Purpose: BVAC-B is an autologous B cell– and monocyte-based immunotherapeutic vaccine that contains cells transfected with a recombinant human epidermal growth factor receptor 2 (HER2) gene and loaded with the natural killer T cell ligand alpha-galactosylceramide. Here, we report the first BVAC-B study in patients with HER2-positive advanced gastric cancer. Materials and Methods: Patients with advanced gastric cancer refractory to standard treatment with HER2+ immunohistochemistry ≥ 1 were eligible for treatment. Patients were administered low (2.5×107 cells/dose), medium (5.0×107 cells/dose), or high dose (1.0×108 cells/dose) of BVAC-B intravenously four times every 4 weeks. Primary endpoints included safety and maximum tolerated BVAC-B dose. Secondary endpoints included preliminary clinical efficacy and BVAC-B-induced immune responses. Results: Eight patients were treated with BVAC-B at low (n=1), medium (n=1), and high doses (n=6). No dose-limiting toxicity was observed, while treatment-related adverse events (TRAEs) were observed in patients treated with medium and high doses. The most common TRAEs were grade 1 (n=2) and grade 2 (n=2) fever. Out of the six patients treated with high-dose BVAC-B, three had stable disease with no response. Interferon gamma, tumor necrosis factor-α, and interleukin-6 increased after BVAC-B treatment in all patients with medium and high dose, and HER2-specific antibody was detected in some patients. Conclusion BVAC-B monotherapy had a safe toxicity profile with limited clinical activity; however, it activated immune cells in heavily pretreated patients with HER2-positive gastric cancer. Earlier treatment with BVAC-B and combination therapy is warranted for evaluation of clinical efficacy.

Background: Human adipose-derived mesenchymal stem cells (AMSCs) are an attractive resource for wound healing because their regenerative capacity improves injury repair. Recently, stem cell-derived exosomes have been shown to play a positive role in stem cell-based therapies. However, the effects of exosomes derived from AMSCs (AEXOs) on wound healing are unclear. In this study, we aimed to examine the role of AEXOs in attenuating inflammation and explore their effects in normal wound healing. Methods: We isolated exosomes from AMSCs and established a cellular model of inflammation by treatment with the inflammatory cytokines, interferon gamma and tumor necrosis factor alpha, to determine whether AEXOs can inhibit inflammation. We examined the wound healing effects of AEXOs in in vitro wound healing models and performed a miRNA array to understand the role of AEXOs in inflammation and wound healing. Results: A significant difference was observed in wound closure and the expression of anti-inflammatory and wound-healing-related factors between control and AEXO-treated cells. Conclusion Our results showed that besides alleviating the inflammation response, AEXOs also promote wound healing. Thus, AEXOs represent a novel, stem-cell-based, therapeutic strategy for wound healing.

Purpose: Coronavirus disease-2019 (COVID-19) is a novel respiratory infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); there are few specific treatments. Convalescent plasma (CP), donated by people who have recovered from COVID-19, is an investigational therapy for severe or critically ill patients with COVID-19. Materials and Methods: This retrospective cohort study evaluated the effectiveness of CP therapy in patients with severe or lifethreatening cases of COVID-19 at two hospitals in Seoul, Korea, between May and September 2020. Clinical outcomes were evaluated in 20 patients with CP therapy in a descriptive manner. Additionally, the changes in cycle threshold (Ct) values of 10 patients with CP therapy were compared to those of 10 controls who had the same (±0.8) initial Ct values but did not receive CP. Results: Of the 20 patients (mean age 66.6 years), 18 received high-dose oxygen therapy using mechanical ventilators or high-flow nasal cannulas. Systemic steroids were administered to 19 patients who received CP. The neutralizing antibody titers of the administered CP were between 1:80 and 1:10240. There were two ABO-mismatched transfusions. The World Health Organization ordinal scale score and National Institutes of Health severity score improved in half of the patients within 14 days. Those who received CP showed a higher increase in Ct values at 24 h and 72 h after CP therapy compared to controls with similar initial Ct values (p=0.002).No transfusion-related side effects were observed. Conclusion CP therapy may be a potential therapeutic option in severe or critically ill patients with COVID-19.

Background: Human adipose-derived mesenchymal stem cells (AMSCs) are an attractive resource for wound healing because their regenerative capacity improves injury repair. Recently, stem cell-derived exosomes have been shown to play a positive role in stem cell-based therapies. However, the effects of exosomes derived from AMSCs (AEXOs) on wound healing are unclear. In this study, we aimed to examine the role of AEXOs in attenuating inflammation and explore their effects in normal wound healing. Methods: We isolated exosomes from AMSCs and established a cellular model of inflammation by treatment with the inflammatory cytokines, interferon gamma and tumor necrosis factor alpha, to determine whether AEXOs can inhibit inflammation. We examined the wound healing effects of AEXOs in in vitro wound healing models and performed a miRNA array to understand the role of AEXOs in inflammation and wound healing. Results: A significant difference was observed in wound closure and the expression of anti-inflammatory and wound-healing-related factors between control and AEXO-treated cells. Conclusion Our results showed that besides alleviating the inflammation response, AEXOs also promote wound healing. Thus, AEXOs represent a novel, stem-cell-based, therapeutic strategy for wound healing.

Purpose: Coronavirus disease-2019 (COVID-19) is a novel respiratory infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); there are few specific treatments. Convalescent plasma (CP), donated by people who have recovered from COVID-19, is an investigational therapy for severe or critically ill patients with COVID-19. Materials and Methods: This retrospective cohort study evaluated the effectiveness of CP therapy in patients with severe or lifethreatening cases of COVID-19 at two hospitals in Seoul, Korea, between May and September 2020. Clinical outcomes were evaluated in 20 patients with CP therapy in a descriptive manner. Additionally, the changes in cycle threshold (Ct) values of 10 patients with CP therapy were compared to those of 10 controls who had the same (±0.8) initial Ct values but did not receive CP. Results: Of the 20 patients (mean age 66.6 years), 18 received high-dose oxygen therapy using mechanical ventilators or high-flow nasal cannulas. Systemic steroids were administered to 19 patients who received CP. The neutralizing antibody titers of the administered CP were between 1:80 and 1:10240. There were two ABO-mismatched transfusions. The World Health Organization ordinal scale score and National Institutes of Health severity score improved in half of the patients within 14 days. Those who received CP showed a higher increase in Ct values at 24 h and 72 h after CP therapy compared to controls with similar initial Ct values (p=0.002).No transfusion-related side effects were observed. Conclusion CP therapy may be a potential therapeutic option in severe or critically ill patients with COVID-19.

BACKGROUND: Safety, efficacy, and time to onset of effect of botulinum toxin type A is of importance to persons who seek improvement in glabellar frown lines, but this has not been well studied. The aim of this study was to determine the safety, efficacy, and onset of action of a newly developed botulinum toxin type A (Nabota) for the treatment of glabellar frown lines. METHODS: This was a single-arm, open-label, and phase 4 clinical study. Forty-two subjects with glabellar lines were treated with five times of intramuscular injection of 0.1 mL (4 U/0.1 mL) for a total of 20 U of Nabota. Efficacy and safety were assessed at 2, 3, 4, 5, and 14 days. Efficacy was assessed by the investigator and it was defined as a 1-point change on a 4-point scale. RESULTS: Improvement in glabellar frown lines at maximum frown was observed in 85.4% of subjects 2 days after administration. Improvement in glabellar lines at rest was observed in 51.2% of subjects 2 days after administration, and the proportion of subjects showing improvement increased with time. No severe adverse events were recorded. CONCLUSION: Onset of action was observed in the majority of subjects by 2 days after administration of Nabota. In addition, Nabota was found to be safe and effective for the treatment of glabellar frown lines.
Botulinum Toxins* ; Botulinum Toxins, Type A* ; Clinical Study* ; Humans ; Injections, Intramuscular ; Prospective Studies* ; Research Personnel

BACKGROUND: Fractional CO₂ laser is an effective treatment for scars, but most patients complain about sharp burning pain, even after the application of lidocaine ointment. This study analyzed the impact of a vibrating device to nonpharmacologically reduce the acute pain of laser treatment, in accordance with the gate control theory of pain management. METHODS: This is a prospective study performed from May 2013 through March 2014. Fifty-three patients (mean age, 26.7 years; range, 16–44 years) who had donated livers for liver transplantation were treated with a fractional CO2 laser (10,600 nm; model eCO₂, Lutronic Corp) for their abdomen scars. Laser treatment was applied 4 months after surgery. A commercially available, locally applied vibrating device (model UM-30M, Unix Electronics Co. Ltd.) was used, in an on-and-off pattern, together with the CO2 laser. A visual analogue scale (VAS; 0, no pain; 10, most severe pain) of pain sensation was assessed and statistically analyzed using a paired t-test. RESULTS: The average VAS score for pain with the vibrating device was 4.60 and the average VAS score without the vibrating device was 6.11. The average difference between scores was 1.51 (P=0.001). CONCLUSIONS: A locally applied vibrating device was demonstrated to be effective in reducing pain when treating with a fractional CO₂ laser. Vibration treatment could be helpful when treating scars with fractional CO₂ laser in pain-sensitive patients, particularly children.
Abdomen ; Acute Pain ; Burns ; Child ; Cicatrix* ; Humans ; Laser Therapy* ; Lasers, Gas ; Lidocaine ; Liver ; Liver Transplantation ; Pain Management ; Prospective Studies ; Sensation ; Vibration*

Approximately 80-85% of D-negative (D-) persons produce anti-D antibodies after exposure to D-positive (D+) red blood cells (RBCs). Previously, anti-D was the most commonly detected Rh antibody, but its incidence has greatly decreased due to the prophylactic use of Rh immunoglobulin (RhIG). Anti-D antibody formation may occur following RhD-incompatible organ transplantation when D- recipients are exposed to D+ RBCs that originate from a donor organ. As a large volume of donor blood may be contained within the transplanted organ, the use of a large amount of RhIG is required in RhD-incompatible liver transplantation. Here, we describe the use of a large amount of RhIG to treat a patient following RhD-incompatible liver transplantation. This patient was a 71-yr-old woman with hepatitis C virus-related liver cirrhosis, who had an A/D- blood type. The donor was her grandson, whose blood type was O/D+. The recipient's preoperative anti-D antibody test was negative. One unit of O/D- irradiated leukoreduced RBCs and three units of A/D- fresh frozen plasma were transfused during liver transplantation. An equal amount (12,000 IU) of RhIG was infused intravenously, immediately after liver transplantation and a second time on post-operation day 1. The anti-D titer was 1:64 on the first post-operation day, and had increased to 1:128 by the following day. By 1 month after the surgery, the titer had decreased to 1:4. In this case of liver transplantation, RhIG was actively used to prevent RhD sensitization and the subsequent occurrence of adverse events associated with RhD-incompatible liver transplantation.
Antibodies ; Antibody Formation ; Erythrocytes ; Female ; Hepatitis C ; Humans ; Immunoglobulins* ; Incidence ; Liver Cirrhosis ; Liver Transplantation* ; Organ Transplantation ; Plasma ; Tissue Donors ; Transplants

BACKGROUND: Bullous pemphigoid (BP) is an autoimmune subepidermal bullous disease associated with autoantibodies against BP180 and BP230. Enzyme-linked immunosorbent assay (ELISA) is a sensitive tool for the detection of immunoglobulin G (IgG) anti-BP180 and anti-BP230 autoantibodies. OBJECTIVE: The aim of this study was to evaluate the usefulness of ELISA for diagnosing and monitoring the disease activity of BP. METHODS: We evaluated serum IgG levels of anti-BP180 and anti-BP230 autoantibodies in 47 BP patients, 16 epidermolysis bullosa aquisita patients, and 15 healthy volunteers using ELISA. Through retrospective review of the medical records, the clinical characteristics of BP including disease activity, duration, pruritus severity and peripheral blood eosinophil counts were assessed. RESULTS: The sensitivity of BP180 ELISA was 97.9%, BP230 ELISA 72.3%, and a combination of the two was 100%. The specificity of BP180 ELISA was 90.3%, BP230 ELISA 100%, and a combination of the two was 90.3%. BP180 ELISA scores showed strong associations with disease activity, pruritus severity, peripheral blood eosinophil counts, and disease duration, whereas BP230 ELISA scores did not. CONCLUSION: BP180 and BP230 ELISAs are highly sensitive methods for the diagnosis of BP, and BP180 ELISA, in particular, is a sensitive tool for monitoring the disease activity of BP.
Autoantibodies ; Enzyme-Linked Immunosorbent Assay ; Eosinophils ; Epidermolysis Bullosa ; Humans ; Immunoglobulin G ; Medical Records ; Pemphigoid, Bullous ; Pruritus ; Retrospective Studies ; Serologic Tests

BACKGROUND: ABO blood grouping reagent verification is essential to ascertain safe blood transfusions. However, the research use of donated blood products has been hampered in Korea by the blood transfusion law and management policies. In this study, we developed cryopreserved red blood cell (RBC) panels utilizing the high glycerol method to verify the ABO and D blood grouping reagents. In addition, we evaluated the stability of ABO and D antigenicity. METHODS: Fresh blood was frozen by the high glycerol method, aliquoted and cryopreserved in 2 mL cryotubes. Twenty-four vials of bloods with types A (n=5), B (n=5), AB (n=4) and O (n=10) for ABO RBC panels, and eleven vials of blood types D positive (n=5), D negative (n=5) and D weak (n=1) for D RBC panels were established. Potency, avidity and specificity tests were carried out with four different commercial ABO and D blood grouping reagents. RESULTS: The potency of cryopreserved RBCs after thawing showed no statistical difference compared with pre-freezing RBCs. Avidity time measurements were 5 seconds in ABO blood and 20 seconds in D positive blood. Specificity test uniformly showed 100% specificity. When thawed RBCs were stored at 4degrees C for 7 days, the potency test measured at intervals of 2 days showed no variation. CONCLUSION: Cryopreserved RBC panels produced by the high glycerol method showed excellent results in stability test with reagents produced by manufacturers in Korea. Therefore, these panels can be utilized as a reliable method of verifying blood grouping reagents.
Blood Grouping and Crossmatching ; Blood Transfusion ; Erythrocytes ; Glycerol ; Indicators and Reagents ; Jurisprudence ; Korea ; Sensitivity and Specificity