Prevalence of elevated serum concentrations of biotin in patients from South East England, Korea, Singapore and Thailand and risk of immunoassay interference.

Biotin interference in immunoassays using biotin-streptavidin binding technology is well recognised by clinical laboratories, though the prevalence of elevated biotin in patient populations is largely unknown. We determined serum biotin concentrations in 4385 patient samples received sequentially by 6 laboratories for routine immunoassay analysis in England, and Korea, Singapore and Thailand (3 countries within the Asia Pacific region, APAC). Samples were initially analysed using a research use-only immunoassay, with those identified as having potentially elevated biotin concentrations referred for definitive analysis by LC-MS/MS. The prevalence of elevated serum biotin was 0.4% and 0.6% for England and APAC, respectively (range 10.0-129.0 µg/L). Our data adds to a report from a different region of England and is the first for APAC. Laboratories and clinicians benefit from an awareness of the prevalence of elevated serum biotin, which coupled with an understanding of the threshold at which interference occurs, reduces clinical impact of analytical error.

Thyroid Function Tests in the First Trimester of Pregnancy According to Maternal Age in Asia.

BACKGROUND: The American Thyroid Association suggested selective performance of the thyroid function test (TFT) in pregnant women with risk factors such as age over 30 years. We evaluated the limited indication of TFT based on age by analyzing our institution's retrospective data about TFT in pregnant women. METHODS: We retrospectively analyzed the results of thyroid stimulating hormone (TSH) and free thyroxine (FT4) with the antithyroid autoantibody test using the Cobas 8000 e801 module (Roche Diagnostics, Mannheim, Germany) performed during the first trimester of pregnancy. Data were analyzed and compared between subjects younger or older than 30 years. RESULTS: The mean values of TSH and FT4 did not show any significant differences according to age. Also, the two groups had similar prevalence of overt/subclinical hypothyroidism. It was analyzed that over 20% of overt hypothyroidism could be missed by applying age-based screening. CONCLUSIONS: Selective screening according to age (> 30 years) can miss a considerable number of pregnant women with hypothyroidism. Considering the value of appropriate screening and treatment in pregnant women with hypothyroidism, universal screening is necessary rather than selective screening considering the age of pregnant women.

Neutrophil-to-Monocyte-Plus-Lymphocyte Ratio as a Potential Marker for Discriminating Pulmonary Tuberculosis from Nontuberculosis Infectious Lung Diseases.

OBJECTIVE: To determine whether NMLR has more statistical strength than NLR in discriminating TB from non-TB infectious lung diseases. METHODS: Among patients who underwent 3 or more TB culture tests with molecular study between January 2016 and December 2017, 110 patients with TB, and 159 patients diagnosed with non-TB infectious lung diseases were enrolled. The original complete blood count (CBC) parameters and modified CBC indices, including NLR and NMLR, were analyzed. RESULTS: The NLR and NMLR were significantly lower in TB patients than in patients with other infectious lung diseases. However, the area under the curve (AUC) for NMLR (0.90; 95% confidence interval [CI], 0.86-0.93) was significantly greater than that for NLR (0.88 [0.84-0.92]). CONCLUSIONS: The neutrophil-to-monocyte-plus-lymphocyte ratio (NMLR) can be used as a new index that is more powerful than neutrophil-to-lymphocyte ratio (NLR) in discriminating tuberculosis (TB) from non-TB infectious lung diseases.NMLR had more statistical strength than NLR in discriminating TB from non-TB infectious lung diseases.

Misidentification of Acinetobacter baumannii as Alcaligenes faecalis by VITEK 2 System; Case Report.

Acinetobacter baumannii (A. baumannii) is widely known as an opportunistic bacterial pathogen that causes infection more frequently among immunocompromised individuals. Our case demonstrated the limitation of the current VITEK 2 system for the idendification of A. baumannii. Four clinical isolates of A. baumannii were identified as Alcaligenes faecalis by the VITEK 2 system. Misidentification might lead to unnecessary tests and inappropriate treatments. Additional methods appear to be helpful for the accurate identification of A. baumannii for clinical microbiology laboratories.

Modified Complete Blood Count Indices as Predicting Markers of Preeclampsia from Gestational Hypertension: Neutrophil to Lymphocyte Ratio, Platelet to Lymphocyte Ratio, and Platelet to Neutrophil Ratio.

BACKGROUND: To evaluate modified complete blood count (CBC) indices as a predicting marker of preeclampsia (PE) from gestational hypertension (GH), we analyzed the neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and platelet to neutrophil ratio (PNR). PNR was a newly designed index in this study based on results of PE patients having a tendency toward higher neutrophil count and lower platelet count compared to normal pregnant women in previous studies. METHODS: We recruited 86 normal pregnant women, 33 patients with GH and 68 patients with PE. Subjects with any history of membrane rupture, infection, or multiple pregnancies were excluded. PNR, NLR, and PLR values including other CBC indices were statistically analyzed. RESULTS: NLR value of PE patients was significantly higher than GH patients (p = 0.011). PNR value was the most statistically significant index separating patients with PE and GH (p < 0.001). PLR value was lower in patients with PE compared to GH; however, statistical significance was low. CONCLUSIONS: NLR as well as PNR is a useful index to help predicting progression from GH to PE. Further studies are required to evaluate the full extent of utility of PNR as a predictive index in PE patients.

Limitations of Preoperative PFA-200 as a Predictor of Postoperative Blood Loss in Total Knee Arthroplasty: According to Use of Tranexamic Acid.

BACKGROUND: Recently, anti-fibrinolytic agents (tranexamic acid) have been used to reduce blood loss or and the need for transfusion. We evaluated the clinical utility of PFA-200 as a predictor of postoperative blood loss in a clinical setting, where hemostasis can be affected by variables such as existing comorbidities and medication use. METHODS: We analyzed retrospectively 243 TKA patients having PFA-200 results between March 2014 and May 2016. We collected the medication history of anti-thrombotic agents, closure time measured by PFA-200, postoperative drainage volume, and perioperative change of hemoglobin values. Parameters associated with postoperative blood loss were compared to the prolongation of closure time and medication use. The influence of variables on postoperative blood loss was analyzed. RESULTS: The closure times of PFA-200 were prolonged in 68 patients (295.8 ± 10.7) and were not prolonged in 175 patients (125.4 ± 35.8). The prolonged closure time did not affect any parameters associated with postoperative blood loss. A history of preoperative anti-platelet agents used was a factor that statistically significantly increased the amount of postoperative drainage and reduction of perioperative hemoglobin values. In addition, postoperative tranexamic acid treatment was the factor that decreased the postoperative hemoglobin levels (OR = 0.297 with p = 0.010) most. CONCLUSIONS: The effectiveness of preoperative PFA-200 in assessments of postoperative bleeding risk is reduced with postoperative use of tranexamic acid.

Diagnostic Utility of New Equation for Active Tuberculosis Based on Parameters of Interferon-γ Release Assay.

BACKGROUND: We derived a new equation to include interferon-γ (IFN-γ) levels in the QuantiFERON-Gold In-Tube (QFT-GIT) assay to discriminate active tuberculosis (ATB) infection from latent TB, and compared the diagnostic performance of the QFT-GIT assay and the new equation. METHODS: From January 2013 through May 2015, we retrospectively enrolled 159 and 408 patients with and without ATB, respectively, in this study. Discriminant analysis was performed to derive an equation to distinguish the ATB group from the non-ATB group. RESULTS: The sensitivity and specificity of the QFT-GIT assay for diagnosing ATB were 90.6% and 63.0%, respectively. The positive and negative predictive values of the QFT-GIT assay were 48.8% and 94.5%, respectively. When the optimal cutoff for the new equation [Z = (0.031 × Nil) + (0.007 × TBAg) - 0.978] was set to -0.435, the sensitivity and specificity were 84.3% and 69.1% (positive predictive value, 51.5%; negative predictive value, 91.9%), respectively. CONCLUSIONS: The QFT-GIT assay and the equation derived from each IFN-γ could not discriminate ATB from latent TB without considering other cytokines involved in immunity against TB.

Pure Red Cell Aplasia Associated with Monoclonal Gammopathy of Undetermined Significance and Literature Review.

BACKGROUND: Pure red cell aplasia (PRCA) is an uncommon disease which involves an almost complete absence of the erythroid lineage in bone marrow (BM) and causes severe anemia. Cases due to monoclonal gammopathy occurring in plasma cell disorder have been infrequently reported. Here we report a case of PRCA associated plasma cell disorder, especially monoclonal gammopathy of undetermined significance (MGUS). METHODS: A 55-year-old male visited the ER due to general weakness. At his initial visit he exhibited severe anemia. Mild intravascular hemolysis was suspected. For anemia evaluation, BM examination was performed. In BM aspiration, almost no erythroid precursor cells were observed. Also, plasma cells were relatively elevated, at 7.2%. Serum electrophoresis and immunofixation revealed paraproteinemia of 5.1 g/L (IgG and lambda). No hypercalcemia, renal insufficiency or lytic bone lesions were found. This unusual case showed MGUS accompanied by PCRA. We were also able to assume the erythroid cell-specific restriction due to paraprotein, because we ruled out possible causes of PRCA. RESULTS: We discovered several reported cases associated with plasma cell dyscrasia. However, most of these cases involved plasma cell myeloma, characterized by high immunoglobulin burden. Our case demonstrates that PRCA is also observed in cases with MGUS, where immunoglobulin burden is low. CONCLUSIONS: It is not yet accurately known, what parts of erythroid precursors are targeted by M-protein nor what the mechanism is. Therefore, additional research into this matter is necessary.

Prevalence and Antibiotic Susceptibility of Mycoplasma hominis and Ureaplasma urealyticum in Pregnant Women.

Mycoplasma hominis (M. hominis) and Ureaplasma urealyticum (U. urealyticum) are important opportunistic pathogens that cause urogenital infections and complicate pregnancy. The aim of this study was to investigate the prevalence, effects on pregnancy outcomes, and antimicrobial susceptibilities of M. hominis and U. urealyticum. We tested vaginal swabs obtained from 1035 pregnant women for the presence of genital mycoplasmas between June 2009 and May 2014. The laboratory and clinical aspects of genital mycoplasmas infection were reviewed retrospectively, and the identification and antimicrobial susceptibility of genital mycoplasmas were determined using the Mycoplasma IST-2 kit. A total of 571 instances of M. hominis and/or U. urealyticum were detected. Of them, M. hominis was detected in two specimens, whereas U. urealyticum was detected in 472 specimens. The remaining 97 specimens were positive for both M. hominis and U. urealyticum. Preterm deliveries were frequently observed in cases of mixed infection of M. hominis and U. urealyticum, and instances of preterm premature rupture of membrane were often found in cases of U. urealyticum. The rates of non-susceptible isolates to erythromycin, empirical agents for pregnant women, showed increasing trends. In conclusion, the prevalence of M. hominis and/or U. urealyticum infections in pregnant women is high, and the resistance rate of antimicrobial agents tends to increase. Therefore, to maintain a safe pregnancy, it is important to identify the isolates and use appropriate empirical antibiotics immediately.

A Case of Sepsis in a 92-Year-Old Korean Woman Caused by Aerococcus urinae and Identified by Sequencing the 16S Ribosomal RNA Gene.

Aerococcus urinae is an uncommon pathogen that was first identified in 1992. Herein, we report a case of bloodstream infection caused by A. urinae, which occurred in a 92-year-old Korean female patient with an underlying urologic infection who had altered consciousness. The blood culture yielded positive results for A. urinae; however, identifying A. urinae was challenging. Ultimately, we used 16S ribosomal RNA (rRNA) gene sequencing to identify the organism. The patient recovered after being treated with ertapenem and meropenem. To our knowledge, this is the first report of a case of A. urinae sepsis in South Korea.

Crystalloid podocytopathy with focal segmental glomerulosclerosis in PCM: a case report.

BACKGROUND: Crystalloid podocytopathy with focal segmental glomerulosclerosis in plasma cell myeloma (PCM) is rare. CASE PRESENTATION: We present a case of crystalline deposition in the bone marrow (BM) and various renal cells with only proteinuria as a symptom. As workup for proteinuria, a renal biopsy sample was obtained. EM showed multiple crystalline depositions in renal tubular cells and podocytes. Focal segmental glomerulosclerosis with crystalloid podocytopathy was diagnosed. Because monoclonal gammopathy was detected in the serum and urine, a BM study was also performed. Plasma cells with needle-shaped inclusion bodies were observed. The crystalline deposits in the plasma cells and podocytes were positive for Masson's trichrome and kappa light-chain staining. These findings indicated that the crystalline deposits originated from paraprotein. The case showed a rare process of focal segmental glomerulosclerosis via crystalline deposition in podocytes in plasma cell myeloma. CONCLUSIONS: Crystalloid podocytopathy is a likely cause of renal damage such as FSGS in PCM, although it is an uncommon mechanism for myeloma kidney.

A case series of autoimmune diseases accompanied by incidentally diagnosed monoclonal gammopathy: is there a link between the two diseases?

AIM: Although the etiology of plasma cell dyscrasia is poorly understood, there is evidence for immune dysregulation or sustained immune stimulation playing a pivotal role in the pathogenesis of these diseases, including chronic infection and autoimmune disorders. In this study, we report four autoimmune disease cases where monoclonal gammopathy (MG) was incidentally found during follow-up. METHODS: We retrospectively reviewed the medical charts and laboratory test results in the following four cases: neuromyelitis optica, Kikuchi disease, Sjögren syndrome and ankylosing spondylosis. RESULTS: The four patients were older than 55 years and the male-to-female ratio was 2 : 2. The autoimmune disease in each case developed differently because two patients had coincidental detection of MG, whereas MG was detected 2 years and 10 years after diagnosis in the other two patients. The amount of M-components in the blood for two cases was ≤ 1 g/dL. For the other two subjects, M-components were ≥ 3 g/dL. CONCLUSION: A high prevalence of MG of undetermined significance (MGUS) has been noted in a series of patients with immune disorders, suggesting a possible association with MG. Further studies should focus on determining how MG relates to various clinical information and laboratory parameters, such as disease duration, disease activity and higher sedimentation rate. In the future, we also need to identify which stimuli, such as cytokine types and levels, can induce lymphocyte clonal transformation and the production of monoclonal antibodies.

Mean platelet volume and mean platelet volume/platelet count ratio in infective endocarditis.

Infective endocarditis (IE), an infection of the endocardial surface, frequently leads to life-threatening complications, such as thromboembolism due to platelet activation. We investigated the mean platelet volume (MPV) in Korean patients with IE and the serial changes thereof, in comparison with other laboratory parameters. We analyzed 248 MPV results from 22 patients diagnosed with IE in our hospital between January 2011 and April 2012. MPV was measured with an Advia 2120 (Siemens Healthcare Diagnostics, Tarrytown, NY) using EDTA-containing tubes. The mean MPV differed significantly between the patient and control groups, 8.74 vs. 7.96 fl, respectively. In addition, the platelet count and MPV/platelet count ratio were significantly decreased in the patient group. The total platelet mass and platelet size in IE might be increased. Further studies should examine more patients to verify the changes in the MPV and MPV/platelet count ratio in IE and assess in greater detail the relationship between MPV and thrombotic complications caused by platelet activation.

Interpretation and clinical significance of small monoclonal peaks in capillary electrophoresis.

BACKGROUND: Although the testing mechanism and interpretation criteria for capillary electrophoresis differ from those for gel-based electrophoresis, there are not that many reports on the efficacy of capillary electrophoresis. MATERIALS AND METHODS: We performed a retrospective analysis, using the Laboratory Information System (LIS) to review a total of 163 capillary electrophoresis results from 117 different patients treated in our hospital between March and August 2012. Capillary electrophoresis was performed on capillary2 (Sebia, Lysse, France). RESULTS: Among the patients' group, 4 patients presented very small M-peaks in capillary electrophoresis. By using the zoom function in capillary electrophoresis, two of them were confirmed to have monoclonality, but the remaining two required reconfirmation in gel electrophoresis, leading to confirmation of a discrete monoclonal band. CONCLUSION: In this study, we found that small peaks in capillary electrophoresis accompanying a skewed K/L ratio deserve particular attention as they can grow into larger peaks within a few months. We suggest that any trivial M-peak in capillary electrophoresis should not be overlooked and that a combination of platform tests such as gel electrophoresis or FLC assay be implemented in order to confirm monoclonality.

Factors influencing discordant results of the QuantiFERON-TB Gold In-tube test in patients with active TB.

OBJECTIVES: Indeterminate or negative results from the QuantiFERON-TB Gold In-tube test (QFT-GIT) for TB-confirmed patients indicate the lower sensitivity of this method. The aim of this study was to determine the factors associated with indeterminate and negative QFT-GIT results in active TB patients. METHODS: We analyzed retrospectively the laboratory and clinical data of patients diagnosed with TB between December 2009 and April 2012 at a tertiary university hospital in Seoul, Korea. RESULTS: Among 1301 patients who underwent QFT-GIT, TB-PCR and TB-culture, 168 (12.9%), those with positive TB-PCR or TB-culture were diagnosed with TB. Thirty-nine (23.2%) had indeterminate or negative results by QFT-GIT assay, which did not correlate with positive results of TB-PCR or TB-culture. These patients were older, had lower lymphocyte, total protein and albumin levels, and showed significantly higher CRP levels than the positive group. Multivariate logistic regression analysis showed that the probability of indeterminate and negative QFT-GIT results increased as CRP (odd ratio, 1.069; 95% CI, 1.013-1.127; P = 0.014) or age (1.030, 1.005-1.056, 0.02) increases. CONCLUSIONS: When levels of markers of inflammation, such as CRP, are high or the patient is older, QFT-GIT results should be interpreted carefully and correlated with additional tests for TB.

Cystatin C as an early marker of diabetic nephropathy in patients with type 2 diabetes.

BACKGROUND: Serum cystatin C has been proposed as an endogenous marker of glomerular filtration rate (GFR) because it shows a correlation with the albumin to creatinine ratio (ACR) in diabetic nephropathy. The aim of this study was to examine the usefulness of cystatin C as an early marker of diabetic nephropathy. METHODS: From February 2010 to July 2010, 205 outpatients with normo- or microalbuminuria and chronic kidney disease (CKD) of stage III or less were included in this study. Various renal markers including serum cystatin C and ACR were evaluated. RESULTS: In the ROC curve analysis, cystatin C showed a performance similar to that of serum creatinine. In addition, cystatin C levels increased with increasing CKD stage I to III and from normo- to microalbuminuria and showed a positive correlation with ACR. In a comparison of renal function markers in diabetic patients according to serum cystatin C level, all markers including ACR, serum creatinine, and eGFR showed significant differences between patients with cystatin C level < 1.06 mg/L and those with cystatin C > or = 1.06 mg/L. CONCLUSIONS: Serum cystatin C is a useful marker of early renal impairment in type 2 diabetic patients because it reflects both a decrease in GFR and elevated ACR.