A 42-year-old female patient presented with a complete ear amputation resulting from a collision with a machine. The ear was avulsed by blunt trauma, meaning that it was torn away rather than being cleanly cut. Fortunately, the auricular cartilage remained intact and preserved its overall shape despite the amputation. However, the surrounding blood vessels were not suitable for microanastomosis. In the first-stage operation, the auricular cartilage was de-epithelialized and embedded into the postauricular area. Three months later, during the second-stage operation, the embedded auricular cartilage framework was elevated to achieve normal auricular projection. During the postoperative period, a customized mold based on the shape of the patient’s contralateral ear was fabricated using 3D printing technology and applied to the reconstructed ear to refine the contour and achieve a natural appearance. The overall outcome was favorable, with no complications observed during the postoperative care period.

It is extensively documented that tumor hypoxia contributes to the failure of chemotherapy and radiotherapy. Recent evidence suggests that hypoxia is also closely involved in the resistance to immunotherapy. In this review, we highlight how immune cells that are essential for the maximized immunotherapy efficacy, including cytotoxic T cells, dendritic cells, and natural killer cells, can adapt to tumor hypoxia. We then outline previous attempts targeting tumor hypoxia (for example, modulators of tumor cell oxygen consumption, perfusion modulators, hypoxia-activated prodrugs, hypoxia-inducible factor inhibitors, and hypoxia-responsive chimeric antigen receptor T cells) discussing how these approaches have resulted in an improvement of the antitumor response to immunotherapy in preclinical or clinical settings. Lastly, we review various non-invasive techniques to detect the tumor hypoxia and immune responses. We believe that an integration of the biological knowledge of immune cell adaptation to tumor hypoxia with the cutting edge non-invasive imaging technologies may ultimately allow us not only to select for patients who would benefit the most from the immunotherapy but also to monitor their responses in a real-time manner so that we can offer them an optimal personalized medicine in the clinic.

Background: and Purpose To compare the epidemiological and clinical features of the rare patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) with age- and sex-matched controls in a nationwide cohort from South Korea. Methods: This observational cohort study analyzed newly diagnosed CADASIL patients aged at least 20 years and matched controls using data from the National Health Information Database for 2004–2022. The cumulative incidence of CADASIL was assessed by age and sex, and compared between regions. Neurologic and systemic diseases were compared between the CADASIL and control groups. Results: The study analyzed 816 CADASIL patients and 816 age- and sex-matched controls aged 56.8±15.2 years (mean±standard deviation), among whom 48.3% were male. The cumulative incidence of CADASIL was 1.86 per 100,000 people (95% confidence interval [CI]=1.85– 1.87 per 100,000), and peaked at 60–69 years of age. In terms of regional distribution, the incidence was highest for Jeju, at 39.67 per 100,000 (95% CI 37.84–41.49 per 100,000). Neurologic diseases were more frequent in CADASIL patients, including Alzheimer’s disease (33.1% vs.20.0%), vascular dementia (84.9% vs. 5.0%), epilepsy (34.6% vs. 15.9%), stroke (70.7% vs. 27.6%), parkinsonism (18.9% vs. 11.0%), and depression (60.8% vs. 44.9%). Systemic diseases such as diabetes mellitus (78.9% vs. 68.9%) were also more common in CADASIL patients, while cancer (27.9% vs. 38.7%) and myocardial infarction (10.0% vs. 13.6%) were less common than in controls. The onset ages of all diseases were lower in CADASIL patients. Conclusions This study has provided a precise nationwide estimate of the CADASIL incidence and its regional distribution in South Korea. CADASIL patients showed higher incidence rates and earlier onsets of diverse clinical manifestations.

This report presents the latest statistics on the stroke population in South Korea, sourced from the Clinical Research Collaborations for Stroke in Korea-National Institute for Health (CRCS-K-NIH), a comprehensive, nationwide, multicenter stroke registry. The Korean cohort, unlike western populations, shows a male-to-female ratio of 1.5, attributed to lower risk factors in Korean women. The average ages for men and women are 67 and 73 years, respectively.Hypertension is the most common risk factor (67%), consistent with global trends, but there is a higher prevalence of diabetes (35%) and smoking (21%). The prevalence of atrial fibrillation (19%) is lower than in western populations, suggesting effective prevention strategies in the general population. A high incidence of large artery atherosclerosis (38%) is observed, likely due to prevalent intracranial arterial disease in East Asians and advanced imaging techniques.There has been a decrease in intravenous thrombolysis rates, from 12% in 2017–2019 to 10% in 2021, with no improvements in door-to-needle and door-to-puncture times, worsened by the coronavirus disease 2019 pandemic. While the use of aspirin plus clopidogrel for noncardioembolic stroke and direct oral anticoagulants for atrial fibrillation is well-established, the application of direct oral anticoagulants for non-atrial fibrillation cardioembolic strokes in the acute phase requires further research. The incidence of early neurological deterioration (13%) and the cumulative incidence of recurrent stroke at 3 months (3%) align with global figures. Favorable outcomes at 3 months (63%) are comparable internationally, yet the lack of improvement in dependency at 3 months highlights the need for advancements in acute stroke care.

Background: For acute ischemic stroke (AIS) patients with history of prior stroke (PS) and diabetes mellitus (DM), intravenous recombinant tissue plasminogen activator (IV-tPA) therapy in the 3- to 4.5-hour window is off-label in Korea. This study aimed to assess the safety and efficacy of IV-tPA in these patients. Methods: Using data from a prospective multicenter stroke registry between January 2009 and March 2021, we identified AIS patients who received IV-tPA in the 3- to 4.5-hour window, and compared the outcomes of symptomatic intracranial hemorrhage (SICH), 3-month mortality, 3-month modified Rankin Scale (mRS) score 0-1 and 3-month mRS distribution between patients with both PS and DM (PS/DM, n=56) versus those with neither PS nor DM, or with only one (non-PS/DM, n=927). Results: The PS/DM group versus the non-PS/DM group was more likely to have a prior disability, hypertension, hyperlipidemia, coronary heart disease and less likely to have atrial fibrillation. The PS/DM and the non-PS/DM groups had comparable rates of SICH (0% vs. 1.7%; p>0.999) and 3-month mortality (10.7% vs. 10.2%; p=0.9112). The rate of 3-month mRS 0-1 was non-significantly lower in the PS/DM group than in the non-PS/DM group (30.4% vs. 40.7%; adjusted odds ratio [95% confidence interval], 0.81 [0.41-1.59]). Conclusions In the 3- to 4.5-hour window, AIS patients with PS/DM, as compared to those with non-PS/DM, might benefit less from IV-tPA. However, given the similar risks of SICH and mortality, IV-tPA in the late time window could be considered in patients with both PS and DM.

Background: and Purpose Serum insulin-like growth factor-1 (IGF-1) is known to have a neuroprotective effect. This study aimed to determine the effects of serum IGF-1 on the severity and clinical outcome of acute ischemic stroke (AIS). Methods: This study included 446 patients with AIS who were admitted to Hallym University Sacred Heart Hospital within 7 days of stroke onset from February 2014 to June 2017. Serum IGF-1 levels were measured within 24 hours of admission. Stroke severity was measured using the National Institutes of Health Stroke Scale (NIHSS) score at admission, and the functional outcome at 3 months after symptom onset was assessed using the modified Rankin Scale score. The effects of serum IGF-1 levels on stroke severity and 3-month functional outcomes were analyzed using multivariate logistic regression analysis. Results: This study evaluated 379 patients with AIS (age 67.2±12.6 years, mean±standard deviation; 59.9% males) after excluding 67 patients who had a history of previous stroke (n=25) or were lost to follow-up at 3 months (n=42). After adjusting for clinically relevant covariates, a higher serum IGF-1 level was associated with a lower NIHSS score at admission (adjusted odds ratio=0.44, 95% confidence interval=0.24–0.80, p=0.01), while there was no significant association at 3 months. Conclusions This study showed that a higher serum IGF-1 level is associated with a lower NIHSS score at admission but not at 3 months. Further studies are required to clarify the usefulness of the serum IGF-1 level as a prognostic marker for ischemic stroke.

Background: and Purpose Serum insulin-like growth factor-1 (IGF-1) is known to have a neuroprotective effect. This study aimed to determine the effects of serum IGF-1 on the severity and clinical outcome of acute ischemic stroke (AIS). Methods: This study included 446 patients with AIS who were admitted to Hallym University Sacred Heart Hospital within 7 days of stroke onset from February 2014 to June 2017. Serum IGF-1 levels were measured within 24 hours of admission. Stroke severity was measured using the National Institutes of Health Stroke Scale (NIHSS) score at admission, and the functional outcome at 3 months after symptom onset was assessed using the modified Rankin Scale score. The effects of serum IGF-1 levels on stroke severity and 3-month functional outcomes were analyzed using multivariate logistic regression analysis. Results: This study evaluated 379 patients with AIS (age 67.2±12.6 years, mean±standard deviation; 59.9% males) after excluding 67 patients who had a history of previous stroke (n=25) or were lost to follow-up at 3 months (n=42). After adjusting for clinically relevant covariates, a higher serum IGF-1 level was associated with a lower NIHSS score at admission (adjusted odds ratio=0.44, 95% confidence interval=0.24–0.80, p=0.01), while there was no significant association at 3 months. Conclusions This study showed that a higher serum IGF-1 level is associated with a lower NIHSS score at admission but not at 3 months. Further studies are required to clarify the usefulness of the serum IGF-1 level as a prognostic marker for ischemic stroke.

Objective: To determine the factors affecting the amount of weight-bearing during gait training in the elderly patients who underwent internal fixation after femur or pelvic fractures and how well they performed the weight-bearing restriction as directed by the physiatrist. Methods: In this retrospective chart review study, we measured the amount of weight-bearing on the affected side in 50 patients undergoing internal fixation surgery and rehabilitation after femur or pelvic fracture using a force plate. Patients receiving non-weight-bearing or partial weight-bearing education were considered to perform weight-bearing restriction well when the amount of weight-bearing was <50 lb. Furthermore, regression analysis was performed to determine the effects of postoperative complications, age, cognitive function, and pain on weightbearing restriction. Results: Variables affecting the amount of weight-bearing were age (r=0.581, p<0.001), weight-bearing education type (r=0.671, p<0.001), manual muscle strength of hip flexion on the non-affected side (r=-0.296, p=0.037), hip abduction (r=-0.326, p=0.021), knee extension (r=-0.374, p=0.007), ankle plantar flexion (r=-0.374, p=0.008), right hand grip strength (r=-0.535, p<0.001), Korean version of Mini-Mental State Examination (r=-0.496, p<0.001), Clinical Dementia Rating (r=0.308, p=0.03), and pain visual analog scale scores (r=0.318, p=0.024). The significant predictor of the amount of weight-bearing among these variables was age (β=0.448, p=0.001). The weight-bearing restriction adherence rate was significantly lower, at 22%, for patients aged ≥65 years as compared to 73% for those <65 years. Conclusion Age was a major variable affecting the amount of weight-bearing. Compliance with weight-bearing restriction was significantly lower in patients aged ≥65 years than in patients <65 years.

In the brain, a reduction in extracellular osmolality causes water-influx and swelling, which subsequently triggers Cl⁻- and osmolytes-efflux via volume-regulated anion channel (VRAC). Although LRRC8 family has been recently proposed as the pore-forming VRAC which is activated by low cytoplasmic ionic strength but not by swelling, the molecular identity of the pore-forming swelling-dependent VRAC (VRAC(swell)) remains unclear. Here we identify and characterize Tweety-homologs (TTYH1, TTYH2, TTYH3) as the major VRAC(swell) in astrocytes. Gene-silencing of all Ttyh1/2/3 eliminated hypo-osmotic-solution-induced Cl⁻ conductance (I(Cl,swell)) in cultured and hippocampal astrocytes. When heterologously expressed in HEK293T or CHO-K1 cells, each TTYH isoform showed a significant I(Cl,swell) with similar aquaporin-4 dependency, pharmacological properties and glutamate permeability as I(Cl,swell) observed in native astrocytes. Mutagenesis-based structure-activity analysis revealed that positively charged arginine residue at 165 in TTYH1 and 164 in TTYH2 is critical for the formation of the channel-pore. Our results demonstrate that TTYH family confers the bona fide VRAC(swell) in the brain.
Arginine ; Astrocytes ; Brain ; Cytoplasm ; Glutamic Acid ; Humans ; Osmolar Concentration ; Permeability

BACKGROUND: Mutations in the KRAS gene have been identified in approximately 50% of colorectal cancers (CRCs). KRAS mutations are well established biomarkers in anti–epidermal growth factor receptor therapy. Therefore, assessment of KRAS mutations is needed in CRC patients to ensure appropriate treatment. METHODS: We compared the analytical performance of the cobas test to Sanger sequencing in 264 CRC cases. In addition, discordant specimens were evaluated by 454 pyrosequencing. RESULTS: KRAS mutations for codons 12/13 were detected in 43.2% of cases (114/264) by Sanger sequencing. Of 257 evaluable specimens for comparison, KRAS mutations were detected in 112 cases (43.6%) by Sanger sequencing and 118 cases (45.9%) by the cobas test. Concordance between the cobas test and Sanger sequencing for each lot was 93.8% positive percent agreement (PPA) and 91.0% negative percent agreement (NPA) for codons 12/13. Results from the cobas test and Sanger sequencing were discordant for 20 cases (7.8%). Twenty discrepant cases were subsequently subjected to 454 pyrosequencing. After comprehensive analysis of the results from combined Sanger sequencing–454 pyrosequencing and the cobas test, PPA was 97.5% and NPA was 100%. CONCLUSIONS: The cobas test is an accurate and sensitive test for detecting KRAS-activating mutations and has analytical power equivalent to Sanger sequencing. Prescreening using the cobas test with subsequent application of Sanger sequencing is the best strategy for routine detection of KRAS mutations in CRC.
Biomarkers ; Codon ; Colorectal Neoplasms* ; Humans