ObjectiveAs a second messenger in intracellular signal transduction, Ca²⁺ plays an important role in cell migration. Previous studies have demonstrated that extracellular Ca²⁺ influx can promote electric field-guided cell migration, known as electrotaxis. However, the effect of intracellular Ca²⁺ flow on electrotaxis is unclear. Therefore, in this study, we investigate the effect of Ca²⁺ flux on the electrotaxis of Dictyostelium discoideum. MethodsThe electrotaxis of Dictyostelium discoideum was investigated by applying a direct current (DC) electric field. Cell migration was recorded using a real-time imaging system. Calcium channel inhibitors, the extracellular Ca²⁺ chelator EGTA, Ca²⁺-free DB buffer, and caffeine were applied to investigate the impact of intra- and extracellular Ca²⁺ flow on electrotaxis. The involvement of G proteins and ERK2 in directed cell migration mediated by endoplasmic reticulum Ca²⁺ release was explored using mutants. ResultsDictyostelium discoideum migrated toward the cathode in the electric field in a voltage-dependent manner. The intracellular Ca²⁺ concentration of the cells was significantly increased in the electric field. Inhibition of both extracellular Ca²⁺ influx and intracellular Ca²⁺ release suppressed cell electrotaxis migration. Inhibition of endoplasmic reticulum Ca²⁺ release induced by caffeine significantly impaired the electrotaxis of Dictyostelium discoideum. Deletion of Gα2, Gβ, Gγ, and Erk2 notably reduced the electrotaxis of the cells. Enhancing Ca²⁺ release mediated by caffeine restored the electrotaxis of the Gα2^-, Gβ ^-, and Erk2^- mutant cells partially or completely, but did not restore electrotaxis in the Gγ^- mutant cells. ConclusionCa²⁺ release from the endoplasmic reticulum regulates electrotaxis migration in Dictyostelium discoideum and is involved in the regulation of cell electrotaxis by G proteins and ERK2.

Background: High-resolution chest computed tomography (CT) is a crucial assessment tool for diagnosing Birt-Hogg-Dubé (BHD) syndrome. This study aimed to analyze differences of lung cysts between BHD and other cystic lung diseases. Methods: From January 2020 to December 2022, patients with multiple lung cysts who underwent chest CT at Gangnam Severance Hospital were included. Results: Over a 3-year period (from January 2020 to December 2022), out of 52,823 patients who underwent a chest CT scan, 301 (0.6%) patients with multiple lung cysts were enrolled in this study. Of enrolled patients, 24 (8.0%) were diagnosed with BHD. In patients with BHD, 95.8% exhibited bilateral cysts, and 83.3% showed basal predominance. The cysts’ maximal diameter averaged 32.1 mm (interquartile range, 26.5 to 43.5). Additionally, 95.8% of patients with BHD had diverse cyst sizes and morphologies. Multivariate logistic regression analysis revealed that bilateral cysts (odds ratio [OR], 12.393; 95% confidence interval [CI], 1.613 to 274.682; p=0.038), basal predominance (OR, 8.511; 95% CI, 2.252 to 39.392; p=0.002), maximum diameter (OR, 1.053; 95% CI, 1.009 to 1.108; p=0.032), and diversity of morphology (OR, 19.513; 95% CI, 2.833 to 398.119; p=0.010) were significant factors associated with BHD diagnosis. A multivariate prediction model for BHD diagnosis demonstrated a sensitivity of 95.83%, a specificity of 81.22%, and an area under the receiver operating characteristic curve of 0.951 (95% CI, 0.914 to 0.987). Conclusion Distinguishing features of lung cysts from other cystic lung diseases include bilateral cysts, basal dominance, large size, and irregular shape.

Background: The management of distal radius fractures (DRFs) has evolved with the introduction of volar locking plate (VLP) fixation.Nevertheless, despite the low occurrence rates, reduction loss following VLP fixation has been reported in several studies. Our objective was to determine the incidence and features of reduction loss in patients despite the appropriate application of VLP fixation for DRF. Methods: This retrospective study was conducted between March 2017 and August 2023, during which a single hand surgeon performed VLP procedures for DRFs. This study included 379 patients (382 wrists) including 3 patients who underwent bilateral surgery. We identified patients who experienced reduction loss after VLP fixation (group 1) and patients without stability problems (group 2) and compared the 2 groups. Results: The mean age of the patients was 63.5 years, with a standard deviation of 13.8. There were 90 male patients (23.6%) and 289 female patients (75.7%). We identified 14 cases of DRFs, in which reduction loss occurred even after VLP fixation during the follow-up period (group 1, 3.7%). The remaining DRFs were assigned to group 2 (n=368, 96.3%). Among the 14 patients, 7 cases of screw breakage were identified as causing the loss of fracture reduction. As the joint surface collapsed and sank down to the distal row locking screw, 4 cases presented with distal locking screws penetrating into the radiocarpal joint. There were no significant differences between the 2 groups in terms of sex, weight, fracture arm direction, and Arbeitsgemeinschaft für Osteosynthesefragen/Orthopaedic Trauma Association (AO/OTA) fracture classification. However, patients in group 1 were statistically significantly older than those in group 2 (average age, 77.5 years vs. 62 years). Among 4 patients experiencing distal screw violation of the radiocarpal joints, 3 underwent partial or complete screw removal immediately after fracture consolidation or union. Conclusions While rare, reduction loss remains a potential complication following VLP fixation, especially in elderly patients with intra-articular DRFs. However, with diligent monitoring and timely intervention, such as implant removal if necessary, acceptable outcomes can still be attained.

Purpose: This study evaluates the prognostic significance of tumor size at disease progression (PD) and depth of response (DOR) in cancer patients. Materials and Methods: We performed post hoc analysis using data from six prospective clinical trials conducted by the Korean Cancer Study Group. Patients with tumor size at PD was categorized into ‘Mild PD’ and ‘Significant PD’ based on the cutoff values of relative change from baseline using maximally selected rank statistics. The overall survival (OS) and progression-free survival (PFS) were compared between PD and DOR categories. Results: Among the 194 evaluable patients, 130 experienced PD. A 35.48% decrease from baseline in tumor size at PD was chosen for the cutoff between mild and significant PD for OS (mild PD: tumor size from the baseline ≤ −35.48%; significant PD > −35.48%). The mild PD had superior OS compared to the significant PD (25.8 vs. 12.8 months; Hazard ratio [HR] 0.47, 95% CI 0.266-0.843, p=0.009). When using an exploratory cutoff based on whether the tumor size was below vs. exceeded from the baseline (mild PD: tumor size from the baseline ≤ 0%; significant PD > 0%), OS remained significantly longer in the mild PD (17.1 vs. 11.8 months; HR 0.60, 95% CI 0.392-0.932, p=0.021). The greatest DOR was associated with the longest OS and PFS (p<0.001 for both). Conclusion Tumor size at PD and DOR were significant prognostic factors for progressive disease. Maintaining a sufficiently reduced tumor size even during PD was associated with better survival outcomes.

Purpose: The Korean Cancer Study Group (KCSG) is a nationwide cancer clinical trial group dedicated to advancing investigator-initiated trials (IITs) by conducting and supporting clinical trials. This study aims to review IITs conducted by KCSG and quantitatively evaluate the survival and financial benefits of IITs for patients. Materials and Methods: We reviewed IITs conducted by KCSG from 1998 to 2023, analyzing progression-free survival (PFS) and overall survival (OS) gains for participants. PFS and OS benefits were calculated as the difference in median survival times between the intervention and control groups, multiplied by the number of patients in the intervention group. Financial benefits were assessed based on the cost of investigational products provided. Results: From 1998 to 2023, KCSG conducted 310 IITs, with 133 completed and published. Of these, 21 were included in the survival analysis. The analysis revealed that 1,951 patients in the intervention groups gained a total of 2,558.4 months (213.2 years) of PFS and 2,501.6 months (208.5 years) of OS, with median gains of 1.31 months in PFS and 1.58 months in OS per patient. When analyzing only statistically significant results, PFS and OS gain per patients was 1.69 months and 3.02 months, respectively. Investigational drug cost analysis from six available IITs indicated that investigational products provided to 252 patients were valued at 10,400,077,294 won (approximately 8,046,481 US dollars), averaging about 41,270,148 won (approximately 31,930 US dollars) per patient. Conclusion Our findings, based on analysis of published research, suggest that IITs conducted by KCSG led to survival benefits for participants and, in some studies, may have provided financial benefits by providing investment drugs.

Background: High-resolution chest computed tomography (CT) is a crucial assessment tool for diagnosing Birt-Hogg-Dubé (BHD) syndrome. This study aimed to analyze differences of lung cysts between BHD and other cystic lung diseases. Methods: From January 2020 to December 2022, patients with multiple lung cysts who underwent chest CT at Gangnam Severance Hospital were included. Results: Over a 3-year period (from January 2020 to December 2022), out of 52,823 patients who underwent a chest CT scan, 301 (0.6%) patients with multiple lung cysts were enrolled in this study. Of enrolled patients, 24 (8.0%) were diagnosed with BHD. In patients with BHD, 95.8% exhibited bilateral cysts, and 83.3% showed basal predominance. The cysts’ maximal diameter averaged 32.1 mm (interquartile range, 26.5 to 43.5). Additionally, 95.8% of patients with BHD had diverse cyst sizes and morphologies. Multivariate logistic regression analysis revealed that bilateral cysts (odds ratio [OR], 12.393; 95% confidence interval [CI], 1.613 to 274.682; p=0.038), basal predominance (OR, 8.511; 95% CI, 2.252 to 39.392; p=0.002), maximum diameter (OR, 1.053; 95% CI, 1.009 to 1.108; p=0.032), and diversity of morphology (OR, 19.513; 95% CI, 2.833 to 398.119; p=0.010) were significant factors associated with BHD diagnosis. A multivariate prediction model for BHD diagnosis demonstrated a sensitivity of 95.83%, a specificity of 81.22%, and an area under the receiver operating characteristic curve of 0.951 (95% CI, 0.914 to 0.987). Conclusion Distinguishing features of lung cysts from other cystic lung diseases include bilateral cysts, basal dominance, large size, and irregular shape.

Background: High-resolution chest computed tomography (CT) is a crucial assessment tool for diagnosing Birt-Hogg-Dubé (BHD) syndrome. This study aimed to analyze differences of lung cysts between BHD and other cystic lung diseases. Methods: From January 2020 to December 2022, patients with multiple lung cysts who underwent chest CT at Gangnam Severance Hospital were included. Results: Over a 3-year period (from January 2020 to December 2022), out of 52,823 patients who underwent a chest CT scan, 301 (0.6%) patients with multiple lung cysts were enrolled in this study. Of enrolled patients, 24 (8.0%) were diagnosed with BHD. In patients with BHD, 95.8% exhibited bilateral cysts, and 83.3% showed basal predominance. The cysts’ maximal diameter averaged 32.1 mm (interquartile range, 26.5 to 43.5). Additionally, 95.8% of patients with BHD had diverse cyst sizes and morphologies. Multivariate logistic regression analysis revealed that bilateral cysts (odds ratio [OR], 12.393; 95% confidence interval [CI], 1.613 to 274.682; p=0.038), basal predominance (OR, 8.511; 95% CI, 2.252 to 39.392; p=0.002), maximum diameter (OR, 1.053; 95% CI, 1.009 to 1.108; p=0.032), and diversity of morphology (OR, 19.513; 95% CI, 2.833 to 398.119; p=0.010) were significant factors associated with BHD diagnosis. A multivariate prediction model for BHD diagnosis demonstrated a sensitivity of 95.83%, a specificity of 81.22%, and an area under the receiver operating characteristic curve of 0.951 (95% CI, 0.914 to 0.987). Conclusion Distinguishing features of lung cysts from other cystic lung diseases include bilateral cysts, basal dominance, large size, and irregular shape.

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: 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: The management of distal radius fractures (DRFs) has evolved with the introduction of volar locking plate (VLP) fixation.Nevertheless, despite the low occurrence rates, reduction loss following VLP fixation has been reported in several studies. Our objective was to determine the incidence and features of reduction loss in patients despite the appropriate application of VLP fixation for DRF. Methods: This retrospective study was conducted between March 2017 and August 2023, during which a single hand surgeon performed VLP procedures for DRFs. This study included 379 patients (382 wrists) including 3 patients who underwent bilateral surgery. We identified patients who experienced reduction loss after VLP fixation (group 1) and patients without stability problems (group 2) and compared the 2 groups. Results: The mean age of the patients was 63.5 years, with a standard deviation of 13.8. There were 90 male patients (23.6%) and 289 female patients (75.7%). We identified 14 cases of DRFs, in which reduction loss occurred even after VLP fixation during the follow-up period (group 1, 3.7%). The remaining DRFs were assigned to group 2 (n=368, 96.3%). Among the 14 patients, 7 cases of screw breakage were identified as causing the loss of fracture reduction. As the joint surface collapsed and sank down to the distal row locking screw, 4 cases presented with distal locking screws penetrating into the radiocarpal joint. There were no significant differences between the 2 groups in terms of sex, weight, fracture arm direction, and Arbeitsgemeinschaft für Osteosynthesefragen/Orthopaedic Trauma Association (AO/OTA) fracture classification. However, patients in group 1 were statistically significantly older than those in group 2 (average age, 77.5 years vs. 62 years). Among 4 patients experiencing distal screw violation of the radiocarpal joints, 3 underwent partial or complete screw removal immediately after fracture consolidation or union. Conclusions While rare, reduction loss remains a potential complication following VLP fixation, especially in elderly patients with intra-articular DRFs. However, with diligent monitoring and timely intervention, such as implant removal if necessary, acceptable outcomes can still be attained.