Glycosylation is among the most important post-translational modifications for proteins and is of intrinsic complex character compared with DNAs and naked proteins. Indeed, over 50%–70% of proteins in circulation are glycosylated, and the “sweet attachments” have versatile structural and functional implications. Both the configuration and composition of the attached glycans affect the biological activities of consensus proteins significantly. Glycosylation is generated by complex biosynthetic pathways comprising hundreds of glycosyltransferases, glycosidases, transcriptional factors, transporters and the protein backbone. In addition, lack of direct genetic templates and glyco-specific antibodies such as those commonly used in DNA amplification and protein capture makes research on glycans and glycoproteins even more difficult, thus resulting in sparse knowledge on the pathophysiological implications of glycosylation. Fortunately, cutting-edge technologies have afforded new opportunities and approaches for investigating cancer-related glycosylation. Thus, glycans as well as aberrantly glycosylated protein-based cancer biomarkers have been increasingly recognized. This mini-review highlights the most recent developments in glyco-biomarker studies in an effort to discover clinically relevant cancer biomarkers using advanced analytical methodologies such as mass spectrometry, high-performance liquid chromatographic/ultra-performance liquid chromatography, capillary electrophoresis, and lectin-based technologies. Recent clinical-centered glycobiological studies focused on determining the regulatory mechanisms and the relation with diagnostics, prognostics and even therapeutics are also summarized. These studies indicate that glycomics is a treasure waiting to be mined where the growth of cancer-related glycomics and glycoproteomics is the next great challenge after genomics and proteomics.

Publicly Available August 31, 2018

Application of NMR metabolomics to search for human disease biomarkers in blood

Zikuan Song, Haoyu Wang, Xiaotong Yin, Pengchi Deng, Wei Jiang

Page range: 417-441

More Download PDF

Abstract

Recently, nuclear magnetic resonance spectroscopy (NMR)-based metabolomics analysis and multivariate statistical techniques have been incorporated into a multidisciplinary approach to profile changes in small molecules associated with the onset and progression of human diseases. The purpose of these efforts is to identify unique metabolite biomarkers in a specific human disease so as to (1) accurately predict and diagnose diseases, including separating distinct disease stages; (2) provide insights into underlying pathways in the pathogenesis and progression of the malady and (3) aid in disease treatment and evaluate the efficacy of drugs. In this review we discuss recent developments in the application of NMR-based metabolomics in searching disease biomarkers in human blood samples in the last 5 years.

Mini Review

Open Access September 5, 2018

Host-response biomarkers for the diagnosis of bacterial respiratory tract infections

Mohammed A.A. Saleh, Ewoudt M.W. van de Garde, J.G. Coen van Hasselt

Page range: 442-451

More Download PDF

Abstract

Appropriate antibiotic treatment for respiratory tract infections (RTIs) necessitates rapid and accurate diagnosis of microbial etiology, which remains challenging despite recent innovations. Several host response-based biomarkers due to infection have been suggested to allow discrimination of bacterial and non-bacterial microbial RTI etiology. This review provides an overview of clinical studies that investigated the diagnostic performance of host-response proteomic biomarkers to identify RTI microbial etiology. Procalcitonin and C-reactive protein have been studied most extensively; whereof procalcitonin has demonstrated the strongest diagnostic performance compared to other biomarkers. Proadrenomedullin, soluble triggering receptor expressed on myeloid cells-1, neopterin and pentraxin-3 need more studies to confirm their diagnostic value. For syndecan-4 and lipocalin-2 currently insufficient evidence exists. Common limitations in several of the studies were the relatively small scale setting, heterogeneous patient population and the absence of statistical power calculation.

Opinion Paper

Publicly Available September 29, 2018

Diabetes alert dogs: a narrative critical overview

Giuseppe Lippi, Mario Plebani

Page range: 452-458

More Download PDF

Abstract

Owing to their virtually incomparable olfactory apparatus and the mutual loving relationship with man, the use of dogs for assisting humans in many activities has become commonplace. Dogs have been used for long for livestock herding, hunting and pulling. More recently, they have been employed for servicing or assisting people with disabilities, for rescuing, for pet therapy and, last but not least, for detecting a vast array of volatile organic compounds related to drugs, narcotics, explosives and foods. Although cancer detection seems the most distinguished use of “man’s best friends” in science and medicine, increasing emphasis is being placed on their capacity to perceive chemical changes or human expressions associated with harmful, even life-threating, blood glucose variations. The evidence available in the current scientific literature attests that diabetes alerting dogs (DADs) have a heterogeneous efficiency for warning owners of episodes of hypoglycemia or hyperglycemia, with sensitivities and specificities ranging between 0.29–0.80 and 0.49–0.96, respectively. Although the adoption of DADs seems effective for improving the quality of life of many diabetics patients, some important drawbacks can be highlighted. These typically include adoption and keeping expenditures, lack of certification or accreditation of dog providers, poor harmonization of training procedures, significant inter-breed, intra-breed and intra-dog variabilities, wide-ranging alert behaviors, ability of owners to identify dog’s alerts, as well as lack of quality assessment of a dog’s “diagnostic” performance. Overcoming many of these limitations shall probably make DADs more efficient tools for improving diabetes management.

EFLM Paper

Publicly Available December 4, 2018

Documenting metrological traceability as intended by ISO 15189:2012: A consensus statement about the practice of the implementation and auditing of this norm element

Marc Thelen, Florent Vanstapel, Pika Meško Brguljan, Bernard Gouget, Guilaine Boursier, Edward Barrett, Christos Kroupis, Maria Lohmander, Luděk Šprongl, Tatjana Vodnik, Francisco Bernabeu-Andreu, Ines Vukasović, Çiğdem Sönmez, Solveig Linko, Duilio Brugnoni, Michel Vaubourdolle, Willem Huisman, Mauro Panteghini, on behalf of the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Working Group Accreditation and ISO/CEN standards (WG-A/ISO)

Page range: 459-464

More Download PDF

Abstract

ISO15189:2012 requires medical laboratories to document metrological traceability of their results. While the ISO17511:2003 standard on metrological traceability in laboratory medicine requires the use of the highest available level in the traceability chain, it recognizes that for many measurands there is no reference above the manufacturer’s selected measurement procedure and the manufacturer’s working calibrator. Some immunoassays, although they intend to measure the same quantity and may even refer to the same reference material, unfortunately produce different results because of differences in analytical selectivity as manufacturers select different epitopes and antibodies for the same analyte. In other cases, the cause is the use of reference materials, which are not commutable. The uncertainty associated with the result is another important aspect in metrological traceability implementation. As the measurement uncertainty on the clinical samples is influenced by the uncertainty of all steps higher in the traceability chain, laboratories should be provided with adequate and appropriate information on the uncertainty of the value assignment to the commercial calibrators that they use. Although the between-lot variation in value assignment will manifest itself as part of the long-term imprecision as estimated by the end-user, information on worst-case to be expected lot-lot variation has to be communicated to the end-user by the IVD provider. When laboratories use ancillary equipment that potentially could have a critical contribution to the reported results, such equipment needs verification of its proper calibration and criticality to the result uncertainty could be assessed by an approach based on risk analysis, which is a key element of ISO15189:2012 anyway. This paper discusses how the requirement for metrological traceability as stated in ISO15189 should be met by the medical laboratory and how this should be assessed by accreditation bodies.

General Clinical Chemistry and Laboratory Medicine

August 29, 2018

Commutability of external quality assessment materials for serum sodium and potassium measurements

Ying Yan, Bingqing Han, Haijian Zhao, Rong Ma, Jing Wang, Donghuan Wang, Cuihua Hu, Wenxiang Chen, Chuanbao Zhang

Page range: 465-475

Abstract

Background The commutability of electrolyte trueness verification materials (ETVs) and commercial general chemistry materials (GCs) was evaluated to investigate their suitability for use in an external quality assessment (EQA) program for serum sodium and potassium measurements. Methods Eighty fresh individual human samples (40 for sodium measurements and 40 for potassium measurements), six ETVs and three GCs were analyzed by five routine methods (validated methods) and by inductively coupled plasma mass spectrometry reference methods (comparative methods) for the determination of sodium and potassium. The commutability was analyzed according to Clinical and Laboratory Standards Institute (CLSI) EP14-A3 protocol and difference in bias approach, respectively. The linearity, bias and imprecision of the routine methods were also assessed according to CLSI guidelines. Results According to EP14-A3 protocol, ETVs were commutable for all assays, and GCs were commutable for 3/5 assays for sodium. ETVs were commutable in most assays except Cobas C501, while GCs showed no commutability except in case of AU5821 for potassium. According to a difference in bias approach, the commutability of ETVs was inconclusive for most routine assays for both sodium and potassium, and GCs were inconclusive for sodium and non-commutable for potassium in most routine assays. The routine methods exhibited excellent linearities and precisions. The majority and minority of relative biases between the routine and reference methods were beyond the bias limits for sodium and potassium, respectively. Conclusions Superiority in the commutability of ETVs over GCs was observed among the sodium and potassium assays whichever evaluation approach was applied.

February 5, 2019

Standardization of measurement procedures for serum uric acid: 8-year experience from Category 1 EQA program results in China

Jiangtao Zhang, Wenbo Luo, Jie Zeng, Tianjiao Zhang, Weiyan Zhou, Haijian Zhao, Ying Yan, Cuihua Hu, Rong Ma, Jing Wang, Wenxiang Chen, Chuanbao Zhang

Page range: 476-482

Abstract

Background Serum uric acid is a critical clinical indicator, and results without equivalence among laboratories cause troubles for disease diagnosis and patient management. External quality assessment (EQA) is a common tool for enhancing harmonization/standardization, therefore, the National Center for Clinical Laboratories in China has initiated a category 1 EQA for serum uric acid measurement since 2010 for evaluating its process of standardization. Methods Commutable EQA samples with target values assigned by reference measurement procedures were sent to participant laboratories. Both concentrations were measured 15 times in 3 days then means and intra-laboratory coefficient of variations (CVs) were reported. Biological variation criteria were used for analysis with CLIA88 criteria as a comparison. Results A total of 1250 laboratories participated in EQA programs from 2010 to 2017, pass rates calculated according to desirable specifications in biological variation database were on a rise overall and inter-laboratory mean bias and CVs were on a decrease. Homogeneous systems showed better inter-laboratory CVs and pass rates than heterogeneous systems. For the mostly used measurement systems; Abbott, Beckman, Roche Modular, Siemens and Hitachi showed desirable performances other than Roche Cobas, according to biological variation criteria. Conclusions Our study provides reliable information on the standardization of measurement procedures for serum uric acid for manufacturers and laboratories. Further improvements for standardization are still needed to make laboratories more patient-centered.

September 29, 2018

Next-generation rapid serum tube technology using prothrombin activator coagulant: fast, high-quality serum from normal samples

Kong-Nan Zhao, Goce Dimeski, John de Jersey, Lambro A. Johnson, Michael Grant, Paul P. Masci, Martin F. Lavin

Page range: 483-497

Abstract

Background Incomplete blood clotting or latent clotting in serum is a common laboratory problem, especially for patients on anticoagulant therapy or when serum tubes are centrifuged before clotting is completed. We describe a novel approach to producing high-quality serum using snake venom prothrombin activator complex (OsPA) as an additive in blood collection tubes for non-anticoagulated (normal) individuals. Methods Plasma clotting assays were performed using a Hyland-Clotek instrument. Blood clotting was visually observed, and thromboelastography was also performed to determine the important parameters of coagulation. Thrombin generation was assayed using the chromogenic substrate S-2238, and biochemical analytes in the serum were determined on chemistry and immunoassay analysers. Fibrinogen was determined by either ELISA or Clauss fibrinogen assay. Results We initially showed that OsPA had strong coagulation activity in clotting not only recalcified citrated plasma and recalcified citrated whole blood, but also fresh whole blood in a clinical setting. The use of TEG clearly showed improved speed of clotting and generation of a firmer clot. We also showed that the use of OsPA to produce serum did not interfere with the determination of commonly measured biochemical analytes. The underlying clotting mechanism involves a burst of thrombin production at the initial stages of the clotting process upon contact with prothrombin in blood. Conclusions These results demonstrate rapid generation of high-quality serum, contributing to faster turnaround times with standardised quality samples, for accurate analyte determinations in normal individuals.

September 19, 2018

Cannabinoids determination in bronchoalveolar lavages of cannabis smokers with lung disease

Maria Concetta Rotolo, Manuela Pellegrini, Paola Martucci, Raffaela Giacobbe, Angela De Palma, Roberta Pacifici, Simona Pichini, Francesco Paolo Busardò, Mario Bisconti

Page range: 498-503

Abstract

Background Cannabis smoke affects the lungs similarly to tobacco smoke, causing symptoms such as increased cough, sputum, hyperinflation and chronic bronchitis. Chronic use can also cause serious lung diseases and airway obstruction. We developed and validated a method for the identification and quantification of cannabinol (CBN), cannabidiol (CBD), Δ-9-tetrahydrocannabinol (THC) and its metabolites 11-hydroxy-THC (11-OH-THC) and 11-nor-9-carboxy-THC (THC-COOH) in bronchoalveolar lavages (BALs) from hospitalized former or current tobacco smoking patients with lung disease and a long history of cannabis consumption and limited current tobacco use. Methods For the extraction of cannabinoids from BALs, a 1 mL sample was added with 300 µL of 0.1 N NaOH and 3 mL of hexane/ethyl acetate (9:1). The solvent was then evaporated to dryness. Trimethylsilyl derivatives were prepared and then analyzed by gas chromatography/mass spectrometry. Results The method was linear for the analytes under investigation with coefficients of determination of at least 0.99. Absolute analytical recovery was always better than 80%, imprecision and inaccuracy was always under 15%. Six cases out of 15 were positive for THC, CBN and CBD. In two BALs samples, the presence of 11-OH-THC was also measured while THC-COOH was not detected. In the six positive cases, the last cannabis smoking occurred in the previous 2–14 days. Conclusions This is the first time that cannabinoids have been detected in BALs, demonstrating the presence of a drug with its metabolites in a target organ of consumers who present with a lung disease. This occurrence let us hypothesize a role of cannabinoids in the development of the disease and prompted an investigation on possible associations between cannabis smoking and clinical outcomes in patients with lung disease and eventually evaluate a cytotoxic effect of cannabinoids themselves.

August 29, 2018

A new method for the determination of ammonium in the vitreous humour based on capillary electrophoresis and its preliminary application in thanatochemistry

Rossella Gottardo, Covadonga Palacio, Kseniia M. Shestakova, Natalia E. Moskaleva, Federica Bortolotti, Franco Tagliaro

Page range: 504-509

Abstract

Background Although the post-mortem increase of ammonium in biological fluids is well known, ammonium analysis in vitreous humour has never been used in recent times for the determination of the post-mortem interval. The present work represents a new application of capillary electrophoresis with indirect UV detection in the field of forensic analysis. Methods The electrophoretic separation was carried out in a running buffer made of 5 mM imidazole, 5 mM 18-crown-6 ether and 6 mM d , l -α-hydroxybutyric acid (HIBA). To overcome the lack of optical absorption of ammonium, indirect UV detection was applied. The used wavelength was 214 nm. Results The method showed good linearity in the concentration range from 0.16 to 5.0 mM. The limit of detection, 0.039 mmol/L, was established on the basis of the linearity curve. Precision and bias studies carried out on the pure ammonium solutions and in real biological samples, revealed %RSDs well below 20%. A preliminary application to real cases where the death time was precisely known (14 bodies) was carried out plotting vitreous humour ammonium vs. post-mortem interval with a resulting good linear correlation until 100 h post-mortem. Conclusions After validation in real cases, the present method can become a powerful tool to unravel one of the most challenging issues of forensic investigation: determination of the time of death.

Reference Values and Biological Variations

September 15, 2018

Defining reference intervals for a serum growth differentiation factor-15 (GDF-15) assay in a Caucasian population and its potential utility in diabetic kidney disease (DKD)

Siobhan M. Hamon, Tomás P. Griffin, Md Nahidul Islam, Deirdre Wall, Matthew D. Griffin, Paula M. O’Shea

Page range: 510-520

Abstract

Background: Growth differentiation factor-15 (GDF-15), a stress responsive cytokine, is a promising biomarker of renal functional decline in diabetic kidney disease (DKD). This study aimed primarily to establish normative data and secondarily to evaluate the potential utility of GDF-15 in DKD using Roche Diagnostics electrochemiluminescence immunoassay (ECLIA) in an Irish Caucasian population. Methods: Following informed consent, 188 healthy volunteers and 128 participants with diabetes (72 with and 56 without DKD) were recruited to a cross-sectional study. Baseline demographics, anthropometric measurements and laboratory measurements were recorded. Blood for GDF-15 measurement was collected into plain specimen tubes kept at room temperature and processed (centrifugation, separation of serum, freezing at −80 °C) within 1 h of phlebotomy pending batch analyses. Reference intervals were determined using the 2.5th and 97.5th percentiles for serum GDF-15 concentration. Results: Of 188 healthy participants, 63 failed to meet study inclusion criteria. The reference interval for serum GDF-15 was 399 ng/L (90% confidence interval [CI]: 399–399) – 1335 ng/L (90% CI: 1152–1445). Receiver operator characteristics (ROC) curve analysis for DKD determined the area under the ROC curve to be 0.931 (95% CI: 0.893–0.959; p<0.001). The optimum GDF-15 cutoff for predicting DKD was >1136 ng/L providing a diagnostic sensitivity and specificity of 94.4% and 79%, respectively, and positive likelihood ratio of 4.5:1 (95% CI: 3.4–6.0). Conclusions: The reference interval for serum GDF-15 in a healthy Irish Caucasian population using Roche Diagnostics ECLIA was established and a preliminary determination of the potential of GDF-15 as a screening test for DKD was made. Further prospective validation with a larger DKD cohort will be required before the cutoff presented here is recommended for clinical use.

Cancer Diagnostics

September 15, 2018

Preanalytical stability of [-2]proPSA in whole blood stored at room temperature before separation of serum and plasma: implications to Phi determination

Ruggero Dittadi, Aline S.C. Fabricio, Giulia Rainato, Edoardo Peroni, Fulvio Di Tonno, Beatrice Vezzù, Chiara Mazzariol, Elisa Squarcina, Laura Tammone, Massimo Gion

Page range: 521-531

Abstract

Background [-2]proPSA seems to outperform free/total prostate-specific antigen (PSA) ratio in prostate cancer diagnosis. However, [-2]proPSA stability remains an underestimated issue. We examined [-2]proPSA stability over time in whole blood before separation of serum and plasma and its implications for prostate health index (Phi) determination. Total PSA (tPSA) and free PSA (fPSA) stabilities were also assessed. Methods Blood was drawn from 26 patients and separated in two tubes for plasma (K2EDTA and K2EDTA plus protease inhibitors – P100) and one for serum (clot activator plus gel separator). Tubes were stored at room temperature before centrifugation 1, 3 and 5 h for serum and EDTA plasma or 1 and 5 h for P100 plasma. To investigate the influence of gel separator on markers’ stability, blood was collected from 10 patients in three types of tubes to obtain serum: tubes with clot activator plus gel separator, with silica particles or glass tubes. Biomarkers were assayed with chemiluminescent immunoassays. Results [-2]proPSA and Phi levels significantly and progressively increased over time in serum (+4.81% and +8.2% at 3 h; +12.03% and +14.91% at 5 h, respectively, vs. 1 h; p<0.001). Conversely, [-2]proPSA levels did not change in plasma (EDTA or P100). tPSA levels did not change over time in serum or plasma, whereas fPSA decreased in serum. All markers were higher in plasma than in serum at any time point. This difference did not seem to be attributable to the use of gel for serum preparation. Conclusions EDTA prevented spurious in vitro modifications in PSA-related isoforms, confirming that a stabilized blood sample is a prerequisite for [-2]proPSA measurement and Phi determination.

Cardiovascular Diseases

September 6, 2018

A de novo mutation of SMYD1 (p.F272L) is responsible for hypertrophic cardiomyopathy in a Chinese patient

Liang-Liang Fan, Dong-Bo Ding, Hao Huang, Ya-Qin Chen, Jie-Yuan Jin, Kun Xia, Rong Xiang

Page range: 532-539

Abstract

Background Hypertrophic cardiomyopathy (HCM) is a serious disorder and one of the leading causes of mortality worldwide. HCM is characterized as left ventricular hypertrophy in the absence of any other loading conditions. In previous studies, mutations in at least 50 genes have been identified in HCM patients. Methods In this research, the genetic lesion of an HCM patient was identified by whole exome sequencing. Real-time polymerase chain reaction (PCR), immunofluorescence and Western blot were used to analyze the effects of the identified mutation. Results According to whole exome sequencing, we identified a de novo mutation (c.814T>C/p.F272L) of SET and MYND domain containing histone methyltransferase 1 ( SMYD1 ) in a Chinese patient with HCM exhibiting syncope. We then generated HIS- SMYD1 -pcDNA3.1+ (WT and c.814T>C/p.F272L) plasmids for transfection into AC16 cells to functionalize the mutation. The immunofluorescence experiments indicated that this mutation may block the SMYD1 protein from entering the nucleus. Both Western blot and real-time PCR revealed that, compared with cells transfected with WT plasmids, the expression of HCM-associated genes such as β-myosin heavy chains, SMYD1 chaperones (HSP90) and downstream targets including TGF-β were all disrupted in cells transfected with the mutant plasmid. Previous studies have demonstrated that SMYD1 plays a crucial role in sarcomere organization and heart development. Conclusions This novel mutation (c.814T>C/p.F272L) may be the first identified disease-causing mutation of SMYD1 in HCM patients worldwide. Our research expands the spectrum of HCM-causing genes and contributes to genetic counseling for HCM patients.

Infectious Diseases

September 21, 2018

Analyzing the capability of PSP, PCT and sCD25 to support the diagnosis of infection in cancer patients with febrile neutropenia

Luis García de Guadiana-Romualdo, Enrique Jiménez-Santos, Pablo Cerezuela-Fuentes, Ignacio Español-Morales, Mario Berger, Patricia Esteban-Torrella, Ana Hernando-Holgado, María Dolores Albaladejo-Otón

Page range: 540-548

Abstract

Background Early diagnosis of infection is essential for the initial management of cancer patients with chemotherapy-associated febrile neutropenia (FN). In this study, we have evaluated two emerging infection biomarkers, pancreatic stone protein (PSP) and soluble receptor of interleukin 2, known as soluble cluster of differentiation 25 (sCD25), for the detection of an infectious cause in FN, in comparison with other commonly used infection biomarkers, such as procalcitonin (PCT). Methods A total of 105 cancer patients presenting to the emergency department were prospectively enrolled. We observed 114 episodes of chemotherapy-associated FN. At presentation, a blood sample was collected for the measurement of PCT, PSP and sCD25. In order to evaluate the discriminatory ability of these markers for the diagnosis of infection, the area under the curve (AUC) of the receiver operating characteristic curves was calculated. Results Infection was documented in 59 FN episodes. PCT, PSP and sCD25 levels were significantly higher in infected patients. PCT was the biomarker with the highest diagnostic accuracy for infection (AUC: 0.901), whereas PSP and sCD25 showed a similar performance, with AUCs of 0.751 and 0.730, respectively. In a multivariable analysis, PCT and sCD25 were shown to be independently associated with infection. Conclusions Two novel biomarkers, PSP and sCD25, correlated with infection in cancer patients with chemotherapy-associated FN, but neither PSP nor sCD25 improved the performance of PCT. Based on the results obtained, the introduction of these novel biomarkers as a tool for the diagnosis of infection in this patient group is not recommended.

August 29, 2018

Mid-regional pro-adrenomedullin predicts poor outcome in non-selected patients admitted to an intensive care unit

Chiara Bellia, Luisa Agnello, Bruna Lo Sasso, Giulia Bivona, Maurizio Santi Raineri, Antonino Giarratano, Marcello Ciaccio

Page range: 549-555

Abstract

Background Mortality risk and outcome in critically ill patients can be predicted by scoring systems, such as APACHE and SAPS. The identification of prognostic biomarkers, simple to measure upon admission to an intensive care unit (ICU) is an open issue. The aim of this observational study was to assess the prognostic value of plasma mid-regional pro-adrenomedullin (MR-proADM) at ICU admission in non-selected patients in comparison to Acute Physiology and Chronic Health Evaluation II (APACHEII) and Simplified Acute Physiology Score II (SAPSII) scores. Methods APACHEII and SAPSII scores were calculated after 24 h from ICU admission. Plasma MR-proADM levels were measured by TRACE-Kryptor on admission (T0) and after 24 h (T24). The primary endpoint was intra-hospital mortality; secondary endpoint was length of stay (LOS). Results One hundred and twenty-six consecutive non-selected patients admitted to an ICU were enrolled. Plasma MR-proADM levels were correlated with LOS (r=0.28; p=0.0014 at T0; r=0.26; p=0.005 at T24). Multivariate analysis showed that T0 MR-proADM was a significant predictor of mortality (odds ratio [OR]: 1.27; 95% confidence interval [95%CI]: 1.03–1.55; p=0.022). Receiver operating characteristic curves analysis revealed that MR-proADM on ICU admission identified non-survivors with high accuracy, not inferior to the one of APACHEII and SAPSII scores (area under the curve [AUC]: 0.71; 95%CI: 0.62–0.78; p=0.0002 for MR-proADM; AUC: 0.71; 95%CI: 0.62–0.79; p<0.0001 for APACHEII; AUC: 0.8; 95%CI: 0.71–0.87; p<0.0001 for SAPSII). Conclusions Our findings point out a role of MR-proADM as a prognostic tool in non-selected patients in ICUs being a reliable predictor of mortality and LOS and support its use on admission to an ICU to help the management of critically ill patients.

September 29, 2018

Validation of Mycobacterium tuberculosis real-time polymerase chain reaction for diagnosis of tuberculous meningitis using cerebrospinal fluid samples: a pilot study

Sérgio M. de Almeida, Conrado M. Borges, Lucas B. Santana, Gilberto Golin, Lísia Correa, Gislene B. Kussen, Keite Nogueira

Page range: 556-564

Abstract

Background Timely diagnosis of tuberculous meningitis (TBM) remains challenging. Molecular diagnostic tools are necessary, particularly in low- and middle-income countries. There is no approved commercial polymerase chain reaction (PCR) assay that can be used to detect Mycobacterium tuberculosis in non-respiratory samples, such as the cerebrospinal fluid (CSF). We aimed to validate the threshold cycle (Ct) cut-off points; calculate the operational characteristics of real-time PCR for detection of M. tuberculosis (MTb qPCR) in the CSF; and the inhibitory affect of CSF red blood cells (RBC) and total proteins on MTb qPCR. Methods A total of 334 consecutive participants were enrolled. Based on clinical, laboratory and imaging data, cases of suspected TBM were categorized as definite, probable, possible or not TBM cases. Receiver operating characteristic curve analysis was used to select the best discriminating Ct value. Results For TBM cases categorized as definite or probable (n=21), the Ct validated for CSF (≤39.5) improved the diagnostic performance of MTb qPCR on CSF samples. The sensitivity was 29%, specificity was 95%, positive predictive value was 26%, negative predictive value was 95%, efficiency was 90% and positive likelihood was 5.3. The CSF RBC and total protein did not affect the positivity of the MTb qPCR. Conclusions These data support the validation of a highly specific but low sensitive MTb qPCR assay for the TBM diagnosis using CSF samples. MTb qPCR contributes significantly to the diagnosis, mainly when associated with conventional microbiology tests and clinical algorithms.

Letters to the Editor

January 30, 2019

Methodological issues are important in cannabinoids determination in bronchoalveolar lavage

Venerino Poletti, Claudia Ravaglia

Page range: e41-e42

February 23, 2019

Clarifying methodological issues in cannabinoids determination in bronchoalveolar lavages

Maria Concetta Rotolo, Manuela Pellegrini, Paola Martucci, Raffaela Giacobbe, Angela De Palma, Roberta Pacifici, Simona Pichini, Francesco Paolo Busardò, Mario Bisconti

Page range: e43-e44

August 23, 2018

Letter to the Editor relating to Clin Chem Lab Med 2018;56(7):1090–1099

Maria Infantino, Valentina Grossi, Maurizio Benucci, Mariangela Manfredi

Page range: e45-e46

September 3, 2018

Authors’ reply to the Letter by Infantino et al. commenting on Bonroy et al.: Anti-DFS70 in different settings, CCLM 2018;56:1090–9

Carolien Bonroy, Mario Berth, Sofie Schouwers, Lieve Van Hoovels

Page range: e47-e48

August 15, 2018

High-sensitivity cardiac troponin-I analytical imprecisions evaluated by internal quality control or imprecision profile

Mehdi Hage-Sleiman, Ladislas Capdevila, Sophie Bailleul, Guillaume Lefevre

Page range: e49-e51

August 29, 2018

Procalcitonin as guide to therapy in endovascular infections: caveat emptor!

Martina Spaziante, Giancarlo Ceccarelli, Mario Venditti

Page range: e52-e53

August 8, 2018

A new suggested approach in screening for Bence Jones protein and potential kidney damage

Patrizia Natali, Elena De Santis, Giovanna Patelli, Maria Rosaria Cucinelli, Manuela Varani, Tommaso Trenti

Page range: e54-e56

September 29, 2018

Establishing assay-specific 97.5th percentile upper reference limit for serum D-2-hydroxyglutarate for the management of patients with acute myeloid leukemia

Phuong-Nhi Bories, Samir Nakib, Luc Cynober, Anne-Sophie Alary, Marie-Magdelaine Coude, Florian Chevillon, Jérôme Tamburini, Rudy Birsen, Olivier Kosmider, Didier Bouscary

Page range: e57-e59

August 29, 2018

Parallel algorithm for myeloproliferative neoplasms testing: the frequency of double mutations is found in the JAK2/MPL genes more often than the JAK2/CALR genes, but is there a clinical benefit?

Aleksey S. Gorbenko, Marina A. Stolyar, Igor A. Olkhovskiy, Evgeniy V. Vasiliev, Mikhail A. Mikhalev

Page range: e60-e62

September 12, 2018

CGH array for the identification of a compound heterozygous mutation in the CYP1B1 gene in a patient with bilateral anterior segment dysgenesis

Barbara Lombardo, Carlo Ceglia, Francesco Verdesca, Andrea Vitale, Carla Perrotta, Eleonora Leggiero, Lucio Pastore

Page range: e63-e66

August 29, 2018

A very rare interference with the valproate method on the Beckman DxC 800 general chemistry analyser

Goce Dimeski, Oliver Treacy, George Marshall

Page range: e67-e70

Congress Abstracts

Publicly Available February 13, 2019

5th EFLM Conference on Preanalytical Phase Zagreb (HR), 22-23 March 2019

Page range: eA1-eA87

Download PDF

About this journal

Objective
Clinical Chemistry and Laboratory Medicine (CCLM) publishes articles on novel teaching and training methods applicable to laboratory medicine. It is focused on basic and applied research and cutting-edge clinical laboratory medicine. CCLM is one of the leading journals in the field, with an impact factor over 8. All contributions submitted for publication in CCLM are single-blind peer reviewed by at least two experts in the field. CCLM is led by a multi-institutional editorial board. It is issued monthly, both in print and electronically. Letters to the Editor and Congress Abstracts are published online only.

Please submit your manuscript here

Topics

clinical biochemistry
clinical genomics and molecular biology
clinical haematology and coagulation
clinical immunology and autoimmunity
clinical microbiology
drug monitoring and analysis
evaluation of diagnostic biomarkers
disease-oriented topics (cardiovascular disease, cancer diagnostics, diabetes)
new reagents, instrumentation and technologies
new methodologies
reference materials and methods
reference values and decision limits
quality and safety in laboratory medicine
translational laboratory medicine
clinical metrology

Article formats
Research Articles, Reviews, Mini Reviews and Opinion Papers on all aspects of clinical chemistry and laboratory medicine, Guidelines and Recommendations, Point/Counterpoint Articles, Letters to the Editor, Editorials

For EFLM Academy Members

To take advantage of all the opportunities offered to members of the EFLM Academy, please access your personal area in the EFLM Academy at the link https://academy.eflm.eu/secretariat/login (if you do not remember your login details, you can use the option FORGOT PASSWORD). Click on the section “International Journals” on the left-hand side where you find CCLM as the first listed journal.