Pub Date : 2025-10-27DOI: 10.1177/00045632251395579
Emma Crossley, Jonathan A Silversides, Cecilia M O'Kane, Paul K Hamilton
Proprotein Convertase Subtilisin-Kexin type 9 (PCSK9) is a key regulator of lipid metabolism, binding to the low-density lipoprotein receptor (LDLR) on the cell surface and preventing its recycling, thereby reducing clearance of LDL cholesterol (LDLc) from the circulation. For this reason, it constitutes an alternative therapeutic target for the control of hypercholesterolaemia, with the development of monoclonal antibodies against PCSK9 occurring within 12 years of the protein's discovery. Recent research has also suggested an inflammatory role played by PCSK9, with elevated plasma levels identified in critical illnesses such as sepsis and Acute Respiratory Distress Syndrome, where PCSK9 is thought to reduce bacterial endotoxin clearance and may exacerbate inflammation. Further work is required in order to clarify the exact role played by PCSK9 in extra-hepatic tissues, and the potential benefits of its pharmacological inhibition.
Proprotein Convertase Subtilisin-Kexin type 9 (PCSK9)是脂质代谢的关键调节因子,与细胞表面的低密度脂蛋白受体(LDLR)结合并阻止其再循环,从而减少LDL胆固醇(LDLc)从循环中的清除。由于这个原因,它构成了控制高胆固醇血症的另一种治疗靶点,在发现PCSK9蛋白的12年内,针对PCSK9的单克隆抗体的发展。最近的研究还表明PCSK9在炎症中起作用,在脓毒症和急性呼吸窘迫综合征等危重疾病中发现PCSK9的血浆水平升高,PCSK9被认为会减少细菌内毒素的清除,并可能加剧炎症。为了阐明PCSK9在肝外组织中的确切作用及其药理抑制的潜在益处,还需要进一步的工作。
{"title":"PCSK9 in critical illness - It's not all about lipids.","authors":"Emma Crossley, Jonathan A Silversides, Cecilia M O'Kane, Paul K Hamilton","doi":"10.1177/00045632251395579","DOIUrl":"10.1177/00045632251395579","url":null,"abstract":"<p><p>Proprotein Convertase Subtilisin-Kexin type 9 (PCSK9) is a key regulator of lipid metabolism, binding to the low-density lipoprotein receptor (LDLR) on the cell surface and preventing its recycling, thereby reducing clearance of LDL cholesterol (LDLc) from the circulation. For this reason, it constitutes an alternative therapeutic target for the control of hypercholesterolaemia, with the development of monoclonal antibodies against PCSK9 occurring within 12 years of the protein's discovery. Recent research has also suggested an inflammatory role played by PCSK9, with elevated plasma levels identified in critical illnesses such as sepsis and Acute Respiratory Distress Syndrome, where PCSK9 is thought to reduce bacterial endotoxin clearance and may exacerbate inflammation. Further work is required in order to clarify the exact role played by PCSK9 in extra-hepatic tissues, and the potential benefits of its pharmacological inhibition.</p>","PeriodicalId":8005,"journal":{"name":"Annals of Clinical Biochemistry","volume":" ","pages":"45632251395579"},"PeriodicalIF":1.0,"publicationDate":"2025-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145375893","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}
Pub Date : 2025-10-17DOI: 10.1177/00045632251388544
Michael J Murphy
{"title":"Blood hydrogen ion concentration: What purpose is served by expressing it as the inverse logarithm (pH)?","authors":"Michael J Murphy","doi":"10.1177/00045632251388544","DOIUrl":"https://doi.org/10.1177/00045632251388544","url":null,"abstract":"","PeriodicalId":8005,"journal":{"name":"Annals of Clinical Biochemistry","volume":" ","pages":"45632251388544"},"PeriodicalIF":1.0,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145306686","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}
Pub Date : 2025-10-14DOI: 10.1177/00045632251391759
R J Shorten, A Sanders, M Farley, S Josse, S Shafiq, C Harris, A Clegg, J Hill
IntroductionThe climate crisis presents a complex and growing challenge for healthcare systems around the world. Healthcare systems can contribute to substantial global emissions, with the UK's National Health Service (NHS) alone responsible for 4%-5% of the country's total carbon footprint. A wide range of clinical disciplines have already begun to assess and design interventions to tackle this issue. However, clinical and diagnostic laboratories remain underexplored.AimsWhat studies have been undertaken to assess and improve the environmental impact of clinical laboratories?MethodsThis scoping review undertook a multi-database search from date of inception to 5th February 2024. All primary studies that assessed the environmental outcomes of clinical laboratories were included. Studies were screened and data extracted by one reviewer with a 10% verification process at each stage. Studies were assessed based upon year of publication, geographical region, interconnectivity and area and type of clinical laboratory or test.FindingsThere has been some longstanding interest in understanding the environmental impact of clinical laboratories, and this field of investigation has gained popularity within the scholarly community in the last decade. Despite this recent increase in popularity there is a relatively limited number of intervention studies aimed at improving sustainability within clinical laboratories. Most research in this area originates from the United States, United Kingdom, and Australia, although the topic appears to be of global scholarly interest. There is limited interconnectivity of studies included in this review. Studies in this field have primarily been conducted at the clinical laboratory level, with a focus on quantifying waste in kilograms, measuring carbon dioxide equivalent (CO2e) emissions, and categorizing laboratory waste by type. To a lesser degree these outcomes have been assessed for specific clinical tests. Across both clinical laboratory and specific test assessments there is notable heterogeneity in both methods used, and areas explored.DiscussionWhile this scoping review highlights a growing interest and awareness in this important field, the diversity of reported outcomes and the limited interconnectivity of studies indicate that it remains a developing area. The lack of consensus in methodologies and outcome measures suggests that establishing a baseline analysis remains a distant goal. Ideally, future efforts should prioritize improving the assessment of individual laboratory tests, fostering greater standardization, and enhancing repeatability to strengthen the reliability of environmental impact evaluations.
{"title":"Environmental sustainability of clinical laboratories: A scoping review.","authors":"R J Shorten, A Sanders, M Farley, S Josse, S Shafiq, C Harris, A Clegg, J Hill","doi":"10.1177/00045632251391759","DOIUrl":"https://doi.org/10.1177/00045632251391759","url":null,"abstract":"<p><p>IntroductionThe climate crisis presents a complex and growing challenge for healthcare systems around the world. Healthcare systems can contribute to substantial global emissions, with the UK's National Health Service (NHS) alone responsible for 4%-5% of the country's total carbon footprint. A wide range of clinical disciplines have already begun to assess and design interventions to tackle this issue. However, clinical and diagnostic laboratories remain underexplored.AimsWhat studies have been undertaken to assess and improve the environmental impact of clinical laboratories?MethodsThis scoping review undertook a multi-database search from date of inception to 5th February 2024. All primary studies that assessed the environmental outcomes of clinical laboratories were included. Studies were screened and data extracted by one reviewer with a 10% verification process at each stage. Studies were assessed based upon year of publication, geographical region, interconnectivity and area and type of clinical laboratory or test.FindingsThere has been some longstanding interest in understanding the environmental impact of clinical laboratories, and this field of investigation has gained popularity within the scholarly community in the last decade. Despite this recent increase in popularity there is a relatively limited number of intervention studies aimed at improving sustainability within clinical laboratories. Most research in this area originates from the United States, United Kingdom, and Australia, although the topic appears to be of global scholarly interest. There is limited interconnectivity of studies included in this review. Studies in this field have primarily been conducted at the clinical laboratory level, with a focus on quantifying waste in kilograms, measuring carbon dioxide equivalent (CO<sub>2</sub>e) emissions, and categorizing laboratory waste by type. To a lesser degree these outcomes have been assessed for specific clinical tests. Across both clinical laboratory and specific test assessments there is notable heterogeneity in both methods used, and areas explored.DiscussionWhile this scoping review highlights a growing interest and awareness in this important field, the diversity of reported outcomes and the limited interconnectivity of studies indicate that it remains a developing area. The lack of consensus in methodologies and outcome measures suggests that establishing a baseline analysis remains a distant goal. Ideally, future efforts should prioritize improving the assessment of individual laboratory tests, fostering greater standardization, and enhancing repeatability to strengthen the reliability of environmental impact evaluations.</p>","PeriodicalId":8005,"journal":{"name":"Annals of Clinical Biochemistry","volume":" ","pages":"45632251391759"},"PeriodicalIF":1.0,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145421092","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}
Pub Date : 2025-10-02DOI: 10.1177/00045632251388531
Amy R Frank, Susan Johnston
The aldosterone renin ratio (ARR) is used as a screening test for primary aldosteronism (PA), and this requires measurement of both aldosterone and renin. Aldosterone is usually measured using immunoassay or liquid chromatography-mass spectrometry techniques. Antihypertensive medications should be discontinued prior to screening as they can interfere with interpretation of results. Indapamide is a thiazide-like diuretic commonly used in the treatment of hypertension. NICE guidance (NG136 2019) recommends the use of indapamide over more conventional thiazide diuretics. Indapamide has been noted to cause interference in a liquid chromatography-mass spectrometry method by interfering in the measurement of aldosterone-d4 internal standard. This leads to falsely increased concentrations of aldosterone which can lead to unnecessary further investigations.
{"title":"Indapamide interference in liquid chromatography-tandem mass spectrometry aldosterone assay.","authors":"Amy R Frank, Susan Johnston","doi":"10.1177/00045632251388531","DOIUrl":"10.1177/00045632251388531","url":null,"abstract":"<p><p>The aldosterone renin ratio (ARR) is used as a screening test for primary aldosteronism (PA), and this requires measurement of both aldosterone and renin. Aldosterone is usually measured using immunoassay or liquid chromatography-mass spectrometry techniques. Antihypertensive medications should be discontinued prior to screening as they can interfere with interpretation of results. Indapamide is a thiazide-like diuretic commonly used in the treatment of hypertension. NICE guidance (NG136 2019) recommends the use of indapamide over more conventional thiazide diuretics. Indapamide has been noted to cause interference in a liquid chromatography-mass spectrometry method by interfering in the measurement of aldosterone-d4 internal standard. This leads to falsely increased concentrations of aldosterone which can lead to unnecessary further investigations.</p>","PeriodicalId":8005,"journal":{"name":"Annals of Clinical Biochemistry","volume":" ","pages":"45632251388531"},"PeriodicalIF":1.0,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145211424","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}
Pub Date : 2025-09-15DOI: 10.1177/00045632251383402
Michelle De Bruyn, Matthias Cuykx
BackgroundMultiple myeloma patients may present with spuriously elevated serum phosphate levels resulting from the presence of paraproteins interfering in the phosphomolybdate UV assay. If this phenomenon is not recognized, patients possibly receive unnecessary treatments. This short report highlights the existence of paraprotein-related pseudohyperphosphatemia, and aims to provide accessible solutions to eliminate this interference.Material and MethodsIn a patient known with IgG multiple myeloma and unexplained hyperphosphatemia, the correlation between serum phosphate levels (phosphomolybdate UV assay) and IgG concentrations (immunoturbidimetry) was evaluated. To investigate the effect of the paraprotein on phosphate levels, phosphate was measured in one serum sample before and after protein removal by either dilution, protein precipitation with sulfosalicylic acid or zinc sulphate, or ultrafiltration.ResultsA patient with multiple myeloma presented with an unexplained hyperphosphatemia which correlated positively with serum IgG concentrations. As serum dilution normalized the phosphate level, it was hypothesized that precipitation of the paraprotein during the assay reaction interfered with the measurement and resulted in pseudohyperphosphatemia. Protein removal by precipitation with sulfosalicylic acid or zinc sulphate efficiently reduced the IgG level below the detection limit but did not result in a reliable phosphate measurement. Successful removal of proteins and a serum phosphate level that matched the patient's other biochemistry parameters and clinical condition were obtained by ultrafiltration.ConclusionParaproteins can interfere with the reaction components in the phosphomolybdate UV assay and result in pseudohyperphosphatemia. If the presence of this phenomenon is established, a reliable phosphate concentration can be obtained after ultrafiltration of the sample.
{"title":"Pseudohyperphosphatemia in multiple myeloma: Removal of interfering paraproteins.","authors":"Michelle De Bruyn, Matthias Cuykx","doi":"10.1177/00045632251383402","DOIUrl":"10.1177/00045632251383402","url":null,"abstract":"<p><p>BackgroundMultiple myeloma patients may present with spuriously elevated serum phosphate levels resulting from the presence of paraproteins interfering in the phosphomolybdate UV assay. If this phenomenon is not recognized, patients possibly receive unnecessary treatments. This short report highlights the existence of paraprotein-related pseudohyperphosphatemia, and aims to provide accessible solutions to eliminate this interference.Material and MethodsIn a patient known with IgG multiple myeloma and unexplained hyperphosphatemia, the correlation between serum phosphate levels (phosphomolybdate UV assay) and IgG concentrations (immunoturbidimetry) was evaluated. To investigate the effect of the paraprotein on phosphate levels, phosphate was measured in one serum sample before and after protein removal by either dilution, protein precipitation with sulfosalicylic acid or zinc sulphate, or ultrafiltration.ResultsA patient with multiple myeloma presented with an unexplained hyperphosphatemia which correlated positively with serum IgG concentrations. As serum dilution normalized the phosphate level, it was hypothesized that precipitation of the paraprotein during the assay reaction interfered with the measurement and resulted in pseudohyperphosphatemia. Protein removal by precipitation with sulfosalicylic acid or zinc sulphate efficiently reduced the IgG level below the detection limit but did not result in a reliable phosphate measurement. Successful removal of proteins and a serum phosphate level that matched the patient's other biochemistry parameters and clinical condition were obtained by ultrafiltration.ConclusionParaproteins can interfere with the reaction components in the phosphomolybdate UV assay and result in pseudohyperphosphatemia. If the presence of this phenomenon is established, a reliable phosphate concentration can be obtained after ultrafiltration of the sample.</p>","PeriodicalId":8005,"journal":{"name":"Annals of Clinical Biochemistry","volume":" ","pages":"45632251383402"},"PeriodicalIF":1.0,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145068969","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}
IntroductionShort Synacthen Test (SST), a standard diagnostic test to confirm Adrenal insufficiency (AI), involves substantial expenses.ObjectivesThis study aimed to assess the predictive value of baseline Cortisol levels for SST outcomes and establish baseline cut-off levels for confirming AI to minimize the necessity of SST.MethodsAll SST data from 2019 to 2024 at National Hospital Kandy, Sri Lanka, were obtained retrospectively. A peak Cortisol ≥500 nmol/L at 30 or 60-min post-SST was considered as a normal adrenal reserve, whereas failure indicated AI. Pearson's correlation and Logistic Regression analysis assessed baseline and post-SST Cortisol at 30 and 60-min. A 2 × 2 table assesses test agreement. Receiver operating characteristic (ROC) curve analysis evaluated the SST outcomes at 30 and 60-min separately assessing sensitivity, specificity, and area under the curve (AUC).ResultsA total of 307 patients were enrolled, and 63.19% exhibited a failed SST response. Baseline Cortisol positively correlated with post-SST Cortisol at 30-min (r = 0.74, P < .05) and 60-min (r = 0.68, P < .05) with a good AUC for both 30 min (AUC = 0.855) and 60 min (AUC = 0.829). Baseline Cortisol demonstrated the higher odds ratio per unit (OR = 1.015 per nmol/L), indicating greater sensitivity to small changes. ROC curves were utilized to derive cut-offs for baseline Cortisol levels predicting SST outcomes. At 30-min, baseline Cortisol <135 nmol/L suggests AI (100% sensitivity, 44% specificity), and >381.5 nmol/L indicates normal adrenal reserve (100% specificity, 21.8% sensitivity). Similarly at 60-min, baseline Cortisol <75.3 nmol/L suggests AI (100% sensitivity, 19.7% specificity), and >357 nmol/L indicates normal adrenal reserve (100% specificity, 16.8% sensitivity).ConclusionsApplying these cut-offs could avoid 41.69% (30 min) or 19% (60 min) of total SSTs, excluding AI and normal adrenal reserve. 30-min SST Cortisol correlates more strongly with baseline Cortisol, showing a higher r-value, higher OR and AUC. Hence, 30-min provides better cut-offs with higher sensitivity and specificity minimizing need for SST. Patients with baseline Cortisol between 135 and 381 nmol/L can undergo SST with only a 30-min Cortisol measurement.
{"title":"Predicting the outcome of short Synacthen test based on baseline cortisol levels: A single-centered retrospective cohort study at a tertiary care hospital in Sri Lanka.","authors":"Premadasa T, Samarathunga Epa, Sujith Em, Shameela Nmf, Basnayaka Bmks, Antonypillai Cn, Jayawardana Rdp","doi":"10.1177/00045632251383417","DOIUrl":"10.1177/00045632251383417","url":null,"abstract":"<p><p>IntroductionShort Synacthen Test (SST), a standard diagnostic test to confirm Adrenal insufficiency (AI), involves substantial expenses.ObjectivesThis study aimed to assess the predictive value of baseline Cortisol levels for SST outcomes and establish baseline cut-off levels for confirming AI to minimize the necessity of SST.MethodsAll SST data from 2019 to 2024 at National Hospital Kandy, Sri Lanka, were obtained retrospectively. A peak Cortisol ≥500 nmol/L at 30 or 60-min post-SST was considered as a normal adrenal reserve, whereas failure indicated AI. Pearson's correlation and Logistic Regression analysis assessed baseline and post-SST Cortisol at 30 and 60-min. A 2 × 2 table assesses test agreement. Receiver operating characteristic (ROC) curve analysis evaluated the SST outcomes at 30 and 60-min separately assessing sensitivity, specificity, and area under the curve (AUC).ResultsA total of 307 patients were enrolled, and 63.19% exhibited a failed SST response. Baseline Cortisol positively correlated with post-SST Cortisol at 30-min (r = 0.74, <i>P</i> < .05) and 60-min (r = 0.68, <i>P</i> < .05) with a good AUC for both 30 min (AUC = 0.855) and 60 min (AUC = 0.829). Baseline Cortisol demonstrated the higher odds ratio per unit (OR = 1.015 per nmol/L), indicating greater sensitivity to small changes. ROC curves were utilized to derive cut-offs for baseline Cortisol levels predicting SST outcomes. At 30-min, baseline Cortisol <135 nmol/L suggests AI (100% sensitivity, 44% specificity), and >381.5 nmol/L indicates normal adrenal reserve (100% specificity, 21.8% sensitivity). Similarly at 60-min, baseline Cortisol <75.3 nmol/L suggests AI (100% sensitivity, 19.7% specificity), and >357 nmol/L indicates normal adrenal reserve (100% specificity, 16.8% sensitivity).ConclusionsApplying these cut-offs could avoid 41.69% (30 min) or 19% (60 min) of total SSTs, excluding AI and normal adrenal reserve. 30-min SST Cortisol correlates more strongly with baseline Cortisol, showing a higher r-value, higher OR and AUC. Hence, 30-min provides better cut-offs with higher sensitivity and specificity minimizing need for SST. Patients with baseline Cortisol between 135 and 381 nmol/L can undergo SST with only a 30-min Cortisol measurement.</p>","PeriodicalId":8005,"journal":{"name":"Annals of Clinical Biochemistry","volume":" ","pages":"45632251383417"},"PeriodicalIF":1.0,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145068947","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}
Pub Date : 2025-09-15DOI: 10.1177/00045632251383404
Kristian Voss Bjerre, Helle Glud Binderup, Mads Nybo, Louise Helskov Jørgensen
BackgroundZinc deficiency is a global concern, particularly in low-income countries, but also among vulnerable groups in Western countries, such as children. Diagnosing mild or moderate zinc deficiency is however challenging because of nonspecific symptoms and due to circulating zinc showing only subtle changes, requiring high accuracy in measurement. Challenges to accurate measurement include variations from choice of analytical instrument, analysis performance, and preanalytical factors such as choice of sample matrices and delayed blood sample processing. This study aimed to examine the stability of zinc in plasma and serum, measured by the recommended inductively coupled plasma optical emission spectrometry (ICP-OES) method and a direct colourimetric assay on the fully automated Roche Cobas c702 analyzer.MethodsA total of 245 whole blood samples were stored at room temperature for 0-8 h after blood sampling, then centrifuged for 10 min at 2000 g (serum) or 5 min at 2650 g (plasma), frozen at -20°C, and analysed, respectively, on ICP-OES and Cobas, the latter with the colourimetric kit from Sentinel diagnostics.ResultsSerum zinc concentrations measured on Cobas and ICP-OES showed no statistically significant change up to 6 h and never exceeded acceptable limits. Plasma zinc concentrations increased steadily over time, exceeding acceptable limits after 6 h. There were statistically significant differences between zinc measurements on ICP-OES and Cobas in both serum and plasma.ConclusionsZinc is stable for at least 8 h in serum and up to 6 h in plasma when measured by either Sentinel diagnostic colourimetric method on Cobas or ICP-OES.
{"title":"Preanalytical stability of zinc in whole blood serum and plasma tubes as measured by ICP-OES and colourimetry.","authors":"Kristian Voss Bjerre, Helle Glud Binderup, Mads Nybo, Louise Helskov Jørgensen","doi":"10.1177/00045632251383404","DOIUrl":"10.1177/00045632251383404","url":null,"abstract":"<p><p>BackgroundZinc deficiency is a global concern, particularly in low-income countries, but also among vulnerable groups in Western countries, such as children. Diagnosing mild or moderate zinc deficiency is however challenging because of nonspecific symptoms and due to circulating zinc showing only subtle changes, requiring high accuracy in measurement. Challenges to accurate measurement include variations from choice of analytical instrument, analysis performance, and preanalytical factors such as choice of sample matrices and delayed blood sample processing. This study aimed to examine the stability of zinc in plasma and serum, measured by the recommended inductively coupled plasma optical emission spectrometry (ICP-OES) method and a direct colourimetric assay on the fully automated Roche Cobas c702 analyzer.MethodsA total of 245 whole blood samples were stored at room temperature for 0-8 h after blood sampling, then centrifuged for 10 min at 2000 g (serum) or 5 min at 2650 g (plasma), frozen at -20°C, and analysed, respectively, on ICP-OES and Cobas, the latter with the colourimetric kit from Sentinel diagnostics.ResultsSerum zinc concentrations measured on Cobas and ICP-OES showed no statistically significant change up to 6 h and never exceeded acceptable limits. Plasma zinc concentrations increased steadily over time, exceeding acceptable limits after 6 h. There were statistically significant differences between zinc measurements on ICP-OES and Cobas in both serum and plasma.ConclusionsZinc is stable for at least 8 h in serum and up to 6 h in plasma when measured by either Sentinel diagnostic colourimetric method on Cobas or ICP-OES.</p>","PeriodicalId":8005,"journal":{"name":"Annals of Clinical Biochemistry","volume":" ","pages":"45632251383404"},"PeriodicalIF":1.0,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145068924","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}
BackgroundThiopurine S-methyltransferase (TPMT) is crucial for metabolizing thiopurine drugs. This study aimed to establish the cutoff values for TPMT activity in a cohort of healthy individuals. We defined normal TPMT activity ranges and identified clinically applicable thresholds to distinguish individuals with normal TPMT function from those with reduced or deficient activity.MethodsA total of 457 participants, including 207 children and 250 healthy adults without prior thiopurine drug exposure, were enrolled. TPMT activity was measured and common defective genetic variants (TPMT*3A, TPMT*3B, and TPMT*3C) were detected. To determine TPMT activity cutoff values and maximize sensitivity and specificity, receiver operating characteristic curve analysis was employed.ResultsThe cutoff values for TPMT activity in children were ≥52.9 nmol 6-MMP/g Hb/h for persons of the wild type and <52.9 nmol 6-MMP/g Hb/h for individuals who were heterozygous. In adults, the cutoff values were ≥44.6, 31.58-44.5, and <31.58 nmol 6-MMP/g Hb/h for wild-type, heterozygous, and compound heterozygous individuals, respectively. The sensitivity and specificity were 79.29% and 100% in children, whereas, in adults, they were 61.86% and 78.57%, 38.46% and 64.73%, and 100% and 95.98% in the wild-type, heterozygous, and compound heterozygous, respectively.ConclusionsIdentifying TPMT activity cutoff values is crucial for managing patients receiving thiopurine therapy, especially in Thailand. This approach allows for personalized treatment plans and minimizes the risk of adverse drug reactions. Since TPMT activity cutoff values can differ by population and testing methods, it is important to establish specific cutoff values locally.
{"title":"Thiopurine S-methyltransferase (TPMT) activity cutoffs in the Thai population.","authors":"Pimonpan Jinda, Pimpun Kitpoka, Wimol Thienphopirak, Suwat Chiawchan, Santirhat Prommas, Rattanaporn Sukprasong, Jiratha Rachanakul, Supaporn Wiwattanakul, Orapa Suteerojntrakool, Chansuda Bongsebandhu-Phubhakdi, Therdpong Tempark, Sittiphong Hunthai, Apichaya Puangpetch","doi":"10.1177/00045632251381058","DOIUrl":"10.1177/00045632251381058","url":null,"abstract":"<p><p>BackgroundThiopurine S-methyltransferase (TPMT) is crucial for metabolizing thiopurine drugs. This study aimed to establish the cutoff values for TPMT activity in a cohort of healthy individuals. We defined normal TPMT activity ranges and identified clinically applicable thresholds to distinguish individuals with normal TPMT function from those with reduced or deficient activity.MethodsA total of 457 participants, including 207 children and 250 healthy adults without prior thiopurine drug exposure, were enrolled. TPMT activity was measured and common defective genetic variants (<i>TPMT*3A, TPMT*3B,</i> and <i>TPMT*3C</i>) were detected. To determine TPMT activity cutoff values and maximize sensitivity and specificity, receiver operating characteristic curve analysis was employed.ResultsThe cutoff values for TPMT activity in children were ≥52.9 nmol 6-MMP/g Hb/h for persons of the wild type and <52.9 nmol 6-MMP/g Hb/h for individuals who were heterozygous. In adults, the cutoff values were ≥44.6, 31.58-44.5, and <31.58 nmol 6-MMP/g Hb/h for wild-type, heterozygous, and compound heterozygous individuals, respectively. The sensitivity and specificity were 79.29% and 100% in children, whereas, in adults, they were 61.86% and 78.57%, 38.46% and 64.73%, and 100% and 95.98% in the wild-type, heterozygous, and compound heterozygous, respectively.ConclusionsIdentifying TPMT activity cutoff values is crucial for managing patients receiving thiopurine therapy, especially in Thailand. This approach allows for personalized treatment plans and minimizes the risk of adverse drug reactions. Since TPMT activity cutoff values can differ by population and testing methods, it is important to establish specific cutoff values locally.</p>","PeriodicalId":8005,"journal":{"name":"Annals of Clinical Biochemistry","volume":" ","pages":"45632251381058"},"PeriodicalIF":1.0,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145013646","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}
Pub Date : 2025-09-01Epub Date: 2025-02-28DOI: 10.1177/00045632251326483
Jemima M Curran, Katherine Onions, Jessica Watts, Arnab Rana, Emma Hughes, James Allison, Jamie G Cooper
Background: Patients with features of mild traumatic brain injury (mTBI) frequently present to the emergency department (ED) and often meet recognized criteria for CT head imaging. Observational studies suggest that use of a tandem ubiquitin C-terminal hydrolase-L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) brain biomarker test may significantly reduce need for CT scanning in this population, though data on patient flow are lacking.Methods: A prospective cohort evaluation of adult ED patients (≥18 years) with features of mTBI who met criteria for CT imaging within 12 hours of head injury had blood drawn for laboratory UCH-L1/GFAP testing. The diagnostic performance for CT-evident brain injury was expressed through the calculation of sensitivity and negative predictive value (NPV) with 95% confidence intervals (95% CI). Times from venepuncture to biomarker result availability, and from CT request to result availability were compared.Results: A laboratory UCH-L1/GFAP test identified 21 of 89 (24%) patients as low-risk for CT-evident TBI with a sensitivity of 100% (95% CI 76%-100%) and NPV of 100% (95% CI 85%-100%). The median time to biomarker and CT results were 88 minutes and 89 minutes, respectively. However, 68 (76%) of patients with a positive biomarker test would then progress to CT imaging, significantly prolonging ED length of stay, and restricting usefulness in adoption into clinical pathways.Conclusion: Evaluation of a laboratory UCH-L1/GFAP test in a UK population with mTBI demonstrates excellent performance for the exclusion of CT-evident brain injury. However, adoption into clinical patient pathways is likely to be limited until the test is available in whole blood at the point-of-care, and evidence of safe rationalization of CT imaging confirmed in randomized studies.
具有轻度创伤性脑损伤(mTBI)特征的患者经常出现在急诊科(ED),并且通常符合公认的CT头部成像标准。观察性研究表明,使用串联泛素c端水解酶- l1 (UCH-L1)和胶质纤维酸性蛋白(GFAP)脑生物标志物测试可以显著减少这一人群对CT扫描的需求,尽管缺乏患者流量的数据。在一项针对英国mTBI患者的前瞻性评估中,实验室UCH-L1/GFAP检测确定89例(24%)患者中有21例(24%)为ct明显TBI低风险患者,其敏感性为100% (95% CI 76-100%), NPV为100% (95% CI 85-100%)。从静脉切除获得生物标志物结果的中位时间为88分钟,与从CT请求到报告的时间(89分钟)相似。然而,这68例(76%)生物标志物阳性的患者都需要后续的CT成像,这大大延长了ED的住院时间,使其难以纳入临床途径。在医疗点测量全血UCH-L1/GFAP的平台的可用性可能会在未来规避这些问题,并允许在不影响ED患者工作流程的情况下在这一人群中安全合理地进行CT成像。
{"title":"Ubiquitin C-terminal hydrolase-L1 and glial fibrillary acidic protein tandem brain biomarker test in the prediction of CT evident brain injury: A prospective evaluation in the emergency department.","authors":"Jemima M Curran, Katherine Onions, Jessica Watts, Arnab Rana, Emma Hughes, James Allison, Jamie G Cooper","doi":"10.1177/00045632251326483","DOIUrl":"10.1177/00045632251326483","url":null,"abstract":"<p><p><b>Background:</b> Patients with features of mild traumatic brain injury (mTBI) frequently present to the emergency department (ED) and often meet recognized criteria for CT head imaging. Observational studies suggest that use of a tandem ubiquitin C-terminal hydrolase-L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) brain biomarker test may significantly reduce need for CT scanning in this population, though data on patient flow are lacking.<b>Methods:</b> A prospective cohort evaluation of adult ED patients (≥18 years) with features of mTBI who met criteria for CT imaging within 12 hours of head injury had blood drawn for laboratory UCH-L1/GFAP testing. The diagnostic performance for CT-evident brain injury was expressed through the calculation of sensitivity and negative predictive value (NPV) with 95% confidence intervals (95% CI). Times from venepuncture to biomarker result availability, and from CT request to result availability were compared.<b>Results:</b> A laboratory UCH-L1/GFAP test identified 21 of 89 (24%) patients as low-risk for CT-evident TBI with a sensitivity of 100% (95% CI 76%-100%) and NPV of 100% (95% CI 85%-100%). The median time to biomarker and CT results were 88 minutes and 89 minutes, respectively. However, 68 (76%) of patients with a positive biomarker test would then progress to CT imaging, significantly prolonging ED length of stay, and restricting usefulness in adoption into clinical pathways.<b>Conclusion:</b> Evaluation of a laboratory UCH-L1/GFAP test in a UK population with mTBI demonstrates excellent performance for the exclusion of CT-evident brain injury. However, adoption into clinical patient pathways is likely to be limited until the test is available in whole blood at the point-of-care, and evidence of safe rationalization of CT imaging confirmed in randomized studies.</p>","PeriodicalId":8005,"journal":{"name":"Annals of Clinical Biochemistry","volume":" ","pages":"412-415"},"PeriodicalIF":1.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531189","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}
BackgroundThere have been no reports on blood glucose metres for measurements in a wide variety of infant patients, from very preterm infants to mature infants and from the early neonatal period onwards. In this study, we evaluated the accuracy of the Glutest Mint II, a point-of-care blood glucose metre, by comparing blood glucose levels measured by this device with those measured by a blood gas analyser in infants of all gestational ages and birth weights at a number of time points after birth.MethodsInfants aged 22 weeks and 0 days of gestation or older who were born at any of six tertiary neonatal intensive care units between March 2022 and January 2023 and needed blood glucose monitoring were enrolled. Samples were collected into capillary tubes when the physician determined that a blood glucose test was necessary and could be taken at any time after birth and any number of times from the same individual. Blood glucose was measured using a Glutest Mint II and then using a blood gas analyser.ResultsIn total, 2943 blood glucose points were measured in 285 infants. Blood glucose levels measured using the Glutest Mint II were significantly correlated with those measured using a blood gas analyser. Neonatal-specific parameters such as hematocrit and total serum bilirubin levels may not have an effect.ConclusionsThe Glutest Mint II device can measure blood glucose levels with very high accuracy in the range used in the neonatal setting, comparable to the blood gas analyser.
背景:目前还没有关于血糖仪用于各种婴儿患者测量的报道,从非常早产的婴儿到成熟的婴儿以及从新生儿早期开始。在这项研究中,我们评估了Glutest Mint II的准确性,这是一种即时护理血糖仪,通过比较该设备测量的血糖水平与血气分析仪在出生后多个时间点测量的所有胎龄和出生体重的婴儿的血糖水平。方法:纳入2022年3月至2023年1月期间在6个三级新生儿重症监护病房中出生并需要血糖监测的22周零0天或以上的婴儿。当医生确定有必要进行血糖测试时,将样本收集到毛细血管中,并且可以在出生后的任何时间和同一个体的任何次数进行血糖测试。血糖测量使用Glutest Mint II,然后使用血气分析仪。结果:285例婴儿共测得2943个血糖点。使用Glutest Mint II测量的血糖水平与使用血气分析仪测量的血糖水平显著相关。新生儿特异性参数,如红细胞压积和血清总胆红素水平可能没有影响。结论:Glutest Mint II设备可以在新生儿环境中以非常高的准确度测量血糖水平,与血气分析仪相当。
{"title":"A multicenter study comparing a point-of-care blood glucose metre with a blood gas analyser in infants by the Shikoku Neonatal Medical Research Group.","authors":"Toru Kuboi, Masashiro Sugino, Takaaki Sadamura, Nana Kawaguchi, Yoko Tadatomo, Kosei Takada, Natsumi Okamoto, Kiwako Miyamoto, Akiko Nakano, Noriko Miura, Yusei Nakata, Kenichi Suga, Masaaki Ota, Shinji Nakamura, Kosuke Koyano, Takashi Kusaka","doi":"10.1177/00045632251326460","DOIUrl":"10.1177/00045632251326460","url":null,"abstract":"<p><p>BackgroundThere have been no reports on blood glucose metres for measurements in a wide variety of infant patients, from very preterm infants to mature infants and from the early neonatal period onwards. In this study, we evaluated the accuracy of the Glutest Mint II, a point-of-care blood glucose metre, by comparing blood glucose levels measured by this device with those measured by a blood gas analyser in infants of all gestational ages and birth weights at a number of time points after birth.MethodsInfants aged 22 weeks and 0 days of gestation or older who were born at any of six tertiary neonatal intensive care units between March 2022 and January 2023 and needed blood glucose monitoring were enrolled. Samples were collected into capillary tubes when the physician determined that a blood glucose test was necessary and could be taken at any time after birth and any number of times from the same individual. Blood glucose was measured using a Glutest Mint II and then using a blood gas analyser.ResultsIn total, 2943 blood glucose points were measured in 285 infants. Blood glucose levels measured using the Glutest Mint II were significantly correlated with those measured using a blood gas analyser. Neonatal-specific parameters such as hematocrit and total serum bilirubin levels may not have an effect.ConclusionsThe Glutest Mint II device can measure blood glucose levels with very high accuracy in the range used in the neonatal setting, comparable to the blood gas analyser.</p>","PeriodicalId":8005,"journal":{"name":"Annals of Clinical Biochemistry","volume":" ","pages":"352-357"},"PeriodicalIF":1.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531188","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}