Investigation of adverse events following bacille CalmetteGuérin immunization using immunization safety surveillance system in Korea Centers for Disease Control and Prevention

Purpose@#The report of adverse events following immunization (AEFI) in Korea has continued since 1994, and the most frequently reported cases of AEFI of Korea Centers for Disease Control and Prevention (KCDC) is bacille Calmette-Guérin (BCG). Meanwhile, various inoculation methods and strains have been used in the past 6 years in Korea. Therefore, we investigated AEFI of BCG by strain types and inoculation methods using immunization safety surveillance of KCDC. @*Materials and Methods@#We reviewed BCG AEFIs registered in the KCDC from January 2013 to June 2018. @*Results@#There were 336 AEFI cases during the period, and average time interval from vaccination to symptom onset was within 2 months. AEFI proportion was 6.4 cases per 100,000 doses for BCG percutaneous Tokyo strain, 41.6 cases per 100,000 doses of BCG intradermal Danish strain, and 25.9 cases per 100,000 doses of BCG intradermal Tokyo strain. Intradermal type was more reported AEFI than percutaneous type in the same strain. The most common adverse events were local reaction like BCG lymphadenitis and severe adverse reactions such as osteomyelitis or disseminated BCG disease were 0.1 to 0.2 cases per 100,000 doses which are correlated with the range of World Health Organization published AEFI rates. @*Conclusion@#The AEFI reporting rate does not equal the actual proportion of AEFI occurrence. Because AEFI monitoring is a passive surveillance system, various factors might influence the number of events reported. Nevertheless, it is important to analyze BCG AEFI by vaccine strains and inoculation method using surveillance data of KCDC.

Investigation of adverse events following bacille CalmetteGuérin immunization using immunization safety surveillance system in Korea Centers for Disease Control and Prevention

Purpose@#The report of adverse events following immunization (AEFI) in Korea has continued since 1994, and the most frequently reported cases of AEFI of Korea Centers for Disease Control and Prevention (KCDC) is bacille Calmette-Guérin (BCG). Meanwhile, various inoculation methods and strains have been used in the past 6 years in Korea. Therefore, we investigated AEFI of BCG by strain types and inoculation methods using immunization safety surveillance of KCDC. @*Materials and Methods@#We reviewed BCG AEFIs registered in the KCDC from January 2013 to June 2018. @*Results@#There were 336 AEFI cases during the period, and average time interval from vaccination to symptom onset was within 2 months. AEFI proportion was 6.4 cases per 100,000 doses for BCG percutaneous Tokyo strain, 41.6 cases per 100,000 doses of BCG intradermal Danish strain, and 25.9 cases per 100,000 doses of BCG intradermal Tokyo strain. Intradermal type was more reported AEFI than percutaneous type in the same strain. The most common adverse events were local reaction like BCG lymphadenitis and severe adverse reactions such as osteomyelitis or disseminated BCG disease were 0.1 to 0.2 cases per 100,000 doses which are correlated with the range of World Health Organization published AEFI rates. @*Conclusion@#The AEFI reporting rate does not equal the actual proportion of AEFI occurrence. Because AEFI monitoring is a passive surveillance system, various factors might influence the number of events reported. Nevertheless, it is important to analyze BCG AEFI by vaccine strains and inoculation method using surveillance data of KCDC.

Dendritic Cell-Based Cancer Immunotherapy against Multiple Myeloma: From Bench to Clinic / 전남의대학술지

Although the introduction of stem cell transplantation and novel agents has improved survival, multiple myeloma (MM) is still difficult to cure. Alternative approaches are clearly needed to prolong the survival of patients with MM. Dendritic cell (DC) therapy is a very promising tool immunologically in MM. We developed a method to generate potent DCs with increased Th1 polarization and migration ability for inducing strong myeloma-specific cytotoxic T lymphocytes. In this review, we discuss how the efficacy of cancer immunotherapy using DCs can be improved in MM.

House dust mite-specific immunoglobulin E and longitudinal exhaled nitric oxide measurements in children with atopic asthma / 소아과

PURPOSE: House dust mite (HDM) has been suggested to be the most important aeroallergen responsible for atopic asthma in Korea. We aimed to investigate that specific IgE antibodies to HDM and other common indoor aeroallergens contribute differently to total serum IgE and show different relationships with longitudinal fractional exhaled nitric oxide (FeNO) measurements in Korean atopic asthmatic patients. METHODS: A total of 193 children aged 8 to 16 years with intermittent or mild persistent atopic asthma were recruited. Sera were assayed for total IgE and specific IgE antibodies to HDM and other common indoor allergens. FeNO was serially measured 10 times or more over 2 years when subjects were not receiving controller medications. RESULTS: In 152 children who completed the study, IgE antibodies to specific HDM were more prevalent than those to other common indoor aeroallergens. In addition, IgE antibody titers to HDM were the strongest contributor to total IgE increases. Furthermore, only HDM-specific IgE antibody titer significantly correlated with maximum FeNO (r=0.21, P=0.029) and the rate of FeNO higher than 21 parts per billion (ppb) (r=0.30, P=0.002). Eight patients (5%) were found to have maximum FeNO of 21 ppb or less, suggesting the presence of a low FeNO phenotype among atopic asthmatic patients. CONCLUSION: The quantity of HDM-specific IgE antibody provides a possible explanation for increases of total IgE and significantly correlates with the amount and frequency of FeNO increases in Korean atopic asthmatic patients.

Relationships of bronchodilator response with asthma control and fractional exhaled nitric oxide in children with atopic asthma

PURPOSE: Because bronchodilator response (BDR) is variable among asthmatic patients, there are practical limitations in using BDR to assess asthma control. We investigated the relationships of BDR with asthma control status and fractional exhaled nitric oxide (FeNO) in children with atopic asthma. METHODS: One hundred ninety-one patients aged 8 to 16 years with atopic asthma were enrolled. Pulmonary function tests including BDR and FeNO were serially measured 10 times or more over 2 years when subjects were not receiving controller medications. During the last year of follow-up, the loss of asthma control was assessed in all participants. RESULTS: We identified 114 children (60%) with at least 1 positive BDR (> or =12%) over the 2-year observation period. Higher levels of BDRs and higher rates of positive BDRs were associated with lower lung function and lower methacholine PC20 (provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second). The loss of asthma control occurred in 106 of individuals (93%) who had positive BDRs, as compared to 52 of 77 (68%) with negative BDRs (P21 parts per billion than those who maintained asthma control (all P<0.001). CONCLUSION: Positive BDRs are linked to a higher probability of asthma control loss in children with atopic asthma. In addition, high FeNO is associated with asthma control loss in asthmatic children with negative BDRs.

Dendritic Cell-Based Cancer Immunotherapy against Multiple Myeloma: From Bench to Clinic / 전남의대학술지

Although the introduction of stem cell transplantation and novel agents has improved survival, multiple myeloma (MM) is still difficult to cure. Alternative approaches are clearly needed to prolong the survival of patients with MM. Dendritic cell (DC) therapy is a very promising tool immunologically in MM. We developed a method to generate potent DCs with increased Th1 polarization and migration ability for inducing strong myeloma-specific cytotoxic T lymphocytes. In this review, we discuss how the efficacy of cancer immunotherapy using DCs can be improved in MM.

Dendritic Cell-Based Cancer Immunotherapy against Multiple Myeloma: From Bench to Clinic / 전남의대학술지

Although the introduction of stem cell transplantation and novel agents has improved survival, multiple myeloma (MM) is still difficult to cure. Alternative approaches are clearly needed to prolong the survival of patients with MM. Dendritic cell (DC) therapy is a very promising tool immunologically in MM. We developed a method to generate potent DCs with increased Th1 polarization and migration ability for inducing strong myeloma-specific cytotoxic T lymphocytes. In this review, we discuss how the efficacy of cancer immunotherapy using DCs can be improved in MM.

A prospective study to assess the efficacy and safety of oral propranolol as first-line treatment for infantile superficial hemangioma / 소아과

PURPOSE: To determine the efficacy and safety of oral propranolol as a first-line treatment for superficially located infantile hemangioma (IH) and propose an assessment tool to measure treatment response. METHODS: Patients with superficial IH under 1 year of age were prospectively recruited between May 2012 and December 2013 at the Department of Pediatrics of Chungbuk National University Hospital. Propranolol was administered to 12 infants (median age, 3.8 months) while monitoring cardiovascular and adverse metabolic effects. If a patient showed no adverse events, the dosage was gradually increased up to 3 mg/kg/day and maintained for 1 year. We used our own scoring system to assess treatment response using parameters like change in color, and longest diameter, and thickness of the IH. RESULTS: Eleven out of 12 patients completed the protocol with consistent improvement of hemangiomas during therapy. Patients on propranolol showed a more than 50% involution in the first 3 months, with additional steady involution until 1 year. Patients with the highest scores at 1 month maintained their score and showed better responses until treatment termination. The patient with the lowest score at 1 month did not show any further regression and stopped propranolol treatment 4 months after initiation. In two children with recurrences after successful therapeutic regression, propranolol was effective after being reintroduced. Propranolol treatment was not interrupted in any patient due to adverse events. CONCLUSION: Oral propranolol at 3 mg/kg/day showed a consistent, rapid, and therapeutic effect on superficial IHs without significant adverse events.

GATA1-positive Acute Megakaryoblastic Leukemia in a 6.9-year-old Patient with Down Syndrome: What is the Prognosis? / 임상소아혈액종양

We describe a very rare case of 6.9-year-old boy with Down syndrome (DS) and a prior history of transient myeloproliferative disorder. He was diagnosed with acute megakaryoblastic leukemia and found to have a novel GATA1 gene mutation, as well as a complex karyotype without recurrent acute myeloid leukemia (AML) aberrations. The patient achieved an early bone marrow response to chemotherapy. However, relapse occurred during treatment, 9 months after the initial diagnosis. Although GATA1 mutations are closely associated with DS-AML, we speculate that factors other than the presence of the GATA1 mutation can affect the overall outcome in older pediatric patients.

GATA1-positive Acute Megakaryoblastic Leukemia in a 6.9-year-old Patient with Down Syndrome: What is the Prognosis? / 임상소아혈액종양

We describe a very rare case of 6.9-year-old boy with Down syndrome (DS) and a prior history of transient myeloproliferative disorder. He was diagnosed with acute megakaryoblastic leukemia and found to have a novel GATA1 gene mutation, as well as a complex karyotype without recurrent acute myeloid leukemia (AML) aberrations. The patient achieved an early bone marrow response to chemotherapy. However, relapse occurred during treatment, 9 months after the initial diagnosis. Although GATA1 mutations are closely associated with DS-AML, we speculate that factors other than the presence of the GATA1 mutation can affect the overall outcome in older pediatric patients.

Cellular immunotherapy using dendritic cells against multiple myeloma

Cellular therapy with dendritic cells (DCs) is emerging as a useful immunotherapeutic tool to treat multiple myeloma (MM). DC-based idiotype vaccination was recently suggested to induce idiotype-specific immune responses in MM patients. However, the clinical results so far have been largely disappointing, and the clinical effectiveness of such vaccinations in MM still needs to be demonstrated. DC-based therapies against MM may need to be boosted with other sources of tumor-associated antigens, and potent DCs should be recruited to increase the effectiveness of treatment. DCs with both high migratory capacity and high cytokine production are very important for effective DC-based cancer vaccination in order to induce high numbers of Th1-type CD4+ T cells and CD8+ cytotoxic T lymphocytes. The tumor microenvironment is also important in the regulation of tumor cell growth, proliferation, and the development of therapeutic resistance after treatment. In this review, we discuss how the efficacy of DC vaccination in MM can be improved. In addition, novel treatment strategies that target not only myeloma cells but also the tumor microenvironment are urgently needed to improve treatment outcomes.

In vitro induction of anterior gradient-2-specific cytotoxic T lymphocytes by dendritic cells transduced with recombinant adenoviruses as a potential therapy for colorectal cancer

Anterior gradient-2 (AGR2) promotes tumor growth, cell migration, and cellular transformation, and is one of the specific mRNA markers for circulating tumor cells in patients with gastrointestinal cancer. We investigated the feasibility of AGR2 as a potent antigen for tumor immunotherapy against colorectal cancer (CRC) cells using dendritic cells (DCs) transduced with a recombinant adenovirus harboring the AGR2 gene (AdAGR2). DCs transduced with a recombinant adenovirus encoding the AGR2 gene (AdAGR2/DCs) were characterized. These genetically-modified DCs expressed AGR2 mRNA as well as AGR2 protein at a multiplicity of infection of 1,000 without any significant alterations in DC viability and cytokine secretion (IL-10 and IL-12p70) compared with unmodified DCs as a control. In addition, AdAGR2 transduction did not impair DC maturation, but enhanced expression of HLA-DR, CD80, and CD86. AdAGR2/DCs augmented the number of IFN-gamma-secreting T-cells and elicited potent AGR2-specific cytotoxic T lymphocytes capable of lysing AGR2-expressing CRC cell lines. These results suggest that AGR2 act as a potentially important antigen for immunotherapy against CRC in clinical applications.

Alpha-Type 1 Polarized Dendritic Cells Loaded with Apoptotic Allogeneic Breast Cancer Cells Can Induce Potent Cytotoxic T Lymphocytes against Breast Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Various tumor antigens can be loaded onto dendritic cells (DCs) to induce a potent cytotoxic T lymphocyte (CTL) response in DC-based immunotherapy against breast cancer. However, in the clinical setting, obtaining a sufficient number of autologous tumor cells as a source of tumor antigens is a laborious process. We therefore investigated the feasibility of immunotherapy using breast-cancer-specific CTLs generated in vitro by use of alpha-type 1 polarized DCs (alpha DC1s) loaded with ultraviolet B-irradiated cells of the breast cancer cell line MCF-7. MATERIALS AND METHODS: alphaDC1s were induced by loading allogeneic tumor antigen generated from the MCF-7 UVB-irradiated breast cancer cell line. Antigen-pulsed alphaDC1s were evaluated by morphological and functional assays, and the breast-cancer-specific CTL response was analyzed by cytotoxic assay. RESULTS: The alphaDC1s significantly increased the expression of several molecules related to DC maturation without differences according to whether the alphaDC1s were loaded with tumor antigens. The alphaDC1s showed a high production of interleukin-12 both during maturation and after subsequent stimulation with CD40L, which was not significantly affected by loading with tumor antigens. Breast-cancer-specific CTLs against autologous breast cancer cells were successfully induced by alphaDC1s loaded with apoptotic MCF-7 cells. CONCLUSION: Autologous DCs loaded with an allogeneic breast cancer cell line can generate potent breast-cancer-specific CTL responses. This may be a practical method for cellular immunotherapy in patients with breast cancer.

Endovascular Treatment of Massive Retroperitoneal Hemorrhage Due to Spontaneous Rupture of Right Adrenal Gland Metastasis that was Secondary to Invasive Hepatocellular Carcinoma: A Case Report

The reported incidence of spontaneous rupture of primary hepatocellular carcinoma (HCC) is up to 14.5%. However, rupture of the metastatic lesions of HCC is very rare. We describe here a case of massive retroperitoneal hemorrhage due to spontaneous rupture of right adrenal gland metastasis that was secondary to invasive HCC. This was successfully controlled by performing transcatheter arterial embolization (TAE).

Intrabiliary Growth of Recurrent Tumor after Percutaneous RF ablation for Treating Liver Metastasis from Colon Cancer: A Case Report

A 64-year-old man who underwent right hemicolectomy 3.5 years ago for ascending colon cancer and then RF ablation for two metastatic nodules in the liver was admitted to our hospital with a new metastatic nodule in the S6/7 segment of the liver. The CT scan showed a low attenuating metastatic nodule 2.2 cm in diameter in the S6/7 segment of the liver, and the liver showed peripheral bile duct dilatation. This nodule was treated with percutaneous RF ablation. A follow-up CT seven months after RF ablation showed the presence of a viable tumor in the RF ablation zone, with tumor extension along the dilated bile duct. These findings were confirmed on the resected specimen.

Adenoid Basal Carcinoma of the Uterine Cervix

We report a case of adenoid basal carcinoma of the uterine cervix unexpectedly found in a 68-year-old female. She was diagnosed with a high-grade squamous intraepithelial lesion (HSIL) on a cervical smear and subsequent cervical punch biopsy. Total abdominal hysterectomy was performed, and there were no significant gross findings in the uterine cervix. Microscopically, the epithelial surface showed a HSIL with glandular extension. Below the neoplastic epithelial lesion were numerous small nests of uniform small cells, which extended to the parametrium. These tumor cells contained hyperchromatic nuclei, inconspicuous nucleoli, and scant cytoplasm. Peripheral palisading and gland-like or acinar structures in the nests were noted. The latter were positive for mucicarmine stain. Foci of squamous differentiation exhibiting occasional mitoses and large atypical cells were seen in the small nests. Stromal reaction was not obvious. Immunohistochemically, the HSIL lesion and adenoid basal carcinoma lesion were negative for human papillowa virus. The tumor cells forming nests were positive for carcinoembryonic antigen, S-100 protein, and high molecular weight cytokeratin, but were negative for -smooth muscle actin and chromogranin A.

Serum Level of G-CSF and GM-CSF and CFU-GM Response to Hematopoietic Growth Factors in a Patient with Cyclic Neutropenia

PURPOSE: Serum levels of G-CSF and GM-CSF were measured and CFU-GM assay using G- CSF, GM-CSF and SCF was conducted to evaluate the influence of hematopoietic growth factor on the precursor cells of cyclic neutropenia. METHODS: A 7-year-old male with cyclic neutropenia was studied. Marrow mononuclear cells were isolated at neutrophil nadir and recovery and cultured in methylcellulose media with or without G-CSF, GM- CSF and SCF. CD34 positive cells were evaluated using flow cytometry. Serum levels of G-CSF and GM-CSF were measured by ELISA. RESULTS: The Numbers of CFU-GM without growth factors were 50 at neutrophil nadir and 33 at the recovery phase in the patient and show increased colony forming capacity. CD34 positive cells were 9.32% at nadir and 14.17% at recovery. Increasement of CFU-GM with G-CSF at nadir and recovery were 46% and 118% and those with GM-CSF were 70% and 78% respectively, compared with 54.4% and 78.2% in control groups. In contrast, the presence of SCF did not enhance CFU-GM number in the patient, but in the control group, increasement with SCF was 28.9 %. There an was inverse relationship between serum G-CSF levels and peripheral neutrophil count whereas those of GM-CSF were constant. CONCLUSION: Serum G-CSF level showed inverse relationship with neutrophil counts. The response of progenitor cells to G-CSF and GM-CSF was not impaired. The presence of SCF did not enhance CFU-GM number in the patient. This result suggests that the abnormality in hematopoiesis in cyclic neutropenia may involve more immature progenitor cells responsive to SCF.

A Demonhstration of a Tracheal Bronchus by Bronchoscopy and Computed Tompgraphy

Tracheal bronchus is an aberrant bronchus that arises most often from the right tracheal wall above the carina and is the result of an additional tracheal outgrowth early in embryonic life. It; incidence ranges between 0.1 and 5%. This anomaly is usually diagnosed incidentally during bronchoscopy, bronchography or computed tomography. Occasionally, it represents the underlying etiology for chronic pulmonary disease, especially if it involves the right upper lobe and reflects an abnorrnal pulmonary clearing mechanism. The tracheal bronchus may be associated with other bronchopulmonary anomalies, tracheal stenosis, or Down's syndrome. Asymptornatic tracheal bronchus does not require any treatment. In case of tracheal bronchus associated recurrent right upper lobe diseases, tracheal bronchus therapy should include resection of the aberrant bronchus as well as the lob it supplies. (J Korgan Pediatr Soc 2000;43:1501-1504)

Long-term Outcome of Chronic Childhood Idiopathic Thrombocytopenic Purpura according to Therapeutic Methods / 대한소아혈액종양학회지

PURPOSE: Idiopathic thrombocytopenic purpura (ITP) was the most common disease of thrombocytopenic purpura in children, chronic course was shown in 10%. Splenectomy had been used in chronic thrombocytopenic purpura as classic therapy, and many therapeutic method had been tried. We define response to therapy and long-term outcome of chronic childhood idiopathic thrombocytopenic purpura. METHODS: We retrospectively analyzed 41 patients that treated and diagnosed as chronic thrombocytopenic purpura at the Department of Pediatrics, Severance Hospital between Aug. 1981 and Aug. 1999 and followed for mean 8.2 years. The mean age was 6.2 years (range from 1month to 12.3 years) and sex-ratio of male to female was 1:2. According to therapeutic methods, they were divided into splenectomy group, spleen irradiation group, azathioprine group, interferon group, high-dose oral dexamethasone group, vincristine group, intravenous gammaglobulin group, low-dose prednisone group, and low-dose prednisone with intermittent intravenous gammaglobulin group. The results were classified into complete response (CR: platelets> 100,000/mm3), partial response (PR: platelets> 50,000/mm3), no response (NR: platelets <50,000/mm3). RESULTS: The treatment response and number of patients according to therapeutic methods were as follows; splenectomy group, 12 cases (CR-9 cases, PR-1 case, NR-2 cases), spleen irradiation group, 1 case (CR), azathioprine group, 6 cases (CR-1 case, NR-5 cases), interferon group, 3 cases (CR-1 case, PR-1 case, NR-1 case), high-dose oral dexamethasone group, 4 cases (CR-2 cases, PR-1 case, NR-1 case), vincristine group, 2 cases (NR), intravenous gammaglobulin group, 35 cases (CR-5 cases, PR-5 cases, NR-25 cases), low-dose prednisone group, 5 cases (NR), and low-dose prednisone with intermittent intravenous gammaglobulin group, 30 cases (CR-7 cases, PR-3 cases, NR-20 cases). CONCLUSION: The results of therapeutic method in splenectomy group were the most highest score (12 cases: CR-9 cases, PR-1 case, NR-2 cases), high-dose oral dexamethasone group, interferon group, and low-dose prednisone with intermittent intravenous gammaglobulin group in high incidence order. Spleen irradiation was supposed to trial method of treatment before splenectomy, because the risk was lower than splenectomy, although they had 1 case.

Normal Values of IgG and IgG Subclass Concentrations According to Age in Children / 소아알레르기및호흡기학회지

PURPOSE: Currently the most widely used method of measuring IgG concentration is the method employing ELISA. This method has an advantage to detect smaller quantities than other standard methods, but in certain cases, consistent results cannot be obtained, thus impairing reliable data analysis. In this study, we attempt to determine the advantages in data analysis offered by the new method developed by Binding Site Ltd. (England) that employs a nephelometry. METHODS: 20 healthy subjects were studied from each of the following age groups : neonates, 1-4 months old, 5-10 months old, 11-24 months old, and 2-5 years old children. Serum IgG and IgG subclass concentrations were measured by nephelometry (Gehring Nephelometer Analyzer II, Germany) using Human IgG subclass, Liquid reagents BNII kit (Binding Site Ltd., England). RESULTS: 1) The r values for the standard curves of IgG, IgG1, IgG2, IgG3, IgG4 concentrations were 0.991, 0.997, 0.980, 0.973, 0.997, respectively. 2) IgG, IgG3, and IgG4 concentrations were lowest at the age of 5-10 months and increased to normal adult levels at 2-5 years of age. 3) IgG1 and IgG2 were lowest at the age of 1-4 months and increased to normal adult levels at 2-5 years of age. CONCLUSION: The method employing nephelometry for measuring serum IgG & IgG subclasses concentration is not as sensitive as ELISA in detecting the lower concentrations. However, our studies indicate that it presents the advantage of better quality control in measuring values in the average range.