We observed that treatment with dimethyl α-ketoglutarate (DMK) increased the amount of intracellular α-ketoglutarate significantly more than that of α-ketoglutarate in HaCaT cells. DMK also increased the level of intracellular 4-hydroxyproline and promoted the production of collagen in HaCaT cells. In addition, DMK decreased the production of collagenase and elastase and downregulated the expression of selected matrix metalloproteinases (MMPs), such as MMP-1, MMP-9, MMP-10, and MMP-12, via transcriptional inhibition. The inhibition of MMPs by DMK was mediated by the suppression of the IL-1 signaling cascade, leading to the attenuation of ERK1/2 phosphorylation and AP-1 transactivation. Our study results illustrate that DMK, an alkylated derivative of α-ketoglutarate, increased the level of 4-hydroxyproline, promoted the production of collagen, and inhibited the expression of selected MMPs by affecting the IL-1 cascade and AP-1 transactivation in HaCaT cells. The results suggest that DMK might be useful as an anti-wrinkle ingredient.

Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease that affects multiple organs. More than half of the patients with SLE have kidney involvement, and up to 10% of patients with lupus nephritis develop end-stage renal disease (ESRD). Central nervous system (CNS) involvement in SLE occurs in 21% to 95% of patients. Severe neurological manifestations such as seizures, cerebrovascular disease, meningitis, and cerebrovascular accidents can develop in childhood-onset SLE, but cerebral infections, such as brain abscess and hemorrhage, are seldom reported in lupus nephritis, even in adults. Here, we report a rare case of childhood-onset SLE with ESRD, a cerebral abscess, and hemorrhage. A 9-year-old girl diagnosed with lupus nephritis was administered high-dose steroids and immunosuppressant therapy to treat acute kidney injury (AKI) and massive proteinuria. The AKI deteriorated, and after 3 months, she developed ESRD. She received hemodialysis three times a week along with daily peritoneal dialysis to control edema. She developed seizures, and imaging showed a brain abscess. This was complicated by spontaneous cerebral hemorrhage, and she became unstable. She died shortly after the hemorrhage was discovered. In conclusion, CNS complications should always be considered in clinical practice because they increase mortality, especially in those with risk factors for infection.

Background/Aims: Appropriate tissue tension and clear visibility of the dissection area using traction are essential for effective and safe endoscopic submucosal dissection (ESD). In this study, we developed a retractable robot-assisted traction device and evaluated its performance in colorectal ESD. Methods: An experienced endoscopist performed ESD 18 times on an ex vivo porcine colon using the robot and 18 times using the conventional method. The outcome measures were procedure time, dissection speed, procedure-related adverse events, and blind dissection rate. Results: Thirty-six colonic lesions were resected from ex vivo porcine colon samples. The total procedure time was significantly shorter in robot-assisted ESD (RESD) than in conventional ESD (CESD) (20.1±4.1 minutes vs 34.3±8.3 minutes, p<0.05). The submucosal dissection speed was significantly faster in the RESD group than in the CESD group (36.8±9.2 mm 2 /min vs 18.1±4.7 mm 2 /min, p<0.05). The blind dissection rate was also significantly lower in the RESD group (12.8%±3.4% vs 35.1%±3.9%, p<0.05). In an in vivo porcine feasibility study, the robotic device was attached to a colonoscope and successfully inserted into the proximal colon without damaging the colonic wall, and ESD was successfully performed. Conclusions The dissection speed and safety profile improved significantly with the retractable RESD. Thus, our robotic device has the potential to provide simple, effective, and safe multidirectional traction during colonic ESD.

Leiomyosarcoma (LMS) within the scrotum is a rare malignant genitourinary tumor in adults. Due to its rarity, a consensus on a clear approach to diagnosis and treatment guidelines has not yet been reached. We present a case of a paratesticular LMS in a 64-yearold man with a painless swelling of the right scrotum. Scrotal ultrasound and pelvic MRI were performed and revealed an extratesticular mass with a heterogeneous appearance.The patient underwent a right radical orchiectomy, and the mass was confirmed to be LMS, originating from the right spermatic cord. Preoperative diagnosis of LMS is challenging since it has overlapping clinical and imaging features with other sarcomas. MRI is a valuable imaging modality for the definitive characterization of the tumor. To provide timely and appropriate treatment, the correlation of the patient’s clinical information and imaging findings is necessary.

Small cell neuroendocrine carcinoma of the uterine cervix (SCNCC) is a rare form of cervical carcinoma. Precise and early diagnosis of SCNCC is crucial because of its poor prognosis and distinct therapeutic approach compared with other common squamous cervical cancers. This report presents a case of SCNCC in a 50-year-old woman with vaginal bleeding. On computed tomography and magnetic resonance imaging (MRI), the tumor presents as a bulky, expansile, solid mass with a homogenous texture, low apparent diffusion coefficient (ADC) value, and extensive nodal and distant metastases. Mimicking lymphoma, the tumor did not exhibit cervical epithelial distortion. The diagnosis of SCNCC was confirmed by punch biopsy, and the patient was treated with systemic chemotherapy. MRI features that suggest SCNCC are lesion homogeneity, low ADC values, and frequent nodal metastases, which are commonly observed in lymphomas. Therefore, despite its rarity, SCNCC should be considered in the differential diagnosis when a cervical mass presents with these findings.

Background/Aims: Percutaneous transhepatic cholangioscopy (PTCS) is used for the diagnosis and treatment of biliary diseases in patients with failed endoscopic retrograde cholangiopancreatography, particularly those with surgically altered anatomy. However, few studies are available on the clinical use of Spyglass DS direct visualization system (SpyDS)-assisted PTCS. This study aimed to assess the efficacy and safety of SpyDS-assisted PTCS in patients with surgically altered anatomy, particularly those with a Roux-en-Y reconstruction. Methods: Thirteen patients (six women, median age 71.4 years [range, 53 to 83 years]) with surgically altered anatomy (four Roux-en-Y choledochojejunostomies, seven Roux-en-Y hepaticojejunostomies, and two Roux-en-Y esophagojejunostomies) who underwent SpyDS-assisted PTCS between January 2019 and August 2020 were included and the data was acquired by retrospectively reviewing electronic medical record. Results: A total of 19 SpyDS-assisted PTCS procedures were performed in the 13 patients: eight had bile-duct stones, and five had biliary strictures. All SpyDS-assisted PTCS procedures were successfully performed. The total procedure time was 42.42±18.0 minutes (mean±standard deviation). Bile duct clearance was achieved in all bile duct stone cases after a median of 2 (range, 1 to 3) procedures. In the five biliary stricture cases, the results of SpyBite forceps-guided targeted biopsy were consistent with adenocarcinoma (100% accuracy). The median hospitalization duration was 20 days (range, 14 to 30 days). No procedure-related morbidity or mortality occurred. Conclusions SpyDS-assisted PTCS may be a safe, feasible, and effective procedure for the diagnosis and treatment of biliary diseases in patients with surgically altered anatomy, particularly in those with the Roux-en-Y reconstruction requiring a percutaneous approach. However, our findings need to be validated in further studies.

Background/Aims: Controversy regarding the effectiveness of neoadjuvant therapy for resectable pancreatic ductal adenocarcinoma (PDAC) still exists. Here, we aimed to identify the potential benefits of neoadjuvant therapy followed by surgery for resectable PDAC. Methods: We reviewed radiologically resectable PDAC patients who received resection with curative intent at a tertiary hospital in South Korea between January 2012 and August 2019. A total of 202 patients underwent curative resection for resectable PDAC: 167 underwent surgical resection first during this period, and 35 received neoadjuvant chemotherapy/chemoradiation therapy followed by surgery. Resectable PDAC patients were subdivided, and 1:3 propensity score matching (PSM) was performed to reduce selection bias. Results: Compared with the group that received surgery first, the group that received neoadjuvant treatment followed by surgery had significantly smaller tumors (22.0 mm vs 27.0 mm, p=0.004), a smaller proportion of patients with postoperative pathologic T stage (p=0.026), a smaller proportion of patients with lymphovascular invasion (20.0% vs 40.7%, p=0.022), and a larger proportion of patients with negative resection margins (74.3% vs 51.5%, p=0.049). After PSM, the group that received neoadjuvant therapy had a significantly longer progression-free survival than those in the group that underwent surgery first (29.6 months vs 15.1 months, p=0.002). Overall survival was not significantly different between the two groups after PSM analysis. Conclusions We observed significantly better surgical outcomes and progression-free survival with the addition of neoadjuvant therapy to the management of resectable PDAC. However, despite PSM, there was still selection bias due to the use of different regimens between the groups receiving surgery first and neoadjuvant therapy. Large homogeneous samples are needed in the future prospective studies.

Background/Aims: Chitosan, a natural polymer widely used in the biomaterials field, has been proposed as a potential submucosal injection solution. The purpose of this study was to compare the performance and efficacy of aqueous chitosan solution and commercialized submucosal injection fluids using a three-dimensional sensor and to evaluate the efficacy of the measured parameters. Methods: Normal saline (0.9% NaCl), as a control, Eleview ® (Poloxamer 188), Blue Eye TM (0.4% hyaluronic acid), and aqueous chitosan solution (2.0%) were injected into the submucosa of porcine stomachs ex vivo. The mucosal elevation height, elevated surface area, and angle of the tangent of the submucosal fluid cushion were measured using a three-dimensional sensor. The rates of change for each variable were calculated, and the correlation between parameters was analyzed. Tissue specimens were stained with hematoxylin and eosin. Results: All variables exhibited the highest values under chitosan injection. The mucosal elevation height rate of change differed significantly between normal saline and chitosan solution (p=0.024). The elevated surface area rates of change for normal saline and Eleview® were significantly different from those for TS-905 and chitosan solution (p=0.006 and p=0.009, respectively). Further, height, area, and angle showed a positive correlation (p<0.001). A histological examination revealed an even distribution of aqueous chitosan within the submucosa without tissue damage. Conclusions Aqueous chitosan was superior to normal saline and Eleview® and was noninferior to TS-905. A three-dimensional sensor and the measured parameters were effective and useful for evaluating the performance of submucosal fluids.

Background: Chronic kidney disease (CKD) has a negative impact on growth and development in children and is a risk factor for neurocognitive impairment; however, there is limited research on the cognitive function of children and adolescents with CKD. This study therefore aimed to investigate the mean intelligence and risk factors for low intelligence in children and adolescents with CKD. Methods: Eighty-one patients with CKD under 18 years old were included in the KoreaN cohort study for Outcomes in patients With Pediatric Chronic Kidney Disease (KNOW-Ped CKD). Participants completed either the Wechsler Intelligence Scale for Children (6–16 years), or Wechsler Adult Intelligence Scale (> 16 years). Results: The mean full-scale intelligence quotient (IQ) was 91 ± 19; 24.7% of participants scored a full-scale IQ below 80. Participants with a short stature (height Z scores < −1.88), failure to thrive (weight Z scores < −1.65), more severe CKD stage (≥ IIIb), longer duration of CKD (≥ 5 years), and those who were Medicare or Medicaid beneficiaries, had significantly lower mean full-scale IQs. Conclusion On linear regression analysis, the association between the full-scale IQ, and longer duration of CKD and growth failure, remained significant after controlling for demographic and clinical variables. It is therefore necessary to investigate cognitive impairment in pediatric patients with CKD who exhibit growth failure or for a longer postmorbid period. It is believed that early interventions, such as kidney transplantation, will have a positive effect on IQ in children with CKD, as the disease negatively affects IQ due to poor glomerular filtration rate over time.