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.

This study examined the variability in the length of stay (LOS) and daily medical expenses (DME) for hypertension and pneumonia inpatient care. Using 10 years of National Health Insurance Service data (2010–2019), a multilevel analysis assessed variability at the patient and institutional levels. During the study period, the mean LOS decreased, whereas the DME increased for both hypertension and pneumonia. Institutional level variability in the LOS increased during the study period, demonstrating greater variability than that for pneumonia. For both conditions, institutional-level variability was more marked in smaller institutions (hospitals and clinics) than in larger institutions (general and tertiary hospitals).These findings indicate a need for standardized healthcare service protocols to promote consistent and efficient patient care.

Background: Patients with diabetic hindfoot ulcers typically harbor significant concerns regarding their prospects for healing or the potential for major amputation. Nonetheless, a scarcity of data addressing this prevalent and critical query exists. Thus, the aim of this study was to create an initial risk-scoring system to forecast the prognosis of individuals with diabetic hindfoot ulcers, leveraging assessments of ischemia and infection severity, which are recognized as the principal risk factors for amputation. Methods: Ischemia severity was categorized as iS0, iS1, or iS2 based on transcutaneous partial oxygen tension values, while infection severity was classified as iN0, iN1, or iN2 according to the results of tissue and bone biopsy cultures. Risk scores were determined by summing the scores for ischemia and infection severity, yielding a range of 0 to 4. Wound healing outcomes were graded as either healed with or without major amputation. Wound healing outcomes were assessed based on the assigned risk scores. Results: With ascending risk scores, the proportion of patients subjected to major amputation also increased (P value for trend < 0.001). Univariable logistic regression analysis revealed a significant positive correlation between escalating risk scores and major amputation incidence. Patients with a risk score of 4 exhibited a 41-fold higher likelihood of undergoing major amputation compared to those with a risk score of 0. Conclusion Risk scores can serve as a reliable predictor of the major amputation rate in patients with diabetic hindfoot ulcers.

This case report investigates the effects of semi-occluded vocal tract exercises (SOVTEs) on voice improvement in elderly female patients with presbyphonia. Elderly female patients with presbyphonia commonly present with symptoms such as hoarseness, decreased vocal intensity, and phonatory difficulties. These symptoms are often associated with age-related vocal fold atrophy, leading to compensatory muscle tension and inefficient phonation, which necessitate targeted therapeutic interventions. In this study, two elderly female patients, aged 73 years and 71 years, participated in a voice therapy program centered on SOVTEs designed to promote vocal fold vibration efficiency and reduce compensatory tension. Case 1 underwent five therapy sessions, while Case 2 completed sixteen sessions. Pre- and post-treatment voice assessments revealed notable improvements in vocal quality, suggesting that SOVTEs may be an effective therapeutic approach for managing presbyphonia in elderly women.

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.

This study examined the variability in the length of stay (LOS) and daily medical expenses (DME) for hypertension and pneumonia inpatient care. Using 10 years of National Health Insurance Service data (2010–2019), a multilevel analysis assessed variability at the patient and institutional levels. During the study period, the mean LOS decreased, whereas the DME increased for both hypertension and pneumonia. Institutional level variability in the LOS increased during the study period, demonstrating greater variability than that for pneumonia. For both conditions, institutional-level variability was more marked in smaller institutions (hospitals and clinics) than in larger institutions (general and tertiary hospitals).These findings indicate a need for standardized healthcare service protocols to promote consistent and efficient patient care.

Background: Patients with diabetic hindfoot ulcers typically harbor significant concerns regarding their prospects for healing or the potential for major amputation. Nonetheless, a scarcity of data addressing this prevalent and critical query exists. Thus, the aim of this study was to create an initial risk-scoring system to forecast the prognosis of individuals with diabetic hindfoot ulcers, leveraging assessments of ischemia and infection severity, which are recognized as the principal risk factors for amputation. Methods: Ischemia severity was categorized as iS0, iS1, or iS2 based on transcutaneous partial oxygen tension values, while infection severity was classified as iN0, iN1, or iN2 according to the results of tissue and bone biopsy cultures. Risk scores were determined by summing the scores for ischemia and infection severity, yielding a range of 0 to 4. Wound healing outcomes were graded as either healed with or without major amputation. Wound healing outcomes were assessed based on the assigned risk scores. Results: With ascending risk scores, the proportion of patients subjected to major amputation also increased (P value for trend < 0.001). Univariable logistic regression analysis revealed a significant positive correlation between escalating risk scores and major amputation incidence. Patients with a risk score of 4 exhibited a 41-fold higher likelihood of undergoing major amputation compared to those with a risk score of 0. Conclusion Risk scores can serve as a reliable predictor of the major amputation rate in patients with diabetic hindfoot ulcers.

Previous studies have shown that testosterone activates the GPRC6A-Duox1 axis, resulting in the production of H 2O 2 which leads to the apoptosis of keratinocytes and ultimately hair loss. Here, we elucidated a molecular mechanism by which the non-genomic action of testosterone regulates cellular redox status in androgenetic alopecia (AGA). Building upon this molecular understanding, we conducted a high-throughput screening assay of Nox inhibitors from a natural compounds library. This screening identified diterpenoid compounds, specifically Tanshinone I, Tanshinone IIA, Tanshinone IIB, and Cryptotanshinone, derived from Salviae Miltiorrhizae Radix. The IC50 values for Nox isozymes were found to be 2.6-12.9 μM for Tanshinone I, 1.9-7.2 μM for Tanshinone IIA, 5.2-11.9 μM for Tanshinone IIB, and 2.1-7.9 μM for Cryptotanshinone. Furthermore, 3D computational docking analysis confirmed the structural basis by which Tanshinone compounds inhibit Nox activity. These compounds were observed to substitute for NADPH at the π-π bond site between NADPH and FAD, leading to the suppression of Nox activity. Notably, Tanshinone I and Tanshinone IIA effectively inhibited Nox activity heightened by testosterone, consequently reducing the production of intracellular H2O2 and preventing cell apoptosis. In an animal study involving the application of testosterone to the back skin of 8-week-old C57BL/6J mice to inhibit hair growth, subsequent treatment with Tanshinone I or Tanshinone IIA alongside testosterone resulted in a substantial increase in hair follicle length compared to testosterone treatment alone. These findings underscore the potential efficacy of Tanshinone I and Tanshinone IIA as therapeutic agents for AGA by inhibiting Nox activity.

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.

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.