Red Blood Cell Deformability and Distribution Width in Patients with Hematologic Neoplasms.

BACKGROUND: Despite increasing evidence that red blood cell (RBC) deformability is impaired in pathologic conditions, little research has been done on RBC deformability in hematologic diseases. The authors measured RBC deformability in patients with various hematologic diseases, including hematologic malignancies. METHODS: A total of 568 patients who underwent bone marrow (BM) examination for initial diagnosis were enrolled. We collected the subjects' age, gender, diagnosis of BM examination, and complete blood count results. The RBC deformability, which was quantified by an elongation index, was measured by a microfluidic ektacytometer. RESULTS: RBC deformability was lower in primary myelofibrosis, acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), chronic myeloid leukemia (CML), and acute lymphoblastic leukemia (ALL) from least to greatest. When the correlation between red blood cell distribution width (RDW) and RBC deformability was analyzed for 370 subjects in hematologic neoplasms, the correlation coefficient of RDW was -0.2974 (p < 0.01). When comparing MDS and aplastic anemia (AA), the deformability of MDS was significantly lower than that of AA. CONCLUSIONS: RBC deformability was decreased in leukemic diseases such as AML, MDS, CML, and ALL compared to control, and RDW showed a negative correlation with deformability. RBC deformability may be used as a complementary differential diagnostic test for MDS and AA.

Comparing SARS-CoV-2 Antibody Responses after Various COVID-19 Vaccinations in Healthcare Workers.

Coronavirus disease 2019 (COVID-19) vaccination began for healthcare workers in South Korea at the end of February 2021. This study investigated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody responses after various COVID-19 vaccinations in healthcare workers. Blood specimens of 497 vaccinated healthcare workers were collected. Inoculated vaccines were ChAdOx1 (AstraZeneca/Oxford), BNT162b2 (Pfizer/BioNTech), JNJ-78436735 (Janssen), and mRNA-1273 (Moderna). Each specimen was tested for antibodies against SARS-CoV-2 using Elecsys Anti-SARS-CoV-2 S assay (Roche Diagnostics), SARS-CoV-2 IgG II Quant assay (Abbott), and R-FIND SARS-CoV-2 Neutralizing Antibody kit (SG medical Inc.). A questionnaire was used to investigate adverse events related to vaccination. We found that 99.5% of the subjects showed a 96-100% positive rate in all three antibody assays, regardless of the vaccine type. The antibody-positive rate of completed vaccination groups reached 96-100%, and antibody quantities significantly increased 2 weeks after vaccination. The antibody values measured approximately 3 months after BNT162b2 inoculation significantly correlated with adverse events.

Severe Acute Respiratory Syndrome Coronavirus-2 Antibody Responses in Hospitalized Patients with Coronavirus Disease 2019 in Daegu, Korea.

BACKGROUND: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) started to spread in Daegu beginning at the end of February 2020. IgG and IgM antibodies against SARS-CoV-2 were measured in hospitalized patients with COVID-19 with moderate to severe symptoms to improve the understanding of antibody responses. METHODS: We enrolled 312 patients with COVID-19 admitted to seven hospitals located in Daegu. Using serum (or plasma) samples from patients with polymerase chain reaction (PCR)-confirmed SARS-CoV-2 infections, both IgG and IgM antibodies were measured using commercial enzyme-linked immunosorbent assay (R-FIND CO¬VID-19 ELISA, SG medical, Seoul, Korea). RESULTS: The median value from the initial diagnosis, confirmed by SARS-CoV-2 PCR, to the sampling date was 24 days (day 1 to 88). The total positive rate of IgG was 93.9% and the positive IgM rate was 39.4%, without considering the elapsed period after diagnosis. Positive IgG and IgM rates were highest at 100.0% and 59.0%, respectively, at 3 weeks (15 - 21 days). IgG showed a high positive rate of 79.3% even within 7 days after the initial diag-nosis of the disease and maintained a positive rate of 97.8% until after 8 weeks. CONCLUSIONS: Among hospitalized patients with COVID-19, IgG was detected from the beginning of the diagnosis and persisted for an extended time period.

Prevalence of SARS-CoV-2 Antibody in 2,935 Healthcare Workers at 6 Major Hospitals, Daegu, Korea.

BACKGROUND: In Korea, the first community outbreak of coronavirus disease 2019 (COVID-19) occurred in Daegu on February 18, 2020. This study was performed to investigate the prevalence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) antibodies in healthcare workers (HCWs) at 6 major hospitals in Daegu. METHODS: Blood specimens of 2,935 HCWs at 6 major hospitals in Daegu from January 2021 to February 2021 were collected. Every specimen was tested for antibody against SARS-CoV-2 using both Elecsys Anti-SARS-CoV-2 electrochemiluminescence immunoassay (Roche Diagnostics, Rotkreuz, Switzerland) and R-FIND COVID-19 IgG/M/A enzyme-linked immunosorbent assay kit (SG medical Inc., Seoul, Korea) as screening tests. If 1 or more of these screening test results was positive, 2 additional antibody tests were performed using Abbott Anti-SARS-CoV-2 IgG assay (Abbott, Abbott Park, IL, USA) and cPass SARS-CoV-2 Neutralization Antibody Detection Kit (GenScript USA Inc., Piscataway, NJ, USA). If 2 or more of the total 4 test results were positive, it was determined as positive for the antibody against SARS-CoV-2. RESULTS: According to the criteria of SARS-CoV-2 antibody positivity determination, 12 subjects were determined as positive. The overall positive rate of the SARS-CoV-2 antibody was 0.41% (12/2,935). Of the 12 subjects determined as positive, 7 were diagnosed with COVID-19, and the remaining 5 were nondiagnosed cases of COVID-19. CONCLUSION: In early 2021, the overall seroprevalence of SARS-CoV-2 antibody among HCW located in Daegu was 0.41%, and 0.17% excluding COVID-19 confirmed subjects. These results were not particularly high compared with the general public and were much lower than HCWs in other countries.

Characterization of the novel DQA1*01:01:09 allele by next-generation sequencing.

HLA-DQA1*01:01:09 differs from HLA-DQA1*01:01:01:01 by one nucleotide substitution in codon-12 in exon 1.

Erythrocyte Alloimmunity and Genetic Variance: Results from the Collaborative Study of Alloimmunity to Antigen Diversity in Asian Populations (All ADP).

As an East-Asian international study, we evaluated erythrocyte alloimmunity by gender and history of transfusion or pregnancy. In total, data from more than 1,826,000 patients were analyzed, from whom 26,170 irregular erythrocyte antibodies were detected in 22,653 cases. Antibody frequencies in these cases were as follows: anti-E, 26.8%; anti-Lea, 20.0%; anti-P1, 7.1%; anti-M, 6.4%; anti-Mia, 5.6%; anti-c + E, 5.6%; anti-Leb, 4.6%; anti-D, 2.8%; anti-Fyb, 2.6%; anti-Lea+Leb, 2.5%; anti-Dia, 2.0%; and others. For pregnant patients, anti-D (12.7%) was statistically more frequent. For transfused patients, anti-E (37.3%), anti-c + E (9.5%), anti-C + e (3.3%) and anti-Jka (3.1%) were significantly more frequent.

COVID-19 transmission and blood transfusion: A case report.

The recent outbreak of the novel coronavirus disease 2019 (COVID-19) has been labelled as a pandemic by the World Health Organization. Although person-to-person transmission of the etiologic agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been confirmed, it is not known whether COVID-19 may be transmitted by blood transfusion. Notwithstanding the urgent requirement of blood, it is critical to know whether the SARS-CoV-2 virus can be transmitted by blood transfusion because many individuals may be asymptomatic carriers and may donate blood. Several cases in which specific viral RNA could be detected in the serum from patients with COVID-19 have already been reported; these findings suggest that blood donation may be an unexplored route of transmission. However, the American Association of Blood Banks and Centers for Disease Control and Prevention have not recommended any specific SARS-CoV-2-related actions to be taken at blood collection centres at this time. In this report, we describe a case of a 21-year-old man with very severe aplastic anaemia who received apheresis platelet transfusion from an individual who was subsequently diagnosed with COVID-19. Our patient tested negative for COVID-19 and is awaiting allogeneic stem cell transplantation.

Erythrocyte deformability reduction in various pediatric hematologic diseases.

BACKGROUND: Previously, hemorheology studies using Rheoscan mainly focused on chronic kidney disease, cardiovascular disease, and endocrine disease in adults. The study using LORCA focused on erythrocyte disease. There were no studies using Rheoscan in children. OBJECTIVE: We aimed to investigate erythrocyte deformability among various hematologic diseases occurring in children, namely, iron deficiency anemia (IDA), hereditary spherocytosis (HS), immune thrombocytopenia (ITP), and aplastic anemia (AA). METHODS: Differences between those with HS, IDA, ITP, AA and healthy controls were compared among 43 patients, comprising 7 patients with HS, 8 patients with IDA, 6 patients with AA, 9 patients with ITP, and 13 healthy controls. Erythrocyte deformability was measured using a microfluidic ektacytometer (RheoScan-D, RheoMeditech, Seoul, Korea). The erythrocyte elongation index (EI) was defined as (L - W)/(L + W), where L and W are the major and minor axes of the ellipse, respectively. RESULTS: The EI values of IDA, HS and AA were significantly decreased compared with healthy controls, but those of ITP were similar to healthy controls. CONCLUSIONS: This study showed that erythrocyte deformability differed among various hematologic diseases. Further study concerning correlation in relation to the diagnostic and prognostic significance of erythrocyte deformability in hematologic disease is needed.

Favorable long-term survival using consolidation chemotherapy without allogeneic hematopoietic cell transplantation for acute myeloid leukemia with wild-type NPM1 without FLT3-ITD.

BACKGROUND: The role of allogeneic hematopoietic cell transplantation (allo-HCT) compared with consolidation chemotherapy alone in intermediate-risk acute myeloid leukemia (AML) patients with wild-type nucleophosmin/negative or a low level of Fms related tyrosine kinase 3 internal tandem duplication (NPM1 wt/FLT3-ITDneg/low) has not yet been elucidated. METHODS: In this study, we retrospectively investigated 88 patients newly diagnosed with AML who received intensive induction chemotherapy at Kyungpook National University Hospital from March 2015 to July 2017. The selection criteria included the presence of results on genetic abnormalities including NPM1 and FLT3-ITD. RESULTS: According to the European LeukemiaNet (ELN) risk classification, 25 patients (28%) were categorized as favorable, 44 (50%) as intermediate, and 19 (22%) as adverse risk. Among the intermediate-risk patients, 40 were identified as NPM1 wt/FLT3-ITDneg/low. Among the patients with NPM1 wt/FLT3-ITDneg/low, complete remission (CR) was achieved in 26 patients out of 40 (65%). One-year overall survival (OS) rate was 100% in the favorable-risk group and 87.9% in the NPM1 wt/FLT3-ITDneg/low group (P=0.233). Among the intermediate-risk NPM1 wt/FLT3-ITDneg/low patients, there was no survival benefit with allo-HCT (N=19) compared to consolidation chemotherapy (N=21; P=0.372). In the multivariate analysis, the ELN risk group [hazard ratio (HR), 6.36; P=0.019] and the achievement of CR (HR, 2.95; P=0.017) were both identified as factors affecting OS of patients with newly diagnosed AML. CONCLUSION: Among the AML patients, intermediate-risk NPM1 wt/FLT3-ITDneg/low patients and favorable-risk patients showed similar OS rates. Our results suggested that allo-HCT might have limited clinical benefit for the intermediate-risk NPM1 wt/FLT3-ITDneg/low patients. Well controlled studies are needed to confirm the current results.

Impact of Consolidation Cycles Before Allogeneic Hematopoietic Cell Transplantation for Acute Myeloid Leukemia in First Complete Remission.

BACKGROUND: The optimal number of high-dose cytarabine (HDAC) consolidation cycles before allogeneic hematopoietic cell transplantation (HCT) for acute myeloid leukemia is not fully standardized. PATIENTS AND METHODS: This study evaluated the impact of HDAC consolidation cycles before allogeneic HCT in 194 patients with acute myeloid leukemia in first complete remission between 1998 and 2014. The patients were reclassified into 3 groups-no consolidation (C0, n = 20), 1 consolidation (C1, n = 115), and ≥ 2 consolidations (C2, n = 59)-by pre-HCT consolidation cycle. RESULTS: The 3-year relapse-free survival rates was 45.9%, 66.9%, and 73.3% for the C0, C1, and C2 groups, respectively (P = .064), while the 3-year overall survival rates were 35.0%, 55.2%, and 67.5%, respectively (P = .106). The cumulative incidence of acute graft-versus-host disease (GVHD) was higher in the C2 group (38.7%) than in the C0 (22.2%) or C1 (17.7%) group (P = .018). However, the incidence of chronic GVHD showed no difference between the groups. Multivariate analysis for overall survival revealed the following independent factors: adverse cytogenetic risk (hazard ratio [HR] = 1.84, P = .046), C2 versus C0 (HR = 0.41, P = .037), pre-HCT status beyond CR1 versus CR1 (HR = 5.78, P < .001), and presence of chronic GVHD (HR = 0.45, P = .004). CONCLUSION: One or two cycles of HDAC consolidation therapy led to better subsequent HCT outcomes compared to the no-consolidation therapy group.

Corrigendum: Hemorheologic Alterations in Patients with Type 2 Diabetes Mellitus Presented with an Acute Myocardial Infarction.

This corrects the article on p. 155 in vol. 42, PMID: 29676545.

Hemorheologic Alterations in Patients with Type 2 Diabetes Mellitus Presented with an Acute Myocardial Infarction.

BACKGROUND: Hemorheologic indices are known to be related to vascular complications in variable clinical settings. However, little is known about the associations between hemorheologic parameters and acute myocardial infarction (AMI) in type 2 diabetes mellitus (T2DM). The purpose of this study was to demonstrate the changes of hemorheologic environment inside of blood using hemorheologic parameters, especially the elongation index (EI) and critical shear stress (CSS) in diabetics with versus without AMI. METHODS: A total of 195 patients with T2DM were enrolled. Patients were divided into the study group with AMI (AMI+, n=77) and control group (AMI-, n=118) who had no history of coronary artery disease. Hemorheologic parameters such as EI and CSS were measured and compared between the two groups. RESULTS: The EI was lower (30.44%±1.77% in AMI+ and 31.47%±1.48% in AMI-, P<0.001) but the level of CSS was higher (316.13±108.20 mPa in AMI+ and 286.80±85.34 mPa in AMI-, P=0.040) in the AMI+. The CSS was significantly related to the erythrocyte sedimentation rate (R²=0.497, P<0.001) and use of dipeptidyl peptidase-4 inhibitors (R²=0.574, P=0.048). CONCLUSION: Diabetics with AMI resulted in adverse hemorheologic changes with lower EI and higher CSS compared to diabetic subjects without AMI. Evaluation of the hemorheologic parameters may provide valuable supplementary information for managing patients with AMI and T2DM.

A Novel Flow Cytometric Method for the Simultaneous Detection of Antibodies Against Platelet, Lymphocyte, And Neutrophil.

BACKGROUND: Platelet or neutrophil antibodies (Ab) detected by an indirect method need to be further investigated to confirm that they are HLA (lymphocyte)-specific. This can only be determined by the assessment of lymphocytes from the same donor. We have developed an improved flow cytometric method for the simultaneous detection of Abs against three distinct cell types (platelets, lymphocytes, and neutrophils) in a single suspension. METHODS: We prepared white blood cell (WBC) suspensions using an overlay procedure. To enhance the retrieval of the three cell types during flow cytometry, the acquisition time was divided into two periods, platelet phase and WBC phase, and a different live acquisition gate was applied to each phase. The sample/control ratio of mean fluorescence intensity (MFI) was measured for each cell type. RESULTS: The number of cells in the starting cell suspension and the retrieved cell numbers of the three cell types were sufficient to detect their cognate antibodies. There was no significant difference between the MFI ratios observed in the current protocol and those from the conventional method (P > 0.05), and positive correlations were found (P < 0.05) for all three cell types. Each positive control serum with a specific set of Abs showed the typical comprehensive reaction pattern to the three cell types. Based on such patterns, 47% (14/30) of the patient sera that reacted with platelets were demonstrated to be due to anti-HLA Abs without platelet Abs. CONCLUSIONS: Our method could enhance both interpretation accuracy of the diagnostic test results and laboratory efficiency. As an increased reaction with platelets is commonly due to anti-HLA Abs, the reactivity of the lymphocytes from the same donor should also be tested, which can be routinely done by using our protocol. © 2016 International Clinical Cytometry Society.

Adipose-Derived Regenerative Cell Injection Therapy for Postprostatectomy Incontinence: A Phase I Clinical Study.

PURPOSE: We report our initial experience with transurethral injection of autologous adipose-derived regenerative cells (ADRCs) for the treatment of urinary incontinence after radical prostatectomy. MATERIALS AND METHODS: After providing written informed consent, six men with persistent urinary incontinence after radical prostatectomy were enrolled in the study. Under general anesthesia, about 50 mL of adipose tissue was obtained from the patients by liposuction. ADRCs were obtained by separation with centrifugation using the Celution cell-processing device. A mixture of ADRCs and adipose tissue were transurethrally injected into the submucosal space of the membranous urethra. Functional and anatomical improvement was assessed using a 24-h pad test, validated patient questionnaire, urethral pressure profile, and magnetic resonance imaging (MRI) during 12-week follow-up. RESULTS: Urine leakage volume was improved with time in all patients in the 24-h pad test, with the exemption of temporal deterioration at the first 2 weeks post-injection in 2 patients. Subjective symptoms and quality of life assessed on the basis of questionnaire results showed similar improvement. The mean maximum urethral closing pressure increased from 44.0 to 63.5 cm H2O at 12 weeks after injection. MRI showed an increase in functional urethral length (from 6.1 to 8.3 mm) between the lower rim of the pubic bone and the bladder neck. Adverse events, such as pelvic pain, inflammation, or de novo urgency, were not observed in any case during follow-up. CONCLUSION: This study demonstrated that transurethral injection of autologous ADRCs can be a safe and effective treatment modality for postprostatectomy incontinence.

POEMS Syndrome with IgG-λ/IgA-κ Biclonal Gammopathy and Abnormal Serum Free Light Chain Ratio: a Case Report.

BACKGROUND: POEMS syndrome is a rare paraneoplastic disorder with atypical plasma cell proliferation. Cases of POEMS syndrome presented with either biclonal gammopathy or an abnormal serum free light chain ratio are considered uncommon. The present authors encountered a case of POEMS syndrome with IgG-λ/IgA-κ biclonal gammopathy with dominant κ free light chain and abnormal serum free light chain ratio. CASE: A 56-year-old man with a history of Castleman disease was suspected with POEMS syndrome and admitted for further evaluation for B-cell proliferative disease to rule out multiple myeloma. He also had a sustained tingling sensation on both feet and gait disturbance, which were compatible with diffuse peripheral sensorimotor polyneuropathy with demyelinating features. His laboratory findings revealed hyperlipidemia and hypothyroidism, and he had hypertrichosis. The results of the serum and urine protein electrophoresis seemed normal, except a very weak band at the end of the serum gamma region. Serum immunofixation electrophoresis confirmed IgG-λ and IgA-κ biclonal gammopathy, with an increased serum IgA concentration and normal levels of IgG, IgM, and IgD. Both serum free light chain κ and λ values were increased, and the κ/λ ratio was higher than normal. CONCLUSIONS: The finding of IgG-λ/IgA-κ biclonal gammopathy and abnormal serum free light chain ratio with dominant κ clonality in our case was definitely rare. However, a primary pathogenic role of the different paraproteinemia in POEMS syndrome remains unclear. Further studies to identify better management modalities for POEMS syndrome is needed.

Highly sensitive and novel point-of-care system, aQcare Chlamydia TRF kit for detecting Chlamydia trachomatis by using europium (Eu) (III) chelated nanoparticles.

BACKGROUND: The bacterium Chlamydia trachomatis is one of the leading causes of sexually transmitted diseases worldwide. Since no simple and effective tool exists to diagnose C. trachomatis infections, we evaluated a novel point-of-care (POC) test, aQcare Chlamydia TRF kit, which uses europium-chelated nanoparticles and a time-resolved fluorescence reader. METHODS: The test performance was evaluated by comparing the results obtained using the novel POC testing kit with those obtained using a nucleic acid amplification test (NAAT), using 114 NAAT-positive and 327 NAAT-negative samples. RESULTS: The cut-off value of the novel test was 20.8 with a detection limit of 0.27 ng/mL. No interference or cross-reactivity was observed. Diagnostic accuracy showed an overall sensitivity of 93.0% (106/114), specificity of 96.3% (315/327), positive predictive value (PPV) of 89.8% (106/118), and negative predictive value (NPV) of 97.5% (315/323). The sensitivity of the novel test was much higher than that of currently available POC tests. Furthermore, the relative ease and short turnaround time (30 min) of this assay enables C. trachomatis-infected individuals to be treated without a diagnostic delay. CONCLUSIONS: This simple and novel test is a potential tool to screen a larger population, especially those in areas with limited resources.

Outcomes of allogeneic hematopoietic cell transplantation in acute myeloid leukemia patients with monosomal karyotypes.

This study investigated the outcomes of allogeneic hematopoietic cell transplantation (allo-HCT) in acute myeloid leukemia (AML) patients with monosomal karyotypes (MK). A total of 114 AML patients who received allo-HCT were retrospectively analyzed. At the time of diagnosis, 13 patients were categorized with a favorable cytogenetic risk, 78 with an intermediate risk, and 23 with an adverse risk. MK was found in 12 patients among 23 with adverse cytogenetic risk. Pretransplant disease status was active disease in 5 cases (45.5%) in the adverse-risk without MK group, and 8 cases (66.7%) in the corresponding group with MK, 15 (19.2%) in the intermediate group and 4 (30.8%) in the favorable group. In multivariate analysis, active disease before transplant (hazard ratio, HR 3.913, p < 0.001), acute graft-versus-host disease (GVHD) ≥grade 2 (HR 1.908, p = 0.048) and chronic GVHD (HR 0.364, p = 0.001) affected overall survival (OS). The initial cytogenetic risk groups were not a significant risk factor for OS in allogeneic settings. The 2-year OS rate was 44.0 ± 15.9% without MK and 20.7 ± 17.9% with MK (p = 0.246). However, the OS rate was better for patients with chronic GVHD (p = 0.025). In conclusion, a survival benefit was observed for MK-positive patients with chronic GVHD in an allogeneic setting. However, the prognosis still remained poor for patients with MK.