Development and Roll-Out of A Coronavirus Disease 2019 Clinical Pathway for Standardized Qualified Care in Public Hospitals in Korea

Despite the coronavirus disease 2019 (COVID-19) vaccination roll-out, variant-related outbreaks have occurred repeatedly in Korea. Although public hospitals played a major role in COVID-19 patients’ care, difficulty incorporating evolving COVID-19 treatment guidelines called for a clinical pathway (CP). Eighteen public hospitals volunteered, and a professional review board was created. CPs were formulated containing inclusion/exclusion criteria, application flow charts, and standardized order sets. After CP roll-out, key parameters improved, such as increased patient/staff five-point satisfaction scores (0.41/0.57) and decreased hospital stays (1.78 days)/medical expenses (17.5%). The CPs were updated consistently after roll-out as new therapeutics drugs were introduced and quarantine policies changed.

Strong SARS-CoV-2 Antibody Response After Booster Dose of BNT162b2 mRNA Vaccines in Uninfected Healthcare Workers

Despite strict guidelines for coronavirus disease 2019 (COVID-19), South Korea is facing its fourth pandemic wave. In this study, by using an automated electrochemiluminescence immunoassay assay, we tracked anti-spike protein receptor-binding domain (anti-S-RBD) antibody titer from the second dose to 2 weeks after the booster dose vaccination. After the second dose, 234 participants had their anti-S-RBD antibody titers decrease over time. We also showed the booster dose (the third dose) increased antibody titer by average 14 (min–max, 2–255)-fold higher compared to the second dose among the 211-booster group participants, therefore, the booster dose could be recommended for low responders to the second dose. Our findings showed a distinct humoral response after booster doses of BNT162b2 mRNA vaccines and may provide further evidence of booster vaccination efficacy. These data will also be helpful in vaccination policy decisions that determine the need for the booster dose.

Positivity of SARS-CoV-2 Antibodies among Korean Healthy Healthcare Workers 1 and 2 Weeks after Second Dose of Pfizer-BioNTech Vaccination

The antibody titer of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was observed in 289 healthy healthcare workers who had completed the second dose of the Pfizer-BioNTech coronavirus disease 2019 (COVID-19) vaccine. Antibody tests were performed using both the automated electrochemiluminescence immunoassay (ECLIA) and the chromatographic lateral flow immunoassay (LFIA). All subjects had antibodies against the receptor binding domain of the spike protein of SARS-CoV-2 only one week after completing the vaccination, and the antibody titer became significantly higher after another week (P < 0.001). Since there was a large amount of antibody formation within two weeks after completion of vaccination, the less sensitive method, LFIA, also showed high sensitivity.There was no significant difference between whole blood and serum in detecting SARS-CoV-2 antibodies after vaccination. This is an early study of vaccinations among Koreans and is expected to contribute to the establishment of national guidelines on COVID-19 vaccination.

Positivity of SARS-CoV-2 Antibodies among Korean Healthy Healthcare Workers 1 and 2 Weeks after Second Dose of Pfizer-BioNTech Vaccination

The antibody titer of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was observed in 289 healthy healthcare workers who had completed the second dose of the Pfizer-BioNTech coronavirus disease 2019 (COVID-19) vaccine. Antibody tests were performed using both the automated electrochemiluminescence immunoassay (ECLIA) and the chromatographic lateral flow immunoassay (LFIA). All subjects had antibodies against the receptor binding domain of the spike protein of SARS-CoV-2 only one week after completing the vaccination, and the antibody titer became significantly higher after another week (P < 0.001). Since there was a large amount of antibody formation within two weeks after completion of vaccination, the less sensitive method, LFIA, also showed high sensitivity.There was no significant difference between whole blood and serum in detecting SARS-CoV-2 antibodies after vaccination. This is an early study of vaccinations among Koreans and is expected to contribute to the establishment of national guidelines on COVID-19 vaccination.

Evaluation of Three Multiplex Realtime Reverse Transcription PCR Assays for Simultaneous Detection of SARS-CoV-2, Influenza A/B, and Respiratory Syncytial Virus in Nasopharyngeal Swabs

Background@#In the coronavirus disease 2019 (COVID-19) pandemic era, the simultaneous detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza virus (Flu), and respiratory syncytial virus (RSV) is important in the rapid differential diagnosis in patients with respiratory symptoms. Three multiplex real-time reverse transcription polymerase chain reaction (rRT-PCR) assays have been recently developed commercially in Korea: PowerChek™ SARS-CoV-2, Influenza A&B Multiplex Real-time PCR Kit (PowerChek; KogeneBiotech); STANDARD™ M Flu/SARS-CoV-2 Real-time Detection Kit (STANDARD M; SD BioSensor); and Allplex™ SARS-CoV-2/FluA/FluB/RSV Assay (Allplex; Seegene). We evaluated the analytical and clinical performances of these kits. @*Methods@#A limit of detection tests were performed and cross-reactivity analysis was executed using clinical respiratory samples. Ninety-seven SARS-CoV-2-positive, 201 SARS-CoV-2-negative, 71 influenza A-positive, 50 influenza B-positive, 78 RSV-positive, and 207 other respiratory virus-positive nasopharyngeal swabs were tested using the three assays. The AdvanSure™ respiratory viruses rRT-PCR assay (AdvanSure; LG Life Sciences) was used as a comparator assay for RSV. @*Results@#Except in influenza B, in SARS-CoV-2 and influenza A, there were no significant differences in detecting specific genes of the viruses among the three assays. All three kits did not cross-react with common respiratory viruses. All three kits had greater than 92% positive percent agreement and negative percent agreement and ≥ 0.95 kappa value in the detection of SARS-CoV-2 and flu A/B. Allplex detected RSV more sensitively than AdvanSure. @*Conclusion@#The overall performance of three multiplex rRT-PCR assays for the concurrent detection of SARS-CoV-2, influenza A/B, and RSV was comparable. These kits will promote prompt differential diagnosis of COVID-19, influenza, and RSV infection in the COVID-19 pandemic era.

Carrier Frequency of Spinal Muscular Atrophy in a Large-scale Korean Population

Spinal muscular atrophy (SMA) is an autosomal recessive disease characterized by progressive proximal muscle weakness and atrophy. Given the recent introduction of gene therapies, knowledge of the SMA carrier frequency in various populations has become important for developing screening programs for this disease. In total, 1,581 anonymous DNA samples from an umbilical cord blood bank were tested for SMN1 and SMN2 gene copies using a multiplex ligation-dependent probe amplification assay. Twenty-nine of the 1,581 newborns [1.83%; 95% confidence interval (CI), 1.25–2.66%] were SMA carriers with one copy of SMN1, and no homozygous SMN1 deletion was detected. The carrier frequency in this population was estimated to be 1,834 per 100,000 (95% CI, 1,254–2,659) or 1 in 55 (95% CI, 1/79–1/38). Our data indicate that SMA carriers are not uncommon in the Korean population and may serve as a reference for designing a population screening program in Korea.

Facklamia hominis Isolated from a Wound: A Case Report and Review of the Literature / 대한임상미생물학회지

Facklamia hominis is a facultative anaerobic Gram-positive coccus generally displaying weak alpha-hemolysis and negativity for catalase and oxidase. Facklamia species are part of the normal flora of the female genitourinary tract and have been reported in invasive diseases such as meningitis and infective endocarditis, albeit rarely. A 67 year-old-man presented to hospital with a tender, erythematous epidermal cyst on the right side of his upper back. Simple excision of the cyst was performed and the pus was taken with a sterile swab for culture, yielding no growth. One week later, discharge was observed in the patient's wound site and a sterile swab for culture was taken. The colonies grown were identified as F. hominis by the Vitek 2 system (bioMérieux, France), and the result was then reported to clinicians, and later confirmed by 16S rRNA gene sequencing and matrix-assisted laser desorption/ ionization time-of-flight mass spectrometry. To the best of our knowledge, this is the first reported case of F. hominis isolation from a clinical specimen in Korea.

Identification of MicroRNA Related to the CD34+ Cell Fraction of Cord Blood Stem Cells / 대한수혈학회지

BACKGROUND: Cord blood (CB) is a reliable source of hematopoietic stem cells, and its utilization in stem cell transplantation is increasing continuously. The CD34+ cell count is arguably one of the most important parameters for evaluating the quality of a cord blood unit (CBU), but there is little evidence on the post-genetic modifications that can affect the CD34+ cell counts. In this study, the difference in the miRNA expression profiles between low and high CD34+ CBU was evaluated. METHODS: Paired CB and maternal samples with low (0.9%) were selected for analysis. MicroRNA profiling was performed, and differentially expressed miRNA were identified. In addition, gene ontology analysis was conducted on the miRNA to elucidate the genes that could potentially affect the CD34+ cell count. RESULTS: Ten miRNA were identified to show significantly different expression between the low and high CD34+ groups. Four of the 10 miRNA were hematopoiesis-related (miR-199a-5p, miR-22-5p, miR-140-5p, and miR-181b-5p). From a total of 119 associated genes, nine (CALCA, FARP2, FSHR, ITGAM, MELK, MLF1, PRG4, TREM2 and VCAM1) were associated with two or more of the aforementioned miRNA. CONCLUSION: This is the first study that examined the difference in the miRNA expression profiles between high and low CD34+ CB cells and revealed the relevant genes associated with hematopoiesis. These results provide basic insight into the genetic processes involving hematopoietic stem cell proliferation.

Biases in the Assessment of Left Ventricular Function by Compressed Sensing Cardiovascular Cine MRI

PURPOSE: We investigate biases in the assessments of left ventricular function (LVF), by compressed sensing (CS)-cine magnetic resonance imaging (MRI). MATERIALS AND METHODS: Cardiovascular cine images with short axis view, were obtained for 8 volunteers without CS. LVFs were assessed with subsampled data, with compression factors (CF) of 2, 3, 4, and 8. A semi-automatic segmentation program was used, for the assessment. The assessments by 3 CS methods (ITSC, FOCUSS, and view sharing (VS)), were compared to those without CS. Bland-Altman analysis and paired t-test were used, for comparison. In addition, real-time CS-cine imaging was also performed, with CF of 2, 3, 4, and 8 for the same volunteers. Assessments of LVF were similarly made, for CS data. A fixed compensation technique is suggested, to reduce the bias. RESULTS: The assessment of LVF by CS-cine, includes bias and random noise. Bias appeared much larger than random noise. Median of end-diastolic volume (EDV) with CS-cine (ITSC or FOCUSS) appeared −1.4% to −7.1% smaller, compared to that of standard cine, depending on CF from (2 to 8). End-systolic volume (ESV) appeared +1.6% to +14.3% larger, stroke volume (SV), −2.4% to −16.4% smaller, and ejection fraction (EF), −1.1% to −9.2% smaller, with P < 0.05. Bias was reduced from −5.6% to −1.8% for EF, by compensation applied to real-time CS-cine (CF = 8). CONCLUSION: Loss of temporal resolution by adopting missing data from nearby cardiac frames, causes an underestimation for EDV, and an overestimation for ESV, resulting in underestimations for SV and EF. The bias is not random. Thus it should be removed or reduced for better diagnosis. A fixed compensation is suggested, to reduce bias in the assessment of LVF.

Simultaneous Unwrapping Phase and Error Recovery from Inhomogeneity (SUPER) for Quantitative Susceptibility Mapping of the Human Brain

PURPOSE: The effect of global inhomogeneity on quantitative susceptibility mapping (QSM) was investigated. A technique referred to as Simultaneous Unwrapping Phase with Error Recovery from inhomogeneity (SUPER) is suggested as a preprocessing to QSM to remove global field inhomogeneity-induced phase by polynomial fitting. MATERIALS AND METHODS: The effect of global inhomogeneity on QSM was investigated by numerical simulations. Three types of global inhomogeneity were added to the tissue susceptibility phase, and the root mean square error (RMSE) in the susceptibility map was evaluated. In-vivo QSM imaging with volunteers was carried out for 3.0T and 7.0T MRI systems to demonstrate the efficacy of the proposed method. RESULTS: The SUPER technique removed harmonic and non-harmonic global phases. Previously only the harmonic phase was removed by the background phase removal method. The global phase contained a non-harmonic phase due to various experimental and physiological causes, which degraded a susceptibility map. The RMSE in the susceptibility map increased under the influence of global inhomogeneity; while the error was consistent, irrespective of the global inhomogeneity, if the inhomogeneity was corrected by the SUPER technique. In-vivo QSM imaging with volunteers at 3.0T and 7.0T MRI systems showed better definition in small vascular structures and reduced fluctuation and non-uniformity in the frontal lobes, where field inhomogeneity was more severe. CONCLUSION: Correcting global inhomogeneity using the SUPER technique is an effective way to obtain an accurate susceptibility map on QSM method. Since the susceptibility variations are small quantities in the brain tissue, correction of the inhomogeneity is an essential element for obtaining an accurate QSM.

Long-Term Quality Control Program Plan for Cord Blood Banks in Korea: A Pilot Study for Cryopreservation Stability

BACKGROUND: Maintaining the quality of cryopreserved cord blood is crucial. In this pilot study, we describe the results of the internal quality control program for a cord blood bank thus far. METHODS: Donated cord blood units unsuitable for transplantation were selected for internal quality control once a month. One unit of cord blood, aliquoted into 21 capillaries, was cryopreserved and thawed annually to analyze the total nucleated cell count, CD34⁺ cell count, cell viability test, and colony-forming units assay. RESULTS: No significant differences in the variables (total nucleated cell count, cell viability, CD34⁺ cell count) were observed between samples cryopreserved for one and two years. Upon comparing the variables before cryopreservation and post thawing with the capillaries of one year of storage, cell viability and CD34⁺ cell counts decreased significantly. The use of cord blood samples in capillaries, which can be easily stored for a long period, was similar to the methods used for testing segments attached to the cord blood unit. CONCLUSIONS: The results of this study may be useful for determining the period during which the quality of cryopreserved cord blood units used for transplantation is maintained.

Preparation of Internal Quality Control Material for Lymphocyte Subset Analysis

Lymphocyte subset analysis is widely used in clinical laboratories, and more than two levels of daily QC materials are required for reliable results. Commercially available, expensive QC materials have short shelf lives and may not be suitable in resource-poor settings. We compared different methods for preparing homemade QC material, including fixation with 1%, 2%, or 4% paraformaldehyde (PFA); freezing with 10% dimethylsulfoxide (DMSO), 0.1% bovine serum albumin-phosphate buffered saline, or after ethanolic dehydration; and using cryopreservation temperatures of -20℃, -80℃, or -196℃. We found an optimal experimental condition, which is 'fixation with 4% PFA, freezing with 10% DMSO, and storage at 80℃'. To evaluate long-term stability of QC materials prepared in this optimal condition, two levels of QC materials (QM1 and QM2) were thawed after 30, 33, 35, 37, 60, 62, 64, and 67 days of cryopreservation. Lymphocyte subset was analyzed with BD Multitest IMK kit (BD Biosciences, USA). QM1 and QM2 were stable after 1-2 months of cryopreservation (CV <3% for CD3, CD4, and CD8 and 5-7% for CD16/56 and CD19). We propose this method as an alternative cost-effective protocol for preparing homemade internal QC materials for lymphocyte subset analysis in resource-poor settings.

Reference Intervals of Hematology and Clinical Chemistry Analytes for 1-Year-Old Korean Children

BACKGROUND: Reference intervals need to be established according to age. We established reference intervals of hematology and chemistry from community-based healthy 1-yr-old children and analyzed their iron status according to the feeding methods during the first six months after birth. METHODS: A total of 887 children who received a medical check-up between 2010 and 2014 at Boramae Hospital (Seoul, Korea) were enrolled. A total of 534 children (247 boys and 287 girls) were enrolled as reference individuals after the exclusion of data obtained from children with suspected iron deficiency. Hematology and clinical chemistry analytes were measured, and the reference value of each analyte was estimated by using parametric (mean±2 SD) or nonparametric methods (2.5-97.5th percentile). Iron, total iron-binding capacity, and ferritin were measured, and transferrin saturation was calculated. RESULTS: As there were no differences in the mean values between boys and girls, we established the reference intervals for 1-yr-old children regardless of sex. The analysis of serum iron status according to feeding methods during the first six months revealed higher iron, ferritin, and transferrin saturation levels in children exclusively or mainly fed formula than in children exclusively or mainly fed breast milk. CONCLUSIONS: We established reference intervals of hematology and clinical chemistry analytes from community-based healthy children at one year of age. These reference intervals will be useful for interpreting results of medical check-ups at one year of age.

Performance of LIFECODES HLA-DQB1 Typing Kit Using Luminex Platform in Koreans

Intermediate-resolution HLA-DQ typing has gained importance in organ transplantation recently. We evaluated the performance of the LIFECODES HLA-DQB1 typing kit (Immucor, USA) using sequence-specific oligonucleotide (SSO) probe and Luminex platform (Luminex Corp., USA) on 100 samples tested by sequence-based typing (SBT) using the AlleleSEQR HLA-DQB1 kit (Abbott Molecular, USA) in Korean individuals. No sample showed ambiguity in the assignment of 4-digit HLA-DQB1 allele with the LIFECODES HLA-DQB1 SSO typing kit, and the results were fully concordant with those of high-resolution typing of AlleleSEQR HLA-DQB1 SBT up to 4-digit level. Three samples required adjustment of false reactions (3/100, 3.0%): two samples with DQB1*03:03/*06:01 showed false-positive result in probe 253, and 1 sample with DQB1*04:02/*05:02 showed false-negative result in probe 217. We tested an additional sample with DQB1*03:03/*06:01, which showed same false-positivity in probe 253 and 2 samples with DQB1*04:02/*05:02, which showed no false reaction. The false reactions did not result in ambiguity or change in the HLA allele assignment. We could assign HLA-DQB1 alleles to 4 digit-level without ambiguity, with 100% concordance with the SBT results. Thus, LIFECODES HLA-DQB1 SSO typing kit showed good performance for intermediate-resolution HLA-DQB1 typing in clinical laboratory for organ transplantation in Koreans.

Sister Mary Joseph Nodule as a Metastasis of Gallbladder Carcinoma / 대한피부과학회지

Cutaneous metastasis into the umbilicus, known as a Sister Mary Joseph nodule, is quite rare. Gastric adenocarcinoma is the most common primary origin overall, whereas gynecologic tumors such as ovarian cancer are the leading cause in women. In most cases, the nodule manifests after the primary tumor had been diagnosed. In rare cases, however, it serves as the first sign of the underlying malignancy. Here, we report the case of a 59-year-old woman who presented with a nodule on the umbilicus and was diagnosed with metastatic adenocarcinoma originating in the gallbladder.

A Case of Spitzoid Melanoma

Spitzoid melanoma is a subtype of melanoma that, clinically and histologically, resembles a Spitz nevus. Clinically, spitzoid melanomas usually evolve from amelanotic nodular lesions, growing to 1 cm or more in diameter. They often remain clinically undiagnosed because of their wide variety of clinical appearances and a lack of pigmentation. Distinguishing a Spitz nevus from a spitzoid melanoma can be extremely difficult. Features that favor the diagnosis of a spitzoid melanoma are asymmetrical shape, diameter greater than 1 cm, a lesion with a deep invasive component, and a high degree of cytologic atypia. There have been only rare reports in the literature of the presence of giant cells in malignant melanoma, and the presence of these cells may result in its misdiagnosis as a histiocytic tumor. We present a case of spitzoid melanoma on the right ankle of a 22-year-old-woman.

Uric Acid as a Predictor of Severe Intraventricular Hemorrhage in Very Low Birth Weight Infants

PURPOSE: To determine whether serum uric acid levels in the first 7 days of life can predict development of severe intraventricular hemorrhage (IVH) among very low birth weight (VLBW) infants. METHODS: VLBW infants admitted to the neonatal intensive care unit of Asan Medical Center between January 2009 and December 2012 were selected for chart review. Infants were divided into groups with and without severe IVH (grade> or =3). To determine whether uric acid is a predictor of severe IVH, uric acid levels on the first day (within 24 hours of birth), peak uric acid levels (during the first 7 days for infants without severe IVH, prior to IVH documentation by cranial sonogram for infants with severe IVH, and trend in uric acid levels were analyzed for both groups. Various antenatal and postnatal factors were compared between the groups, and risk factors associated with severe IVH were identified. RESULTS: A total of 397 VLBW infants were included, with mean birth weight of 1,075+/-292 g and a mean gestational age of 29.6+/-3.3 weeks. Higher levels of uric acid on day 1, higher peak levels, and rising uric acid levels were all found to be associated with the development of severe IVH on univariate analysis. Multivariate analysis confirmed that rising uric acid levels predicted subsequent development of severe IVH. Other factors associated with development of severe IVH included higher sodium, higher potassium, higher PaCO2, higher lactic acid, and lower PaO2. CONCLUSION: Careful attention to uric acid levels, which are easily measured, may be useful in predicting subsequent development of severe IVH among VLBW infants.

Flavobacterium ceti From Blood Samples of a Korean Patient With Alcoholic Liver Cirrhosis

No abstract available.

Acceptability of Sputum Specimens for Diagnosing Pulmonary Tuberculosis

The evaluation of the quality of a sputum specimen prior to bacterial culture has been an accepted practice. However, optimal sputum criteria for pulmonary tuberculosis (TB) are not well established. We investigated indicators for sputum acceptability in tuberculosis cultures and acid-fast bacilli (AFB) smear. A post-hoc analysis of a randomized trial with 228 sputum specimens from 77 patients was conducted. In the trial, pulmonary TB suspects were requested for collecting three sputum specimens. We performed both TB study (AFB smear and M. tuberculosis culture) and Gram staining in each specimen. By using generalized estimating equations, the association between sputum characteristics and positive TB testings were analyzed. Although acceptable specimens for bacterial pneumonia showed higher TB-culture positive rates than unacceptable specimens (adjusted odds ratio [aOR]=1.66; 95% confidence interval [CI]=1.11-2.49), a specimen with > or =25 white blood cells/low-power field was the better predictor for positive M. tuberculosis cultures (aOR=2.30; 95% CI=1.48-3.58) and acid-fast bacilli smears (aOR=1.85; 95% CI=1.05-3.25). Sputum leukocytosis could be an indicator of sputum acceptability for diagnosing pulmonary tuberculosis.

Quality of cord blood cryopreserved for up to 5 years

BACKGROUND: Although cord blood (CB) is a well-known source of hematopoietic stem cells, uncertainties exist regarding the quality of cryopreserved CB. We investigated the changes in quality of CB units according to the duration of cryopreservation. METHODS: We analyzed CB units that were rejected from the Seoul Metropolitan Government Public Cord Blood Bank inventory after conventional processing, because of unsuitability for allogeneic transplantation. Two hundred CB units that were cryopreserved from 1 year to 5 years were selected. After thawing the cryopreserved CB units, the total nucleated cell (TNC) count, CD34+ cell count, number of colony-forming units (CFU), aldehyde dehydrogenase (ALDH) level, cell viability, and apoptosis were analyzed. We conducted a comparative analysis to identify the presence of statistically significant differences in the recovery rates of the TNC and CD34+ cell counts and to compare the results of ALDH level, the cell viability test, the apoptosis test, and CFU analysis among groups according to the duration of cryopreservation. RESULTS: The recovery rates of the TNC count, the CD34+ cell count, and cell viability did not differ significantly according to the duration of cryopreservation. ALDH analysis, the cell viability test, and the apoptosis test did not reveal any increasing or decreasing trend according to the duration of cryopreservation. Further, the numbers of CFU-granulocyte/macrophage and CFU-granulocyte/erythrocyte/macrophage/megakaryocyte did not differ significantly according to the duration of cryopreservation. CONCLUSION: These results suggest that the quality of CB is not affected by cryopreservation for up to a period of 5 years.