Background: Bulky or multiple lymph node (LN) metastases are associated with poor prognosis in cervical cancer, and the size or number of LN metastases is not yet reflected in the staging system and therapeutic strategy. Although the therapeutic effects of surgical resection of bulky LNs before standard treatment have been reported in several retrospective studies, wellplanned randomized clinical studies are lacking. Therefore, the aim of the Korean Gynecologic Oncology Group (KGOG) 1047/DEBULK trial is to investigate whether the debulking surgery of bulky or multiple LNs prior to concurrent chemoradiation therapy (CCRT) improves the survival rate of patients with cervical cancer IIICr diagnosed by imaging tests. Methods The KGOG 1047/DEBULK trial is a phase III, multicenter, randomized clinical trial involving patients with bulky or multiple LN metastases in cervical cancer IIICr. This study will include patients with a short-axis diameter of a pelvic or para-aortic LN ≥2 cm or ≥3 LNs with a short-axis diameter ≥1 cm and for whom CCRT is planned. The treatment arms will be randomly allocated in a 1:1 ratio to either receive CCRT (control arm) or undergo surgical debulking of bulky or multiple LNs before CCRT (experimental arm). CCRT consists of extended-field external beam radiotherapy/pelvic radiotherapy, brachytherapy and LN boost, and weekly chemotherapy with cisplatin (40 mg/m 2 ), 4–6 times administered intravenously.The primary endpoint will be 3-year progression-free survival rate. The secondary endpoints will be 3-year overall survival rate, treatment-related complications, and accuracy of radiological diagnosis of bulky or multiple LNs.

Background: Bulky or multiple lymph node (LN) metastases are associated with poor prognosis in cervical cancer, and the size or number of LN metastases is not yet reflected in the staging system and therapeutic strategy. Although the therapeutic effects of surgical resection of bulky LNs before standard treatment have been reported in several retrospective studies, wellplanned randomized clinical studies are lacking. Therefore, the aim of the Korean Gynecologic Oncology Group (KGOG) 1047/DEBULK trial is to investigate whether the debulking surgery of bulky or multiple LNs prior to concurrent chemoradiation therapy (CCRT) improves the survival rate of patients with cervical cancer IIICr diagnosed by imaging tests. Methods The KGOG 1047/DEBULK trial is a phase III, multicenter, randomized clinical trial involving patients with bulky or multiple LN metastases in cervical cancer IIICr. This study will include patients with a short-axis diameter of a pelvic or para-aortic LN ≥2 cm or ≥3 LNs with a short-axis diameter ≥1 cm and for whom CCRT is planned. The treatment arms will be randomly allocated in a 1:1 ratio to either receive CCRT (control arm) or undergo surgical debulking of bulky or multiple LNs before CCRT (experimental arm). CCRT consists of extended-field external beam radiotherapy/pelvic radiotherapy, brachytherapy and LN boost, and weekly chemotherapy with cisplatin (40 mg/m 2 ), 4–6 times administered intravenously.The primary endpoint will be 3-year progression-free survival rate. The secondary endpoints will be 3-year overall survival rate, treatment-related complications, and accuracy of radiological diagnosis of bulky or multiple LNs.

Background: Bulky or multiple lymph node (LN) metastases are associated with poor prognosis in cervical cancer, and the size or number of LN metastases is not yet reflected in the staging system and therapeutic strategy. Although the therapeutic effects of surgical resection of bulky LNs before standard treatment have been reported in several retrospective studies, wellplanned randomized clinical studies are lacking. Therefore, the aim of the Korean Gynecologic Oncology Group (KGOG) 1047/DEBULK trial is to investigate whether the debulking surgery of bulky or multiple LNs prior to concurrent chemoradiation therapy (CCRT) improves the survival rate of patients with cervical cancer IIICr diagnosed by imaging tests. Methods The KGOG 1047/DEBULK trial is a phase III, multicenter, randomized clinical trial involving patients with bulky or multiple LN metastases in cervical cancer IIICr. This study will include patients with a short-axis diameter of a pelvic or para-aortic LN ≥2 cm or ≥3 LNs with a short-axis diameter ≥1 cm and for whom CCRT is planned. The treatment arms will be randomly allocated in a 1:1 ratio to either receive CCRT (control arm) or undergo surgical debulking of bulky or multiple LNs before CCRT (experimental arm). CCRT consists of extended-field external beam radiotherapy/pelvic radiotherapy, brachytherapy and LN boost, and weekly chemotherapy with cisplatin (40 mg/m 2 ), 4–6 times administered intravenously.The primary endpoint will be 3-year progression-free survival rate. The secondary endpoints will be 3-year overall survival rate, treatment-related complications, and accuracy of radiological diagnosis of bulky or multiple LNs.

Tolvaptan reduces height-adjusted total kidney volume (htTKV) and renal function decline in autosomal dominant polycystic kidney disease (ADPKD). This study was aimed at investigating the efficacy and safety of tolvaptan in Korean patients with ADPKD during the titration period. Methods: This study is a multicenter, single-arm, open-label phase 4 study. We enrolled 108 patients with ADPKD (age, 19–50 years) with an estimated glomerular filtration rate (eGFR) of >30 mL/min/1.73 m2 and factors defined as indicative of rapid disease progression. After tolvaptan titration, we evaluated efficacy and side effects and assessed factors associated with the effects. Results: After titration for 4 weeks, eGFR and htTKV decreased by 6.4 ± 7.9 mL/min/1.73 m2 and 16 ± 45 mL/m, respectively. No serious adverse drug reactions were observed during the titration period. The greatest eGFR decline was observed in the first week, with a starting tolvaptan dose of 45 mg. Multivariate linear regression for htTKV decline showed that the greater the change in urine osmolality (Uosm), the greater the decrease in htTKV (β, 0.436; p = 0.009) in the 1D group stratified by the Mayo Clinic image classification. Higher baseline eGFR was related to a higher htTKV reduction rate in the 1E group (β, –0.642; p = 0.009). Conclusion: We observed short-term effects and safety during the tolvaptan titration period. The decline of htTKV can be predicted as a short-term effect of tolvaptan by observing Uosm changes from baseline to end of titration in 1D and baseline eGFR in 1E groups.

Purpose: To develop a deep learning model that can predict the axial lengths of eyes using ultra-widefield (UWF) fundus photography. Methods: We retrospectively enrolled patients who visited the ophthalmology clinic at the Seoul National University Hospital between September 2018 and December 2021. Patients with axial length measurements and UWF images taken within 3 months of axial length measurement were included in the study. The dataset was divided into a development set and a test set at an 8:2 ratio while maintaining an equal distribution of axial lengths (stratified splitting with binning). We used transfer learning-based on EfficientNet B3 to develop the model. We evaluated the model’s performance using mean absolute error (MAE), R-squared (R2), and 95% confidence intervals (CIs). We used vanilla gradient saliency maps to illustrate the regions predominantly used by convolutional neural network. Results: In total, 8,657 UWF retinal fundus images from 3,829 patients (mean age, 63.98 ±15.25 years) were included in the study. The deep learning model predicted the axial lengths of the test dataset with MAE and R2 values of 0.744 mm (95% CI, 0.709–0.779 mm) and 0.815 (95% CI, 0.785–0.840), respectively. The model’s accuracy was 73.7%, 95.9%, and 99.2% in prediction, with error margins of ±1.0, ±2.0, and ±3.0 mm, respectively. Conclusions We developed a deep learning-based model for predicting the axial length from UWF images with good performance.

Objective: To investigate the relationship between reduced glutathione (GSH), a key molecule of the antioxidant defense system in the blood, and glutathione reductase (GR), which reduces oxidized glutathione (glutathione disulfide [GSSG]) to GSH and maintains the redox balance, with the prevalence of Alzheimer’s dementia and cognitive decline. Methods: In all, 20 participants with Alzheimer’s dementia who completed the third follow-up clinical evaluation over 6 years were selected, and 20 participants with normal cognition were selected after age and sex matching. The GSH and GR concentrations were the independent variables. Clinical diagnosis and neurocognitive test scores were the dependent variables indicating cognitive status. Results: The higher the level of GR, the greater the possibility of having normal cognition than of developing Alzheimer’s dementia. Additionally, the higher the level of GR, the higher the neurocognitive test scores. However, this association was not significant for GSH. After 6 years, the conversion rate from normal cognition to cognitive impairment was significantly higher in the lower 50th percentile of the GR group than in the upper 50th percentile. Conclusion The higher the GR, the lower the prevalence of Alzheimer’s dementia and incidence of cognitive impairment and the higher the cognitive test scores. Therefore, GR is a potential protective biomarker against Alzheimer’s dementia and cognitive decline.

Background: Melatonin receptors are present in the human skin and retina. These receptors can be stimulated by light emitting diodes (LEDs) at specific wavelengths, thereby inducing cutaneous photorejuvenation. However, the underlying mechanism remains unclear. Objective: To evaluate the influence of LEDs at specific wavelengths on melatonin membrane receptor (MT1) and cutaneous photorejuvenation via the MT1 pathway in vitro. Methods: Normal human dermal fibroblasts (HDFs) were irradiated using LEDs at different wavelengths (410~940 nm) at a dose of 1 J/cm 2 . MT1 activity was evaluated after melatonin stimulation and LED irradiation. Thereafter, the expressions of collagen (COL) and matrix metalloproteinases (MMPs), with and without luzindole (MT1/2 receptor antagonist), were investigated via semi-quantitative reverse transcription polymerase chain reaction (PCR), real-time PCR, western blotting, and enzyme-linked immunosorbent assay. Results: In HDFs, the MT1 mRNA and protein levels increased significantly in response to melatonin (dose, 50 nM) (p<0.01) and LED irradiation at 595, 630, 850, and 940 nm (p<0.01). LED irradiation up-regulated COL type I and down-regulated MMP-1. Compared to LED irradiation without luzindole, LED irradiation with luzindole produced no significant increase in COL type I mRNA and protein levels (p<0.01). Conclusion We found that LED irradiation induces collagen synthesis and MMP-1 inhibition in HDFs via MT1 activation. Additionally, multiple LED wavelengths (595, 630, 850, and 940 nm) stimulated MT1 in HDFs, unlike in the eyes, where only blue light induced plasma melatonin suppression. This suggests the possibility of the melatoninergic pathway in photorejuvenation.

Purpose: This study aimed to evaluate the long-term effect of esophagectomy in patients with esophageal squamous cell carcinoma (ESCC) by comparing the chemoradiotherapy (CRT)-only group and the trimodality treatment (TMT) group who received concurrent CRT followed by surgery. Materials and Methods: We included 412 operable ESCC patients treated with TMT or CRT between January 2005 and December 2015. The oncological outcomes of the two groups were compared using a weighted Cox proportional-hazards model with inverse probability of treatment weighting (IPTW). Results: The median survival time was 64 and 32 months in the TMT (n=270) and CRT (n=142) groups, respectively (p < 0.001). After IPTW, the median overall survival (OS) remained significantly higher in the TMT group than in the CRT group (61 months vs. 32 months, p=0.016). Moreover, the TMT group showed a better local recurrence-free rate (LRFR, p < 0.001) and distant metastasis-free rate (p=0.007). In the subgroup of patients with clinical complete response (cCR), the OS was not significantly different between the two groups, both before and after IPTW adjustment (p=0.35 and p=0.93). However, among non-cCR patients, the OS was significantly higher in the TMT group (64% vs. 45%, p < 0.001). Conclusion In patients with locally advanced ESCC, TMT was superior to CRT in terms of OS and LRFR. Such difference was more prominent in the non-cCR subgroup. In patients who achieved cCR, esophagectomy was effective in improving LRFR but not OS, suggesting that esophagectomy may be omitted in complete responders.

Purpose: This study aimed to evaluate the real-world efficacy of immune checkpoint inhibitors (ICIs), and to identify clinicolaboratory factors to predict treatment outcomes in patients with advanced esophageal squamous cell carcinoma (ESCC) receiving ICIs. Materials and Methods: Sixty patients with metastatic or unresectable ESCC treated with nivolumab (n=48) or pembrolizumab (n=12) as ≥ second-line treatment between 2016 and 2019 at Asan Medical Center were included. Results: The median age of the patients was 68 years (range, 52 to 76 years), and 93.3% were male. Most patients had metastatic disease (81.7%) and had been previously treated with fluoropyrimidines, platinum, and taxane. In 53 patients with measurable disease, the overall response rate and disease control rate were 15.1% and 35.8%, respectively. With a median follow-up duration of 16.0 months, the median progression-free survival (PFS) and overall survival (OS) were 1.9 months (95% confidence interval [CI], 1.54 to 2.19) and 6.4 months (95% CI, 4.77 to 8.11), respectively. After multivariate analysis, recent use of antibiotics, low prognostic nutrition index (< 35.93), high Glasgow Prognosis Score (≥ 1) at baseline, and ≥ 1.4-fold increase in neutrophil-to-lymphocyte ratio after one cycle from baseline were significantly unfavorable factors for both PFS and OS. Younger age (< 65 years) was a significant factor for unfavorable PFS and hyponatremia (< 135 mmol/L) for unfavorable OS. Conclusion The use of ICIs after the failure of chemotherapy showed comparable efficacy in patients with advanced ESCC in real practice; this may be associated with host immune-nutritional status, which could be predicted by clinical and routine laboratory factors.