MicroRNA-765 is upregulated in myelodysplastic syndromes and induces apoptosis via PLP2 inhibition in leukemia cells

Background@#Epigenetic studies, particularly research on microRNA (miRNA), have flourished. The abnormal expression of miRNA contributes to the development of hematologic malignancies.miR-765 has been reported to inhibit cell proliferation by downregulating proteolipid protein 2 (PLP2), which causes apoptosis. We investigated miR-765 dysregulation in myelodysplastic syndromes (MDS). @*Methods@#We compared the expression profiles of miR-765 in 65 patients with MDS and 11 controls.Cell proliferation and apoptosis assays were performed to determine the in vitro effects of miR-765 on leukemia cells transfected with the miR-765 mimic. Reverse transcription quantitative PCR (RT-qPCR) and western blotting were performed to examine the targets of miR-765. @*Results@#We found that miR-765 levels were upregulated 10.2-fold in patients with MDS compared to controls. In refractory cytopenia with multilineage dysplasia, the percentage of patients with elevated miR-765 levels was significantly higher than in other forms of MDS.Experiments with leukemia cells revealed that transfection with a miR-765 mimic inhibited cell proliferation and induced apoptosis. RT-qPCR and western blotting demonstrated that the target of miR-765 was PLP2. @*Conclusion@#These findings imply that upregulation of miR-765 induces apoptosis via downregulation of PLP2 and may have a role in MDS pathogenesis.

Eyeball deviation by orbital mucocele after midface sinus injury

A mucocele is an epithelium-lined, mucus-filled cavity in the paranasal sinuses. Mucocele may develop due to scarring and obstruction of the sinus ostium caused by midface sinus trauma, such as orbital bone fracture or endoscopic sinus surgery. The authors report two cases of orbital mucocele as complications following midface sinus injury (endoscopic sinus surgery in one case, and orbital fracture repair in the other). In both cases, imaging studies showed a large orbital mucocele accompanied by bony erosion and orbital wall remodeling, compressing the ocular muscle. Using an open approach, the lesion was excised and marsupialized. The symptoms resolved, and the postoperative eyeball position was normal. Orbital mucocele may cause serious complications such as ocular symptoms, orbital cellulitis, osteomyelitis, and the formation of an abscess with the potential to invade the brain. Therefore, surgeons should consider the possibility of mucocele as a late complication of surgery and initiate an immediate work-up and surgical treatment if needed.

Survey on the Preparation Status of Medical Institutions Regarding the Full Revision of the Korean Blood Inventory Monitoring System / 대한수혈학회지

Background@#The current Korean Blood Inventory Monitoring System (BMS) has several drawbacks. It does not provide real-time data and only monitors 211 of the more than 2500 institutes that performed blood transfusions.This survey study investigated the status of BMS use and the preparation status of the data input system of medical institutions to help in the revision of BMS in preparation for the full surveillance of BMS. @*Methods@#A survey questionnaire was given to 200 hospitals participating in the current BMS, along with another set of questionnaires to 150 non-participating hospitals. The questionnaire consisted of the method of data registry to BMS, the current status of electronic medical records (EMR) and order communication system (OCS), perception, and readiness of adaptation of an open application programming interface system (API). @*Results@#Two hundred and one BMS participating hospitals responded to the survey. Approximately 75% entered data with a comma-separated value (CSV) or Excel spreadsheet (xls) files, and approximately half had an in-house developed EMR and OCS. The majority showed enthusiasm for the introduction to an open API. Among the non-participating hospitals, 138 responded. Approximately 70% counted the blood inventory daily, but approximately half did not use electronic methods for this process. The response to the introduction to an open API was positive, but the readiness for a prompt introduction was low at 15.9%. @*Conclusion@#These results will help revise the current BMS. On the other hand, full surveillance of BMS is anticipated to be hindered by the ready state of each medical institute. Moreover, the encouragement of participation would require supportive government administrative measures.

Survey on the Preparation Status of Medical Institutions Regarding the Full Revision of the Korean Blood Inventory Monitoring System / 대한수혈학회지

Background@#The current Korean Blood Inventory Monitoring System (BMS) has several drawbacks. It does not provide real-time data and only monitors 211 of the more than 2500 institutes that performed blood transfusions.This survey study investigated the status of BMS use and the preparation status of the data input system of medical institutions to help in the revision of BMS in preparation for the full surveillance of BMS. @*Methods@#A survey questionnaire was given to 200 hospitals participating in the current BMS, along with another set of questionnaires to 150 non-participating hospitals. The questionnaire consisted of the method of data registry to BMS, the current status of electronic medical records (EMR) and order communication system (OCS), perception, and readiness of adaptation of an open application programming interface system (API). @*Results@#Two hundred and one BMS participating hospitals responded to the survey. Approximately 75% entered data with a comma-separated value (CSV) or Excel spreadsheet (xls) files, and approximately half had an in-house developed EMR and OCS. The majority showed enthusiasm for the introduction to an open API. Among the non-participating hospitals, 138 responded. Approximately 70% counted the blood inventory daily, but approximately half did not use electronic methods for this process. The response to the introduction to an open API was positive, but the readiness for a prompt introduction was low at 15.9%. @*Conclusion@#These results will help revise the current BMS. On the other hand, full surveillance of BMS is anticipated to be hindered by the ready state of each medical institute. Moreover, the encouragement of participation would require supportive government administrative measures.

Correction of post-traumatic enophthalmos with anatomical absorbable implant and iliac bone graft

BACKGROUND: Trauma is one of the most common causes of enophthalmos, and post-traumatic enophthalmos primarily results from an increased volume of the bony orbit. We achieved good long-term results by simultaneously using an anatomical absorbable implant and iliac bone graft to correct post-traumatic enophthalmos.METHODS: From January 2012 to December 2016, we performed operations on seven patients with post-traumatic enophthalmos. In all seven cases, reduction surgery for the initial trauma was performed at our hospital. Hertel exophthalmometry, clinical photography, three-dimensional computed tomography (3D-CT), and orbital volume measurements using software to calculate the specific volume captured on 3D-CT (ITK-SNAP, Insight Toolkit-SNAP) were performed preoperatively and postoperatively.RESULTS: Patients were evaluated based on exophthalmometry, clinical photographs, 3D-CT, and orbital volume measured by the ITK-SNAP program at 5 days and 1 year postoperatively, and all factors improved significantly compared with the preoperative baseline. Complications such as hematoma or extraocular muscle limitation were absent, and the corrected orbital volume was well maintained at the 1-year follow-up visit.CONCLUSION: We present a method to correct enophthalmos by reconstructing the orbital wall using an anatomical absorbable implant and a simultaneous autologous iliac bone graft. All cases showed satisfactory results for enophthalmos correction. We suggest this method as a good option for the correction of post-traumatic enophthalmos.

Serum Procollagen Type I N-Terminal Propeptide and Osteocalcin Levels in Korean Children and Adolescents

PURPOSE: Bone markers can be useful for the diagnosis and treatment of skeletal diseases in children and adolescents. Owing to high skeletal growth velocity and rapid bone turnover, children and adolescents have higher bone marker levels than adults. Thus, a valid age- and sex-specific reference should be established for pediatric populations living in similar environments. We aimed to assess the associations of procollagen type I N-terminal propeptide (P1NP) and osteocalcin with age and sex in a group of healthy Korean children and adolescents. MATERIALS AND METHODS: The participants (290 boys and 290 girls, age range 0–18 years) were Korean outpatients. Serum P1NP and osteocalcin levels were measured in control materials and patient samples by electrochemiluminescence immunoassay using an automated Cobas e411 analyzer. RESULTS: Significant age-dependent variations in bone marker levels were observed in both sexes (p<0.001). The highest P1NP levels were observed during the first year of life; thereafter, levels decreased until puberty. There was no postnatal peak for osteocalcin; however, its levels remained higher than the adult reference range throughout childhood. Significant differences were observed between boys and girls (p<0.05), especially between the ages of 12 and 17 years. Cobas e411 results for P1NP showed satisfactory precision and linearity. CONCLUSION: We established reference data for P1NP and osteocalcin levels in healthy Korean children and adolescents, as the first and only study of these parameters in pre-adulthood in Korea. Cobas e411-quantified bone markers may be useful for determining bone metabolism indices.

Identification and Antifungal Susceptibility Profiles of Cyberlindnera fabianii in Korea

Invasive fungal infections caused by Cyberlindnera fabianii have recently increased. However, biochemical kits such as API 20 C AUX and Vitek-2C have misidentified this species as other Candida spp. such as C. pelliculosa or C. utilis due to no information of Cy. fabianii in yeast database. During our 2016–2017 surveys, eleven isolates of Cy. fabianii were obtained in International St. Mary's Hospital in Korea. Here, we describe its morphological and molecular characteristics and tested its antifungal susceptibility against nine antifungal agents. The sequences of the ITS region and the D1/D2 region of LSU revealed 100% identity with the sequences of Cy. fabianii. In comparison with the results from MALDI-TOF mass spectrometry, we found that Cy. fabianii can be distinguished from other species. In antifungal susceptibility test, voriconazole and echinocandins exhibited good antifungal activities against the majority of Cy. fabianii isolates despite the absence of standard criteria.

Efficient Utilization of Korean Medical Fungal Pathogen Resource Bank for Clinical Research / 대한의진균학회지

A “pathogen resource” contains information about pathogens (e.g., bacteria, fungi, viruses, and protozoa) and microbial derivatives (e.g., DNA, RNA, plasmid, clone, and cDNA). Pathogen resources are important for their potential use in healthcare research because they contain clinical and epidemiological information that is different from microbial resources. In October 2014, the “Nagoya Protocol” on access and benefit-sharing with the Convention on Biological Diversity was enacted to restrict the movement of transboundary pathogens and protect the natural pathogen resources of each country. On July 2017, the Korean Medical Fungal Pathogen Resource Bank (KMFRB) was established to secure, discover, and develop biological resources focused on medical fungi. KMFRB has since been operating under the National Culture Collection for Pathogens of the National Institute of Health based on the Act No. 13992. This report aims to provide general information regarding KMFRB and suggest efficient ways to utilize human fungal pathogen resources for clinical research.

Reconstruction of the Three-Dimensional Mandibulofacial Defects Using a Single Cutaneous Perforator-Based Fibula Osteocutaneous Flap

The reconstruction of the mandibulofacial defects is a difficult task when there are full-thickness cheek defects involving mandible, inner mucosa and outer skin. There are several reconstructive options for the coverage of large defects, but most of the methods are complicated, and time- and effort-consuming. We hereby present a case of fibula osteocutaneous flap based on a single peroneal artery perforator in the reconstruction of a three-dimensional mandibulofacial defects.

Double-Fold Operation with a Partial Incision and Continuous Buried Suture

BACKGROUND: The double fold operation is one of the most common aesthetic surgeries in Korea. There are many methods to make double fold using non-incision, incision and partial incision. Patients seeking double folds prefer natural appearance, less downtime, minimal scarring technique. The most favorable method is the minimal invasive but long-lasting fold formation technique. METHODS: From October 2003 to September 2016, this procedure was applied in 7,963 patients who worried about surgical scar or preferred non-incision method with puffy eyelids. Five stab incisions including two small incisions were taken in the upper eyelid. Through the small incision lines, the pretarsal muscle and the orbital fat were removed to facilitate tissue adhesion. The double fold line was made with the continuous buried suture. The suture was tied in the fifth stab incision site and the knot was placed deeply to prevent granuloma formation. RESULTS: This method was performed in all patients. The complications were asymmetry (52 cases), fold loosening (43 cases), granuloma (12 cases), conjunctival hemorrhage (5 cases), and scar (4 cases). Especially 74% of fold loosening cases were developed in mild ptotic patients. CONCLUSIONS: This method achieves good cosmetic result, shorter operation time, less morbidity, faster recovery in puffy eyelids than the other method.

Identification of the ABO*cis-AB04 Allele With a Unique Substitution C796A: The First Case in Korea

No abstract available.

Correlation between the Severity of Bone Pain and the Amount of CD34+ Cells after Peripheral Blood Stem Cell Mobilization / 대한수혈학회지

BACKGROUND: Peripheral blood stem cells (PBSCs) are mobilized by granulocyte-colony stimulating factor (G-CSF), which causes several side effects in allogeneic donors. We report on side effects of G-CSF administration and determine which side effects could be used in predicting the amount of harvested CD34+ cells. METHODS: Data from the first PBSC collections of 155 healthy donors between 2007 and 2010 were analyzed. Side effects were assessed using adverse event inventory, which was graded from 1 (mild) to 3 (severe) or 4 (disabling). RESULTS: G-CSF administration caused an elevation of WBC counts (mean 44,834/microL) and 86% of them were neutrophils. The mean mononuclear cells in apheresis products was 6.6x10(8)/kg and mean CD34+ cells was 6.0x10(6)/kg. Bone pain was reported by 151 healthy donors (97%) and severe bone pain was related to more CD34+ cells in apheresis products (P=0.041): 39 for grade 1 (5.1x10(6) CD34+cells/kg), 86 for grade 2 (6.0x10(6)), and 26 for grade 3 (7.1x10(6)). In addition, the percentage of collecting more than 5.0x10(6) CD34+cells/kg during the first leukapheresis showed correlation with the severity of bone pain. CONCLUSION: Bone pain was the most common side effect of G-CSF mobilization and more CD34+ cells were harvested in cases of severe bone pain.

ABO*Ael03/O Genotype with ABO Discrepancy: The First Case in Korea

The Ael subgroup expresses the least amount of A antigens and could only be detected by performing the adsorption-elution test. The frequency of the Ael subgroup is about 0.001% in Koreans, and the Ael02 allele, which originates from A102, is the most frequently identified allele in the Korean population. We report a Korean family with the Ael03 allele identified by molecular genetic analysis. To the best of our knowledge, this is the first such report in Korea to date.

Performance of the Elecsys HIV combi PT Assay Compared to the ARCHITECT HIV Ag/Ab Combo Assay

BACKGROUND: The aim of this study was to compare the analytical sensitivity and specificity of the recently updated 4th generation Elecsys HIV combi PT assay (Roche Diagnostics GmbH, Germany) to those of the ARCHITECT HIV Ag/Ab Combo assay (Abbott Laboratories, Germany). METHODS: A total of 2,003 fresh random clinical samples, 4 HIV seroconversion panels, a WHO International Standard p24 antigen sensitivity panel, 5 HIV-1 subtype viral lysates, and 5 HIV-1 subtype antibodies were tested in comparative studies with the Elecsys HIV combi PT and ARCHITECT HIV Ag/Ab Combo assays. Samples were assayed with both tests on the same day. The MP Diagnostics HIV Western Blot 2.2 Assay, the Elecsys HIV p24 Ag Test and Confirmatory Test, and the COBAS AmpliPrep/COBAS TaqMan HIV-1 Test were performed as supplementary tests. RESULTS: Both the Elecsys and ARCHITECT assays detected viral antigens in all four seroconversion panels on the same bleed days, and had lower limits of detection of <1 IU/mL with the p24 antigen sensitivity panel. The ARCHITECT assay showed slightly higher sensitivity in detecting viral antigens with some HIV-1 subtype viral lysates, while the Elecsys assay was more sensitive in detecting each of the 5 HIV-1 subtype antibodies. Both assays detected 5/5 HIV+ clinical samples correctly. The analytical specificities of the Elecsys and ARCHITECT assays were 99.90% and 99.80%, respectively. CONCLUSIONS: The Elecsys HIV combi PT assay performed comparably to the ARCHITECT HIV Ag/Ab Combo assay. Thus, the Elecsys HIV combi PT assay is suitable for diagnostic testing in university hospital settings.

An Imported Case of Severe Falciparum Malaria with Prolonged Hemolytic Anemia Clinically Mimicking a Coinfection with Babesiosis

While imported falciparum malaria has been increasingly reported in recent years in Korea, clinicians have difficulties in making a clinical diagnosis as well as in having accessibility to effective anti-malarial agents. Here we describe an unusual case of imported falciparum malaria with severe hemolytic anemia lasting over 2 weeks, clinically mimicking a coinfection with babesiosis. A 48-year old Korean man was diagnosed with severe falciparum malaria in France after traveling to the Republic of Benin, West Africa. He received a 1-day course of intravenous artesunate and a 7-day course of Malarone (atovaquone/proguanil) with supportive hemodialysis. Coming back to Korea 5 days after discharge, he was readmitted due to recurrent fever, and further treated with Malarone for 3 days. Both the peripheral blood smears and PCR test were positive for Plasmodium falciparum. However, he had prolonged severe hemolytic anemia (Hb 5.6 g/dl). Therefore, 10 days after the hospitalization, Babesia was considered to be potentially coinfected. A 7-day course of Malarone and azithromycin was empirically started. He became afebrile within 3 days of this babesiosis treatment, and hemolytic anemia profiles began to improve at the completion of the treatment. He has remained stable since his discharge. Unexpectedly, the PCR assays failed to detect DNA of Babesia spp. from blood. In addition, during the retrospective review of the case, the artesunate-induced delayed hemolytic anemia was considered as an alternative cause of the unexplained hemolytic anemia.

Factors Affecting the Freshness of Transfused Packed Red Blood Cells / 대한수혈학회지

BACKGROUND: The relationship between the storage age of packed red blood cells (pRBCs) and clinical outcomes is controversial. However, no systematic study regarding how fresh pRBCs were transfused to patients have been available so far. Therefore, we newly defined concepts for supply age (period from blood collection to supply to hospital), storage age (period from supply to transfusion to patient), and transfusion age (supply age plus storage age) and investigated them. The factors affecting each age were also analyzed. METHODS: A retrospective analysis for three ages of pRBCs was performed for patients who were transfused > or =1 pRBCs unit at three university hospitals between January 2009 and December 2013. Inventory age (period from blood collection to inventory check point at each blood bank) was prospectively checked on a daily basis for 30 days. Four blood centers and blood groups of transfused pRBCs were included. RESULTS: The mean supply, storage, and transfusion ages of pRBCs were 6.2, 6.0, and 12.0 days, respectively. 58%, 61%, and 66% of total transfused pRBCs were in a fresh category of supply, storage, and transfusion ages correspondingly. Storage and transfusion ages were affected by ABO blood group, hospitals, and years in listing orders. Inventory age was mainly affected by ABO blood group and hospitals. CONCLUSION: The freshness of transfused pRBCs was affected by hospitals and blood centers. Therefore, using the supply, storage, transfusion, and inventory ages as new norms can be useful to establishment of inventory and supply policies of hospitals and blood centers.

Hemolytic Disease of the Newborn Associated with Anti-Jr(a) Alloimmunization in a Twin Pregnancy: The First Case Report in Korea / 대한진단검사의학회지

Jr(a) is a high-frequency antigen found in all ethnic groups. However, the clinical significance of the anti-Jr(a) antibody has remained controversial. Most studies have reported mild hemolytic disease of the newborn and fetus (HDNF) in Jr(a)-positive patients. Recently, fatal cases of HDNF have also been reported. We report the first case of HDNF caused by anti-Jr(a) alloimmunization in twins in Korea. A 33-yr-old nulliparous woman with no history of transfusion or amniocentesis was admitted at the 32nd week of gestation because of vaginal bleeding caused by placenta previa. Anti-Jr(a) antibodies were detected in a routine laboratory examination. An emergency cesarean section was performed at the 34th week of gestation, and 2 premature infant twins were delivered. Laboratory examination showed positive direct antiglobulin test and Jr(a+) phenotype in the red blood cells and the presence of anti-Jr(a) antibodies in the serum in both neonates. The infants underwent phototherapy for neonatal jaundice; this was followed by conservative management. They showed no further complications and were discharged on the 19th postpartum day. Preparative management to ensure the availability of Jr(a-) blood, via autologous donation, and close fetal monitoring must be performed even in cases of first pregnancy in Jr(a-) women.

Establishment of Mixed Passive Hemagglutination Assay Using In-House Anti-Rh(D) Sensitized Human O RBCs for the Detection of Granulocyte Specific Antibodies / 대한수혈학회지

BACKGROUND: Granulocyte specific antibodies are associated with several clinical conditions including febrile transfusion reaction and transfusion-related acute lung injury as well as immune neutropenias. The identification of granulocyte specific antibodies is important for the diagnosis of these disorders. However, there have been rarely confirmed clinical reports in Korea since the testing techniques are complicated and difficult to maintain. In this study, development of in-house indicator cells and renewedly establishment of the mixed passive hemagglutination assay (MPHA) as a serologic test to detect and identify granulocyte specific antibodies were conducted. METHODS: The in-house indicator cells for MPHA were made by sensitizing human Rh(D) positive O RBCs with human IgG anti-Rh(D) (DiaMed AG, Switzerland) and then combining with AHG anti-IgG (Immucor Inc., USA). To determine the optimal conditions, various combinations of anti-Rh(D) IgG sensitization strengths of indicator cells, microwell coated antigens (intact granulocyte vs. extracted granulocyte) and reaction conditions were compared. RESULTS: The best test conditions for MPHA were as follows: optimal results were obtained with the anti-Rh(D) sensitization dilutions of 1/64-1/192 and the reaction condition of 4 hours incubation at room temperature in humid chamber. Extracted granulocytes coated at the plate showed better results than intact granulocytes. HLA antigens were completely removed from extracted granulocyte antigens after acidified chloroquine treatment. CONCLUSION: Granulocyte MPHA using in-house anti-Rh(D) sensitized indicator cells was developed for the first time in Korea. The newly established MPHA would be effectively used for the diagnosis and treatment of disorders associated with granulocyte specific antigen-antibody reactions in Korea.

The Frequency and Distribution of Unexpected Red Cell Antibodies at National Cancer Center / 대한수혈학회지

BACKGROUND: Performing antibody screening and identification tests before blood transfusion are important since unexpected red cell antibodies can cause acute or delayed hemolytic transfusion reactions. We investigated the frequency and distribution of unexpected red cell antibodies that were detected in cancer patients at National Cancer Center (NCC) and we compared our results with the previously published data. METHODS: From January 2001 to June 2009, 56,660 sera of the cases from NCC were screened and 197 sera were identified with using the Ortho BioVue System (Ortho-Clinical Diagnostics, Raritan, USA) and the conventional tube method. In case of the presence of autoantibody, the ZZAP method was performed to distinguish alloantibody from autoantibody. RESULTS: 759 cases (1.34%) showed positive results out of all 56,660 cases that underwent unexpected antibodies screening. Among them, unexpected antibodies were identified in 197 cases. The most frequently detected antibody was anti-Le(a) in 62 cases (31.47%), followed by anti-E in 32 cases (16.24%) and anti-Le(b) in 18 cases (9.14%). Unidentified antibodies were detected in 43 cases (21.83%). In the cases with a previous history of transfusion at the NCC and the screening results were altered from negative to positive, anti-E was the most frequently detected antibody (8/30 cases, 26.67%), and this included the mixed antibodies. CONCLUSION: Compared with the previous reports, this study showed that the frequency and distribution of the unexpected red cell antibodies of cancer patients were not different from those of general patients. Moreover, there was no apparent difference of frequency of the unexpected red cell antibodies among the diagnosed cancers. Our research may provide data for the frequency and characteristics of red cell antibodies because we targeted only cancer patients.

A Korean Family with Wilson Disease Occurred in Two Consecutive Generations / 대한진단검사의학회지

Wilson disease (WD) is one of the most common inborn errors of metabolism characterized by degenerative changes in the brain, liver and kidney dysfunction, and Kayser-Fleischer rings due to toxic accumulation of copper. We investigated a Korean family with WD occurred in two consecutive generations. The proband, a 14-yr-old girl, was noticed to have abnormal liver function on a routine health examination at school and was diagnosed of having WD by further laboratory tests and liver biopsy. Molecular genetic analysis of ATP7B gene demonstrated that she was homozygous for Ala-874Val mutation, one of the three common mutations in Korean patients with WD. Further study for her family members revealed that the proband's father, a paternal uncle, and the youngest sister were compound heterozygous for Ala874Val and Asn1270Ser mutations of the ATP7B gene. In addition, the proband's mother and a younger sister were heterozygous carriers of Ala874Val mutation. Therefore, WD occurred in two consecutive generations due to a WD father and a heterozygous mother. Actually, abnormal results on liver function tests were found in the proband's father and a paternal uncle a few years ago but a diagnosis of WD has not been made. Therefore, although WD has been thought to be uncommon in Korea, it should be considered in a differential diagnosis of patients exhibiting abnormal liver function with unknown cause.