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: 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.

Background: The Omicron variant has become the most prevalent SARS-CoV-2 variant. Omicron is known to induce milder lesions compared to the original Wuhan strain. Fatal infection of the Wuhan strain into the brain has been well documented in COVID-19 mouse models and human COVID-19 cases, but apparent infections into the brain by Omicron have not been reported in human adult cases or animal models. In this study, we investigated whether Omicron could spread to the brain using K18-hACE2 mice susceptible to SARS-CoV-2 infection. Results: K18-hACE2 mice were intranasally infected with 1 × 105 PFU of the original Wuhan strain and the Omicron variant of SARS-CoV-2. A follow-up was conducted 7 days post infection. All Wuhan-infected mice showed > 20% body weight loss, defined as the lethal condition, whereas two out of five Omicron-infected mice (40%) lost > 20% body weight. Histopathological analysis based on H&E staining revealed inflammatory responses in the brains of these two Omicron-infected mice. Immunostaining analysis of viral nucleocapsid protein revealed severe infection of neuron cells in the brains of these two Omicron-infected mice. Lymphoid depletion and apoptosis were observed in the spleen of Omicron-infected mice with brain infection. Conclusion Lethal conditions, such as severe body weight loss and encephalopathy, can occur in Omicron-infected K18-hACE2 mice. Our study reports, for the first time, that Omicron can induce brain infection with lymphoid depletion in the mouse COVID-19 model.

Background: This study aimed to determine the effect of ramen sauce on tooth tone changes over time, after selecting three different ramen colors from the ramens sold in the market, and applying the sauce to bovine teeth. Methods: Healthy bovine teeth were selected, and cutting discs were used to produce 60 specimens (5×5×3 mm), with 15 specimens distributed per county. Three types of ramen (buldak, chacharoni black bean sauce, and ottogi curry noodle) were used as the experimental group, and water was used as the negative control group. Tooth tone measurement was performed using a spectrophotometer (CM-700d) to measure the color before and after 1 (3 h 44 min), 2 (7 h 28 min), 3 (11 h 12 min), and 4 weeks (14 h 56 min). Analysis of the color tone change was performed using Statistical Package for the Social Sciences version 28. Results: In the experimental group, there was a significant color tone change before and after immersion. L* indicated the largest change in black bean sauce ramen, a* indicated buldak ramen, and b* indicated the largest change in curry ramen. The amount of color change (ΔE*) was the largest in curry ramen, followed by buldak and black bean sauce ramens. The results of the post-hoc analysis showed significant differences between all groups except buldak and black bean sauce ramens. Conclusion All three types of ramen revealed significant color change before and after immersion, and curry ramen showed the largest amount of color change among them.

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.

Background: Chronic lymphocytic leukemia (CLL) is the most common type of adult leukemia in Western countries but is rare in the East Asian countries. Due to its rarity and the lack of feasible novel agents and laboratory prognostic tools, there are limited data on the clinical outcomes of this disease in Asia. To clarify the current treatment status, we performed a multicenter retrospective analysis of patients with CLL in Korea. Methods: The medical records of 192 eligible patients between 2008 and 2019 were reviewed for clinical characteristics, treatment courses, and outcomes. The first-line treatment regimens of the patients included in this analysis were as follows: fludarabine/cyclophosphamide/rituximab (FCR) (N=117, 52.7%), obinutuzumab plus chlorambucil (GC) (N=30, 13.5%), and chlorambucil monotherapy (N=24, 10.8%). Results: The median progression-free survival (PFS) was 55.6 months, and the average 2-year PFS rate was 80.3%. PFS was not significantly different between the patients receiving FCR and those receiving GC; however, chlorambucil treatment was associated with significantly inferior PFS (P ＜0.001). The median overall survival was 136.3 months, and the average 5- and 10-year OS rates were 82.0% and 57.4%, respectively. Conclusion This is one of the largest studies involving Korean patients with CLL. Although the patients had been treated with less favored treatment regimens, the outcomes were not different from those reported in Western studies.

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.

BACKGROUND: Increasing evidence suggests a pivotal role for neuronal inflammation in response to replicating varicella zoster virus in the development of postherpetic neuralgia (PHN). OBJECTIVE: In this study, we investigated the value of serum levels of various inflammatory markers in acute herpes zoster (HZ) as predictors for the development of PHN. METHODS: A total of 116 patients with acute HZ were enrolled in this study. We measured scores on the pain visual analogue scale (VAS) at baseline and at 1, 3, and 6 months after diagnosis of HZ. We defined PHN as pain greater than 1 on the VAS lasting for more than 6 months. Serum samples for laboratory assay, including complete blood count were obtained at the initial visit. Correlations between the levels of each inflammatory marker and the development of PHN were evaluated. RESULTS: Levels of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), lymphocyte count, and albumin showed significant correlations with development of PHN in univariate analysis. Levels of ESR, CRP, and lymphocyte count also showed significant correlations in multivariate analysis. ESR level showed stronger correlations with development of PHN than levels of CRP and lymphocyte count. CONCLUSION: In this study, we confirmed that elevated ESR was an independent and significant predictor of PHN in patients with acute HZ. To validate these results, further well-designed, randomized clinical trials are needed.
Blood Cell Count ; Blood Sedimentation ; C-Reactive Protein ; Diagnosis ; Herpes Zoster* ; Herpesvirus 3, Human ; Humans ; Inflammation ; Lymphocyte Count ; Multivariate Analysis ; Neuralgia, Postherpetic* ; Neurons

BACKGROUND: The subcutaneous formulation of biologic disease-modifying antirheumatic drugs (DMARDs) was preferred due to favored self-administration and would be an economical treatment option for patients with rheumatoid arthritis. This study was to compare the economic impact of biologic DMARDs administered by subcutaneous injection in patients with rheumatoid arthritis who had inadequate response to conventional DMARDs. METHODS: The cost-minimization analysis was conducted to estimate the lifetime health care costs of treatment sequences with subcutaneous biologic DMARDs as first-line therapy from a health care system perspective. The Markov model was developed to represent the transitions through treatment sequences based on American College of Rheumatology response rate and discontinuation rate. The health care costs comprised the cost of medications, administration, dispensing, outpatient visits, test/diagnostic examination, palliative therapy and treatment of serious infection. All costs were expressed in 2016 Korean Won (KRW) and discounted at 5%. RESULTS: The mean lifetime health care cost per patient was lowest in the etanercept sequence, which was estimated at KRW 63,441,679. The incremental costs of the treatment sequence started with adalimumab, golimumab, abatacept, and tocilizumab were KRW 7,985,730, KRW 4,064,669, KRW 2,869,947, and KRW 4,282,833, respectively, relative to etanercept sequence. These differences in costs mainly were attributable to medication costs. One-way and probabilistic sensitivity analyses confirmed that etanercept represented the option with the lowest cost compared with comparators. CONCLUSION: This study found that etanercept is likely a cost-saving treatment option among subcutaneous biologic DMARDs in patients with rheumatoid arthritis.
Antirheumatic Agents* ; Arthritis, Rheumatoid* ; Delivery of Health Care ; Health Care Costs ; Humans ; Injections, Subcutaneous* ; Outpatients ; Palliative Care ; Rheumatology ; Abatacept ; Adalimumab ; Etanercept

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