Purpose: Programmed death-1 blockade with pembrolizumab has shown promising activity in relapsed/refractory (R/R) extranodal natural killer/T-cell lymphoma (NKTCL), but studies are limited, with small patient numbers. Materials and Methods: Thirteen institutes involved with the Consortium for Improving Survival of Lymphoma, a Korean lymphoma study group, collected the clinical data of 59 patients treated with pembrolizumab as salvage therapy between 2016 and 2022. Results: The median age of the patients was 60 years (range, 22 to 87 years), and 76.3% had advanced Ann Abor stage disease. Pembrolizumab was given to 35.6%, 40.7%, and 23.7% of the patients as second-, third-, and fourth- or higher-line chemotherapy, respectively. The overall response rate was 40.7%, with 28.8% having complete response. The estimated 2-year progression-free survival (PFS) and overall survival rates for all patients were 21.5% and 28.7%, respectively; for responders, the rates were 53.0% and 60.7%, respectively. Although not statistically significant, Eastern Cooperative Oncology Group performance status ≥ 2 (hazard ratio [HR], 1.91; 95% confidence interval [95% CI], 0.93 to 3.94; p=0.078) and stage III or IV disease (HR, 2.59; 95% CI, 0.96 to 6.96; p=0.060) were associated with a trend toward shorter PFS in multivariate analysis. Grade 3 or 4 adverse events (AEs) were noted in 12 patients (20.3%); neutropenia (10.2%), fatigue (6.8%), and pneumonitis (5.1%) were most common AEs. Conclusion In conclusion, while pembrolizumab had a modest effect on patients with R/R NKTCL, it may be a useful salvage therapy for patients with localized disease and good performance status.

Background: Type 2 diabetes mellitus (T2DM) induces endothelial dysfunction and inflammation, which are the main factors for atherosclerosis and cardiovascular disease. The present study aimed to compare the effects of rosuvastatin monotherapy and rosuvastatin/ezetimibe combination therapy on lipid profile, insulin sensitivity, and vascular inflammatory response in patients with T2DM. Methods: A total of 101 patients with T2DM and dyslipidemia were randomized to either rosuvastatin monotherapy (5 mg/day, n=47) or rosuvastatin/ezetimibe combination therapy (5 mg/10 mg/day, n=45) and treated for 12 weeks. Serum lipids, glucose, insulin, soluble intercellular adhesion molecule-1 (sICAM-1), and peroxiredoxin 4 (PRDX4) levels were determined before and after 12 weeks of treatment. Results: The reduction in low density lipoprotein cholesterol (LDL-C) by more than 50% from baseline after treatment was more in the combination therapy group. The serum sICAM-1 levels increased significantly in both groups, but there was no difference between the two groups. The significant changes in homeostasis model assessment of insulin resistance (HOMA-IR) and PRDX4 were confirmed only in the subgroup in which LDL-C was reduced by 50% or more in the combination therapy group. However, after adjusting for diabetes mellitus duration and hypertension, the changes in HOMA-IR and PRDX4 were not significant between the two groups. Conclusion Although rosuvastatin/ezetimibe combination therapy had a greater LDL-C reduction effect than rosuvastatin monotherapy, it had no additional effects on insulin sensitivity and vascular inflammatory response. Further studies are needed on the effect of long-term treatment with ezetimibe on insulin sensitivity and vascular inflammatory response.

Background: Brentuximab vedotin (BV), a potent antibody-drug conjugate, targets the CD30 antigen.In Korea, BV has been approved for the treatment of relapsed or refractory Hodgkin lymphoma (HL), anaplastic large-cell lymphoma (ALCL), and cutaneous T-cell lymphomas, including mycosis fungoides (MF). However, there are limited data reflecting real-world experiences with BV treatment for HL, ALCL, and MF. Methods: This was a multicenter, non-interventional registry study of the efficacy and safety of BV in patients with relapsed or refractory CD30-positive lymphoma (CISL1803/BRAVO).Outcomes were determined based on the occurrence of relapse or progression and overall survival after BV treatment. Results: A total of 85 patients were enrolled in this study. The median number of BV cycles was 10 (range, 2‒16) in the patients with HL. The objective response rate (ORR) of patients with HL to BV was 85.4% (41/48), comprising 27 complete responses (CRs) and 14 partial responses (PRs). The ORR of ALCL was 88% (22/25), consisting of 17 CRs and five PRs, whereas the ORR of MF was 92% (11/12). At the median follow-up of 44.6 months after BV treatment, the median post-BV progression-free survival of HL, ALCL, and MF patients was 23.6 months, 29.0 months, and 16.7 months, respectively (P =0.641). The most common side effect of BV was peripheral neuropathy; 22 patients (25.9%, 22/85) experienced peripheral neuropathy (all grades). Conclusion The treatment outcomes of patients with relapsed or refractory CD30-positive lymphoma improved with BV treatment, and the safety profile was manageable.

Interstitial lung disease (ILD) involves persistent inflammation and fibrosis, leading to respiratory failure and even death. Adult tissue-derived mesenchymal stem cells (MSCs) show potential in ILD therapeutics but obtaining an adequate quantity of cells for drug application is difficult. Daewoong Pharmaceutical’s MSCs (DW-MSCs) derived from embryonic stem cells sustain a high proliferative capacity following long-term culture and expansion. The aim of this study was to investigate the therapeutic potential of DW-MSCs in experimental mouse models of ILD. DW-MSCs were expanded up to 12 passages for in vivo application in bleomycin-induced pulmonary fibrosis and collagen-induced connective tissue diseaseILD mouse models. We assessed lung inflammation and fibrosis, lung tissue immune cells, fibrosis-related gene/protein expression, apoptosis and mitochondrial function of alveolar epithelial cells, and mitochondrial transfer ability. Intravenous administration of DWMSCs consistently improved lung fibrosis and reduced inflammatory and fibrotic markers expression in both models across various disease stages. The therapeutic effect of DW-MSCs was comparable to that following daily oral administration of nintedanib or pirfenidone.Mechanistically, DW-MSCs exhibited immunomodulatory effects by reducing the number of B cells during the early phase and increasing the ratio of Tregs to Th17 cells during the late phase of bleomycin-induced pulmonary fibrosis. Furthermore, DW-MSCs exhibited antiapoptotic effects, increased cell viability, and improved mitochondrial respiration in alveolar epithelial cells by transferring their mitochondria to alveolar epithelial cells. Our findings indicate the strong potential of DW-MSCs in the treatment of ILD owing to their high efficacy and immunomodulatory and anti-apoptotic effects.

Background: Gestational diabetes mellitus (GDM) is the most common metabolic complication of pregnancy. To define the altered pathway in GDM placenta, we investigated the transcriptomic profiles from human placenta between GDM and controls. Methods: Clinical parameters and postpartum complications were reviewed in all participants.Differentially expressed canonical pathways were analyzed between the GDM and control groups based on transcriptomic analysis. CD4 + T, CD8 + T, and senescent T cell subsets were determined by flow cytometry based on staining for specific intracellular cytokines. Results: Gene ontology analysis revealed that the placenta of GDM revealed upregulation of diverse mitochondria or DNA replication related pathways and downregulation of T-cell immunity related pathways. The maternal placenta of the GDM group had a higher proportion of CD4 + T and CD8 + T cells than the control group. Interestingly, senescent CD4 + T cells tended to increase and CD8 + T cells were significantly increased in GDM compared to controls, along with increased programmed cell death-1 (CD274 + ) expression. Programmed death-ligand 1 expression in syncytotrophoblasts was also significantly increased in patients with GDM. Conclusion This study demonstrated increased proinflammatory T cells, senescent T cells and immune-check point molecules in GDM placentas, suggesting that changes in senescent T cells and immune-escape signaling might be related to the pathophysiology of GDM.

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.

Purpose: The purpose of our study was to identify the bleeding risk factors and to validate the safety of shortening the bed rest time after bone marrow examination in pediatric hemato-oncologic patients. Methods: From July 2019 to September 2020, 145 patients were enrolled from a single center. Medical records were reviewed retrospectively. Descriptive statistics were presented, and the data were analyzed using x2 -test, Fisher’s exact test, and a logistic regression. Results: After two hours of bed rest, most of the patients (91.7%) did not have bleeding complications, and only 8.3% of the patients had a minor bleeding. The rate of major bleeding complications, including hematoma, retroperitoneal hemorrhage rate was zero. The bleeding complications was frequently found on bilateral procedures than unilateral procedures and the difference were statistically significant (p<.05). Conclusion Two hours of bed rest time after bone marrow examination could be safe and adequate in pediatric hemato-oncologic patients.

Purpose: The purpose of our study was to identify the bleeding risk factors and to validate the safety of shortening the bed rest time after bone marrow examination in pediatric hemato-oncologic patients. Methods: From July 2019 to September 2020, 145 patients were enrolled from a single center. Medical records were reviewed retrospectively. Descriptive statistics were presented, and the data were analyzed using x2 -test, Fisher’s exact test, and a logistic regression. Results: After two hours of bed rest, most of the patients (91.7%) did not have bleeding complications, and only 8.3% of the patients had a minor bleeding. The rate of major bleeding complications, including hematoma, retroperitoneal hemorrhage rate was zero. The bleeding complications was frequently found on bilateral procedures than unilateral procedures and the difference were statistically significant (p<.05). Conclusion Two hours of bed rest time after bone marrow examination could be safe and adequate in pediatric hemato-oncologic patients.

Background: As an instrument for measuring body composition in experimental animals, dual energy X-ray absorptiometry (DXA) is ideal for accuracy, cost, and measurement efficiency. However, there is too little insight into the effectiveness of the various aspects of applying DXA to experimental animals. We investigated whether to compare and verify the precision and accuracy of DXA and nuclear magnetic resonance (NMR) animal body composition analyzers. Methods: We used 30 Institution of Cancer Research mice in the study. First, in order to evaluate the reproducibility of DXA and NMR, we did repeated measurements by repositioning each mouse in anesthesia and euthanasia states. Subsequently, the accuracy of each device was evaluated by comparing the weight measured before the experiment, the weight of the tissue extracted from the mice after the experiment, and the measured DXA and NMR. In addition, when measuring the body composition of animals, we compared the time and the measurable body composition parameters and summarized the advantages and disadvantages of the 2 devices. Results: Compared to NMR, DXA had the advantage of a fast measurement of bone composition and rapid image analysis. In addition, DXA showed a higher correlation (>95%) with fat mass, lean mass baseline than did NMR (>85%). Conclusions In conclusion, DXA was confirmed to have higher precision and measurement accuracy than did NMR. Therefore, DXA is an effective method for evaluating the body composition of experimental animals.

BACKGROUND: The Korean Society of Infectious Diseases recommends non-mandatory vaccination of newly employed healthcare workers (HCWs) with 2 measles–mumps–rubella (MMR) vaccine doses. Here, we aimed to investigate the seroprevalence of mumps among HCWs exposed to index patients with mumps and the efficacy of MMR vaccination as postexposure prophylaxis (PEP) when a mumps outbreak was encountered among HCWs in a tertiary university hospital in Korea. MATERIALS AND METHODS: Four HCWs were diagnosed with mumps over a 4-day period in January 2016. Three were working at a dental clinic and one visited the clinic on the day of symptoms onset of the first patient. We investigated all HCWs who either worked in that dental clinic, visited the clinic, or being within 1.5 meter of the patients with mumps without wearing surgical masks. Seventy HCWs were exposed to 4 HCWs with mumps. We interviewed all the exposed HCWs to investigate mumps infection and MMR vaccination history; they were all tested for mumps IgG. RESULTS: Of the 70 exposed HCWs, 56 (80%) were females; the median age was 34 years (range 21–59 years) and 3 had a history of mumps infection. The vaccination status verification of mumps among the HCWs was unavailable. As for serologic testing, 54 (77.1%) were seropositive. Seropositivity rate for the mumps virus in males was significantly lower than that in females (50.0% vs. 83.9% respectively, P = 0.007). A lower seroprevalence of mumps was observed among HCWs aged ≥40 years than those aged <40 years; however, this difference was not significant (65.2% vs. 83.0%, P = 0.096). During the initial intervention, all exposed HCWs were vaccinated because the turnaround time for serologic testing was expected to be >2 days. Thirty-four (62.9%) of 54 seropositive HCWs and 16 seronegative HCWs were administered MMR vaccines as PEP and following this, no additional cases of mumps were encountered during the maximum incubation period. CONCLUSION Of the exposed HCWs, 77.1% were mumps-seropositive. Seropositive rates differed according to factors such as age and sex. Eligible HCWs received a MMR vaccine as PEP and no additional mumps cases occurred during the incubation period. It was useful in our infection control activities during the mumps outbreak.