Purpose: Diffuse large B-cell lymphoma (DLBCL) is the most common hematologic malignancy worldwide. Although substantial improvement has been achieved by the frontline rituximab-based chemoimmunotherapy, up to 40%-50% of patients will eventually have relapsed or refractory disease, whose prognosis is extremely dismal. Materials and Methods: We have carried out two prospective cohort studies that include over 1,500 DLBCL patients treated with rituximab plus CHOP (#NCT01202448 and #NCT02474550). In the current report, we describe the outcomes of refractory DLBCL patients. Patients were defined to have refractory DLBCL if they met one of the followings, not achieving at least partial response after 4 or more cycles of R-CHOP; not achieving at least partial response after 2 or more cycles of salvage therapy; progressive disease within 12 months after autologous stem cell transplantation. Results: Among 1,581 patients, a total of 260 patients met the criteria for the refractory disease after a median time to progression of 9.1 months. The objective response rate of salvage treatment was 26.4%, and the complete response rate was 9.6%. The median overall survival (OS) was 7.5 months (95% confidence interval, 6.4 to 8.6), and the 2-year survival rate was 22.1%±2.8%. The median OS for each refractory category was not significantly different (p=0.529). Conclusion In line with the previous studies, the outcomes of refractory DLBCL patients were extremely poor, which necessitates novel approaches for this population.

Purpose: We conducted a nationwide, multicenter, prospective registry study for newly diagnosed patients with peripheral T-cell lymphoma (PTCL) to better define the clinical characteristics, treatment patterns, survival outcomes, and the role of upfront autologous stem cell transplantation (ASCT) in these patients. Materials and Methods: Patients with PTCL receiving chemotherapy with curative intent were registered and prospectively monitored. All patients were pathologically diagnosed with PTCL. Results: A total of 191 patients with PTCL were enrolled in this prospective registry study. PTCL, not otherwise specified (PTCL-NOS) was the most common pathologic subtype (n=80, 41.9%), followed by angioimmunoblastic T-cell lymphoma (AITL) (n=60, 31.4%). With a median follow-up duration of 3.9 years, the 3-year progression-free survival (PFS) and overall survival (OS) rates were 39.5% and 60.4%, respectively. The role of upfront ASCT was evaluated in patients who were considered transplant-eligible (n=59). ASCT was performed as an upfront consolidative treatment in 32 (54.2%) of these patients. There were no significant differences in PFS and OS between the ASCT and non-ASCT groups for all patients (n=59) and for patients with PTCL-NOS (n=26). However, in patients with AITL, the ASCT group was associated with significantly better PFS than the non-ASCT group, although there was no significant difference in OS. Conclusion The current study demonstrated that the survival outcomes with the current treatment options remain poor for patients with PTCL-NOS. Upfront ASCT may provide a survival benefit for patients with AITL, but not PTCL-NOS.

Purpose: Febrile neutropenia (FN) can cause suboptimal treatment and treatment-related mortality (TRM) in diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP). Materials and methods: We conducted a prospective cohort study to evaluate the effectiveness of pegfilgrastim prophylaxis in DLBCL patients receiving R-CHOP, and we compared them with the PROCESS cohort (n=485). Results: Since January 2015, 986 patients with DLBCL were enrolled. Pegfilgrastim was administered at least once in 930 patients (94.3%), covering 90.3% of all cycles. FN developed in 137 patients (13.9%) in this cohort (23.7% in the PROCESS cohort, p<0.001), and 4.2% of all cycles (10.2% in the PROCESS cohort, p<0.001). Dose delay was less common (≥3 days: 18.1% vs. 23.7%, p=0.015; ≥5 days: 12.0% vs. 18.3%, p=0.023) in this cohort than in the PROCESS cohort. The incidence of TRM (3.2% vs. 5.6%, p=0.047) and infection-related death (1.8% vs. 4.5%, p=0.004) was lower in this cohort than in the PROCESS cohort. The 4-year overall survival (OS) and progression-free survival (PFS) rates of the two cohorts were not different (OS: 73.0% vs. 71.9%, p=0.545; PFS: 69.5% vs. 68.8%, p=0.616). However, in patients aged ≥75 years, the 4-year OS and PFS rates were higher in this cohort than in the PROCESS cohort (OS: 49.6% vs. 33.7%, p=0.032; PFS: 44.2% vs. 30.3% p=0.047). Conclusion Pegfilgrastim prophylaxis is effective in the prevention of FN and infection-related death in DLBCL patients receiving R-CHOP, and it also improves OS in patients aged ≥75 years.

Objectives: ：This study aimed to investigate quality of life, severity of depression, suicidality, subjective health and subjective stress of depression with subjective cognitive decline in Korean adults. Methods: ：We used the 7th KNHANES data to enroll 415 participants with a score of 10 or higher on Patient Health Questionnaire-9 (PHQ-9), aged 20-64. Depression was divided into two groups based on the presence/absence of subjective cognitive decline. Demographic and psychological characteristics were compared between two groups. Correlation analysis of subjective cognitive decline, quality of life, depression, suicidal idea was car-ried out. To detect which variables influenced quality of life, a multiple regression analysis was carried out. Results: ：Among the 415 participants, 98 had depression with subjective cognitive decline. We identified sig-nificant differences in age, marital status, education, employment between the two groups. After adjusting for these variables, depression with subjective cognitive decline had lower EuroQol-5D index scores, more severe depressive symptoms without cognition and worse subjective health than depression without cognitive decline. There was a significant correlation between subjective cognitive decline and quality of life (r=-0.236, p<0.001), suicidal idea (r=0.182, p<0.001), depression score without cognition (r=0.108, p=0.028). Through multiple regression analysis, subjective cognitive decline was predictor of reduced quality of life (β=-0.178, p<0.001). Conclusions ：Depression with subjective cognitive decline has poor quality of life and severe depression. Cognitive decline should be considered to improve treatment result in depression.

The aim of the present study was to investigate the pathophysiological etiology of osteoarthritis that is mediated by the apoptosis of chondrocytes exposed to 25-hydroxycholesterol (25-HC), an oxysterol synthesized by the expression of cholesterol-25-hydroxylase (CH25H) under inflammatory conditions. Interleukin-1β induced the apoptosis of chondrocytes in a dose- dependent manner. Furthermore, the production of 25-HC increased in the chondrocytes treated with interleukin-1β through the expression of CH25H. 25-HC decreased the viability of chondrocytes. Chondrocytes with condensed nucleus and apoptotic populations increased by 25- HC. Moreover, the activity and expression of caspase-3 were increased by the death ligand-mediated extrinsic and mitochondria-dependent intrinsic apoptotic pathways in the chondrocytes treated with 25-HC. Finally, 25-HC induced not only caspasedependent apoptosis, but also induced proteoglycan loss in articular cartilage ex vivo cultured rat knee joints. These data indicate that 25-HC may act as a metabolic pathophysiological factor in osteoarthritis that is mediated by progressive chondrocyte death in the articular cartilage with inflammatory condition.

The aim of the present study was to investigate the pathophysiological etiology of osteoarthritis that is mediated by the apoptosis of chondrocytes exposed to 25-hydroxycholesterol (25-HC), an oxysterol synthesized by the expression of cholesterol-25-hydroxylase (CH25H) under inflammatory conditions. Interleukin-1β induced the apoptosis of chondrocytes in a dose- dependent manner. Furthermore, the production of 25-HC increased in the chondrocytes treated with interleukin-1β through the expression of CH25H. 25-HC decreased the viability of chondrocytes. Chondrocytes with condensed nucleus and apoptotic populations increased by 25- HC. Moreover, the activity and expression of caspase-3 were increased by the death ligand-mediated extrinsic and mitochondria-dependent intrinsic apoptotic pathways in the chondrocytes treated with 25-HC. Finally, 25-HC induced not only caspasedependent apoptosis, but also induced proteoglycan loss in articular cartilage ex vivo cultured rat knee joints. These data indicate that 25-HC may act as a metabolic pathophysiological factor in osteoarthritis that is mediated by progressive chondrocyte death in the articular cartilage with inflammatory condition.

BACKGROUND/OBJECTIVES: This study investigated the antioxidant activities and hepatoprotective effects of Schisandra chinensis Baillon extract (SCE) against tert-butyl hydroperoxide (t-BHP)-induced oxidative hepatic damage in rats. MATERIALS/METHODS: Sprague-Dawley (SD) rats were pretreated with SCE (300, 600, and 1,200 mg/kg BW) or saline once daily for 14 consecutive days. On day 14, each animal, except those belonging to the normal control group, were injected with t-BHP (0.8 mmol/kg BW/i.p.), and all of the rats were sacrificed 16 h after t-BHP injection. RESULTS: Although no significant differences in AST and ALT levels were observed among the TC and SCE groups, the high-dose SCE group showed a decreasing tendency compared to the TC group. However, erythrocyte SOD activity showed a significant increase in the low-dose SCE group compared with the TC group. On the other hand, no significant differences in hepatic total glutathione (GSH) level, glutathione reductase (GR), and glutathione peroxidase (GSH-Px) activities were observed among the TC and SCE groups. Hepatic histopathological evaluation revealed that pretreatment with SCE resulted in reduced t-BHP-induced incidence of lesions, such as neutrophil infiltration, swelling of liver cells, and necrosis. In particular, treatment with a high dose of SCE resulted in induction of phase II antioxidant/detoxifying enzyme expression, such as glutathione S-transferase (GST) and glutamate-cysteine ligase catalytic subunit (GCLC). CONCLUSIONS: Based on these results, we conclude that SCE exerts protective effects against t-BHP induced oxidative hepatic damage through the reduction of neutrophil infiltration, swelling of liver cells, and necrosis. In addition, SCE regulates the gene expression of phase II antioxidant/detoxifying enzymes independent of hepatic antioxidant enzyme activity.
Animals ; Catalytic Domain ; Erythrocytes ; Gene Expression* ; Glutamate-Cysteine Ligase ; Glutathione ; Glutathione Peroxidase ; Glutathione Reductase ; Glutathione Transferase ; Hand ; Incidence ; Liver ; Necrosis ; Neutrophil Infiltration ; Rats* ; Rats, Sprague-Dawley ; Schisandra* ; tert-Butylhydroperoxide

The hepatoprotective activity of Acanthopanax koreanum Nakai extract (AE) was investigated against D-Galactosamine/Lipopolysaccharide (D-GalN/LPS)-induced liver failure rats compared with that of acanthoic acid (AA) isolated from AE. Although D-GalN/LPS (250 mg/kg body weight/10 microg/kg body weight, i.p.) induced hepatic damage, pretreatments with AE (1 and 3% AE/g day) and AA (0.037% AA, equivalent to 3% AE/g day) alleviated the hepatic damage. This effect was the result of a significant decrease in the activity of alanine transaminase. Concomitantly, both the nitric oxide and IL-6 levels in the plasma were significantly decreased by high-dose AE (AE3) treatment compared to the GalN/LPS control (AE0). This response resulted from the regulation of pro-inflammatory signaling via a decrease in TLR4 and CD14 mRNA levels in the liver. While a high degree of necrosis and hemorrhage were observed in the AE0, pretreatment with AE3 and AA reduced the extent of hepatocyte degeneration, necrosis, hemorrhage and inflammatory cell infiltrates compared to the AE0. In conclusion, these results suggest that especially high-dose AE are capable of alleviating D-GalN/LPS-induced hepatic injury by decreasing hepatic toxicity, thereby mitigating the TLR 4-dependent cytokine release. The anti-inflammatory effect of AE could be contributing to that of AA and AE is better than AA.
Eleutherococcus* ; Alanine Transaminase ; Animals ; Body Weight ; Diterpenes ; Hemorrhage ; Hepatocytes ; Inflammation ; Interleukin-6 ; Liver ; Liver Failure ; Models, Animal* ; Necrosis ; Nitric Oxide ; Plasma ; Rats* ; RNA, Messenger ; Shock, Septic* ; Toll-Like Receptor 4

PURPOSE: To examine the effect of suboptimal chemotherapy in patients undergoing preoperative chemoradiotherapy for the treatment of rectal cancer. MATERIALS AND METHODS: The medical records of 43 patients who received preoperative concurrent chemoradiotherapy, followed by radical surgery for the treatment of pathologically proven adenocarcinoma of the rectum from April 2003 to April 2006 were retrospectively reviewed. The delivered radiation dose ranged from 41.4 to 50.4 Gy. The standard group consisted of patients receiving two cycles of a 5-FU bolus injection for three days on the first and fifth week of radiotherapy or twice daily with capecitabine. The standard group included six patients for each regimen. The non-standard group consisted of patients receiving one cycle of 5-FU bolus injection for three days on the first week of radiotherapy. The non-standard group included 31 patients. Radical surgery was performed at a median of 58 days after the end of radiotherapy. A low anterior resection was performed in 36 patients, whereas an abdominoperineal resection was performed in 7 patients. RESULTS: No significant difference was observed between the groups with respect to pathologic responses ranging from grades 3 to 5 (83.3% vs. 67.7%, p=0.456), downstaging (75.0% vs. 67.7%, p=0.727), and a radial resection margin greater than 2 mm (66.7% vs. 83.9%, p=0.237). The sphincter-saving surgery rate in low-lying rectal cancers was lower in the non-standard group (100% vs. 75%, p=0.068). There was no grade 3 or higher toxicity observed in all patients. CONCLUSION: Considering that the sphincter-saving surgery rate in low-lying rectal cancer was marginally lower for patients treated with non-standard, suboptimal chemotherapy, and that toxicity higher than grade 2 was not observed in the both groups, suboptimal chemotherapy should be avoided in this setting.
Adenocarcinoma ; Chemoradiotherapy ; Deoxycytidine ; Fluorouracil ; Humans ; Medical Records ; Rectal Neoplasms ; Rectum ; Retrospective Studies ; Capecitabine

We experienced a case of diastasis of the symphysis pubis accompanying severe pubic pain and serious gait disturbance, which was developed at 34 weeks gestation before labor pain in 36-year-old primiparous woman, who has experienced previous cesarean section at her first pregnancy due to pelvic pain before onset of labor, so we report a case with a review of the literature.
Adult ; Cesarean Section ; Female ; Gait* ; Humans ; Labor Pain* ; Pelvic Pain ; Pregnancy