Purpose: GC1118 is a novel antibody targeting epidermal growth factor receptor (EGFR) with enhanced blocking activity against both low- and high-affinity EGFR ligands. A phase 1b/2a study was conducted to determine a recommended phase 2 dose (RP2D) of GC1118 in combination with 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) (phase 1b) and to assess the safety and efficacy of GC1118 plus FOLFIRI as a second-line therapy for recurrent/metastatic colorectal cancer (CRC) (phase 2a). Materials and Methods: Phase 1b was designed as a standard 3+3 dose-escalation study with a starting dose of GC1118 (3 mg/kg/week) in combination with biweekly FOLFIRI (irinotecan 180 mg/m2; leucovorin 400 mg/m2; 5-fluorouracil 400 mg/m2 bolus and 2,400 mg/m2 infusion over 46 hours) in patients with solid tumors refractory to standard treatments. The subsequent phase 2a part was conducted with objective response rate (ORR) as a primary endpoint. Patients with KRAS/NRAS/BRAF wild-type, EGFR-positive, recurrent/metastatic CRC resistant to the first-line treatment were enrolled in the phase 2a study. Results: RP2D of GC1118 was determined to be 3 mg/kg/wk in the phase 1b study (n=7). Common adverse drug reactions (ADRs) observed in the phase 2a study (n=24) were acneiform rash (95.8%), dry skin (66.7%), paronychia (58.3%), and stomatitis (50.0%). The most common ADR of ≥ grade 3 was neutropenia (33.3%). ORR was 42.5% (95% confidence interval [CI], 23.5 to 62.0), and median progression-free survival was 6.7 months (95% CI, 4.0-8.0). Conclusion GC1118 administered weekly at 3 mg/kg in combination with FOLFIRI appears as an effective and safe treatment option in recurrent/metastatic CRC.

Viral load and the duration of viral shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are important determinants of the transmission of coronavirus disease 2019.In this study, we examined the effects of viral doses on the lung and spleen of K18-hACE2 transgenic mice by temporal histological and transcriptional analyses. Approximately, 1×105 plaque-forming units (PFU) of SARS-CoV-2 induced strong host responses in the lungs from 2 days post inoculation (dpi) which did not recover until the mice died, whereas responses to the virus were obvious at 5 days, recovering to the basal state by 14 dpi at 1×102 PFU. Further, flow cytometry showed that number of CD8+ T cells continuously increased in 1×102 PFU-virusinfected lungs from 2 dpi, but not in 1×105 PFU-virus-infected lungs. In spleens, responses to the virus were prominent from 2 dpi, and number of B cells was significantly decreased at 1×105PFU; however, 1×102 PFU of virus induced very weak responses from 2 dpi which recovered by 10 dpi. Although the defense responses returned to normal and the mice survived, lung histology showed evidence of fibrosis, suggesting sequelae of SARS-CoV-2 infection. Our findings indicate that specific effectors of the immune response in the lung and spleen were either increased or depleted in response to doses of SARS-CoV-2. This study demonstrated that the response of local and systemic immune effectors to a viral infection varies with viral dose, which either exacerbates the severity of the infection or accelerates its elimination.

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.

Purpose: Immune checkpoint inhibitors (ICIs) have been shown significant oncological improvements in several cancers.However, ICIs are still in their infancy in hepatocellular carcinoma (HCC). Programmed cell death-ligand 1 (PD-L1), tumorinfiltrating lymphocytes (TILs), and epithelial-mesenchymal transition (EMT) have been known as prognostic factors in HCC. Therefore, we have focused on identifying the molecular mechanisms between each marker to evaluate a predictive role. Methods: Formalin-fixed paraffin-embedded samples were obtained from 166 patients with HCC who underwent surgery. The expression of PD-L1 and TILs and EMT marker were evaluated by immunohistochemical analysis. Results: The multivariate analysis showed that TIL expression (hazard ratio [HR], 0.483; 95% confidence interval [CI], 0.269–0.866; P = 0.015) were independent prognostic factors for overall survival. The prognostic factors for disease-free survival were EMT marker expression (HR, 1.565; 95% CI, 1.019–2.403; P = 0.005). Patients with high expression of TILs had significantly better survival compared to patients with low expression (P = 0.023). Patients who were TIL+/EMT– showed a significantly better prognosis than those who were TIL–/EMT+ (P = 0.049). Conclusion This study demonstrates that PD-L1 expression of TILs is closely associated with EMT marker expression in HCC. Clinical investigations using anti–PD-1/PD-L1 inhibitors in patients with EMT-associated PD-L1 upregulation are warranted.

Purpose: This study was conducted to establish whether an ethanol extract of Lycium barbarum leaves (LLE) and an ethanol extract of Lycium barbarum leaves from which chlorophyll has been removed, denoted as LLE(Ch−), have a protective effect against hepatic fat accumulation. Methods: The inhibitory effects of LLE and LLE(Ch−) on liver fat accumulation were examined in C57BL/6 mice with non-alcoholic fatty liver disease (NAFLD) induced by an methionine and choline deficient diet and in HepG2 cells with palmitic acid-induced fat accumulation. Results: The plasma triglyceride, aspartate aminotransferase, and alanine aminotransferase levels were lower in the LLE(Ch−) group, whereas the plasma ALT activity decreased significantly in the LLE group. In both the LLE and the LLE(Ch−) groups, the triglyceride and cholesterol contents in the hepatic tissue were significantly reduced. A greater inhibitory effect on tissue fat accumulation was observed in the LLE(Ch−) group than in the LLE group. In HepG2 cells, LLE and LLE(Ch−) were non-toxic up to a concentration of 1,000 µg/mL. Compared to the control group, intracellular fat accumulation in the LLE and LLE(Ch−) groups were significantly reduced at concentrations of 200 µg/mL and 500 µg/mL, respectively. The expression of phosphorylated adenosine monophosphate-activated protein kinase and phosphorylated acetyl-CoA carboxylase in both LLE groups increased at the concentrations of 100 μg/mL and 500 μg/mL. The fatty acid synthase expression was suppressed in a concentration-dependent manner at 10 μg/mL. Conclusion The examined two ethanol extracts of LLE inhibit hepatic fat accumulation in NAFLD. This effect was more pronounced in the LLE(Ch−) group. Therefore, these 2 extracts have an anti-steatosis effect and can be used for NAFLD treatment.

BACKGROUND/OBJECTIVES: Atopic dermatitis (AD) is a chronic disease with an increasing incidence globally; therefore, there is a growing demand for natural compounds effective in treating dermatitis. In this study, the protective effects of Lycium barbarum leaves with and without chlorophyll (LLE and LLE[Ch-]) on AD were investigated in animal models of AD and HaCaT cells. Further, we investigated whether LLE and LLE(Ch-) show any differences in physiological activity.MATERIALS/METHODS: AD was induced by 2,4-dinitrochlorobenzene (DNCB) for three weeks, while NC/Nga mice were fed LLE or LLE(Ch-) extracts for 7 weeks. Serum immunoglobulin E (IgE) and cytokine (tumor necrosis factor [TNF]-α, interleukin [IL]-6, and IL-4) concentrations and the degree of DNA fragmentation in lymphocytes were examined. A histopathological examination (haematoxylin & eosin staining and blue spots of toluidine) of the dorsal skin of mice was performed. To elucidate the mechanism of action, the expression of the thymus and activation-regulated chemokine (TARC) and macrophage-derived chemokine (MDC) were measured in HaCaT cells. RESULTS: Serum IgE and cytokines (TNF-α and IL-6) levels as well as DNA fragmentation of lymphocytes were significantly decreased in AD-induced mice treated with LLE or LLE(Ch-) compared to those of the control group. The epidermal thickness of the dorsal skin and mast cell infiltration in the LLE group significantly reduced compared to that in the control group. The LLE extracts showed no cytotoxicity up to 1,000 µg/mL in HaCaT cells. LLE or LLE(Ch-)-treated group showed a reduction of TARC and MDC in TNF-α-and IFN-γ-stimulated HaCaT cells. CONCLUSIONS These results suggest that LLE potentially improves inflammation by reducing the expression of chemokines that inhibit T helper 2 cell migration. LLE(Ch-) showed similar effects to LLE on blood levels of IgE, TNF-α and IL-6 and protein expression in HaCat cells, but the ultimate effect of skin improvement was not statistically significant.Therefore, both LLE and LLE(Ch-) can be used as functional materials to alleviate AD, but LLE(Ch-) appears to require more research to improve inflammation.

Purpose: Natural medicinal plant extracts have recently attracted attention as health beneficial foods and potential therapeutic agents for prevention of various diseases. This study was undertaken to measure the anti-inflammatory effect of the ethanol-water fraction obtained from the above-ground portion of Spiraea prunifolia var. simpliciflora, a wild-growing plant in Korea. The final fraction used in this study was the H 2 O-EtOH (40:60) fraction (SP60), which had the highest antioxidant activity, as determined in previous studies. Methods: The amounts of nitric oxide (NO), tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1β production were measured in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells exposed to SP60. Western blot was performed to measure the expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, and the activation of nuclear factor (NF)-κB. Results: SP60 exerted no cytotoxicity up to concentrations of 125 μg/mL. The levels of inflammatory cytokines, such as NO, TNF-α, IL-6, and IL-1β, were significantly decreased in LPS-stimulated RAW264.7 cells exposed to SP60. In addition, the expression levels of iNOS, COX-2, and phosphorylated p65 showed a concentration-dependent decrease subsequent to SP60 treatment. These results indicate that SP60 inhibits the LPS-induced production of inflammatory cytokines, iNOS, and COX-2, by inhibiting the activation of NF-κB, which is responsible for the expression of inflammatory mediators. Conclusion The results presented in this study indicate that the H 2 O-EtOH (40:60) fraction (SP60) extracted from the above-ground portion of Spiraea prunifolia var. simpliciflora has

PURPOSE: The purpose of this study was to evaluate the clinical and radiological results after meniscal allograft transplantation (MAT). MATERIALS AND METHODS: From October, 2010 to August, 2013, 45 patients, 47 cases who underwent MAT were reviewed. The mean age was 39.9 years and the mean follow-up period was 24.9 months. The clinical results were evaluated using Lysholm score and International Knee Documentation Committee (IKDC) score. All cases were evaluated by serial postoperative radiograph. And 18 cases were performed postoperative magnetic resonance imaging (MRI). Eighteen cases including the 13 cases that had graft dislocation or subluxation and signal changes in MRI underwent second-look arthroscopy. RESULTS: Lysholm score was elevated from mean 58.4 at preoperative to 92.4 at last follow-up. IKDC score was elevated from mean 50.3 at preoperative to 90.1 at last follow-up. Among the 18 cases who underwent postoperative MRI, subluxation was found in 10 cases (55.6%) and graft dislocation with grade III signal change was found in 3 cases (16.7%). However, the 13 cases showed a well healed state of the graft capsule in second-look arthroscopy. There was no joint space narrowing on radiograph during the follow-up period. CONCLUSION: After MAT, 93.6% of cases showed improved the clinical results above good. Thus, it is effective in relatively young and active patients with meniscus functional deficit and minor meniscal degeneration.
Allografts* ; Arthroscopy ; Dislocations ; Follow-Up Studies ; Humans ; Joints ; Knee ; Magnetic Resonance Imaging ; Transplants

Klippel-Trenaunay syndrome is a rare congenital mesodermal abnormality characterized by varicose veins, cutaneous hemangiomas, soft tissue and bony hypertrophy of limb. Potential complications such as deep venous thrombosis and pulmonary thromboembolism have not been reported in Korea to date. We demonstrate the case of a 48-year-old woman with Klippel-Trenaunay syndrome with extensive varicose veins on right lower limb, hypertrophy of left big toe and basilar artery tip aneurysm, complicated with acute submassive pulmonary thromboembolism treated successfully with intravenous thrombolytic therapy.
Aneurysm ; Basilar Artery ; Extremities ; Female ; Heart Failure ; Hemangioma ; Humans ; Hypertrophy ; Intracranial Aneurysm ; Klippel-Trenaunay-Weber Syndrome* ; Korea ; Lower Extremity ; Mesoderm ; Middle Aged ; Pulmonary Embolism* ; Thrombolytic Therapy* ; Toes ; Varicose Veins ; Venous Thromboembolism ; Venous Thrombosis

PURPOSE: Ureteral calculi are commonly encountered in the emergency department. Ureteral calculi influence the quality of life of patients, causing pain and economic burden. The optimal management of ureteral calculi remains a challenge for practicing physicians; therefore, this study was designed to determine which factors are related to the failure of their spontaneous passage. METHODS: This study was a retrospective review of the medical records of one hundred ninety-five patients who visited the emergency department complaining of renal colic from February 2012 to December 2012. Bivariate analyses were conducted relating physical, laboratory, and radiological methods to predict the failure of spontaneous passage. A multivariate logistic regression model was then derived, with all variables in the final model significant at p<0.05. RESULTS: One hundred twenty-eight stones were spontaneously expelled and sixty-seven were not. The mean stone size was significantly larger in the non-passage group than the passage group (p<0.001). When the stones were located in the upper ureter, or on the right side, the spontaneous passage rate was lower (p<0.001, p=0.035). Increased neutrophils and positive tests for urinary protein and bilirubin were also associated with the decreased likelihood of spontaneous passage (p=0.046, p=0.029, and p=0.048, respectively). In addition, the longer duration of symptoms and a previous history of ureteral calculi were related to a lower chance of spontaneous passage (p=0.005, p=0.019). CONCLUSION: Prognostic factors of failure, after the initial expectant management of ureteral calculi, included: calculi size, location (e.g., side), the duration of symptoms, the previous history, neutrophil levels, urinary bilirubin levels, and urinary protein levels. Therefore, emergency physicians need to cautiously decide between watchful waiting and interventions in these patients.
Bilirubin ; Calculi ; Emergencies ; Humans ; Logistic Models ; Medical Records ; Neutrophils ; Quality of Life ; Renal Colic ; Retrospective Studies ; Ureter ; Ureteral Calculi ; Watchful Waiting