Jenny E. Kootstra-Ros, Eline A. E. van der Hagen, M. van Schrojenstein Lantman, M. Thelen, M. van Berkel
The calculation of the ‘ anion gap ’ (AG) is common practice in the diagnostic workup of patients with a metabolic acidosis. The AG is mostly calculated by subtracting the anions chloride (Cl − ) and bicarbonate (HCO 3 − ) from the cation sodium and aids in differentiating between two types of metabolic acidosis: normalAGacidosis,whereadecreasedHCO 3 − concentrationis compensated increased Cl − , and high AG acidosis, where the concentration of other anions than HCO 3 − Cl − is management, calculation accurate
{"title":"(In)direct chloride ISE measurements, room for improvement","authors":"Jenny E. Kootstra-Ros, Eline A. E. van der Hagen, M. van Schrojenstein Lantman, M. Thelen, M. van Berkel","doi":"10.1515/cclm-2022-0220","DOIUrl":"https://doi.org/10.1515/cclm-2022-0220","url":null,"abstract":"The calculation of the ‘ anion gap ’ (AG) is common practice in the diagnostic workup of patients with a metabolic acidosis. The AG is mostly calculated by subtracting the anions chloride (Cl − ) and bicarbonate (HCO 3 − ) from the cation sodium and aids in differentiating between two types of metabolic acidosis: normalAGacidosis,whereadecreasedHCO 3 − concentrationis compensated increased Cl − , and high AG acidosis, where the concentration of other anions than HCO 3 − Cl − is management, calculation accurate","PeriodicalId":10388,"journal":{"name":"Clinical Chemistry and Laboratory Medicine (CCLM)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75698251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. Carobene, Frida Milella, Lorenzo Famiglini, F. Cabitza
Abstract The current gold standard for COVID-19 diagnosis, the rRT-PCR test, is hampered by long turnaround times, probable reagent shortages, high false-negative rates and high prices. As a result, machine learning (ML) methods have recently piqued interest, particularly when applied to digital imagery (X-rays and CT scans). In this review, the literature on ML-based diagnostic and prognostic studies grounded on hematochemical parameters has been considered. By doing so, a gap in the current literature was addressed concerning the application of machine learning to laboratory medicine. Sixty-eight articles have been included that were extracted from the Scopus and PubMed indexes. These studies were marked by a great deal of heterogeneity in terms of the examined laboratory test and clinical parameters, sample size, reference populations, ML algorithms, and validation approaches. The majority of research was found to be hampered by reporting and replicability issues: only four of the surveyed studies provided complete information on analytic procedures (units of measure, analyzing equipment), while 29 provided no information at all. Only 16 studies included independent external validation. In light of these findings, we discuss the importance of closer collaboration between data scientists and medical laboratory professionals in order to correctly characterise the relevant population, select the most appropriate statistical and analytical methods, ensure reproducibility, enable the proper interpretation of the results, and gain actual utility by using machine learning methods in clinical practice.
{"title":"How is test laboratory data used and characterised by machine learning models? A systematic review of diagnostic and prognostic models developed for COVID-19 patients using only laboratory data","authors":"A. Carobene, Frida Milella, Lorenzo Famiglini, F. Cabitza","doi":"10.1515/cclm-2022-0182","DOIUrl":"https://doi.org/10.1515/cclm-2022-0182","url":null,"abstract":"Abstract The current gold standard for COVID-19 diagnosis, the rRT-PCR test, is hampered by long turnaround times, probable reagent shortages, high false-negative rates and high prices. As a result, machine learning (ML) methods have recently piqued interest, particularly when applied to digital imagery (X-rays and CT scans). In this review, the literature on ML-based diagnostic and prognostic studies grounded on hematochemical parameters has been considered. By doing so, a gap in the current literature was addressed concerning the application of machine learning to laboratory medicine. Sixty-eight articles have been included that were extracted from the Scopus and PubMed indexes. These studies were marked by a great deal of heterogeneity in terms of the examined laboratory test and clinical parameters, sample size, reference populations, ML algorithms, and validation approaches. The majority of research was found to be hampered by reporting and replicability issues: only four of the surveyed studies provided complete information on analytic procedures (units of measure, analyzing equipment), while 29 provided no information at all. Only 16 studies included independent external validation. In light of these findings, we discuss the importance of closer collaboration between data scientists and medical laboratory professionals in order to correctly characterise the relevant population, select the most appropriate statistical and analytical methods, ensure reproducibility, enable the proper interpretation of the results, and gain actual utility by using machine learning methods in clinical practice.","PeriodicalId":10388,"journal":{"name":"Clinical Chemistry and Laboratory Medicine (CCLM)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79389591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
G. Résimont, L. Vranken, H. Pottel, F. Jouret, J. Krzesinski, E. Cavalier, P. Delanaye
Abstract Objectives Severity of chronic kidney disease is defined by glomerular filtration rate (GFR) and albuminuria (ACR) by the KDIGO and are related to cardiovascular outcomes and end-stage-kidney-failure. However, proteinuria (PCR) is more often available than ACR in records. Recently, equations were developed to estimate ACR from PCR. We investigated their performances in our population. Methods In the academic medical hospital of Liège, we retrospectively analysed same day measurement of ACR and PCR and staged them according to the KDIGO A1-A2-A3 categories. Analyser Roche Cobas (R) gathered 2,633 urinalysis (May 2018-May 2019) and analyser Abbott Alinity (A) 2,386 urinalysis (May 2019-March 2020). We compared the KDIGO staging of mACR and eACR obtained from Weaver’s and Sumida’s equations. Results Median age was 63 [52;71]/64 [53;72] years old, 43/42% were female; 78/74% had diabetes; proportion of mACR-A1 was 65.6%/64.2%, A2 was 25.5%/25.5% and A3 was 8.8%/10.3% (Method R/A, respectively). Both equations gave similar distribution of KDIGO staging of eACR. Overall agreements were higher than 88% regardless of the analyser or of the equation. Performances in between equations were equivalent according to the multi-level AUC (multinomial logistic regression model). Conclusions Good concordance was observed between mACR and eACR regardless of the equation or of the analyser. No patient with an A3-measured ACR was estimated within the KDIGO A1 category. Though ACR should be measured when clinically needed, it may be reasonably estimated from the PCR through these equations, for epidemiologic retrospective studies or research purposes.
{"title":"Estimating urine albumin to creatinine ratio from protein to creatinine ratio using same day measurement: validation of equations","authors":"G. Résimont, L. Vranken, H. Pottel, F. Jouret, J. Krzesinski, E. Cavalier, P. Delanaye","doi":"10.1515/cclm-2022-0049","DOIUrl":"https://doi.org/10.1515/cclm-2022-0049","url":null,"abstract":"Abstract Objectives Severity of chronic kidney disease is defined by glomerular filtration rate (GFR) and albuminuria (ACR) by the KDIGO and are related to cardiovascular outcomes and end-stage-kidney-failure. However, proteinuria (PCR) is more often available than ACR in records. Recently, equations were developed to estimate ACR from PCR. We investigated their performances in our population. Methods In the academic medical hospital of Liège, we retrospectively analysed same day measurement of ACR and PCR and staged them according to the KDIGO A1-A2-A3 categories. Analyser Roche Cobas (R) gathered 2,633 urinalysis (May 2018-May 2019) and analyser Abbott Alinity (A) 2,386 urinalysis (May 2019-March 2020). We compared the KDIGO staging of mACR and eACR obtained from Weaver’s and Sumida’s equations. Results Median age was 63 [52;71]/64 [53;72] years old, 43/42% were female; 78/74% had diabetes; proportion of mACR-A1 was 65.6%/64.2%, A2 was 25.5%/25.5% and A3 was 8.8%/10.3% (Method R/A, respectively). Both equations gave similar distribution of KDIGO staging of eACR. Overall agreements were higher than 88% regardless of the analyser or of the equation. Performances in between equations were equivalent according to the multi-level AUC (multinomial logistic regression model). Conclusions Good concordance was observed between mACR and eACR regardless of the equation or of the analyser. No patient with an A3-measured ACR was estimated within the KDIGO A1 category. Though ACR should be measured when clinically needed, it may be reasonably estimated from the PCR through these equations, for epidemiologic retrospective studies or research purposes.","PeriodicalId":10388,"journal":{"name":"Clinical Chemistry and Laboratory Medicine (CCLM)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90102341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Arite Bigalke, Charles Neu, Ricardo Esper Treml, S. Coldewey, M. Kiehntopf
We read with great interest the recent article by Zerimech et al. proposing a protease-antiprotease imbalance as a key pathophysiological mechanism in the progression of COVID-19 to severe ARDS (acute respiratory distress syndrome) [1]. In this correspondence, we would like to offer new evidence relating to this finding by providing the concentrations of two C-terminal protease cleavage products of alpha-1-antitrypsin (AAT) in plasma. A deficiency in alpha-1-antitrypsin, a protease inhibitor and acute-phase protein with anti-inflammatory properties, has been proposed to play a role in the pathogenesis of COVID-19. A first association was observed by Vianello et al. who found regions in Italy with higher incidence of hereditary AAT deficiency to be affected more severely by the pandemic [2]. Aside from its anti-inflammatory effects, AAT also has antiviral properties. It has been shown that AAT inhibits the transmembrane protease serine subtype 2 (TMPRSS2), which is necessary for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to enter the cell [3]. In patients with COVID-19, the ratio of proinflammatory IL-6 and AAT was able to predict disease severity andmortality [4]. Similarly to chronic lung disease [5], an antiprotease–protease imbalance has been proposed to contribute to disease severity in patients with COVID-19 by Zerimech et al. [1]. The study found higher peak values of neutrophil elastase (NE) and matrix metalloprotease-12 (MMP-12) in patients who died from severe COVID-19. A variety of enzymes and pathophysiological conditions has been identified that are associated with the formation of C-terminal peptides of AAT (CAAPs) including NE and MMP-12. Some CAAPs have also been proposed to serve as putative biomarkers for a variety of diseases. Analysis of sepsis patients demonstrate that certain CAAPs are significantly increased in blood during systemic inflammation compared to healthy individuals [6]. To the best of our knowledge, there is hitherto no evidence for the formation of CAAPs during viral infections. However, a recent proteomic study comparing mild and severe patients with COVID-19 found different concentrations of AAT peptides in the urine, indicating a distinct AAT cleavage pattern during host response to viral infection [7]. To clarify the role of CAAPs during severe COVID-19, we have analyzed plasma concentrations of two AAT fragments, C-36 (cleavage product of i.a. NE) and C-42 (cleaved i.a. by MMP-12), using our newly developed LC/MS-MS method [6]. Patients samples were obtained from a subgroup of an ongoing single-center prospective cohort study on days three (T1) and seven (T2) after onset of severe disease in patients with severe COVID-19 (n=10) and compared with patients with bacterial sepsis of pulmonary origin (n=10) and healthy controls (n=10) [8]. All three cohorts showed no significant differences in sex (all cohorts 30% female) and age (median healthy: 65 y, sepsis: 63 y, COVID-19: 61.5 y). Patie
{"title":"Fragments of alpha-1-antitrypsin in patients with severe COVID-19 and bacterial pulmonary sepsis","authors":"Arite Bigalke, Charles Neu, Ricardo Esper Treml, S. Coldewey, M. Kiehntopf","doi":"10.1515/cclm-2022-0361","DOIUrl":"https://doi.org/10.1515/cclm-2022-0361","url":null,"abstract":"We read with great interest the recent article by Zerimech et al. proposing a protease-antiprotease imbalance as a key pathophysiological mechanism in the progression of COVID-19 to severe ARDS (acute respiratory distress syndrome) [1]. In this correspondence, we would like to offer new evidence relating to this finding by providing the concentrations of two C-terminal protease cleavage products of alpha-1-antitrypsin (AAT) in plasma. A deficiency in alpha-1-antitrypsin, a protease inhibitor and acute-phase protein with anti-inflammatory properties, has been proposed to play a role in the pathogenesis of COVID-19. A first association was observed by Vianello et al. who found regions in Italy with higher incidence of hereditary AAT deficiency to be affected more severely by the pandemic [2]. Aside from its anti-inflammatory effects, AAT also has antiviral properties. It has been shown that AAT inhibits the transmembrane protease serine subtype 2 (TMPRSS2), which is necessary for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to enter the cell [3]. In patients with COVID-19, the ratio of proinflammatory IL-6 and AAT was able to predict disease severity andmortality [4]. Similarly to chronic lung disease [5], an antiprotease–protease imbalance has been proposed to contribute to disease severity in patients with COVID-19 by Zerimech et al. [1]. The study found higher peak values of neutrophil elastase (NE) and matrix metalloprotease-12 (MMP-12) in patients who died from severe COVID-19. A variety of enzymes and pathophysiological conditions has been identified that are associated with the formation of C-terminal peptides of AAT (CAAPs) including NE and MMP-12. Some CAAPs have also been proposed to serve as putative biomarkers for a variety of diseases. Analysis of sepsis patients demonstrate that certain CAAPs are significantly increased in blood during systemic inflammation compared to healthy individuals [6]. To the best of our knowledge, there is hitherto no evidence for the formation of CAAPs during viral infections. However, a recent proteomic study comparing mild and severe patients with COVID-19 found different concentrations of AAT peptides in the urine, indicating a distinct AAT cleavage pattern during host response to viral infection [7]. To clarify the role of CAAPs during severe COVID-19, we have analyzed plasma concentrations of two AAT fragments, C-36 (cleavage product of i.a. NE) and C-42 (cleaved i.a. by MMP-12), using our newly developed LC/MS-MS method [6]. Patients samples were obtained from a subgroup of an ongoing single-center prospective cohort study on days three (T1) and seven (T2) after onset of severe disease in patients with severe COVID-19 (n=10) and compared with patients with bacterial sepsis of pulmonary origin (n=10) and healthy controls (n=10) [8]. All three cohorts showed no significant differences in sex (all cohorts 30% female) and age (median healthy: 65 y, sepsis: 63 y, COVID-19: 61.5 y). Patie","PeriodicalId":10388,"journal":{"name":"Clinical Chemistry and Laboratory Medicine (CCLM)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88833236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In this issue of the Journal, Hansen et al. are reporting an interesting observation on the proposed WHO standard for anti-SARS-CoV-2 antibodies [1]. In their opinion, introducing separate units for results obtained using neutralising antibody (Nab) assays and for results from binding antibody (bAb) assays is not appropriate as it represents ‘a deviation from international nomenclature conventions used by WHO to assign International Units to CRM’. In addition, the authors bring on a proposal to use a common term for international units (IU) while maintaining a distinction according to the target antibodies of different assays, e.g., neutralizing antibodies targeting specific portions of SARS-CoV-2 spike proteins, binding antibodies to spike or binding antibodies to the nucleocapsid. We recognize this point to be valid, but we would like to add some comments. From the reference they used [2] it looks like they consider the units of that WHO standard as SI units, that by definition have recognized dimensions and are independent of measurement procedure. However, this is not the case for biological controls where the measurand is classified as a class B. The three elements of a class B analyte, together making up the measurand, are the system (sample matrix) the component such as Ig class and target specificity, and the kind of quantity (e.g., the biological activity) [3]. As we commented in a previously published Editorial [4], the signal generated by antibody assays is influenced by the Ig class(es) involved and by the relative affinity to the antigenic targets, and thus to time after infection as a low affinity antibody response is raised in the early stages of infection and a high affinity characterizes past as well as chronic infections. Both factors (Ig classes andaffinity)will hamper the reliability of antibody standards that are usually preparedby pooling plasma specimens collected from many individuals whose infection stage is unknown. By a probabilistic estimate, majority of samples should come from people in late stages, with an overabundance of high affinity IgG, which willmake the standardization of different methods detecting only IgG, only IgMor all Ig classes (‘total’antibodyassays) an almost impossible task. A living example of the difficulties in manufacturing and using reliable standards for infectious diseases serology is provided by the standardization of IgG antibodies to Rubella virus, that has been proposed since many years but is still failing to reach a sustained agreement across assays, both in general and at the supposed ‘immunity’ threshold of 10 IU/mL [3]. We may therefore conclude that even adopting this target-based distinction proposed by Hansen et al. [1] will not be sufficient to harmonize, let alone standardize, the results generated by different SARS-CoV-2 antibody assays. We may also comment on this issue from a wider perspective. More than 30 years ago Roger Ekins established the two categories for assays emplo
{"title":"The never-ending quest for antibody assays standardization and appropriate measurement units","authors":"M. Plebani, C. Galli","doi":"10.1515/cclm-2022-0392","DOIUrl":"https://doi.org/10.1515/cclm-2022-0392","url":null,"abstract":"In this issue of the Journal, Hansen et al. are reporting an interesting observation on the proposed WHO standard for anti-SARS-CoV-2 antibodies [1]. In their opinion, introducing separate units for results obtained using neutralising antibody (Nab) assays and for results from binding antibody (bAb) assays is not appropriate as it represents ‘a deviation from international nomenclature conventions used by WHO to assign International Units to CRM’. In addition, the authors bring on a proposal to use a common term for international units (IU) while maintaining a distinction according to the target antibodies of different assays, e.g., neutralizing antibodies targeting specific portions of SARS-CoV-2 spike proteins, binding antibodies to spike or binding antibodies to the nucleocapsid. We recognize this point to be valid, but we would like to add some comments. From the reference they used [2] it looks like they consider the units of that WHO standard as SI units, that by definition have recognized dimensions and are independent of measurement procedure. However, this is not the case for biological controls where the measurand is classified as a class B. The three elements of a class B analyte, together making up the measurand, are the system (sample matrix) the component such as Ig class and target specificity, and the kind of quantity (e.g., the biological activity) [3]. As we commented in a previously published Editorial [4], the signal generated by antibody assays is influenced by the Ig class(es) involved and by the relative affinity to the antigenic targets, and thus to time after infection as a low affinity antibody response is raised in the early stages of infection and a high affinity characterizes past as well as chronic infections. Both factors (Ig classes andaffinity)will hamper the reliability of antibody standards that are usually preparedby pooling plasma specimens collected from many individuals whose infection stage is unknown. By a probabilistic estimate, majority of samples should come from people in late stages, with an overabundance of high affinity IgG, which willmake the standardization of different methods detecting only IgG, only IgMor all Ig classes (‘total’antibodyassays) an almost impossible task. A living example of the difficulties in manufacturing and using reliable standards for infectious diseases serology is provided by the standardization of IgG antibodies to Rubella virus, that has been proposed since many years but is still failing to reach a sustained agreement across assays, both in general and at the supposed ‘immunity’ threshold of 10 IU/mL [3]. We may therefore conclude that even adopting this target-based distinction proposed by Hansen et al. [1] will not be sufficient to harmonize, let alone standardize, the results generated by different SARS-CoV-2 antibody assays. We may also comment on this issue from a wider perspective. More than 30 years ago Roger Ekins established the two categories for assays emplo","PeriodicalId":10388,"journal":{"name":"Clinical Chemistry and Laboratory Medicine (CCLM)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89862655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ivar Tjernberg, Paula Gyllemark, H. Zetterberg, K. Blennow, J. Ernerudh, P. Forsberg, J. Sjöwall, A. Henningsson
Abstract Objectives The purpose of this study was to evaluate levels and kinetics of cerebrospinal fluid (CSF) markers of inflammation and brain injury in patients with Lyme neuroborreliosis (LNB). Methods Adult patients with clinically suspected LNB were enrolled, in a prospective clinical study in the South East of Sweden. Patients were classified according to the European Federation of Neurological Societies’ guidelines. Definite cases of LNB were re-examined one month later including a repeat CSF investigation. Routine laboratory parameters were investigated along with CSF levels of neurodegenerative markers glial fibrillary acidic protein (GFAp), total tau (t-tau) and neurofilament light protein (NFL), as well as neuroinflammatory markers soluble triggering receptor expressed on myeloid cells 2 (sTREM2), YKL-40 and CXCL13. Non-LNB served as controls. An additional comparison group consisted of spinal anesthesia subjects (SAS) without known central nervous system conditions. Results CSF levels of sTREM2 and CXCL13 were elevated in definite LNB patients at diagnosis compared with non-LNB patients (p<0.001) and SAS (p≤0.01). In addition, CSF levels of sTREM2, YKL-40 and CXCL13 rapidly declined in at follow-up after antibiotic treatment. In contrast, CSF levels of GFAp and t-tau did not differ across LNB groups, and did not change after treatment. Conclusions Although in a limited number of LNB patients, the results indicate a predominance of microglial and neuroinflammatory involvement rather than parenchymal CNS injury in CSF at diagnosis of LNB with a prompt decline after antibiotic treatment. The findings provide pathogenetic insights and may be of value in differential diagnosis of CSF findings.
{"title":"Cerebrospinal fluid markers of inflammation and brain injury in Lyme neuroborreliosis – a prospective follow-up study","authors":"Ivar Tjernberg, Paula Gyllemark, H. Zetterberg, K. Blennow, J. Ernerudh, P. Forsberg, J. Sjöwall, A. Henningsson","doi":"10.1515/cclm-2022-0097","DOIUrl":"https://doi.org/10.1515/cclm-2022-0097","url":null,"abstract":"Abstract Objectives The purpose of this study was to evaluate levels and kinetics of cerebrospinal fluid (CSF) markers of inflammation and brain injury in patients with Lyme neuroborreliosis (LNB). Methods Adult patients with clinically suspected LNB were enrolled, in a prospective clinical study in the South East of Sweden. Patients were classified according to the European Federation of Neurological Societies’ guidelines. Definite cases of LNB were re-examined one month later including a repeat CSF investigation. Routine laboratory parameters were investigated along with CSF levels of neurodegenerative markers glial fibrillary acidic protein (GFAp), total tau (t-tau) and neurofilament light protein (NFL), as well as neuroinflammatory markers soluble triggering receptor expressed on myeloid cells 2 (sTREM2), YKL-40 and CXCL13. Non-LNB served as controls. An additional comparison group consisted of spinal anesthesia subjects (SAS) without known central nervous system conditions. Results CSF levels of sTREM2 and CXCL13 were elevated in definite LNB patients at diagnosis compared with non-LNB patients (p<0.001) and SAS (p≤0.01). In addition, CSF levels of sTREM2, YKL-40 and CXCL13 rapidly declined in at follow-up after antibiotic treatment. In contrast, CSF levels of GFAp and t-tau did not differ across LNB groups, and did not change after treatment. Conclusions Although in a limited number of LNB patients, the results indicate a predominance of microglial and neuroinflammatory involvement rather than parenchymal CNS injury in CSF at diagnosis of LNB with a prompt decline after antibiotic treatment. The findings provide pathogenetic insights and may be of value in differential diagnosis of CSF findings.","PeriodicalId":10388,"journal":{"name":"Clinical Chemistry and Laboratory Medicine (CCLM)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79321776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abstract Objectives Diagnostic samples are exposed to a spectrum of variables during transport to laboratories; therefore, the evaluation of a rather comprehensive stability profile of measurands is warranted. While appropriate testing standards have been established for pharmaceuticals and reagents, this is not the case for diagnostic samples. The aim of our work was to develop and evaluate a protocol applicable to diagnostic samples. Methods An isochronous approach with representation of temperature and exposure duration in a two-dimensional matrix was established. The deviations of the measurement results from the baseline associated with the exposure are evaluated with respect to the measurement uncertainty of the analytical measurement procedure applied. Variables of the experiment are documented in a standardized matrix. As a proof-of-concept, we profiled the stability patterns of a number of measurands at four temperature levels over up to 72 h in primary serum sample tubes. Results The protocol proved to be workable and allowed the description of a comprehensive stability profile of a considerable number of compounds based on 21 small-volume primary samples collected from each volunteer and exposed according to this protocol. Conclusions A straightforward and feasible isochronous protocol can be used to investigate in detail the effects of different pre-processing conditions on the stability of measurands in primary samples during transport to diagnostic laboratories. This is of significance as pre-analytical logistics become increasingly important with the centralization of analytical services.
{"title":"Transport stability profiling – a proposed generic protocol","authors":"Lars Willems, M. Paal, M. Vogeser","doi":"10.1515/cclm-2022-0032","DOIUrl":"https://doi.org/10.1515/cclm-2022-0032","url":null,"abstract":"Abstract Objectives Diagnostic samples are exposed to a spectrum of variables during transport to laboratories; therefore, the evaluation of a rather comprehensive stability profile of measurands is warranted. While appropriate testing standards have been established for pharmaceuticals and reagents, this is not the case for diagnostic samples. The aim of our work was to develop and evaluate a protocol applicable to diagnostic samples. Methods An isochronous approach with representation of temperature and exposure duration in a two-dimensional matrix was established. The deviations of the measurement results from the baseline associated with the exposure are evaluated with respect to the measurement uncertainty of the analytical measurement procedure applied. Variables of the experiment are documented in a standardized matrix. As a proof-of-concept, we profiled the stability patterns of a number of measurands at four temperature levels over up to 72 h in primary serum sample tubes. Results The protocol proved to be workable and allowed the description of a comprehensive stability profile of a considerable number of compounds based on 21 small-volume primary samples collected from each volunteer and exposed according to this protocol. Conclusions A straightforward and feasible isochronous protocol can be used to investigate in detail the effects of different pre-processing conditions on the stability of measurands in primary samples during transport to diagnostic laboratories. This is of significance as pre-analytical logistics become increasingly important with the centralization of analytical services.","PeriodicalId":10388,"journal":{"name":"Clinical Chemistry and Laboratory Medicine (CCLM)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75773222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"COVID-19 related mortality and religious denomination vs. genetics","authors":"J. Delanghe, M. Speeckaert, M. D. De Buyzere","doi":"10.1515/cclm-2022-0393","DOIUrl":"https://doi.org/10.1515/cclm-2022-0393","url":null,"abstract":"","PeriodicalId":10388,"journal":{"name":"Clinical Chemistry and Laboratory Medicine (CCLM)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84480558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Joost L. van Pelt, S. Klatte, Talent Hwandih, A. Barcaru, I. Riphagen, J. Linssen, S. Bakker
Abstract Objectives Our aim was to derive reference intervals for all Sysmex XN hematology analyzer parameters. The rationale behind the study was the lack of reference intervals for the XN analyzer cell population data (CPD) and functional parameters. Methods Fresh fasting blood samples from 18,484 participants in the Dutch Lifelines study were analyzed using two automated XN analyzers. Structured health questionnaire data were used to select a subgroup of 15,803 apparently healthy individuals for inclusion in the reference population. The Latent Abnormal Values Exclusion (LAVE) approach was used to reduce the influence of latent diseases in the reference population on the resulting reference intervals. We applied analysis of variance to judge the need for partitioning of the reference intervals by sex or age. Results We report reference intervals for 105 XN analyzer hematological parameters with and without applying LAVE. Sex-related partitioning was required for red blood cells, (RBC, RBC-O), hemoglobin (HGB, HGB-O), hematocrit (HCT), mean corpuscular hemoglobin concentration (MCHC), reticulocyte production index (RPI), and side scattered light intensity of the red blood cell population in the RET channel (RBC-Z). Partitioning for age was not warranted. Body mass index (BMI) and smoking had moderate influence on a minority of the parameters. Conclusions We provide reference intervals for all Sysmex XN analyzer routine, CPD and functional parameters, using a direct approach in a large cohort in the Netherlands.
{"title":"Reference intervals for Sysmex XN hematological parameters as assessed in the Dutch Lifelines cohort","authors":"Joost L. van Pelt, S. Klatte, Talent Hwandih, A. Barcaru, I. Riphagen, J. Linssen, S. Bakker","doi":"10.1515/cclm-2022-0094","DOIUrl":"https://doi.org/10.1515/cclm-2022-0094","url":null,"abstract":"Abstract Objectives Our aim was to derive reference intervals for all Sysmex XN hematology analyzer parameters. The rationale behind the study was the lack of reference intervals for the XN analyzer cell population data (CPD) and functional parameters. Methods Fresh fasting blood samples from 18,484 participants in the Dutch Lifelines study were analyzed using two automated XN analyzers. Structured health questionnaire data were used to select a subgroup of 15,803 apparently healthy individuals for inclusion in the reference population. The Latent Abnormal Values Exclusion (LAVE) approach was used to reduce the influence of latent diseases in the reference population on the resulting reference intervals. We applied analysis of variance to judge the need for partitioning of the reference intervals by sex or age. Results We report reference intervals for 105 XN analyzer hematological parameters with and without applying LAVE. Sex-related partitioning was required for red blood cells, (RBC, RBC-O), hemoglobin (HGB, HGB-O), hematocrit (HCT), mean corpuscular hemoglobin concentration (MCHC), reticulocyte production index (RPI), and side scattered light intensity of the red blood cell population in the RET channel (RBC-Z). Partitioning for age was not warranted. Body mass index (BMI) and smoking had moderate influence on a minority of the parameters. Conclusions We provide reference intervals for all Sysmex XN analyzer routine, CPD and functional parameters, using a direct approach in a large cohort in the Netherlands.","PeriodicalId":10388,"journal":{"name":"Clinical Chemistry and Laboratory Medicine (CCLM)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91316368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abstract Objectives The prognostic role of thyroglobulin in predicting recurrence in differentiated thyroid cancer (DTC) patients treated by lobectomy is controversial. This systematic review with meta-analysis aimed to update the current evidence deepening the reliability of circulating thyroglobulin in assessing the early response and in predictive recurrence. Methods The methodology was registered in the PROSPERO database under the protocol number CRD42021288189. A systematic search was carried out on PubMed, Embase, Web of Science, and Scopus from September to November 2021 without time and language restrictions. The literature search strategy was based on the following keywords: Thyroglobulin AND (Lobectomy OR Hemithyroidectomy). Results After screening 273 articles, seven studies were included in the systematic review, and only six of them were included in the meta-analysis for a total of 2,455 patients. Circulating thyroglobulin was found non-reliable in assessing early response and predicting recurrence in patients with hemithyroidectomy, especially those with a low initial ATA classification. Conclusions Our study does not support serum thyroglobulin levels for monitoring patients with low-risk DTC treated with lobectomy, and weak evidence supports its role for intermediate- or high-risk patients. Studies with longer follow-up, different study designs, and stringent inclusion/exclusion criteria are needed to evaluate the role of thyroglobulin in recurrence prediction.
【摘要】目的甲状腺球蛋白在预测分化型甲状腺癌(DTC)术后患者复发中的预后作用尚存争议。本系统综述与荟萃分析旨在更新现有证据，深化循环甲状腺球蛋白在评估早期反应和预测复发方面的可靠性。方法在PROSPERO数据库中注册，协议号为CRD42021288189。在没有时间和语言限制的情况下，于2021年9月至11月在PubMed、Embase、Web of Science和Scopus上进行了系统检索。文献检索策略基于以下关键词:甲状腺球蛋白AND (Lobectomy OR Hemithyroidectomy)。结果在筛选273篇文献后，7项研究被纳入系统评价，其中只有6项研究被纳入meta分析，共纳入2455例患者。循环甲状腺球蛋白在评估甲状腺切除术患者的早期反应和预测复发方面不可靠，特别是那些初始ATA分级低的患者。结论:本研究不支持血清甲状腺球蛋白水平监测经肺叶切除术治疗的低危DTC患者，且微弱证据支持其对中危或高危患者的作用。需要更长的随访时间、不同的研究设计和严格的纳入/排除标准来评估甲状腺球蛋白在预测复发中的作用。
{"title":"Is thyroglobulin a reliable biomarker of differentiated thyroid cancer in patients treated by lobectomy? A systematic review and meta-analysis","authors":"L. Giovanella, L. Ceriani, M. Garo","doi":"10.1515/cclm-2022-0154","DOIUrl":"https://doi.org/10.1515/cclm-2022-0154","url":null,"abstract":"Abstract Objectives The prognostic role of thyroglobulin in predicting recurrence in differentiated thyroid cancer (DTC) patients treated by lobectomy is controversial. This systematic review with meta-analysis aimed to update the current evidence deepening the reliability of circulating thyroglobulin in assessing the early response and in predictive recurrence. Methods The methodology was registered in the PROSPERO database under the protocol number CRD42021288189. A systematic search was carried out on PubMed, Embase, Web of Science, and Scopus from September to November 2021 without time and language restrictions. The literature search strategy was based on the following keywords: Thyroglobulin AND (Lobectomy OR Hemithyroidectomy). Results After screening 273 articles, seven studies were included in the systematic review, and only six of them were included in the meta-analysis for a total of 2,455 patients. Circulating thyroglobulin was found non-reliable in assessing early response and predicting recurrence in patients with hemithyroidectomy, especially those with a low initial ATA classification. Conclusions Our study does not support serum thyroglobulin levels for monitoring patients with low-risk DTC treated with lobectomy, and weak evidence supports its role for intermediate- or high-risk patients. Studies with longer follow-up, different study designs, and stringent inclusion/exclusion criteria are needed to evaluate the role of thyroglobulin in recurrence prediction.","PeriodicalId":10388,"journal":{"name":"Clinical Chemistry and Laboratory Medicine (CCLM)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77303603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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