Clinical impact of cell-free serum Epstein–Barr virus status in patients with newly diagnosed malignant lymphoma

Background@#We analyzed cell-free serum Epstein‒Barr virus (EBV) DNA to identify its prognostic role in patients with newly diagnosed lymphoma. @*Methods@#We retrospectively reviewed patients diagnosed with lymphoma between January 2014 and July 2020. Patients were enrolled according to the following criteria: i) pathologically confirmed lymphomas according to the World Health Organization criteria, ii) age over 18 years, iii) serum EBV DNA measurement using polymerase chain reaction prior to first-line therapy, and iv) receipt of curative standard chemotherapy. In total, 263 patients met these criteria and were included in this study. @*Results@#Serum EBV DNA was detected in 79 patients (30.0%). Patients with positive serum EBV tended to be older (P =0.090), and the proportion of T-cell lineage lymphomas was higher than that of B-cell lymphomas (P =0.003). EBV positivity was significantly associated with more advanced disease based on the Ann Arbor staging system (P =0.008) and the International Prognostic Index (P =0.009). EBV positivity was also associated with higher disease relapse (P =0.038) and death rates (P =0.005). EBV-positive lymphomas further showed inferior long-term survival outcomes in terms of progression-free survival (PFS) (P =0.053) and overall survival (OS) (P =0.014). In the subgroup analyses, serum EBV positivity was a significant prognostic factor for patients with B-cell lineage lymphomas in terms of PFS (P =0.003) and OS (P =0.033). @*Conclusion@#We demonstrated that cell-free serum EBV DNA status at the time of diagnosis has potential as a prognostic biomarker for patients with newly diagnosed malignant lymphomas.

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.

Clinical impact of cell-free serum Epstein–Barr virus status in patients with newly diagnosed malignant lymphoma

Background@#We analyzed cell-free serum Epstein‒Barr virus (EBV) DNA to identify its prognostic role in patients with newly diagnosed lymphoma. @*Methods@#We retrospectively reviewed patients diagnosed with lymphoma between January 2014 and July 2020. Patients were enrolled according to the following criteria: i) pathologically confirmed lymphomas according to the World Health Organization criteria, ii) age over 18 years, iii) serum EBV DNA measurement using polymerase chain reaction prior to first-line therapy, and iv) receipt of curative standard chemotherapy. In total, 263 patients met these criteria and were included in this study. @*Results@#Serum EBV DNA was detected in 79 patients (30.0%). Patients with positive serum EBV tended to be older (P =0.090), and the proportion of T-cell lineage lymphomas was higher than that of B-cell lymphomas (P =0.003). EBV positivity was significantly associated with more advanced disease based on the Ann Arbor staging system (P =0.008) and the International Prognostic Index (P =0.009). EBV positivity was also associated with higher disease relapse (P =0.038) and death rates (P =0.005). EBV-positive lymphomas further showed inferior long-term survival outcomes in terms of progression-free survival (PFS) (P =0.053) and overall survival (OS) (P =0.014). In the subgroup analyses, serum EBV positivity was a significant prognostic factor for patients with B-cell lineage lymphomas in terms of PFS (P =0.003) and OS (P =0.033). @*Conclusion@#We demonstrated that cell-free serum EBV DNA status at the time of diagnosis has potential as a prognostic biomarker for patients with newly diagnosed malignant lymphomas.

Myelodysplastic Syndrome and Minimal Change Nephrotic Syndrome treated with Steroid Challenge / 대한내과학회지

Glomerulonephritis associated with malignancy is deemed to be paraneoplastic glomerulonephritis. Myelodysplastic syndrome (MDS) is a group of heterogeneous clonal hematopoietic stem cell disorders characterized by impaired hematopoietic cell differentiation and cytopenia. The pathophysiology of MDS is thought to be immune-mediated in part. A few reports have documented various forms of glomerulonephritis in patients with MDS and suggested that immune dysregulation is important in the development of paraneoplastic glomerulonephritis. Here, we report a patient with MDS and refractory anemia with excess blast-2 accompanied by minimal change nephrotic syndrome. The patient was treated with prednisolone, and the nephrotic-range proteinuria and pancytopenia improved markedly.

A Case of Pseudohyperphosphatemia in a Patient with Multiple Myeloma / 대한내과학회지

Hyperphosphatemia develops when there is impaired renal phosphate excretion or massive extracellular fluid phosphate load. For example, renal insufficiency, hypoparathyroidism, exogenous phosphate administration, and extensive cellular injury induce a hyperphosphatemic state. In patients with multiple myeloma, renal insufficiency occurs as a result of hypercalcemia, light chain tubulopathy, urate nephropathy or infection, and hyperphosphatemia usually results from renal failure. We report here a case of a patient with multiple myeloma who had an elevated serum phosphate level measured by the phosphomolybdate UV method without significant renal insufficiency and was finally diagnosed with pseudohyperphosphatemia.

Relationship between Antiphospholipid Antibodies and Major Adverse Cardiovascular Events after Drug-Eluting Stent Implantation in Patients with Acute Myocardial Infarction / 대한내과학회지

BACKGROUND/AIMS: Several studies have reported an association between antiphospholipid antibodies (APA) and major adverse cardiovascular events (MACE) following acute myocardial infarction (AMI). However, the relationship between APA and the prognosis after drug-eluting stent (DES) implantation in patients with AMI is not known. METHODS: Thus, we investigated the relationship between the incidence of MACE and APA levels in patients with AMI who underwent successful DES implantation. RESULTS: Of 182 patients, 78 (42.9%) tested positive for APA. Lupus anticoagulant was positive in 37.6% (68 of 181) patients, anticardiolipin antibody IgM was positive in 8.3% (15 of 180), and anticardiolipin antibody IgG was positive in 1.7% (3 of 180) patients. At follow up, a MACE had occurred in 11 (14.1%) patients in the APA-positive group and in seven (6.7%) patients in the APA-negative group (p = 0.099). CONCLUSIONS: No significant association was found between the incidence of MACE and the presence of APA in patients with AMI who underwent successful DES implantation.

FLT3 Gene Mutations as a Prognostic Factor for Acute Myeloid Leukemia / 대한진단검사의학회지

BACKGROUND: Two distinct types of fms-like tyrosine kinase 3 (FLT3) gene mutations have been identified in acute myeloid leukemia (AML): D835 and internal tandem duplication (ITD) mutations. These mutations are known to cause the proliferation of leukemic cells and inhibit the apoptosis of leukemic cells due to ligand-independent activation of their receptors. Therefore, the current study attempted to investigate the frequency of FLT3 gene mutations and their prognostic implications for AML in terms of treatment response, survival, and relapse. METHODS: Polymerase chain reaction (PCR) was performed to detect D835 and ITD mutations in 84 newly diagnosed AML patients from February 2001 to October 2004. Restriction fragment length polymorphism (RFLP) and direct sequencing were performed to analyze the D835 mutations. The results were examined based on a comparison with previously known prognostic factors, and the treatment outcomes analyzed according to the existence of the mutations in relation to the event free survival (EFS), overall survival (OS), and complete remission (CR) rates. RESULTS: D835 and IDT mutations were detected in 4.7% (4/84) and 19.0% (16/84), respectively, of the AML patients. The FLT3 gene mutations were not found to be associated with previously known prognostic factors, such as the WBC count, age, and cytogenetic risk group, but were associated with the lactate dehydrogenase levels. The EFS and OS rates were also significantly lower in the FLT3 gene mutation group, especially in AML with normal karyotypes. CONCLUSIONS: FLT3 gene mutations were observed in 23.8% of AML patients and appeared to have a prognostic implication on patient survival. Accordingly, the presence of FLT3 gene mutations, which could be tested easily by using PCR/RFLP methods, should be investigated routinely at the time of diagnosis.

Two Cases of Heparin-Induced Thrombocytopenia in Hemodialysis Patients / 대한신장학회잡지

Heparin, a widely used anticoagulant, is currently the anticoagulant of choice in long-term hemodialysis (HD). Heparin-induced thrombocytopenia (HIT) is one of the most serious side effects of heparin which can cause arterial or venous thromboembolism associated with substantial morbidity and mortality. We experienced two patients who had thrombocytopenia and vascular access occlusion during the induction period of HD with the use of unfractionated heparin. Thrombocytopenia was improved after discontinuation of heparin. HIT was confirmed with anti-heparin/platelet factor 4 antibody test. HD was conducted and arteriovenous fistula was created successfully after switch of heparin to argatroban (Novastan(R)) or nafamostat mesilate (Futhan(R)). Nephrologist should rule out HIT first when thrombocytopenia and thromboembolic complications occur after use of heparin, especially during the induction period of HD. For suspicious patients, immediate cessation of heparin and switch to alternative anticoagulant is very important to avoid serious complications.

Two Cases of Heparin-Induced Thrombocytopenia Diagnosed by Particle Gel Immunoassay / 대한진단검사의학회지

Heparin-induced thrombocytopenia (HIT) is a serious complication of heparin therapy. It represents initially as thrombocytopenia and is associated with venous or arterial thrombosis. It has been reported that platelet factor 4/heparin complex antibody plays an important role in the pathogenesis of HIT. Patients on hemodialysis have a high risk of developing HIT because heparin is administrated in hemodialysis as anticoagulant. Thrombocytopenia usually occurs 5 to 10 days after the onset of administration, but occasionally, it may occur rapidly in patients who have preformed antibodies from recent heparin use. We report here 2 cases of HIT with platelet factor 4-heparin reactive antibody in hemodialysis patients.

Determination of Propofol in Blood by HPLC Method / 대한임상병리학회지

BACKGROUND: Propofol (2,6-diisopropylphenol) is one of the intravenous anesthetic drugs used for induction and maintenance of general anesthesia as well as for sedation in ICU patients and one-day surgery. The monitoring of propofol in blood helps to maintain anesthetic state and promote earlier recovery. So we attempted to find the rapid and simple method for blood propofol determination. METHODS: We compared the precipitation method with extraction one using whole blood, plasma and deionized water added a fixed amount of propofol. According to the extraction method, propofol was extracted from 500 microliter sample adding KH2PO4, ethyl acetate, and tetra-ethylammonium hydroxide using thymol as an internal standard. For the precipitation method, the precipitating solution (500 microliter) containing thymol was added to a 500 microliter sample, then mixed. After centrifugation, the supernatant was injected into HPLC system. A Waters 2690 separations module, Waters 474 fluorescence and 486 UV detector and a Symmetry column were used. We used Millennium software to control analyzing process and quantify propofol. RESULTS: The precipitation method using thymol as an internal standard and Waters 474 fluorescence detector showed the most excellent results. For the calibration curves, we found very good linearity in whole blood, plasma and deionized water (r> or =9976). Intra-assay and inter-assay coefficient of variation (CV) values of propofol for the precipitation method were 4.4% and 8.9% at 2 microgram/mL of propofol and 2.0% and 6.2% at 8 microgram/mL, respectively. The recovery rates of propofol for plasma and whole blood were 104.1% and 92.7% at 2 microgram/mL and 99.4% and 91.6% at 7 microgram/mL, respectively. CONCLUSIONS: For the measurement of the blood propofol level, the precipitation method using thymol as an internal standard and fluorescence detector seemed to be the rapid and simple method to apply for the clinical purpose.

Amino Acid Derangements in Plasma and Erythrocytes of Patients with Sepsis / 대한임상병리학회지

BACKGROUND: Sepsis is a major insult leading to increased muscle breakdown and oxidation of amino acids. Disturbed plasma and brain amino acid levels may be important in the altered mental status observed in patients with infections and alteration in mental status due to sepsis has been associated with an increased mortality rate. Erythrocytes have been suggested as transport cells for amino acids and may be better than plasma for utilization and storage of amino acids in the body. Several reports suggested that amino acid alterations in plasma and erythrocytes have had an important role in sepsis. So we investigated the association between severity and prognosis of sepsis and amino acid levels in plasma and erythrocytes. METHODS: Heparinized plasma and erythrocytes were taken from 25 healthy controls, 10 infected patients and 15 septic patients. The amino acid levels were determined using high performance liquid chromatography after deproteinization with sulfosalicylic acid. RESULTS: Plasma amino acid pattern showed elevated levels of the aromatic amino acids (tyrosine and phenylalanine) and sulfur-containing amino acid (cystine) but decreased level of branched chain amino acid (isoleucine) in septic patients compared with healthy controls or infected patients. Patients with septic encephalopathy had higher levels of tyrosine, phenylalanine and sulfur-containing amino acid (methionine) than patients without septic encephalopathy. The ratios of erythrocytes to plasma showed no significant decrease in septic patients compared with healthy controls or infected patients. However, in patients with septic encephalopathy, methionine, leucine and phenylalanine levels were lower than in patients without septic encephalopathy. CONCLUSIONS: The results showed a characteristic pattern of amino acid derangements in plasma and erythrocytes of septic patients. This pattern was more prominent in severe sepsis. It was suggested that the severity and prognosis of septic patients could be predicted by measuring the amino acid levels of plasma and erythrocytes.

Irregular Antibody Screening in Cord Blood by Column Agglutination Test / 대한수혈학회지

BACKGROUND: Irregular antibodies are antibodies that are not regularly present in the serum of particular blood groups and its presence results in many problems including HDN (hemolytic disease of newborn) in transfusion medicine. Column agglutination test was recently introduced and has been widely used for advantages of standardized working procedures, standard reactions, stable reactions for hours and Coombs test without washing steps. We tested irregular antibodies in cord blood by column agglutination test and investigated its incidence and relation with HDN. METHODS: We tested the cord blood collected during delivery from 200 pregnant women. Column agglutination test was done on DiaMed ID MicroTyping System (DiaMed, Switzerland) and both LISS/Coombs and NaCl/Enzyme ID-cards were used. The antibody screening test was done first and antibody identification test was done to positive cases in same way. The cell typing and Rh phenotyping for cord blood of positive cases were also done. RESULTS: 2 cases of 200 samples (1%) were positive in the antibody screening test and each was identified as anti-D and anti-E antibody. CONCLUSIONS: Irregular antibody screening in cord blood by column agglutination test is thought to be helpful in early diagnosis and treatment of HDN.