- and re-habilitation strategies and is designed for seamless integration into routine clinical practice. By facilitating proactive rehabilitation interventions, it aims to improve outcomes in GI cancer patients who are at high risk of postoperative complications, functional decline, and malnutrition.

Radiation-induced cavernous malformations (RICMs) are rare but significant late complications of highdose radiation therapy, particularly in young survivors of brain tumors. This report presents two cases of RICMs following aggressive multimodal treatment, including surgery, chemotherapy, and radiation therapy. Case 1 was a 22-year-old male patient with medulloblastoma treated with craniospinal irradiation, tumor bed boost, and tandem autologous peripheral blood stem cell transplantation. Approximately 8 years after treatment completion, routine follow-up imaging revealed a small focal hemorrhage in the right cerebellum, consistent with an RICM. The lesion was asymptomatic and managed conservatively with regular imaging, showing spontaneous resolution over time, with a significant size reduction noted 9 years post-treatment. Case 2 describes a 32-year-old male with an intracranial germinoma treated with whole-ventricular irradiation. Three years after treatment, the patient developed a symptomatic hemorrhagic RICM near a pre-existing developmental venous anomaly. Surgical resection and Gamma Knife Surgery stabilized the lesion; however, residual symptoms, including tremors and gait disturbances, persisted, affecting the patient’s daily activities. These cases illustrate the diverse clinical courses of RICMs, ranging from spontaneous resolution to the necessity of surgical intervention, and emphasize the importance of long-term surveillance and tailored management strategies for late-onset complications.

Background: Barriers to treatment with intravenous thrombolysis (IVT) for patients with acute ischemic stroke (AIS) in South Korea remain incompletely characterized. We analyze a nationwide prospective cohort to determine patient-level features associated with delayed presentation and non-treatment of potential IVT-eligible patients. Methods: We identified consecutive patients with AIS from 01/2011 to 08/2023 from a multicenter and prospective acute stroke registry in Korea. Patients were defined as IVT candidates if they presented within 4.5 hours from the last known well, had no lab evidence of coagulopathy, and had National Institute of Health Stroke Scale (NIHSS) ≥ 4. Multivariable generalized linear mixed regression models were used to investigate the associations between their characteristics and the IVT candidates or the use of IVT among the candidates. Results: Among 84,103 AIS patients, 41.0% were female, with a mean age of 69 ± 13 years and presentation NIHSS of 4 [interquartile range, 1–8]. Out of these patients, 13,757 (16.4%) were eligible for IVT, of whom 8,179 (59.5%) received IVT. Female sex (adjusted risk ratio [RR], 0.90; 95% confidence interval [CI], 0.86–0.94) and lower years of education (adjusted RR, 0.90; 95% CI, 0.84–0.97 for 0–3 years, compared to ≥ 13 years) were associated with a decreased likelihood of presenting as eligible for IVT after AIS; meanwhile, young age (adjusted RR, 1.12; 95% CI, 1.01–1.24 for ≤ 44 years, compared to 75–84 years) was associated with an increased likelihood of being an IVT candidate. Among those who were eligible for IVT, only age was significantly associated with the use of IVT (adjusted RR, 1.09; 95% CI, 1.03–1.16 for age 65–74 and adjusted RR, 0.83; 95% CI, 0.76–0.90 for ≥ 85 years, respectively). Conclusion Most patients with AIS present outside IVT eligibility in South Korea, and only 60% of eligible patients were ultimately treated. We identified increased age, female sex and lower education as key features on which to focus interventions for improving IVT utilization.

Background: With growing elderly populations, management of patients with acute stroke is increasingly important. In South Korea, the Acute Stroke Quality Assessment Program (ASQAP) has contributed to improving the quality of stroke care and practice behavior in healthcare institutions. While the mortality of hemorrhagic stroke remains high, there are only a few assessment indices associated with hemorrhagic stroke. Considering the need to develop assessment indices to improve the actual quality of care in the field of acute stroke treatment, this study aims to investigate the current status of human resources and practices related to the treatment of patients with acute stroke through a nationwide survey. Methods: For the healthcare institutions included in the Ninth ASQAP of the Health Insurance Review and Assessment Service (HIRA), data from January 2022 to December 2022 were collected through a survey on the current status and practice of healthcare providers related to the treatment of patients with acute stroke. The questionnaire consisted of 19 items, including six items on healthcare providers involved in stroke care and 10 items on the care of patients with acute stroke. Results: In the treatment of patients with hemorrhagic stroke among patients with acute stroke, neurosurgeons were the most common providers. The contribution of neurosurgeons in the treatment of ischemic stroke has also been found to be equivalent to that of neurologists. However, a number of institutions were found to be devoid of healthcare providers who perform definitive treatments, such as intra-arterial thrombectomy for patients with ischemic stroke or cerebral aneurysm clipping for subarachnoid hemorrhage. The intensity of the workload of healthcare providers involved in the care of patients with acute stroke, especially those involved in definitive treatment, was also found to be quite high. Conclusion Currently, there are almost no assessment indices specific to hemorrhagic stroke in the ASQAP for acute stroke. Furthermore, it does not reflect the reality of the healthcare providers and practices that provide definitive treatment for acute stroke. The findings of this study suggest the need for the development of appropriate assessment indices that reflect the realities of acute stroke care.