Realistic Estimation of COVID-19Infection by Seroprevalence Surveillance of SARS-CoV-2Antibodies: An Experience From Korea Metropolitan Area From January to May 2022

Background@#Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally, leading to the coronavirus disease 2019 (COVID-19) pandemic. Because a significant proportion of the COVID-19 confirmed cases were concentrated in the capital metropolitan area of South Korea, and a large proportion of the population in the area had been adequately vaccinated against COVID-19, we conducted a seroprevalence surveillance study focusing on the residents of the capital metropolitan area in South Korea. @*Methods@#We used a quota-sampling method to obtain blood samples from 1,000 individuals per round, equally stratified across seven age categories and sexes and regions, from five medical institutions located within the capital metropolitan area of South Korea. During five consecutive months (rounds) between January 2022 and May 2022, a total of 5,000 samples were analyzed for anti-spike (S) and anti-nucleocapsid (N) antibodies. @*Results@#High anti-S seropositivity was observed in all age groups, which corresponded to the vaccine coverage during the study period. Both the cumulative incidence based on polymerase chain reaction (PCR) and the estimated seroprevalence based on anti-N seropositivity increased in the fourth and fifth rounds, which corresponded to April 2022 and May 2022. Seroprevalence coincided with the cumulative incidence during the first three rounds, but exceeded from the fourth survey onwards when infection with omicron variants was increased rapidly in Korea. @*Conclusion@#Seroprevalence confirmed the number of infection cases outside of PCR testing-based surveillance. Seroepidemiological surveillance can help us understand vaccine responses and detect hidden infections, thereby providing appropriate public health guidance for achieving population-level immunity.

Development and Characterization of Synthetic Norovirus RNA for Use in Molecular Detection Methods

Background@#Reference materials are essential for the quality assurance of molecular detection methods. We developed and characterized synthetic norovirus GI and GII RNA reference materials. @*Methods@#Norovirus GI and GII RNA sequences including the ORF1–ORF2 junction region were designed based on 1,495 reported norovirus sequences and synthesized via plasmid preparation and in vitro transcription. The synthetic norovirus GI and GII RNAs were evaluated using six commercial norovirus detection kits used in Korea and subjected to homogeneity and stability analyses. A multicenter study involving five laboratories and using four commercial real-time PCR norovirus detection assays was conducted for synthetic norovirus RNA characterization and uncertainty measurements. @*Results@#The synthetic norovirus GI and GII RNAs were positively detected using the six commercial norovirus detection kits and were homogeneous and stable for one year when stored at –20°C or –70°C. All data from the five laboratories were within a range of 1.0 log copies/μL difference for each RNA, and the overall mean concentrations for norovirus GI and GII RNAs were 7.90 log copies/μL and 6.96 log copies/μL, respectively. @*Conclusions@#The synthetic norovirus GI and GII RNAs are adequate for quality control based on commercial molecular detection reagents for noroviruses with high sequence variability. The synthetic RNAs can be used as reference materials in norovirus molecular detection methods.

Collaborative Study to Establish National Reference Standards for Anti-HIV-1 Antibody

Background@#National reference standards for anti-HIV-1 antibody are needed to evaluate the performance and maintain the quality control of anti-HIV-1 antibody assays. The aim of this study was to prepare a mixed-titer performance panel and assess its suitability as a national reference standard for anti-HIV-1 antibody according to stability, collaboration, and other studies. @*Methods@#Nineteen serum samples from different HIV patients were obtained, along with 15 units of fresh frozen plasma samples with negative anti-HIV-1 antibody results. Ten anti-HIV-1 antibody-positive candidate standards and two negative candidate standards were prepared based on the reactivity in the Alinity i HIV Ag/Ab combo assay (Abbott Laboratories, Wiesbaden, Germany). A collaborative study was conducted across eight laboratories using five anti-HIV-1 antibody assays. Real-time and accelerated stability were evaluated to assess the long-term stability. @*Results@#In the collaborative study, results of all five anti-HIV-1 antibody assays were positive for all 10 candidate standards prepared using HIV patient samples. The CV of each assay for every candidate standard was within 10%, except for one assay result. No real-time and accelerated stability change trend was observed at −70°C or −20°C, supporting that the reference standards were maintained in a stable state at −70°C for long-term storage. @*Conclusions@#The overall results suggest that the 12 candidate standards could serve as national reference standards for anti-HIV-1 antibody.

Revision of Laboratory Testing Guidelines for Initial Diagnosis of Hematologic Neoplasms

Clinicopathological Characteristics of Hyperdiploidy with High-Risk Cytogenetics in Multiple Myeloma

In multiple myeloma (MM), hyperdiploidy (HD) is known to impart longer overall survival. However, it is unclear whether coexistent HD ameliorates the adverse effects of known high-risk cytogenetics in MM patients. To address this issue, we investigated the clinicopathological characteristics of HD with high-risk cytogenetics in MM. Ninety-seven patients with MM were included in the study. For metaphase cytogenetics (MC), unstimulated cells from bone marrow aspirates were cultured for either 24 or 48 hours. To detect HD by interphase fluorescence in situ hybridization (iFISH), we assessed trisomies of chromosomes 5, 7, 9, 11, 15, and 17. Of the 97 MM patients, 40 showed HD. The frequency of co-occurrence of HD and high-risk cytogenetics was 14% (14/97). When the clinicopathological characteristics were compared between the two groups of HD with high-risk cytogenetics vs. non-HD (NHD) with high-risk cytogenetics, the level of beta 2 microglobulin and stage distribution significantly differed (P=0.020, P=0.032, respectively). This study shows that some of the clinicopathological characteristics of MM patients with high-risk cytogenetics differ according to HD or NHD status.

Variable Natural Killer Cell Activity in Hematological Malignancies at Diagnosis

BACKGROUND: Natural killer (NK) cells play a key role in innate immune responses and are an important component of anti-cancer defenses. This study aimed to investigate the clinicopathological characteristics of NK cell activity (NKA) among various hematological malignancies at diagnosis and to evaluate their clinical value as a monitoring marker. METHODS: A total of 111 patients that were newly diagnosed with hematological malignancies were recruited, comprising 18 acute myeloid leukemia (AML), 31 multiple myeloma (MM), and 62 lymphoma. Twenty-three normal control subjects from our health examination center were recruited. NKA was measured using a commercially available enzyme-linked immunosorbent assay kit, which measures interferon-gamma secreted by ex vivo-stimulated NK cells in whole blood. RESULTS: The 111 patients had a median NKA of 202.80 pg/mL (range 40–2,000). NKA was significantly decreased in patients with AML (median 47.05 pg/mL, 40–2,000, P<0.0001), MM (275.00, 40–2,000, P<0.0001), and lymphoma (289.49, 40–2,000, P<0.0001) compared with that in normal controls (1,891, 412–2,000). There was a difference in NKA between AML and lymphoma (P=0.0499). Serial changes in NKA correlated with disease progression. NKA did not correlate with the NK cell count in any group of hematological malignancies. CONCLUSIONS: The measurement of NKA could be useful to evaluate the immunological status in hematological malignancies at diagnosis and during follow-up.

Central Nervous System Involvement in a Patient with Multiple Myeloma Manifesting as an Intraventricular Mass with Leptomeningeal Spread

Central nervous system involvement in multiple myeloma (CNS-MM) is a rare condition. Various manifestations of CNS-MM have been reported, including dural, parenchymal, and leptomeningeal involvement. Among them, leptomeningeal involvement is less common and intraventricular involvement is exceptional, with only one case reported in the literature. Herein, we report the first case of CNS-MM manifesting as an intraventricular mass with leptomeningeal involvement combined with perineural spread. We also describe characteristic computed tomography and magnetic resonance imaging findings of intraventricular multiple myeloma.

Clinical value of procalcitonin for suspected nosocomial bloodstream infection

BACKGROUND/AIMS@#Procalcitonin (PCT) may prove to be a useful marker to exclude or predict bloodstream infection (BSI). However, the ability of PCT levels to differentiate BSI from non-BSI episodes has not been evaluated in nosocomial BSI.@*METHODS@#We retrospectively reviewed the medical records of patients ≥ 18 years of age with suspected BSI that developed more than 48 hours after admission.@*RESULTS@#Of the 785 included patients, 105 (13.4%) had BSI episodes and 680 (86.6%) had non-BSI episodes. The median serum PCT level was elevated in patients with BSI as compared with those without BSI (0.65 ng/mL vs. 0.22 ng/mL, p = 0.001). The optimal PCT cut-off value of BSI was 0.27 ng/mL, with a corresponding sensitivity of 74.6% (95% confidence interval [CI], 66.4% to 81.7%) and a specificity of 56.5% (95% CI, 52.7% to 60.2%). The area under curve of PCT (0.692) was significantly larger than that of C-reactive protein (CRP; 0.526) or white blood cell (WBC) count (0.518). However, at the optimal cut-off value, PCT failed to predict BSI in 28 of 105 cases (26.7%). The PCT level was significantly higher in patients with an eGFR < 60 mL/min/1.73 m² than in those with an eGFR ≥ 60 mL/min/1.73 m² (0.68 vs. 0.17, p = 0.01).@*CONCLUSIONS@#PCT was more useful for predicting nosocomial BSI than CRP or WBC count. However, the diagnostic accuracy of predicting BSI remains inadequate. Thus, PCT is not recommended as a single diagnostic tool to avoid taking blood cultures in the nosocomial setting.

GATA1 Expression in BCR/ABL1-negative Myeloproliferative Neoplasms

BACKGROUND: This study aimed to determine GATA1 expression levels to better characterize subgroups in BCR/ABL1-negative myeloproliferative neoplasms (MPNs). METHODS: This study enrolled 49 patients diagnosed as having BCR/ABL1-negative MPN on the basis of the 2016 World Health Organization classification : nine polycythemia vera (PV), 17 essential thrombocythemia (ET), 12 prefibrotic primary myelofibrosis (prePMF), and 11 overt primary myelofibrosis (PMF). Relevant clinical and laboratory data were retrieved from the medical records. The molecular analysis of CALR and MPL mutations and quantification of JAK2 V617F allele burden were performed. GATA1 expression was assessed by an immunohistochemical assay on bone marrow biopsy. GATA1 expression was analyzed serially in 18 patients. RESULTS: GATA1 expression decreased significantly in PMF compared with that in other subtypes, while no statistical difference was identified between ET and prePMF. GATA1 expression did not differ according to the mutation profiles or the allele burden of JAK2 V617F, but it decreased significantly in patients with overt fibrosis or leukemic transformation. CONCLUSIONS: Our results suggest that GATA1 expression is significantly low in PMF and decreases with progressive fibrosis and possibly with leukemic transformation, although our attempt to accurately distinguish between subgroups using GATA1 immunohistochemical approach did not achieve statistical significance. A large patient cohort with long term follow-up is required to evaluate the prognostic value of GATA1 expression.

Neutrophilic Leukemoid Reaction Associated with Malignancy Initially Suspected as Chronic Neutrophilic Leukemia

Although neutrophilia can manifest from various causes, it is important to be able to distinguish chronic neutrophilic leukemia (CNL) from neutrophilic leukemoid reactions (NLR). In this paper, we describe four cases of leukocytosis with neutrophilia, including one case of CNL with a T618I mutation in colony stimulating factor 3 receptor (CSF3R) and three cases of NLR associated with malignancy or sepsis, which were initially suspected as CNL. Of the three NLR cases, one was associated with ovarian cancer, one with monoclonal gammopathy of undetermined significance and one with multiple myeloma with sepsis. This study demonstrated that confirming the clonality of myeloid cells with CSF3R T618I could contribute to making an accurate differential diagnosis between CNL and NLR in patients with solid cancers or plasma cell neoplasms caused by paraneoplastic syndromes and/or infection.

Sigma-Metrics of Electrolyte Tests From a Recently Launched New-Generation Proficiency Testing Program of the Korean Association of Quality Assurance for Clinical Laboratory

No abstract available.

Clinical Manifestations of Group A Streptococcal Pharyngitis and Comparison of Usefulness of Two Rapid Streptococcal Antigen Tests

BACKGROUND: Throat culture is the golden standard for diagnosis of group A streptococcal (GAS) pharyngitis. However, because it is a time-consuming procedure, antibiotics are often empirically administrated. Rapid antigen tests (RATs) can detect bacterial infections within 15 minutes, thus helping to reduce unnecessary administration of antibiotics. METHODS: In total, 108 patients, between 3 and 17 yr of age, who visited our hospital from August 2011 to July 2012, were tested for suspected acute pharyngitis with two RATs––SD Bioline Strep A (SD, Korea) and BinaxNOW Strep A (Binax, Inc., USA)––as well as throat culture. We compared the sensitivity, specificity, and consistency of the two RATs and assessed the clinical manifestations of GAS pharyngitis. RESULTS: Of the 108 patients, 15 were confirmed to have GAS pharyngitis by throat culture. The SD test showed a sensitivity of 93.3% and a specificity of 97.8%; the positive and negative predictive values were 87.5% and 98.9%, respectively. The Binax test showed a sensitivity of 86.7% and a specificity of 100%; the positive and negative predictive values were 100% and 97.9%, respectively. The Kappa values for conformity degree were high, 0.887 and 0.918 in the SD and the Binax tests, respectively (P=0.00). Clinical manifestation assessment of GAS pharyngitis indicated that scarlatiniform rash and strawberry tongue were significantly associated signs (P<0.05). CONCLUSIONS: GAS pharyngitis diagnosis based on clinical manifestations alone has practical limitations. The two RATs are useful as substitutes for throat culture and their frequent use in clinical settings is advisable.

Comparison of Automated Treponemal and Nontreponemal Test Algorithms as First-Line Syphilis Screening Assays

BACKGROUND: Automated Mediace Treponema pallidum latex agglutination (TPLA) and Mediace rapid plasma reagin (RPR) assays are used by many laboratories for syphilis diagnosis. This study compared the results of the traditional syphilis screening algorithm and a reverse algorithm using automated Mediace RPR or Mediace TPLA as first-line screening assays in subjects undergoing a health checkup. METHODS: Samples from 24,681 persons were included in this study. We routinely performed Mediace RPR and Mediace TPLA simultaneously. Results were analyzed according to both the traditional algorithm and reverse algorithm. Samples with discordant results on the reverse algorithm (e.g., positive Mediace TPLA, negative Mediace RPR) were tested with Treponema pallidum particle agglutination (TPPA). RESULTS: Among the 24,681 samples, 30 (0.1%) were found positive by traditional screening, and 190 (0.8%) by reverse screening. The identified syphilis rate and overall false-positive rate according to the traditional algorithm were lower than those according to the reverse algorithm (0.07% and 0.05% vs. 0.64% and 0.13%, respectively). A total of 173 discordant samples were tested with TPPA by using the reverse algorithm, of which 140 (80.9%) were TPPA positive. CONCLUSIONS: Despite the increased false-positive results in populations with a low prevalence of syphilis, the reverse algorithm detected 140 samples with treponemal antibody that went undetected by the traditional algorithm. The reverse algorithm using Mediace TPLA as a screening test is more sensitive for the detection of syphilis.

Anemia in Individuals over Age 80: Unattended Issue in Clinical Practice / 이화의대지

OBJECTIVES: To assess the current state of anemia evaluation in the elderly over 80 years of age. METHODS: Patients who were more than 80 years old and visited Dongguk University Ilsan Hospital from April 2005 to February 2014 were included. Statistical analysis were assessed using the logistic regression model. RESULTS: Total 548 patients, who had anemia according to WHO criteria, were identified. The median age was 85 years old (range, 82 to 99 years) and median hemoglobin level was 11.0 g/dL (range, 2.7 to 12.9 g/dL). Twenty-eight, 468, and 52 patients were classified as microcytic anemia, normocytic anemia, and macrocytic anemia, respectively. Among them, 397 patients (72.4%) did not undergo proper evaluation for the cause anemia i.e., 8 cases (28.5%) of microcytic anemia, 361 cases (77.1%) of normocytic anemia, and the 28 cases (53.84%) of 52 macrocytic anemia patients. The remaining 151 patients (27.6%) had completed the evaluation, and 24 patients (15.9%) were diagnosed as solid malignancies. In the assessment of iron deficiency anemia, hemoglobin levels, and age had no effect on whether or not to perform esophagogastroduodenoscopy. CONCLUSION: This finding showed that physicians often neglected anemia in individuals over 80 years of age. Though these patients have limited life expectancy, physicians should carefully discriminate the sub-population who will be benefit from adequate evaluation and treatment.

Unusual association of CD8+ T-cell lymphocytosis with invasive thymoma

No abstract available.

Establishment and Multicenter Evaluation of a National Reference Panel for Syphilis Antibodies in Korea

BACKGROUND: Establishment of a national reference panel for syphilis antibodies is necessary to evaluate the performance of in-vitro diagnostic tests for syphilis and to verify test quality. This study aimed to establish a national reference panel for syphilis antibodies, to assess the suitability of a panel for non-treponemal and treponemal testing, and to assess the reactivity of the various tests currently in use. METHODS: Treponemal pallidum particle agglutination (TPPA)-positive and -negative fresh frozen plasma samples were obtained. After the fresh frozen plasma was converted to serum by defibrination, the samples were pooled. Two candidate reference standards containing no syphilis antibodies and 10 candidate reference standards containing syphilis antibodies were prepared on the basis of reactivity in the TPPA assay. Candidate reference standards were tested by three laboratories using five non-treponemal tests and four treponemal tests. RESULTS: All three laboratories reported positive non-treponemal test results for the mixed-titer performance panel (MP)/6-MP/12. MP/1, MP/2, and MP/3 were negative for non-treponemal tests. MP/4 and MP/5 were reported either as positive or negative according to the laboratories. All laboratories reported positive TPPA results for MP/3-MP/12 and negative results for MP/1 and MP/2. No significant difference was detected among the treponemal testing results in three laboratories. CONCLUSIONS: We established 12 candidate national reference standards containing various concentrations of syphilis antibodies. A collaborative study using nine tests demonstrated that 12 candidate national reference standards presented consistent results, except a few assays with low sensitivity, and thus could be used as a national reference panel for syphilis antibody testing.

A Case of Recurrent Abdominal Pain with Fever and Urticarial Eruption / 대한소화기학회지

Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by recurrent episodes of fever and serosal, synovial, or cutaneous inflammation, caused by a dysfunction of pyrin as a result of mutation within the MEFV gene. It occurs mainly among Mediterranean and Middle Eastern populations, including Jews, Arabs, and Turks. However, FMF cases have been reported outside the Mediterranean and Middle Eastern countries in recent years. Although FMF has been relatively rare in Korea until now, proper recognition of FMF might lead to more frequent diagnoses of FMF. We experienced an interesting case, a 31-year-old Korean man who presented with recurrent abdominal pain with fever and urticarial eruption for 10 years. DNA analysis showed complex mutations (p.Leu110Pro, p.Glu148Gln) in the MEFV gene. To date, three cases have been reported, and this case of FMF with skin conditions is the first case in Korea.

Anaplastic Large Cell Lymphoma Involving Anterior Segment of the Eye

A 36-year-old woman was diagnosed with anaplastic large cell lymphoma (ALCL) by excisional biopsy of a left frontal skin lesion. During the first cycle of chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisolone), the patient complained of right ocular pain and inflammation. Cytologic examination using aqueous humor revealed atypical lymphocytes, suggesting intraocular ALCL involvement. Acute angle closure developed in the anterior chamber due to rapid progression of ALCL, causing pupillary block. Laser and surgical interventions were attempted but failed to relieve the pupillary block. Finally, radiation therapy resolved the pupillary block to restore the anterior chamber and normalize intraocular pressure. This is the first case in the English literature of ALCL involving the iris to cause acute secondary angle closure.

Anaplastic Large Cell Lymphoma Involving Anterior Segment of the Eye

A 36-year-old woman was diagnosed with anaplastic large cell lymphoma (ALCL) by excisional biopsy of a left frontal skin lesion. During the first cycle of chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisolone), the patient complained of right ocular pain and inflammation. Cytologic examination using aqueous humor revealed atypical lymphocytes, suggesting intraocular ALCL involvement. Acute angle closure developed in the anterior chamber due to rapid progression of ALCL, causing pupillary block. Laser and surgical interventions were attempted but failed to relieve the pupillary block. Finally, radiation therapy resolved the pupillary block to restore the anterior chamber and normalize intraocular pressure. This is the first case in the English literature of ALCL involving the iris to cause acute secondary angle closure.

Beta-Thalassemia Minor Is Associated with IgA Nephropathy

No abstract available.