Volume 56, Issue 8

Although effective for bacterial lower respiratory tract infections (LRTIs), antibiotic treatment is often incorrectly prescribed for non-bacterial LRTIs. Procalcitonin has emerged as a promising biomarker to diagnose bacterial infections and guide antibiotic treatment decisions. As part of a regulatory submission to the U.S. Food and Drug Administration, this systematic review and meta-analysis summarizes the effects of procalcitonin-guided antibiotic stewardship on antibiotic use and clinical outcomes in adult LRTI patients. PubMed and the Cochrane Database of Systematic Reviews were searched for English-language randomized controlled trials published between January 2004 and May 2016. Random and fixed effects meta-analyses were performed to study efficacy (initiation of antibiotics, antibiotic use) and safety (mortality, length of hospital stay). Eleven trials were retained, comprising 4090 patients. Procalcitonin-guided patients had lower odds of antibiotic initiation (odds ratio: 0.26; 95% confidence interval [CI]: 0.13–0.52) and shorter mean antibiotic use (weighted mean difference: −2.15 days; 95% CI: −3.30 to −0.99) compared to patients treated with standard care. Procalcitonin use had no adverse impact on mortality (relative risk: 0.94; 95% CI: 0.69–1.28) and length of hospital stay (weighted mean difference: −0.15 days; 95% CI: −0.60 to 0.30). Procalcitonin guidance reduces antibiotic initiation and use among adults with LRTIs with no apparent adverse impact on length of hospital stay or mortality.

Telomeres are the protective end caps of chromosomes and shorten with every cell division. Telomere length has been proposed as a biomarker of biological age and a risk factor for age-related diseases. Epidemiologic studies show an association between leukocyte telomere length (LTL) and mortality. There is solid evidence that links LTL with cardiovascular disease. Short telomeres promote atherosclerosis and impair the repair of vascular lesions. Alzheimer’s disease patients have also a reduced LTL. Telomeres measured in tumor tissue from breast, colon and prostate are shorter than in healthy tissue from the same organ and the same patient. In healthy tissue directly adjacent to these tumors, telomeres are also shorter than in cells that are more distant from the cancerous lesion. A reduced telomere length in cancer tissue from breast, colon and prostate is associated with an advanced disease state at diagnosis, faster disease progression and poorer survival. By contrast, results regarding LTL and cancer are inconsistent. Furthermore, the majority of studies did not find significant associations between LTL, bone mineral density (BMD) and osteoporosis. The present manuscript gives an overview about our current understanding of telomere biology and reviews existing knowledge regarding the relationship between telomere length and age-related diseases.

Background: Procalcitonin (PCT) is a useful biomarker of bacterial infection and its use is associated to reduced duration of antibiotic therapy in the setting of intensive care medicine. To address the need of practical guidance for the use of PCT in various clinical settings, a group of experts was invited to participate at a consensus process with the aims of defining the rationale for appropriate use of PCT and for improving the management of critically ill patients with sepsis. Methods: A group of 14 experts from anesthesiology and critical care, infectious diseases, internal medicine, pulmonology, clinical microbiology, laboratory medicine, clinical pharmacology and methodology provided expert opinion through a modified Delphi process, after a comprehensive literature review. Results: The appropriateness of use of PCT in terms of diagnosis, prognosis and antimicrobial stewardship was assessed for different scenarios or settings such us management of infection in the emergency department, regular wards, surgical wards or in the intensive care unit. Similarly, appropriateness and timing of PCT measurement were evaluated. All the process consisted in three Delphi rounds. Conclusions: PCT use is appropriate in algorithms for antibiotic de-escalation and discontinuation. In this case, reproducible, high sensitive assays should be used. However, initiation or escalation of antibiotic therapy in specific scenarios, including acute respiratory infections, should not be based solely on PCT serum levels. Clinical and radiological findings, evaluation of severity of illness and of patient’s characteristics should be taken into proper account in order to correctly interpret PCT results.

Background: β 1 -Adrenoreceptor ( ADRB1 ) genetic polymorphisms are widely studied for susceptibility to many cardiovascular diseases such as essential hypertension. However, the mRNA expression of ADRB1 is rarely studied. Methods: A case-control pilot study with 292 hypertensives and 324 controls was designed to evaluate the role of the Ser49Gly and Arg389Gly, which are commonly studied single nucleotide polymorphisms (SNP), in the mRNA levels of ADRB1 , in conjunction with its genetic predisposition to essential hypertension. Results: Differential expression of ADRB1 mRNA was seen between hypertensives and controls (p<0.01) based on genetic variants of Ser49Gly. Among hypertensive subjects, Ser49Ser and Gly49Gly were highly expressed in comparison to Ser49Gly (p<0.05 and p<0.01, respectively), whereas genetic variants of Arg389Gly did not demonstrate any such variations. We found no association between the ADRB1 SNPs viz., Ser49Gly and Arg389Gly and essential hypertension. Conclusions: The increased mRNA levels of Gly49Gly may indicate a plausible role in the interindividual variations in drug response. Further, ADRB1 polymorphisms did not contribute to the genetic risk of essential hypertension. Studies with larger sample size are warranted to confirm these observations in the South Indian population.

Background: Determination of blood glucose concentration is one of the most important measurements in clinical chemistry worldwide. Analyzers in central laboratories (CL) and point-of-care tests (POCT) are both frequently used. In Germany, regular participation in external quality assessment (EQA) schemes is mandatory for laboratories performing glucose testing. Methods: Glucose testing data from the two German EQAs “Reference Institute for Bioanalytics” (RfB) and “INSTAND – Gesellschaft zur Förderung der Qualitätssicherung in medizinischen Laboratorien” (Instand) were analyzed from 2012 to 2016. Multivariable odds ratios (OR) for the probability to reach a “good” result were calculated. Imprecision and bias were determined and clinical risk of measurement errors estimated. Results: The device employed was the most important variable required for a “good” performance in all EQAs. Additional participation in an EQA for CL automated analyzers improved performance in POCT EQAs. The reciprocal effect was less pronounced. New participants performed worse than experienced participants especially in CL EQAs. Imprecision was generally smaller for CL, but some POCT devices reached a comparable performance. Large lot-to-lot differences occurred in over 10% of analyzed cases. We propose the “bias budget” as a new metric to express the maximum allowable bias that still carries acceptable medical risk. Bias budgets were smallest and clinical risks of errors greatest in the low range of measurement 60–115 mg/dL (3.3–6.4 mmol/L) for most devices. Conclusions: EQAs help to maintain high analytical performances. They generate important data that serve as the foundation for learning and improvement in the laboratory healthcare system.

Background: Measuring the glucose concentration in whole blood samples is critical due to unsatisfactory glycolysis inhibition. Previous studies showed that Terumo tubes were superior, but they were taken off the European market in 2016 and alternatives were required. This initiated the present evaluation of glucose stability in five available tube types. Methods: Venous blood samples were collected from 61 healthy volunteers to test tubes supplied by Terumo (two sets), Greiner FC-Mix, BD FX-Mixture and BD serum. After sampling, the contents were thoroughly mixed and centrifuged within an hour. The glucose concentrations were determined and the samples resuspended except for BD serum tubes (gel barrier). The first 30 samples were stored at room temperature and the remaining 31 at 4°C. After 24, 48, 72 and 96 h, all tubes were (re)centrifuged, and glucose concentration measurements were repeated. Results: Changes in glucose concentrations over time differed significantly between the investigated tube types and to a certain extent between the two storing conditions. Glycolysis was most evident in the BD FX-mixture tubes. Good glucose stability was observed in samples retrieved form BD serum and Greiner tubes. The stability in both Terumo tubes was comparable to that in other studies. Although Greiner and both Terumo tubes are supposed to contain the same glycolysis inhibitor, glucose stability differed between these tubes. Conclusions: We showed that Greiner is an acceptable alternative to Terumo and that glucose in serum that was rapidly separated from corpuscles by a gel barrier is stable for an extended time.

Background: It is now recommended that all samples with raised prolactin should be examined for the presence of macroprolactin. We performed a retrospective review of our experience of macroprolactin to determine the incidence and the natural history of macroprolactin. Methods: A retrospective study of macroprolactin was made in a large clinical laboratory. Macroprolactin was measured on those samples where it is requested and where the total prolactin is >1000 mIU/L. Prolactin was measured using the Siemens Centaur and macroprolactin was measured following polyethylene glycol (PEG)-precipitation. Results: The incidence of macroprolactin in samples where the total prolactin was >1000 mIU/L was 36/670 (5.4%). During this period, 12,064 samples were received for prolactin analysis. Over the period since 2006, 22 subjects had a sample with an isolated macroprolactin measurement followed by another sample without macroprolactin after a median period of 0.46 years. Twenty-five subjects had multiple consecutive measurements of macroprolactin lasting a median period of 2.1 years. Fourteen subjects had more than six samples which had been subjected to PEG precipitation. In these subjects, the reproducibility of PEG precipitation over a median of 6 years was 1.1% CV (recovery 75% [26–110] (median [range])). Conclusions: The presence of macroprolactin can change over time and we cannot advise that once a test for macroprolactinemia has been performed that it is not necessary to repeat the investigation if a subsequent sample is hyperprolactinemic; nor can one assume that macroprolactin will not develop even if it has been excluded previously.

Background: The detection of anti-cyclic citrullinated peptide (anti-CCP) IgG antibodies in blood is mainly used for the diagnosis of rheumatoid arthritis. Falsely elevated anti-CCP IgG antibodies due to anti-streptavidin IgG antibodies were suspected in our laboratory. Methods: In this study, we evaluated, in a standardized approach, the prevalence of anti-streptavidin IgG antibodies in a primary care setting and the effect of anti-streptavidin IgG antibodies on anti-CCP IgG assays from three different important commercial manufacturers (Abbott, Roche Diagnostics, Thermo Fisher Scientific). Three different populations were consecutively and prospectively studied: serum samples from 1000 ambulatory patients, 286 serum samples from patients for which anti-CCP was requested and 89 serum samples from patients which had previously given a positive anti-CCP result on Architect ® i2000. Results: The frequency of confirmed anti-streptavidin IgG-positive samples detected in this study was 0.6% (8/1375). Anti-CCP IgG was determined on the eight samples with confirmed anti-streptavidin IgG antibodies: with the Cobas ® method, seven positive anti-CCP results were observed and five positive anti-CCP results with the Architect ® method. No positive anti-CCP IgG results were obtained with the EliA™ method. Rheumatoid factor was negative in these eight samples. Conclusions: Anti-streptavidin IgG antibodies rarely cause false-positive results in some anti-CCP assays. However, despite being an infrequent assay problem, it could possibly lead to diagnostic confusion or even an incorrect diagnosis of rheumatoid arthritis.

Background: Acute kidney injury (AKI) can occur rarely in patients exposed to iodinated contrast and result in contrast-induced AKI (CI-AKI). A key risk factor is the presence of preexisting chronic kidney disease (CKD); therefore, it is important to assess patient risk and obtain kidney function measurement prior to administration. Point-of-care (PoC) testing provides an alternative strategy but there remains uncertainty, with respect to diagnostic accuracy and clinical utility. Methods: A device study compared three PoC analysers (Nova StatSensor, Abbott i-STAT and Radiometer ABL800 FLEX) with a reference laboratory standard (Roche Cobas 8000 series, enzymatic creatinine). Three hundred adult patients attending a UK hospital phlebotomy department were recruited to have additional blood samples for analysis on the PoC devices. Results: The ABL800 FLEX had the strongest concordance with laboratory measured serum creatinine (mean bias=−0.86, 95% limits of agreement=−9.6 to 7.9) followed by the i-STAT (average bias=3.88, 95% limits of agreement=−8.8 to 16.6) and StatSensor (average bias=3.56, 95% limits of agreement=−27.7 to 34.8). In risk classification, the ABL800 FLEX and i-STAT identified all patients with an eGFR≤30, whereas the StatSensor resulted in a small number of missed high-risk cases (n=4/13) and also operated outside of the established performance goals. Conclusions: The screening of patients at risk of CI-AKI may be feasible with PoC technology. However, in this study, it was identified that the analyser concordance with the laboratory reference varies. It is proposed that further research exploring PoC implementation in imaging department pathways is needed.

Background: Quantitation of lymphocyte subsets (B cells, T cells, CD4 and CD8 T cells and NK cells) classically relies on quantitation of lymphocytes and immunophenotyping by flow cytometry. AQUIOS CL (Beckman Coulter) is a fully automated system that performs an onboard volumetric cell count, automatically processes the sample (staining, lysing and fixation) and analyzes the results. We compared AQUIOS CL to a dual-platform analysis and evaluated analytical performance. Methods: We evaluated precision, sample stability, inter-sample carryover, linearity and interpanel consistency. AQUIOS CL was compared to a dual-platform method (Sysmex XE-5000 and BD FACSCanto-II). A total of 113 patient samples were included: 45 from posttransplant patients, 44 from children and 24 random routine samples. The degree of automation was scored through the need of manual revisions triggered by AQUIOS CL run notifications and run flags. Results: Intrarun and interrun variability was <9.1% with dedicated control material and <32.1% with patient samples. Relative values of lymphocyte subsets could be determined up to 48 h after venipuncture when the sample was kept at room temperature. There was no carryover and good linearity. Interpanel consistency was 3.3% for relative values and 9.4% for absolute values. Method comparison showed good analytical correlation between AQUIOS CL and a dual-platform method. Thirty-five percent of the samples triggered a run notification. In 74% of these samples, the results could be accepted without intervention, so in 26% of all samples, an unnecessary notification was generated. Conclusions: AQUIOS CL allows for reliable fully automated immunophenotyping of lymphocyte subset quantitation. Gating algorithms could be further improved.

Background: Antiphospholipid antibody syndrome (APS) is characterized by laboratory evidence of antiphospholipid antibodies (aPL) [e.g. lupus anticoagulant (LA), anticardiolipin (ACL), and/or antiβ 2 -glycoprotein I (aB2GPI)] in a clinical setting of thrombosis or pregnancy morbidity. The International Society on Thrombosis and Haemostasis recommends two different testing modalities to detect LA. To evaluate these recommendations in a clinical setting, our hospital, a tertiary care center with a specialized coagulation laboratory, added the dilute Russell’s viper venom time to be performed in parallel with the PTT-lupus anticoagulant to detect LA. Methods: Results of aPL testing were collected on all patients who had LA testing for one year. Chart review was performed to correlate LA results with ACL, aB2GPI, and clinical history. Results: Patients who were initially LA positive by both PTT-lupus anticoagulant and dilute Russell’s viper venom time were more likely to be persistently positive. Patients who were positive for ACL and aB2GPI were likely to be positive by both LA methodologies. No single method was absolutely sensitive, as cases of APS were detected by PTTLA only, DRVVT only, and both methods. Conclusions: The addition of a second testing method for LA provides additional diagnostic information and may be helpful in stratifying risk of thrombosis.

Background: During pregnancy, interpretation of results from coagulation parameters can be difficult as the physiological changes that occur may affect the biochemical parameters. The aim of this study was to describe the normal course of five coagulation parameters in healthy pregnancies, and to estimate the within-subject biological variation (CV I ). Methods: Blood samples were obtained every 4th week during pregnancy and three samples after delivery in 20 healthy women and every 4th week during a 40-week period in 19 healthy non-pregnant women. Activated partial thromboplastin time (APTT), prothrombin time (PT), PT International Normalized Ratio (INR), fibrinogen, factor VIII clot (FVIII:C) and von Willebrand factor antigen (vWF:Ag) were analyzed. The physiological changes during pregnancy were compensated by transformation into multiples of the median (MoM) and it is natural logarithm (lnMoM) in order to establish a kind of steady state, and CV I was calculated from the standard deviation. Results: During pregnancy, APTT, PT and INR remained unchanged or decreased, depending upon the reagent used, while fibrinogen, FVIII:C and vWF:Ag increased gradually until delivery. The CV I in pregnancy were 2.2 and 3.0% for APTT, 2.3 and 2.6% for PT, 2.2 and 2.3% for INR, 7.2% for fibrinogen, 12.2% for FVIII:C and 11.3% for vWF:Ag, and corresponded with the CV I in non-pregnant women. Conclusions: Transformation of coagulation parameters in healthy pregnancies to MoM is a tool to establish a kind of steady state. Although there is a physiological change in these coagulation parameters during pregnancy, the CV I after lnMoM transformation was comparable with the CV I of non-pregnant women.

Background: The complete blood count (CBC) is used to evaluate health status in the contexts of various clinical situations such as anemia, infection, inflammation, trauma, malignancies, etc. To ensure safe clinical application of the CBC, reliable biological variation (BV) data are required. The study aim was to define the BVs of CBC parameters employing a strict protocol. Methods: Blood samples, drawn from 30 healthy subjects (17 females, 13 males) once weekly for 10 weeks, were analyzed using a Sysmex XN 3000 instrument. The data were assessed for normality, trends, outliers and variance homogeneity prior to coefficient of variation (CV)-analysis of variance (ANOVA). Sex-stratified within-subject (CV I ) and between-subjects (CV G ) BV estimates were determined for 21 CBC parameters. Results: For leukocyte parameters, with the exception of lymphocytes and basophils, significant differences were found between female/male CV I estimates. The mean values of all erythrocyte-, reticulocyte- and platelet parameters differed significantly between the sexes, except for mean corpuscular hemoglobin concentration, mean corpuscular volume and platelet numbers. Most CV I and CV G estimates appear to be lower than those previously published. Conclusions: Our study, based on a rigorous protocol, provides updated and more stringent BV estimates for CBC parameters. Sex stratification of data is necessary when exploring the significance of changes in consecutive results and when setting analytical performance specifications.

Background: Immunoglobulin G (IgG) and IgG subclass assays are indicated in patients with suspected primary immunodeficiency (PID). Commercially available assays for IgG subclass determination are calibrated against various preparations, and so specific reference values are required for each of them. Using Optilite ® reagents from The Binding Site Group Ltd., we sought to determine the pediatric IgG and IgG subclass reference intervals with respect to the ERM-DA470k certified reference material. Methods: Levels of IgG and IgG subclasses were analyzed in serum samples collected from a large cohort of PID-free children and adolescents. Reference intervals were calculated for previously published age groups (6–12 months, 12–18 months, 18 months–2 years, 2–3 years, 3–4 years, 4–6 years, 6–9 years, 9–12 years and 12–18 years), according to the Clinical and Laboratory Standards Institute’s C28-A3c protocol. Results: A total of 456 serum samples were analyzed. The correlation between the total IgG and the sum of the IgG subclasses was good (r 2 =0.96). No statistically significant gender-specific differences were observed. Our results for the changes over time in IgG and IgG subclass levels are consistent with previous reports. The differences between our lower/upper reference limits and those in the literature are probably due to variations in calibration. Conclusions: Our present results provide a reliable basis for the diagnosis of PIDs in childhood and for the accreditation of laboratories using Optilite ® immunoturbidimetric reagents for IgG subclass measurement. Laboratory scientists and clinicians should be aware of the need for manufacturer-specific IgG subclass reference intervals.

Background: Carbohydrate sulfotransferases (CHST) were shown to be involved in carcinogenesis. The aim of the study was to assess the diagnostic value of serum CHST7 concentration in differentiation between lung cancer and non-malignant pulmonary inflammations. Methods: Clinical case-control study involving 125 participants was conducted: the control group containing cases of pneumonia and chronic obstructive pulmonary disease was compared to the lung cancer group composed of primary and metastatic cancers. Serum concentrations of CHST7 and routinely used markers including carcinoembryonic antigen (CEA), cytokeratin fragment 21-1 (CYFRA 21-1) and neuron-specific enolase (NSE) were determined for each participant using immunochemical methods. Statistical association, receiver operating characteristic (ROC) analysis and cross-validation were used for the evaluation of CHST7 either as a standalone biomarker or as a part of a biomarker panel. Results: In comparison to the control group, serum CHST7 was elevated in lung cancer (p<0.001), but no differences between the overall stages of primary cancers were detected (p=0.828). The differentiation performance in terms of ROC area under curve (AUC) was 0.848 making CHST7 superior biomarker to the NSE (p=0.031). In comparison to CEA and CYFRA 21-1, the performance differences were not detected. CHST7 was not correlated to other biomarkers, and its addition to the routine biomarker panel significantly improved the cross-validated accuracy (85.6% vs. 75.2%) and ROC AUC (p=0.004) of the differentiation using a machine learning approach. Conclusions: Serum CHST7 is a promising biomarker for the differentiation between lung cancer and non-malignant pulmonary inflammations.

Background: We evaluated the clinical performance of the Minicare cardiac troponin-I (cTnI), a new point-of-care (POC) cTnI test for the diagnosis of acute myocardial infarction (AMI) in a prospective, multicentre study (ISRCTN77371338). Methods: Of 474 patients (≥18 years) admitted to an emergency department (ED) or chest pain unit (CPU) with symptoms suggestive of acute coronary syndrome (ACS; ≤12 h from symptom onset), 465 were eligible. Minicare cTnI was tested immediately, 3 h and 6 h after presentation. AMI diagnoses were adjudicated independently based on current guidelines. Results: The diagnostic performance of the Minicare cTnI test at 3 h was similar for whole blood and in plasma: sensitivity 0.92 vs. 0.90; specificity 0.91 vs. 0.90; positive predictive value (PPV) 0.68 vs. 0.66; negative predictive value (NPV) 0.98 vs. 0.98; positive likelihood ratio (LR+) 10.18 vs. 9.41; negative likelihood ratio (LR–) 0.09 vs. 0.11. The optimal diagnostic performance was obtained at 3 h using cut-offs cTnI >43 ng/L plus cTnI change from admission ≥18.5 ng/L: sensitivity 0.90, specificity 0.96, PPV 0.81, NPV 0.98, and LR+ 21.54. The area under the receiver operating characteristics (ROC) curve for cTnI whole blood baseline value and absolute change after 3 h curve was 0.93. Conclusions: These data support the clinical usefulness of Minicare cTnI within a 0 h/3 h-blood sampling protocol supported by current guidelines for the evaluation of suspected ACS.

Background: The oral glucose tolerance test (OGTT) is recommended to screen for diabetes in patients with coronary artery disease. We hypothesized that testing for glycated hemoglobin (HbA 1c ), in addition to the OGTT, in screening for abnormal glucose regulation may help to reveal patients with β-cell function impairment. Methods: Patients with no history of diabetes who were admitted for coronary angiography were recruited to undergo an OGTT and HbA 1c test 2–4 weeks after hospital discharge. β-cell function and insulin resistance were assessed using the homeostasis model assessment (HOMA-β and HOMA-IR, respectively). For patients with normal glucose tolerance (NGT) based on the OGTT, we compared HOMA-β between two subgroups of patients using an HbA 1c cutoff of 39 mmol/mol or 42 mmol/mol. For patients with prediabetes based on an OGTT, we compared the HOMA-β between two subgroups of patients using an HbA 1c cutoff of 48 mmol/mol. Results: A total of 1044 patients were analyzed. In patients with NGT by OGTT (n=432), those with an HbA 1c ≥42 mmol/mol had a lower HOMA-β compared to those with an HbA 1c <42 mmol/mol (107±82 vs. 132±96, p=0.018). In patients with prediabetes by OGTT (n=423), those with an HbA 1c ≥48 mmol/mol had a lower HOMA-β compared to those with an HbA 1c <48 mmol/mol (91±52 vs. 120±88, p=0.003). No significant between-group difference in HOMA-IR was noted. Conclusions: The use of HbA 1c in addition to the OGTT in screening for abnormal glucose regulation helped to reveal patients with early β-cell function impairment.

Background: HbA 1c is a widely used biomarker for diabetes mellitus management. Here, we evaluated the accuracy of six methods for determining HbA 1c values in Chinese patients with common α- and β-globin chains variants in China. Methods: Blood samples from normal subjects and individuals exhibiting hemoglobin variants were analyzed for HbA 1c , using Sebia Capillarys 2 Flex Piercing (C2FP), Bio-Rad Variant II Turbo 2.0, Tosoh HLC-723 G8 (ver. 5.24), Arkray ADAMS A1c HA-8180V fast mode, Cobas c501 and Trinity Ultra 2 systems. Results: DNA sequencing revealed five common β-globin chain variants and three common α-globin chain variants. The most common variant was Hb E, followed by Hb New York, Hb J-Bangkok, Hb G-Coushatta, Hb Q-Thailand, Hb G-Honolulu, Hb Ube-2 and Hb G-Taipei. Variant II Turbo 2.0, Ultra 2 and Cobas c501 showed good agreement with C2FP for most samples with variants. HLC-723 G8 yielded no HbA 1c values for Hb J-Bangkok, Hb Q-Thailand and Hb G-Honolulu. Samples with Hb E, Hb G-Coushatta, Hb G-Taipei and Hb Ube-2 produced significant negative biases for HLC-723 G8. HA-8180V showed statistically significant differences for Hb E, Hb G-Coushatta, Hb G-Taipei, Hb Q-Thailand and Hb G-Honolulu. HA-8180V yielded no HbA 1c values for Hb J-Bangkok. All methods showed good agreement for samples with Hb New York. Conclusions: Some common hemoglobin variants can interfere with HbA 1c determination by the most popular methods in China.

Background: Relatively high mortality and morbidity rates are reported after liver resection (LR). However, the early predictors of complications after LR are not clear. This study was performed to clarify the usefulness of procalcitonin (PCT) for the early prediction of complications after elective LR. Methods: This observational study included 72 consecutive patients who underwent elective LR from December 2015 to March 2017. Patients were categorized into two groups: those with and without postoperative complications (Clavien-Dindo grade ≥II). The values of postoperative inflammatory markers (white blood cell [WBC] count, C-reactive protein [CRP] and PCT) were compared between the two groups. Results: CRP and PCT were significantly higher in patients with than without complications; however, the WBC count showed no difference within 5 days postoperatively. The maximum area under the receiver operating characteristic curves within 2 days after LR using the WBC count, CRP and PCT were 0.608, 0.697 and 0.860, respectively, PCT had the best predictive ability in the early postoperative period. The PCT level peaked within 2 days postoperatively in 61 patients (85%). The maximum PCT level within 2 days postoperatively (PCT 1−2 ) was significantly higher in patients with than without complications (0.52 vs. 0.19 ng/mL, p<0.001). A cutoff PCT 1−2 level of 0.35 ng/mL achieved 80% sensitivity and 83% specificity. In patients without complications, there was no difference in PCT 1−2 even when the surgical procedure differed (p=0.935). Conclusions: PCT 1−2 is an early predictive marker after LR and can be similarly used regardless of the LR procedure.

Background: Simultaneous determination of the two main actin scavenger proteins in sepsis has not been investigated until now. In our pilot study, we elucidated the predictive values of Gc globulin and gelsolin (GSN) in sepsis by comparing them to classic laboratory and clinical parameters. Methods: A 5-day follow-up was performed, including 46 septic patients, 28 non-septic patients and 35 outpatients as controls. Serum Gc globulin and GSN levels were determined by automated immune turbidimetric assay on a Cobas 8000/c502 analyzer. Patients were retrospectively categorized according to the sepsis-3 definitions, and 14-day mortality was also investigated. Results: First-day GSN also differentiated sepsis from non-sepsis (AUC: 0.88) similarly to C-reactive protein (AUC: 0.80) but was slightly inferior to procalcitonin (PCT) (AUC: 0.98) with a cutoff value of GSN at 22.29 mg/L (sensitivity: 83.3%; specificity: 86.2%). Only first-day SOFA scores (0.88) and GSN (0.71) distinguished septic survivors from non-survivors, whereas lactate (0.99), Gc globulin (0.76) and mean arterial pressure (MAP) (0.74) discriminated septic shock from sepsis. Logistic regression analyses revealed SOFA scores and GSN being significant factors regarding 14-day mortality. First-day GSN levels were higher (p<0.05) in septic survivors than in non-survivors. Gc globulin levels remained higher (p<0.01) in sepsis when compared with septic shock during the follow-up period. Conclusions: Both serum GSN and Gc globulin may have predictive values in sepsis. Considering the small sample size of our study, further measurements are needed to evaluate our results. Measurement of Gc globulin and GSN maybe useful in assessment of sepsis severity and in therapeutic decision-making.

Background: Free light chains (FLC) have been proposed as diagnostic biomarker in patients with inflammatory central nervous system diseases. The objective of this study was to investigate the diagnostic utility of intrathecal κ- and λ-FLC synthesis in patients with neuroborreliosis. Methods: κ- and λ-FLC were measured by nephelometry under blinded conditions in cerebrospinal fluid (CSF) and serum sample pairs of 34 patients with neuroborreliosis and compared to a cohort of 420 control patients. κ-FLC index was calculated as [CSF κ-FLC/serum κ-FLC]/[CSF albumin/serum albumin], and λ-FLC index in analogy. Results: κ-FLC and λ-FLC index were significantly elevated in patients with neuroborreliosis compared to the control group. At a specificity level of 95%, κ-FLC and λ-FLC index showed a diagnostic sensitivity of 88.2% and 100%. In comparison, IgM and IgG synthesis according to Reiber formula, IgG index >0.7 and OCB status reached a sensitivity of 83.9%, 44.1%, 58.8% and 64.7%. Conclusion: These findings support the diagnostic value of intrathecal FLC synthesis in neuroborreliosis patients and demonstrate a valid, easy and rater-independent alternative for the detection of an intrathecal immunoglobulin production.