Trends in category and grade for therapeutic plasma exchange in the latest guideline on therapeutic apheresis by the American Society for Apheresis: Hurdles in pursuing evidence-based medicine.

BACKGROUND AND OBJECTIVES: The Writing Committee of American Society for Apheresis released the ninth edition of guidelines for therapeutic apheresis in 2023. Categories have been a part of the guidelines since the first edition, and the grading system was introduced in the fifth edition, with updates in every new edition. In this study, we investigated the category and grade change trends through the latest five editions, focusing on therapeutic plasma exchange, to suggest future directions as part of evidence-based medicine. MATERIALS AND METHODS: Categories and grades for therapeutic plasma exchange (TPE) were collected and analysed from the fifth through ninth editions. We aligned classification changes to the ninth edition's clinical context and compared its categories and grades with those introduced in the guideline. RESULTS: Among 166 total indications in the ninth edition, 118 included TPE procedure, either as a sole treatment or as one of the therapeutic apheresis techniques. The total number of indications changed, but Category III remained predominant throughout the editions. Similarly, Grade 2C consistently emerged as the most prevalent grade. Notably, 24 cases had grade changes. Of the 16 cases with evidence quality changes, the quality weakened in six and improved in 10. Evidence levels were not improved throughout the study period for 102 clinical conditions. CONCLUSION: To address gaps in evidence quality, international collaboration is imperative to establish comprehensive large-scale studies or randomized controlled trials. This will refine the use of therapeutic apheresis, including TPE, to foster evidence-based advancements in clinical practice.

Evaluation of an eight marker-panel including long mononucleotide repeat markers to detect microsatellite instability in colorectal, gastric, and endometrial cancers.

BACKGROUND: Accurate determination of microsatellite instability (MSI) status is critical for optimal treatment in cancer patients. Conventional MSI markers can sometimes display subtle shifts that are difficult to interpret, especially in non-colorectal cases. We evaluated an experimental eight marker-panel including long mononucleotide repeat (LMR) markers for detection of MSI. METHODS: The eight marker-panel was comprised of five conventional markers (BAT-25, BAT-26, NR-21, NR-24, and NR-27) and three LMR markers (BAT-52, BAT-59 and BAT-62). MSI testing was performed against 300 specimens of colorectal, gastric, and endometrial cancers through PCR followed by capillary electrophoresis length analysis. RESULTS: The MSI testing with eight marker-panel showed 99.3% (295/297) concordance with IHC analysis excluding 3 MMR-focal deficient cases. The sensitivity of BAT-59 and BAT-62 was higher than or comparable to that of conventional markers in gastric and endometrial cancer. The mean shift size was larger in LMR markers compared to conventional markers for gastric and endometrial cancers. CONCLUSIONS: The MSI testing with eight maker-panel showed comparable performance with IHC analysis. The LMR markers, especially BAT-59 and BAT-62, showed high sensitivity and large shifts which can contribute to increased confidence in MSI classification, especially in gastric and endometrial cancers. Further study is needed with large number of samples for the validation of these LMR markers.

Relative immunogenicity of blood group antigens: First report in a Korean population.

BACKGROUND: The immunogenicity of a blood group antigen is a measure of its likelihood of inducing alloantibodies. Although the immunogenicity of blood group antigens has been analyzed in Caucasian populations, immunogenicity to date has not been analyzed in Asian subjects. The present study therefore evaluated the relative immunogenicity of blood group antigens in a Korean population. STUDY DESIGN AND METHODS: All available data of unexpected antibody identification tests performed at Asan Medical Center between 1997 and 2021 were analyzed. The relative immunogenicity of a blood group antigen relative to K antigen was calculated based on relative numbers of alloantibodies and the probabilities of antigen-negative recipients receiving antigen-positive RBC units. RESULTS: A total of 3898 antibody identification results were included, with 1632 (41.9 %) from male patients. The ranking of antigen immunogenicity was: E > c > e > C > K > Jk(a) > Lu(a) > S > Fy(a) > Fy(b) > Jk(b) > Di(b) > Di(a) in the total population and E > c > e > C > Jk(a) > Fy(a) > Fy(b) > S > K > Lu(a) > Jk(b) > Di(b) > Di(a) in male patients. DISCUSSION: The rank order of immunogenicity for blood group antigens in this study provides information about relative immunogenecity in Koreans. These findings also provide supporting evidence regarding antigen selection for extended antigen-matched transfusions in recipients of multiple transfusions.

Clinical significances and distribution of unexpected antibodies found in infants.

INTRODUCTION: The unexpected antibody test is an essential for ensuring the safety of blood transfusions. In infants, different pre-transfusion tests and transfusion strategies are needed due to their immature antigen/antibody system. This study aims to analyze the pattern of unexpected antibodies and their clinical significance in infants. METHODS: A retrospective analysis was conducted on the results of unexpected antibody identification tests performed on infants under one year of age at Asan Medical Center from 1999 to 2022. Patients' unexpected antibody identification test results and clinical information were investigated. The results of unexpected antibody identification and phenotype of each patient's mother were collected. RESULTS: 45 cases of antibody results were studied. 25 cases were found in infants under 4 months of age, and 18 cases (76%) were associated with hemolytic disease of the fetus and newborn (HDFN). The most common unexpected antibody in infants was anti-M (17 cases). There was one case of severe HDFN caused by anti-M. In 10 cases, anti-E and anti-c were found together, and 9 of these cases were associated with HDFN. There were four cases with a history of previous transfusion. CONCLUSIONS: Non-ABO antibodies found in infants showed a different pattern compared to adults. Interpreting unexpected antibody tests in infants, it is important to consider the clinical status of the infant and the test results of the mother, due to possibility of HDFN. To our knowledge, this is the first study to reveal the distribution and clinical significances of unexpected antibodies found in infants in Korea.

Time-temperature indicators versus temperature indicators for transfusion practice: Application in the real hospital setting.

BACKGROUND AND OBJECTIVES: Temperature indicators (TIs) are used to monitor the surface temperature of red blood cell (RBC) units. We compared the utility of a newly developed time-temperature indicator (TTI) prototype, Freshzone TTI (FZTTI) (Freshzone, Seoul, South Korea) and two US Food and Drug Administration-approved TIs, Safe-T-Vue 10 (STV10; Temptime Corporation, Morris Plains, NJ) and Blood Temp 10 (BT10; Timestrip UK Ltd, Cambridge, UK). MATERIALS AND METHODS: FZTTI, STV10 and BT10 were attached to 91 RBC units after issue (including eight units that were stored in refrigerators in the ward before transfusion). The time for colour change (CC) was monitored based on the 30-min rule. The CC of FZTTI indicated the total time elapsed since the temperature of RBC units exceeded 10°C, and the CC of STV10 and BT10 indicated that the temperature of RBC units exceeded 10°C. RESULTS: In 83 units, the median time for CC differed significantly between FZTTI and the TIs (51.4 min in FZTTI vs. 13.9 min in STV10 and 10.5 min in BT10, both at p < 0.001). In addition, 95.2% (n = 79) of FZTTI tags changed colour after 30 min of issue, whereas 96.4% (n = 80) of STV10 and 98.8% (n = 82) of BT10 changed colour within 30 min of issue. In the eight units stored in refrigerators, the time for CC between the TTI and TIs was significantly different. CONCLUSION: FZTTI outperformed the TIs, indicating that it is a feasible option for use in transfusion practice.

Detection of anti-B antibodies in a patient with A1B blood group: A case report and literature review.

ABO antibodies occur naturally and usually exist as alloantibodies. They are the most clinically significant in cases of transfusions. However, there are very few reports on auto-anti-A or B. A 58-year-old man visited our hospital for evaluation of an inguinal mass. Blood typing was performed, while preparing the patient for an excisional biopsy. Forward and reverse typing showed a typical AB and A pattern. Results of the direct antiglobulin and unexpected antibody screening tests were negative. The serum did not react with AB3 cells. The biopsy revealed a diffuse large B-cell lymphoma. After completing four cycles of R-CHOP chemotherapy, the patient achieved complete remission. There were no anti-B antibodies found on repeat ABO typing. This report shares our experience on unexpected anti-B antibody findings in a patient with an A1B blood type. To the best of our knowledge, this is the first report of anti-B antibodies in a patient with an A1B blood type in Korea.

Comparison of Erythrocyte and Reticulocyte Indices for Evaluation of Iron Deficiency by Two Automated Hematologic Analyzers.

The reticulocyte hemoglobin content and hypochromic erythrocyte percentage offer advantages in evaluation of iron deficiency, especially in inflammatory conditions. The aim of this study was to evaluate the correlation of reticulocyte hemoglobin content (CHr, Ret-He) and hypochromic erythrocyte percentage (%HYPO, Hypo-He) between two automated hematologic analyzers. The CHr and %HYPO values were determined using the Advia 2021i (Siemens), while the Ret-He and Hypo-He levels were assessed using the XN-3000 (Sysmex). Data from a total of 971 cases and 834 patients were collected. For reticulocyte hemoglobin content, there was a good linear correlation between CHr and Ret-He (r = 0.857, p < 0.001). For percentage of hypochromic erythrocytes, there was a better correlation between the two measures when using a second-degree polynomial equation (Hypo-He* = 0.4818 - 0.0218 x %HYPO + 0.0069 x %HYPO2) (r = 0.786, p < 0.001).

Monolithic Three-Dimensional Tuning of an Atomically Defined Silicon Tunnel Junction.

A requirement for quantum information processors is the in situ tunability of the tunnel rates and the exchange interaction energy within the device. The large energy level separation for atom qubits in silicon is well suited for qubit operation but limits device tunability using in-plane gate architectures, requiring vertically separated top-gates to control tunnelling within the device. In this paper, we address control of the simplest tunnelling device in Si:P, the tunnel junction. Here we demonstrate that we can tune its conductance by using a vertically separated top-gate aligned with ±5 nm precision to the junction. We show that a monolithic 3D epitaxial top-gate increases the capacitive coupling by a factor of 3 compared to in-plane gates, resulting in a tunnel barrier height tunability of 0-186 meV. By combining multiple gated junctions in series we extend our monolithic 3D gating technology to implement nanoscale logic circuits including AND and OR gates.

A New Trial to Measure ABO Antibodies Using Complement-Dependent Cytotoxicity.

Background and objectives: The ABO antibody (Ab) titration tests are used in monitoring in ABO-incompatible (ABOi) solid organ transplantation (SOT). However, currently developed ABO Ab tests show Ab binding reactions. This study attempted to measure ABO Ab level using complement-dependent cytotoxicity (CDC). Materials and methods: We studied 93 blood group O serum samples from patients who underwent ABOi SOT from January 2019 to May 2021. Patients' sera were incubated with A1 or B cells and added to a human complement solution. Supernatants were collected after centrifugation, and free hemoglobin (Hb) was measured by spectrophotometry. We converted plasma Hb value to hemolysis (%), which were compared with ABO Ab titer. Results: We found a mild correlation between hemolysis and ABO Ab titers. In simple regression analysis, the correlation coefficients were within 0.3660−0.4968 (p < 0.0001) before transplantation. In multiple linear regression analysis, anti-A hemolysis (%) was higher in immunoglobulin M (IgM) (ß = 12.9) than in immunoglobulin G (IgG) (ß = −3.4) (R2 = 0.5216). Anti-B hemolysis was higher in IgM (ß = 8.7) than in IgG (ß = 0.0) (R2 = 0.5114). There was a large variation in hemolysis within the same Ab titer. Conclusions: CDC can be used in a new trial for ABO Ab measurement. Furthermore, IgM rather than IgG seems to play a significant role in vivo activity, consistent with previous knowledge. Thus, this study may help in the development of the ABO Ab titration supplement test for post-transplant treatment policy establishment and pre-transplant desensitization.

Mild Phenotype of Xq Deletion and 3q Duplication Associated with der(X)t(X;3)(q21.1;q22.1) without Loss of XIST Gene.

We report a 10-year-old female patient with der(X)t(X;3)(q21.1;q22.1), resulting in 3q duplication and Xq deletion. The main clinical feature was primary ovarian failure and there was no abnormal phenotype corresponding to 3q duplication syndrome. This might be explained by the XIST gene at the X-inactivation center on Xq13.2, which was not deleted in this case. The conventional karyotyping was preliminarily reported as 46,X,inv(X) (q13q26) due to the similar banding patterns of Xq13.2-q24 and 3q25.33-q29. This case highlights the value of using a chromosomal microarray as a clinical diagnostic test for individuals with developmental delay or congenital anomalies.

Comparison of spectra optia and amicus cell separators for autologous peripheral blood stem cell collection.

INTRODUCTION: Autologous peripheral blood stem cell (PBSC) transplantation has become a standard treatment option for many oncology patients. The aim of this study was to evaluate the performance of two cell separators, Spectra Optia (Terumo BCT, Japan) and Amicus (Fresenius-Kabi) for autologous PBSC collection. METHODS: We retrospectively evaluated 56 apheresis by Spectra Optia with Continuous Mononuclear Cell Collection (cMNC) from 20 patients, and 50 apheresis by Amicus from 27 patients between December 2018 and December 2019. CD34+ collection efficiency (CE2) and platelet (PLT) loss were evaluated. RESULTS: There was no significant difference in CD34+ CE2 between Spectra Optia with cMNC (median, 28.8%) and Amicus (median, 33.1%; P = 0.537). PLT loss was significantly lower in Amicus (median, 28.6%) than in Spectra Optia with cMNC (median, 37.8%; P = 0.009). CONCLUSION: CD34+ CE2 was comparable between Spectra Optia and Amicus, and PLT loss was significantly lower in Amicus. To the best of our knowledge, this is the first report comparing autologous PBSC collection of the Spectra Optia and Amicus. These results may provide general guidance with regard to device selection to apheresis clinics that use both separators for optimal outcomes depending on each patient's characteristics.

Evaluation of safety of using incompatible plasma for therapeutic plasma exchange during shortage of AB plasma.

BACKGROUND: Criteria for selection of FFP blood type has not been clearly established and use of group AB plasma is preferred by numerous transplantation protocols. AIMS: This study assesses the safety and efficacy of alternative group A or B plasma in ABO incompatible solid organ transplantation. MATERIALS & METHODS: Alternative use of group A or B plasma (incompatible plasma) was inevitable during the shortage of group AB plasma. Experience from select number of patients during the period of extreme group AB plasma shortage is described. RESULTS: The result of alternative use of group A or B plasma was within expectation, showing effective reduction of isoagglutinin titers for pre-operative desensitization and efficacy for treatment of post-operative patients. No immediate hemolytic transfusion reaction was reported. DISCUSSION: While validation in a larger cohort of patients is necessary, our limited experience have shown satisfactory clinical outcomes without adverse events. CONCLUSIONS: Use of incompatible group A or B plasma is a viable option when group AB plasma is limited.

Donor protection: Iron supplementation for frequent blood donors in Korea.

OBJECTIVE: This study aimed to evaluate the effect of oral iron supplementation in frequent donors in Korea, based solely on donation history. STUDY DESIGN: The hemoglobin (Hb) level, ferritin level, soluble transferrin receptor (sTfR), total iron binding capacity (TIBC), and transferrin saturation of frequent donors at high risk for iron deficiency were compared to those of first donors. The frequent donors took iron supplements for 4 weeks and the same tests were repeated after 2 and 4 weeks to evaluate their effects. RESULT: A total of 53 male and 57 female frequent donors were recruited. After 4-week iron supplementation, among the men, the prevalence of a: low Hb level (<13.0 g/dL) decreased from 25% to 2%; low ferritin level (<15.0 ng/mL) decreased from 58% to 4%; iron deficient erythropoiesis (IDE) (log(sTfR/ferritin) ≥ 2.07) decreased from 77% to 33%. Among the women, the percentage of a: low Hb level (<12.0 g/dL) decreased from 44% to 9%; low ferritin level decreased from 79% to 11%; IDE decreased from 95% to 47%. In total, 15 male (28.3%) and 29 female (56.9%) blood donors reported undesirable side effects related to iron supplementation. No serious adverse events were reported. CONCLUSION: Ferritin level, a reliable indicator of iron status, increased and IDE decreased significantly after four-week iron supplementation in the female, but not in the male, donor group, compared to those of control donors. Four-week oral iron supplement was not enough to restore iron storage level in the male donor group.

A comparison of the automated blood bank system IH-500 and manual tube method for anti-blood group antibody titration: a quantitative approach.

BACKGROUND: Anti-blood group antibody titers (ABTs) reported in titer values are variable depending on the testing method used. The introduction of new test methods such as automated methods requires proper method comparison. In this study, the automated blood bank system and manual tube method for ABT were compared using a log-transformed dataset to evaluate the alternative statistical approach. METHODS: ABT was conducted using specimens referred for solid organ transplantation. Methods for comparison were conventional manual tube method and IH-500 automated blood bank system using column agglutination (CAT). Criteria for agreement were exact match and 1-titer match. Measured titer values were log-transformed into interval scale for Deming regression analysis. RESULTS: From the comparison of the tube and CAT methods using titer values and the two criteria, the exact and 1-titer match were 15.9-41.5 % and 65.9-97.6 %, respectively. Deming regression was used to demonstrate the presence of both proportional and constant difference between the two methods. CONCLUSION: The method comparison using conventional statistical approaches had limits due to the semi-quantitative value of the test. Log-transformed interval scale values for comparison were useful for interpretation of method comparison datasets. This alternative statistical approach could contribute to a more accurate comparison between assays and standardization of ABT testing.

Neonatal exchange transfusion: Experience in Korea.

BACKGROUND: Exchange transfusion (ET) is an established, efficacious, and reliable practice for severe neonatal hyperbilirubinemia, hemolytic disease of the newborn, and neonatal sepsis. This study assessed the indications and clinical outcomes of ET performed in a tertiary hospital in Korea. MATERIALS AND METHODS: We studied 64 ET sessions performed on 23 neonates between March 1999 and March 2018. ET was performed based on estimated double volume exchange transfusion using fresh red blood cells and fresh frozen plasma. Patients' clinical information, including demographic data and ET indication, and laboratory data were collected pre- and post-ET. RESULTS: The most common ET indication was hyperbilirubinemia with hemolytic anemia due to non-ABO maternal blood group discrepancies. In three preterm babies, ETs were performed for severe anemia, leukocytosis, and hyperkalemia cases. Before ET, the patients showed slightly high WBC counts, low hemoglobin levels, and low platelet counts. After ET, blood examination revealed normal WBC counts, increased hemoglobin levels, and decreased platelet counts (all P < 0.001). Bilirubin levels decreased immediately after ET (P < 0.001). Electrolyte and C-reactive protein levels showed no significant changes after ETs. Adverse events occurred in 11 (47.8 %) patients; the most common were hypoxemia and hypotension. One infant experienced cardiorespiratory arrest due to hypercalcemia and was successfully resuscitated. No one died within 24 h of ET. However, five infants showed hyperbilirubinemia aggravation. CONCLUSIONS: ET is an effective treatment modality for leukocytosis and hyperbilirubinemia with low mortality but involves common adverse events post-ET. This report provides an overview of current ET practices in Korea.

Fatal hemolytic disease of the fetus and newborn caused by anti-Jra antibody: A case report and literature review.

The Jra antigen of the JR blood group system is a highly prevalent red blood cell antigen. Although anti-Jra-associated hemolytic disease of the fetus and newborn (HDFN) is generally considered mild-to-moderate, a rare fatal case was recently reported. We report the third example of HDFN-related anti-Jra with fatal outcomes. The clinical significance of anti-Jra antibody as a cause of HDFN should be reassessed.

Characterization of Chlamydia trachomatis ompA Genotypes Among Sexually Transmitted Disease Patients in Korea.

BACKGROUND: Chlamydia trachomatis is the leading cause of bacterial sexually transmitted diseases (STDs) world-wide. The aim of this study was to characterize the C. trachomatis genetic profiles of clinical isolates in the Korean population by sequence analysis of the ompA gene. METHODS: Endocervical specimens from patients who were confirmed as C. trachomatis infection by real-time PCR were used for ompA sequencing. The individual sequences (about 890 nucleotides) were determined by comparison with those from known C. trachomatis strains using the BLAST search tool. Sequence variations were analyzed by comparing them with sequences from prototype strains. RESULTS: Sequence analysis using BLAST similarity search of the ompA gene from the 106 clinical isolates revealed that the most prevalent genotype corresponded to E (n = 28, 26.2%), followed by F (n = 20, 18.9%), D (n = 16, 15.1%), J (n = 16, 15.1%), G (n = 9, 8.5%), H (n = 8, 7.5%), K (n = 5, 4.7%), B (n = 2, 1.9%), and I (n = 2, 1.9%). Detailed sequence analysis based on comparison with each prototype revealed that there are sequence differences in 44 specimens (41.5%). CONCLUSIONS: This study is the update on the distribution of C. trachomatis ompA genotypes in Korea in more than a decade. The genotypes have become more diversified, with genotypes K, B, and I being newly detected. C. trachomatis genotyping is crucial for regional and global epidemiological studies, as well as for vaccine development.

A comparative evaluation of BACT/ALERT FA PLUS and FN PLUS blood culture bottles and BD BACTEC Plus Aerobic and Anaerobic blood culture bottles for antimicrobial neutralization.

The performance of BACT/ALERT FA and FN PLUS (FA PLUS and FN PLUS) blood culture bottles with the BACT/ALERT VIRTUO (bioMérieux, Inc., Durham, NC) and BD BACTEC Plus Aerobic and Anaerobic (BD Aerobic and BD Anaerobic) blood culture bottles with the BD BACTEC FX (BD Diagnostics, Sparks, MD) for antimicrobial neutralization at peak serum concentration was evaluated. The following antibiotic agents and microbial strains were used: ampicillin, cefepime, cefotaxime, gentamicin, levofloxacin, meropenem, piperacillin-tazobactam, and vancomycin; methicillin-sensitive Staphylococcus aureus, Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Bacteroides fragilis. The detection rate of FA PLUS bottles was 69.1% (259/375) and that of BD Aerobic bottles was 75.5% (283/375) (p = 0.050). In the case of anaerobic culture, the overall detection rate of FN PLUS bottles was 77.0% (231/300) and that of BD Anaerobic bottles was 71.3% (214/300) (p = 0.113). The time to detection (TTD) from aerobic culture was 2.8 h shorter in FA PLUS bottles (12.4 h) compared to BD Aerobic bottles (15.2 h) (p < 0.001). And the TTD from anaerobic culture was 1.6 h shorter in FN PLUS bottles (18.1 h) compared to BD Anaerobic bottles (19.7 h) (p = 0.061). The FA PLUS bottles exhibited a lower detection rate compared to BD Aerobic bottles, while FN PLUS bottles showed a higher detection rate compared to BD Anaerobic bottles. The BACT/ALERT VIRTUO system exhibited shorter TTD compared to the BD BACTEC FX system for both aerobic and anaerobic cultures.

A Myelodysplastic Syndrome with Concurrent Basophilia and Eosinophilia Lacking Oncogenic Mutations in 54 Relevant Genes.

Myelodysplastic syndromes (MDS) with basophilia or eosinophilia are very rare and portend poor prognoses. We present a rare patient who had MDS with excess blasts as well as peripheral basophilia and concurrent bone marrow (BM) basophilia/eosinophilia. She had a complex karyotype including 5q and 7q deletions; however, no oncogenic mutations were observed on next-generation sequencing of 54 genes known to be frequently mutated in acute myeloid leukemia/MDS. Peripheral basophilia resolved after decitabine treatment. Ours is the first report to describe a genome-wide analysis and the use of decitabine to successfully treat basophilia in an MDS patient with concurrent BM basophilia/eosinophilia.

The First Case of Para-Bombay Blood Type Encountered in a Korean Tertiary Hospital.

Para-Bombay phenotypes are rare blood groups that have inherent defects in producing H antigens associated with FUT1 and/or FUT2. We report the first case of para-Bombay blood type in a Southeast Asian patient admitted at a tertiary hospital in Korea. A 23-year-old Indonesian man presented to the hospital with fever and was diagnosed with a disseminated nontuberculous mycobacterium infection and anemia. During blood group typing for blood transfusion, cell typing showed no agglutination with both anti-A and anti-B reagents. Serum typing showed strong reactivity against B cells and trace agglutination pattern with A1 cells. His red blood cells failed to react with anti-H reagents. Direct sequencing of FUT1 and FUT2 revealed a missense variation, c.328G>A (p.Ala110Thr, rs56342683, FUT1*01W.02), and a synonymous variant, c.390C>T (p.Asn130=, rs281377, Se357), respectively. This highlights the need for both forward and reverse grouping.