Sam Rodgers, Timothy Woolley, Joshua Smith, Peter Prinsloo, Natasha Fernando
{"title":"Updated adult ferritin reference intervals based on a large, healthy UK sample, measured on Roche Cobas series analysers.","authors":"Sam Rodgers, Timothy Woolley, Joshua Smith, Peter Prinsloo, Natasha Fernando","doi":"10.1177/00045632241243026","DOIUrl":"10.1177/00045632241243026","url":null,"abstract":"<p><strong>Background: </strong>There is a lack of standardization of reference intervals (RIs) for ferritin across laboratories, particularly for postmenopausal women. Depending on the RI used, there can be more than a 4-fold difference in the upper limit of normal between laboratories, resulting in potential misinterpretation.</p><p><strong>Methods: </strong>This retrospective study used a large dataset of blood test results from 25,425 healthy participants aged 18 to 97 over a 7-year period. Exclusion criteria were used to screen out individuals with conditions known to affect iron metabolism or raise ferritin as part of the acute phase response. Distributions were assessed using density and Q-Q plots, and age-banded cut-offs were determined. The non-parametric method was used to establish RIs for sex and age bands.</p><p><strong>Results: </strong>For females, 4 age bands were established (18-39, 40-49, 50-59 and 60+). For males, 2 bands were identified (18-39 and 40+). Performance against a validation dataset, followed by an expansive validation against an inclusive dataset, demonstrated the robustness of the derived RIs.</p><p><strong>Conclusion: </strong>This study addresses the inconsistency in serum ferritin RIs by presenting intervals based on demographic parameters. This approach can potentially enhance the accuracy of interpreting serum ferritin levels, assisting clinicians in identifying patients requiring further evaluation.</p>","PeriodicalId":8005,"journal":{"name":"Annals of Clinical Biochemistry","volume":" ","pages":"365-371"},"PeriodicalIF":2.1,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140130502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Increased phosphatidylcholine and its hydroperoxides in serum low-density lipoproteins from patients with non-alcoholic steatohepatitis.","authors":"Nanao Murakami, Toshihiro Sakurai, Arisa Yamahata, Akiko Sakurai, Kazuhiro Nouso, Yuki Fujii, Hitoshi Chiba, Shu-Ping Hui","doi":"10.1177/00045632241259658","DOIUrl":"10.1177/00045632241259658","url":null,"abstract":"<p><strong>Background: </strong>Non-alcoholic fatty liver disease is classified into simple steatosis (SS) and non-alcoholic steatohepatitis (NASH) according to histological findings from liver biopsies. Phosphatidylcholine (PC), the main component of phospholipids in serum lipoproteins, is easily oxidized to phosphatidylcholine hydroperoxide (PC-OOH). Although a lipid composition in the low-density lipoproteins (LDL) from patients with NASH could be abnormal, it remains unclear. Here, to better understand the characteristics of lipids in the LDL from NASH and SS, we compared the composition of PC and PC-OOH species in LDL particles (LDL-PC, LDL-PCOOH) from these patients, then clarified the association between these lipids and NASH severity.</p><p><strong>Methods: </strong>The serum samples from patients with NASH (female, <i>n</i> = 9) and SS (female, <i>n</i> = 4; male, <i>n</i> = 2) were used for isolation of LDL. Total lipids were extracted from isolated LDL, and the species of PC and PC-OOH were measured using liquid chromatography-mass spectrometry/mass spectrometry.</p><p><strong>Results: </strong>The sum of LDL-PC and the sum of LDL-PCOOH were significantly higher in NASH than in SS. Several LDL-PC (PC 32:0, 32:1, 32:2, 34:3, 36:2, sum of PC with saturated fatty acyl chains and sum of LDL-PC with polyunsaturated fatty acyl chains) and several LDL-PCOOH (34:2, 36:2, 36:3 and total) were increased significantly with increasing fibrosis score. In particular, a series of LDL-PCOOH were more reflective of the severity of fibrosis score.</p><p><strong>Conclusions: </strong>LDL-PC and LDL-PCOOH species were strongly correlated with the fibrosis score in NASH, which suggests that abnormal LDL is involved in the development of liver fibrosis.</p>","PeriodicalId":8005,"journal":{"name":"Annals of Clinical Biochemistry","volume":" ","pages":"406-409"},"PeriodicalIF":2.1,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141080650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Assay error detection when using common quality control targets across multiple instruments: An analysis using simulated and real-world data.","authors":"Eric S Kilpatrick","doi":"10.1177/00045632241226916","DOIUrl":"10.1177/00045632241226916","url":null,"abstract":"<p><strong>Background: </strong>Clinical laboratories frequently implement the same tests and internal quality control (QC) rules on identical instruments. It is unclear whether individual QC targets for each analyser or ones that are common to all instruments are preferable. This study modelled how common QC targets influence assay error detection before examining their effect on real-world data.</p><p><strong>Methods: </strong>The effect of variable bias and imprecision on error detection and false rejection rates when using common or individual QC targets on two instruments was simulated. QC data from tests run on two identical Beckman instruments (6-month period, same QC lot, <i>n</i> > 100 points for each instrument) determined likely real-world consequences.</p><p><strong>Results: </strong>Compared to individual QC targets, common targets had an asymmetrical effect on systematic error detection, with one instrument assay losing detection power more than the other gained. If individual in-control assay standard deviations (SDs) differed, then common targets led to one assay failing QC more frequently. Applied to two analysers (95 QC levels and 45 tests), common targets reduced one instrument's error detection by ≥ 0.4 sigma on 15/45 (33%) of tests. Such targets also meant 14/45 (31%) of assays on one in-control instrument would fail over twice as frequently as the other (median ratio 1.62, IQR 1.20-2.39) using a 2SD rule.</p><p><strong>Conclusions: </strong>Compared to instrument-specific QC targets, common targets can reduce the probability of detecting changes in individual assay performance and cause one in-control assay to fail QC more frequently than another. Any impact on clinical care requires further investigation.</p>","PeriodicalId":8005,"journal":{"name":"Annals of Clinical Biochemistry","volume":" ","pages":"331-337"},"PeriodicalIF":2.1,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139085592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Sample comparison of BÜHLMANN fCAL Turbo and OC-FCa faecal calprotectin methods.","authors":"Shane O'Driscoll, Carolyn Piggott, Sally C Benton","doi":"10.1177/00045632241273266","DOIUrl":"10.1177/00045632241273266","url":null,"abstract":"<p><strong>Background: </strong>Faecal calprotectin is an inflammatory marker used to triage patients for further investigation with suspected inflammatory bowel disease (IBD). Our current method requires faecal samples be sent to the laboratory, where calprotectin is extracted before analysis. This is a time-consuming, potential bottleneck in the pathway. We have recently evaluated the OC-SENSOR PLEDIA fCAL method that uses the same sampling device as used in some bowel cancer screening and symptomatic colorectal cancer programmes that detect faecal haemoglobin. The below study is a comparison of the OC-FCa method with the BÜHLMANN fCAL Turbo which is used routinely within BSPS.</p><p><strong>Method: </strong>150 homogenised and 110 non-homogenised faecal samples were loaded into OC-Sampling Bottle 3 and BÜHLMANN CALEX cap sampling devices. The samples were then analysed on their respective systems according to manufacturer's instructions.</p><p><strong>Results: </strong>The OC-FCa assay had a mean positive bias of 67.3% (homogenised) and 88.4% (non-homogenised). Homogenised samples showed substantial agreement between the methods for normal (<50 µg/g) and elevated (150+µg/g) risk categories (k = 0.794, k = 0.788, respectively) and moderate agreement for borderline (51-150 µg/g) (k = 0.25) according to the current Berkshire and Surrey Pathology Service (BSPS) guidelines. Non-homogenised samples had none to slight agreement for normal and borderline values (k = 0.02 for both) and moderate agreement for elevated (k = 0.596).</p><p><strong>Conclusion: </strong>The OC-FCa method is a viable alternative for faecal calprotectin testing, but requires an adjustment to clinical cut-off values due to the lack of standardisation and strong positive bias. A clinical comparative study is required to assess the impact of patients collecting their own samples into the devices, as this may negate any potential degradation samples may exhibit during transit to the laboratory.</p>","PeriodicalId":8005,"journal":{"name":"Annals of Clinical Biochemistry","volume":" ","pages":"45632241273266"},"PeriodicalIF":2.1,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141878244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Amira Ibrahim, Geeta Prasad, Eric S Kilpatrick, Timothy J Morris
{"title":"A case of autoimmune hepatitis associated with the PCSK9 inhibitor alirocumab.","authors":"Amira Ibrahim, Geeta Prasad, Eric S Kilpatrick, Timothy J Morris","doi":"10.1177/00045632241269657","DOIUrl":"10.1177/00045632241269657","url":null,"abstract":"<p><p>This is a case of a 61-year-old lady who presented to the lipid clinic with possible familial hypercholesterolaemia (Simon Broome Criteria). She was commenced on atorvastatin; however, 4 weeks later, she developed hepatitis, and therefore her atorvastatin was discontinued. Following that, her liver function tests normalized, and she was diagnosed with statin-induced hepatitis. Three years later, she was seen again in the lipid clinic with an uncontrolled lipid profile, and she was commenced on alirocumab, a Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) inhibitor. A few days later, she developed hepatitis, and subsequently, the alirocumab was discontinued. She underwent a liver biopsy, which confirmed that she had Autoimmune Hepatitis (AIH) with presumed superimposed drug injury. This is the first reported case of autoimmune hepatitis associated with alirocumab.</p>","PeriodicalId":8005,"journal":{"name":"Annals of Clinical Biochemistry","volume":" ","pages":"45632241269657"},"PeriodicalIF":2.1,"publicationDate":"2024-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141888294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Plasma cell-free DNA in patients with acute promyelocytic leukaemia treated with arsenic trioxide.","authors":"Junko Fujihara, Naoki Nishimoto, Haruo Takeshita","doi":"10.1177/00045632231216596","DOIUrl":"10.1177/00045632231216596","url":null,"abstract":"<p><strong>Background: </strong>Cell-free DNA (cfDNA) is free DNA found in circulating blood that originates from apoptosis or necrosis, and elevated cfDNA concentrations have been reported in cancers and other diseases.</p><p><strong>Methods: </strong>In this study, the concentrations and fragment distributions of plasma cfDNA were preliminary investigated in elderly (<i>n</i> = 1) and paediatric (<i>n</i> = 1) patients with acute promyelocytic leukaemia (APL) treated with arsenic trioxide (ATO).</p><p><strong>Results: </strong>A slight increase in cfDNA concentrations was observed in the APL patients compared with healthy controls. The change in plasma cfDNA concentrations corresponded to the change in plasma arsenic concentrations during ATO treatment. The fragment distribution pattern did not differ before and during treatment. Three ladder fragments were observed in part of the cfDNA in the second consolidation therapy in an elderly APL patient and the first consolidation therapy of a paediatric APL patient, while two fragments were observed in all other treatment periods. Moreover, APL-related gene mutations were successfully genotyped from plasma cfDNA by using polymerase chain reaction-based methods and these results are consistent with those from leukocytes.</p><p><strong>Conclusion: </strong>This study is the first to report the concentrations and fragment patterns of cfDNA from APL patients treated with ATO. The results suggested that plasma cfDNA concentration in APL patients increased with ATO treatment and that cfDNA is released mainly via neutrophil extracellular traps (and/or necrosis) in addition to apoptosis. To confirm whether cfDNA concentrations and fragment patterns can be used as a biomarker for APL treated with ATO, further accumulative data are needed.</p>","PeriodicalId":8005,"journal":{"name":"Annals of Clinical Biochemistry","volume":" ","pages":"248-254"},"PeriodicalIF":2.1,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72013209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nicholas Armfield, Bernhard Frank, Carrie Chadwick
{"title":"A rapid, sensitive method for clinical monitoring of ketamine and norketamine by ultra-high-performance reverse-phase liquid chromatography tandem mass spectrometry.","authors":"Nicholas Armfield, Bernhard Frank, Carrie Chadwick","doi":"10.1177/00045632231224215","DOIUrl":"10.1177/00045632231224215","url":null,"abstract":"<p><strong>Background: </strong>Ketamine is an NMDAR antagonist with aggregating use across many areas of medicine. P450 enzymes heavily metabolise ketamine, where norketamine is a first pass formed metabolite following initial N-demethylation. Serum ketamine monitoring is becoming increasingly important, requiring a sensitive method with a robust lower limit of quantitation.</p><p><strong>Methods: </strong>Samples were prepared using protein precipitation or solid phase extraction. Ion suppression was investigated to optimise sample preparation technique, followed by reverse-phase chromatography coupled with tandem mass spectrometry to analyse extractions using a Waters Xevo TQ-S Micro and associated Acquity chromatography systems. Performance characteristics were analysed to validate the assay.</p><p><strong>Results: </strong>Ketamine and norketamine retention times were 1.28 and 1.23 min, respectively. Ketamine and norketamine precursor ions fragmented into 2 distinguishable product ions (238.14 > 207.18/125.06 and 224.1 > 178.96/124.86). Performance characteristics include an assay recovery of 103.7% (ketamine) and 96.3% (norketamine), lower limit of quantitation 36.2 µg/L (ketamine) and 38.9 µg/L (norketamine), and intra-assay imprecision ≤ 7.04% on average.</p><p><strong>Conclusions: </strong>A robust and reproducible assay with limited sample preparation has been designed and validated. The linearity of the assay covers all ranges of interest reported in the literature. Ion suppression was clearly reduced via use of solid phase extraction. The method will form the basis of ketamine monitoring and providing valuable patient information on tolerance and metabolism.</p>","PeriodicalId":8005,"journal":{"name":"Annals of Clinical Biochemistry","volume":" ","pages":"309-318"},"PeriodicalIF":2.1,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138797176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Determination and verification of reference intervals of serum immunoglobulin G at birth.","authors":"Toshihiko Ikuta, Sota Iwatani, Seiji Yoshimoto","doi":"10.1177/00045632231225326","DOIUrl":"10.1177/00045632231225326","url":null,"abstract":"<p><strong>Background: </strong>To accurately assess hypogammaglobulinemia at birth, it is essential to determine the reference intervals of serum immunoglobulin (IgG) levels in newborns. In the present study, we determined the gestational age (GA)-/birth weight (BW)-dependent percentile-based reference intervals of serum IgG levels and converted them into simple formulas for practical use.</p><p><strong>Methods: </strong>Serum IgG levels were measured in cord blood from 2902 newborns delivered at 22 to 41 weeks of GA or 264 to 4642 g of BW after exclusion of those with congenital disorders. Linear regression analysis was used to correlate GA and UC-IgG levels and BW and UC-IgG levels. After calculation of the percentile values of UC-IgG levels for each GA or BW, the distributions were approximated by the least-squares method. Fitness was evaluated by the coefficient of determination (<i>R</i><sup><i>2</i></sup>).</p><p><strong>Results: </strong>Significant positive correlations were found both between GA and UC-IgG levels (<i>r</i><sub><i>s</i></sub> = 0.790, <i>P</i> < 0.001) and BW and UC-IgG levels (<i>r</i><sub><i>s</i></sub> = 0.626, <i>P</i> < 0.001). The distribution of the 5%ile of UC-IgG levels (Y) by GA or BW (X) was approximated as a straight line (Y = 37.5 *X - 775.8; Y = 0.161 *X + 95.34, respectively). The fitness was stronger in the GA-derived formula than the BW-derived formula (<i>R</i><sup><i>2</i></sup> = 0.973 vs 0.913).</p><p><strong>Conclusions: </strong>We established GA-/BW-dependent reference percentile-based intervals for serum IgG levels using cord blood from 2902 newborns without congenital disorders. Using GA-dependent reference intervals may be useful for assessing hypogammaglobulinemia at birth.</p>","PeriodicalId":8005,"journal":{"name":"Annals of Clinical Biochemistry","volume":" ","pages":"319-326"},"PeriodicalIF":2.1,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138884001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Interferences in immunoassay: An estimate based on 'real-world' experience.","authors":"Ruggero Dittadi","doi":"10.1177/00045632241240306","DOIUrl":"10.1177/00045632241240306","url":null,"abstract":"","PeriodicalId":8005,"journal":{"name":"Annals of Clinical Biochemistry","volume":" ","pages":"327-328"},"PeriodicalIF":2.1,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140142675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marina Giralt, Noelia Díaz-Troyano, Immaculada Comas, Albert Blanco, Laura Conesa, Manel Mendoza, Carles Zafon, María Goya, Roser Ferrer
{"title":"Reference ranges of thyroid hormones during the first trimester in Catalan women using the Atellica<sup>®</sup> IM Solution Immunoassay Analyzer.","authors":"Marina Giralt, Noelia Díaz-Troyano, Immaculada Comas, Albert Blanco, Laura Conesa, Manel Mendoza, Carles Zafon, María Goya, Roser Ferrer","doi":"10.1177/00045632231219387","DOIUrl":"10.1177/00045632231219387","url":null,"abstract":"<p><strong>Background: </strong>Gestational hypothyroidism has been shown to be associated with adverse pregnancy outcomes as well as adverse outcomes for the child. Thyroid hormones concentrations change in gestation, especially within the first trimester, so the results of thyroid function test often are outside non-pregnant reference ranges. The objective of this study was to establish the first trimester reference ranges for thyroid stimulating hormone (TSH) and free thyroxine (FT4) for pregnant women in Barcelona (Spain).</p><p><strong>Methods: </strong>It was a prospective study in which 673 women were recruited during their first trimester of gestation (8-13 weeks). Serum TSH, FT4 and antithyroid peroxidase antibodies (TPOAb) were measured with Atellica<sup>®</sup> IM 1600 (Siemens Healthineers). After excluding 418 women, the reference ranges for TSH and FT4 were calculated by the 2.5th and 97.5th percentiles. Potential variables examined in this study were age, body mass index (BMI), ethnicity, iodine supplementation and smoking habit.</p><p><strong>Results: </strong>The reference ranges established on the Atellica<sup>®</sup> IM 1600 for the first trimester pregnancy in our population were 0.111 to 4.291 mIU/L for TSH and 11.45 to 17.76 pmol/L for FT4. No significant differences were found in thyroid hormones concentrations regarding maternal age (≤30 years vs >30 years) (<i>p</i> = .117), iodine supplementation (<i>p</i> = .683) and smoking habit (<i>p</i> = .363). The prevalence of TPOAb was estimated at 10.0%.</p><p><strong>Conclusions: </strong>We found that in our local population, the optimal TSH upper reference limit in the first trimester of gestation was 4.3 mIU/L, similar to that proposed by de ATA-2017 guideline (4.0 mIU/L).</p>","PeriodicalId":8005,"journal":{"name":"Annals of Clinical Biochemistry","volume":" ","pages":"284-290"},"PeriodicalIF":2.1,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138298179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}