Pub Date : 2025-02-01DOI: 10.1080/10408363.2025.2453152
Abdurrahman Coskun, Irem Nur Savas, Ozge Can, Giuseppe Lippi
Monitoring individuals' laboratory data is essential for assessing their health status, evaluating the effectiveness of treatments, predicting disease prognosis and detecting subclinical conditions. Currently, monitoring is performed intermittently, measuring serum, plasma, whole blood, urine and occasionally other body fluids at predefined time intervals. The ideal monitoring approach entails continuous measurement of concentration and activity of biomolecules in all body fluids, including solid tissues. This can be achieved through the use of biosensors strategically placed at various locations on the human body where measurements are required for monitoring. High-tech wearable biosensors provide an ideal, noninvasive, and esthetically pleasing solution for monitoring individuals' laboratory data. However, despite significant advances in wearable biosensor technology, the measurement capacities and the number of different analytes that are continuously monitored in patients are not yet at the desired level. In this review, we conducted a literature search and examined: (i) an overview of the background of monitoring for personalized laboratory medicine, (ii) the body fluids and analytes used for monitoring individuals, (iii) the different types of biosensors and methods used for measuring the concentration and activity of biomolecules, and (iv) the statistical algorithms used for personalized data analysis and interpretation in monitoring and evaluation.
{"title":"From population-based to personalized laboratory medicine: continuous monitoring of individual laboratory data with wearable biosensors.","authors":"Abdurrahman Coskun, Irem Nur Savas, Ozge Can, Giuseppe Lippi","doi":"10.1080/10408363.2025.2453152","DOIUrl":"https://doi.org/10.1080/10408363.2025.2453152","url":null,"abstract":"<p><p>Monitoring individuals' laboratory data is essential for assessing their health status, evaluating the effectiveness of treatments, predicting disease prognosis and detecting subclinical conditions. Currently, monitoring is performed intermittently, measuring serum, plasma, whole blood, urine and occasionally other body fluids at predefined time intervals. The ideal monitoring approach entails continuous measurement of concentration and activity of biomolecules in all body fluids, including solid tissues. This can be achieved through the use of biosensors strategically placed at various locations on the human body where measurements are required for monitoring. High-tech wearable biosensors provide an ideal, noninvasive, and esthetically pleasing solution for monitoring individuals' laboratory data. However, despite significant advances in wearable biosensor technology, the measurement capacities and the number of different analytes that are continuously monitored in patients are not yet at the desired level. In this review, we conducted a literature search and examined: (i) an overview of the background of monitoring for personalized laboratory medicine, (ii) the body fluids and analytes used for monitoring individuals, (iii) the different types of biosensors and methods used for measuring the concentration and activity of biomolecules, and (iv) the statistical algorithms used for personalized data analysis and interpretation in monitoring and evaluation.</p>","PeriodicalId":10760,"journal":{"name":"Critical reviews in clinical laboratory sciences","volume":" ","pages":"1-30"},"PeriodicalIF":6.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01DOI: 10.1080/10408363.2024.2434562
Mauro Panteghini, Magdalena Krintus
Poor analytical quality may be the bane of medical use of laboratory tests, and the fight against excessive analytical variability presents a daily struggle. Laboratories should prioritize the perspectives and needs of their customers (the patients and healthcare personnel). Among them, comparability of results from the same patient sample when measured by different laboratories using different in vitro diagnostic (IVD) medical devices is a logical priority to avoid result misinterpretation and potential patient harm. Harmonization (standardization) of laboratory measurements can be achieved by establishing metrological traceability of the results on clinical samples to stated higher-order references and providing an estimate of the uncertainty of measurement (MU). This estimate should be based on an MU budget including all known MU contributions generated by the employed calibration hierarchy, which in turn should be validated against fit-for-purpose maximum allowable MU derived according to internationally recommended models. In this report, we review the available strategies for establishing, evaluating, and monitoring analytical quality, drawing on three decades experience in the field. We discuss the most important aspects that may influence obtaining and maintaining analytical standardization in laboratory medicine, and offer practical solutions aimed at educating all stakeholders for the achievement of harmonized laboratory results. To fully implement the recommended approaches, all involved parties-i.e. reference providers, IVD manufacturers, medical laboratories, and External Quality Assessment organizers-must agree on their importance and enhance their specific knowledge.
{"title":"Establishing, evaluating and monitoring analytical quality in the traceability era.","authors":"Mauro Panteghini, Magdalena Krintus","doi":"10.1080/10408363.2024.2434562","DOIUrl":"https://doi.org/10.1080/10408363.2024.2434562","url":null,"abstract":"<p><p>Poor analytical quality may be the bane of medical use of laboratory tests, and the fight against excessive analytical variability presents a daily struggle. Laboratories should prioritize the perspectives and needs of their customers (the patients and healthcare personnel). Among them, comparability of results from the same patient sample when measured by different laboratories using different <i>in vitro</i> diagnostic (IVD) medical devices is a logical priority to avoid result misinterpretation and potential patient harm. Harmonization (standardization) of laboratory measurements can be achieved by establishing metrological traceability of the results on clinical samples to stated higher-order references and providing an estimate of the uncertainty of measurement (MU). This estimate should be based on an MU budget including all known MU contributions generated by the employed calibration hierarchy, which in turn should be validated against fit-for-purpose maximum allowable MU derived according to internationally recommended models. In this report, we review the available strategies for establishing, evaluating, and monitoring analytical quality, drawing on three decades experience in the field. We discuss the most important aspects that may influence obtaining and maintaining analytical standardization in laboratory medicine, and offer practical solutions aimed at educating all stakeholders for the achievement of harmonized laboratory results. To fully implement the recommended approaches, all involved parties-i.e. reference providers, IVD manufacturers, medical laboratories, and External Quality Assessment organizers-must agree on their importance and enhance their specific knowledge.</p>","PeriodicalId":10760,"journal":{"name":"Critical reviews in clinical laboratory sciences","volume":" ","pages":"1-34"},"PeriodicalIF":6.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01Epub Date: 2024-07-31DOI: 10.1080/10408363.2024.2379278
Harriet Feilotter, Christine Bruce, Eleftherios P Diamandis, Miyo K Chatanaka, George M Yousef
The journey of translating a molecular discovery into the clinic involves multiple steps and requires planning, time, effort, and money. In this review, we provide a quick guide on the technical and clinical validation parameters that are necessary for successful commercialization of molecular and other markers. We also briefly address the different options for regulatory approvals. Successful clinical implantation depends on rigorous technical and clinical validation, and the ability to develop clear guidelines for the indications for testing (i.e. which patients are eligible to have this test), the frequency of testing, and also a clear interpretation of test results. Successful implementation requires providing evidence that the results of this test can be used to improve patient care. There are currently multiple routes for implementation of clinical molecular tests, which include regulatory agency- approved companion diagnostics, laboratory developed tests, or direct-to-consumer testing. Regulatory approval is considered the gold-standard, but it requires time and resources. There is an ongoing debate about the need for regulatory approval of laboratory developed testing. Ongoing oversight is maintained through lab accreditation and proficiency testing programs, which provide a common approach to ensuring high standards and consistent performance in clinical molecular labs. Before moving into the clinic, confirmation of both the clinical and analytic validity of a new molecular test is essential.
{"title":"Guidance for securing approvals for new biomarkers: from discovery to clinical implementation.","authors":"Harriet Feilotter, Christine Bruce, Eleftherios P Diamandis, Miyo K Chatanaka, George M Yousef","doi":"10.1080/10408363.2024.2379278","DOIUrl":"10.1080/10408363.2024.2379278","url":null,"abstract":"<p><p>The journey of translating a molecular discovery into the clinic involves multiple steps and requires planning, time, effort, and money. In this review, we provide a quick guide on the technical and clinical validation parameters that are necessary for successful commercialization of molecular and other markers. We also briefly address the different options for regulatory approvals. Successful clinical implantation depends on rigorous technical and clinical validation, and the ability to develop clear guidelines for the indications for testing (i.e. which patients are eligible to have this test), the frequency of testing, and also a clear interpretation of test results. Successful implementation requires providing evidence that the results of this test can be used to improve patient care. There are currently multiple routes for implementation of clinical molecular tests, which include regulatory agency- approved companion diagnostics, laboratory developed tests, or direct-to-consumer testing. Regulatory approval is considered the gold-standard, but it requires time and resources. There is an ongoing debate about the need for regulatory approval of laboratory developed testing. Ongoing oversight is maintained through lab accreditation and proficiency testing programs, which provide a common approach to ensuring high standards and consistent performance in clinical molecular labs. Before moving into the clinic, confirmation of both the clinical and analytic validity of a new molecular test is essential.</p>","PeriodicalId":10760,"journal":{"name":"Critical reviews in clinical laboratory sciences","volume":" ","pages":"1-8"},"PeriodicalIF":6.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141859258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01Epub Date: 2024-08-12DOI: 10.1080/10408363.2024.2387038
Rosamaria Capuano, Marco Ciotti, Alexandro Catini, Sergio Bernardini, Corrado Di Natale
The study of metabolomics is revealing immense potential for diagnosis, therapy monitoring, and understanding of pathogenesis processes. Volatilomics is a subcategory of metabolomics interested in the detection of molecules that are small enough to be released in the gas phase. Volatile compounds produced by cellular processes are released into the blood and lymph, and can reach the external environment through different pathways, such as the blood-air interface in the lung that are detected in breath, or the blood-water interface in the kidney that leads to volatile compounds detected in urine. Besides breath and urine, additional sources of volatile compounds such as saliva, blood, feces, and skin are available. Volatilomics traces its roots back over fifty years to the pioneering investigations in the 1970s. Despite extensive research, the field remains in its infancy, hindered by a lack of standardization despite ample experimental evidence. The proliferation of analytical instrumentations, sample preparations and methods of volatilome sampling still make it difficult to compare results from different studies and to establish a common standard approach to volatilomics. This review aims to provide an overview of volatilomics' diagnostic potential, focusing on two key technical aspects: sampling and analysis. Sampling poses a challenge due to the susceptibility of human samples to contamination and confounding factors from various sources like the environment and lifestyle. The discussion then delves into targeted and untargeted approaches in volatilomics. Some case studies are presented to exemplify the results obtained so far. Finally, the review concludes with a discussion on the necessary steps to fully integrate volatilomics into clinical practice.
{"title":"Clinical applications of volatilomic assays.","authors":"Rosamaria Capuano, Marco Ciotti, Alexandro Catini, Sergio Bernardini, Corrado Di Natale","doi":"10.1080/10408363.2024.2387038","DOIUrl":"10.1080/10408363.2024.2387038","url":null,"abstract":"<p><p>The study of metabolomics is revealing immense potential for diagnosis, therapy monitoring, and understanding of pathogenesis processes. Volatilomics is a subcategory of metabolomics interested in the detection of molecules that are small enough to be released in the gas phase. Volatile compounds produced by cellular processes are released into the blood and lymph, and can reach the external environment through different pathways, such as the blood-air interface in the lung that are detected in breath, or the blood-water interface in the kidney that leads to volatile compounds detected in urine. Besides breath and urine, additional sources of volatile compounds such as saliva, blood, feces, and skin are available. Volatilomics traces its roots back over fifty years to the pioneering investigations in the 1970s. Despite extensive research, the field remains in its infancy, hindered by a lack of standardization despite ample experimental evidence. The proliferation of analytical instrumentations, sample preparations and methods of volatilome sampling still make it difficult to compare results from different studies and to establish a common standard approach to volatilomics. This review aims to provide an overview of volatilomics' diagnostic potential, focusing on two key technical aspects: sampling and analysis. Sampling poses a challenge due to the susceptibility of human samples to contamination and confounding factors from various sources like the environment and lifestyle. The discussion then delves into targeted and untargeted approaches in volatilomics. Some case studies are presented to exemplify the results obtained so far. Finally, the review concludes with a discussion on the necessary steps to fully integrate volatilomics into clinical practice.</p>","PeriodicalId":10760,"journal":{"name":"Critical reviews in clinical laboratory sciences","volume":" ","pages":"45-64"},"PeriodicalIF":6.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141916253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01Epub Date: 2024-07-23DOI: 10.1080/10408363.2024.2379286
Yaxin Li, He S Yang, P J Klasse, Zhen Zhao
Immunoglobulin G (IgG) and immunoglobulin M (IgM) testing are commonly used to determine infection status. Typically, the detection of IgM indicates an acute or recent infection, while the presence of IgG alone suggests a chronic or past infection. However, relying solely on IgG and IgM antibody positivity may not be sufficient to differentiate acute from chronic infections. This limitation arises from several factors. The prolonged presence of IgM can complicate diagnostic interpretations, and false positive IgM results often arise from antibody cross-reactivity with various antigens. Additionally, IgM may remain undetectable in prematurely collected samples or in individuals who are immunocompromised, further complicating accurate diagnosis. As a result, additional diagnostic tools are required to confirm infection status. Avidity is a measure of the strength of the binding between an antigen and antibody. Avidity-based assays have been developed for various infectious agents, including toxoplasma, cytomegalovirus (CMV), SARS-CoV-2, and avian influenza, and are promising tools in clinical diagnostics. By measuring the strength of antibody binding, they offer critical insights into the maturity of the immune response. These assays are instrumental in distinguishing between acute and chronic or past infections, monitoring disease progression, and guiding treatment decisions. The development of automated platforms has optimized the testing process by enhancing efficiency and minimizing the risk of manual errors. Additionally, the recent advent of real-time biosensor immunoassays, including the label-free immunoassays (LFIA), has further amplified the capabilities of these assays. These advances have expanded the clinical applications of avidity-based assays, making them useful tools for the diagnosis and management of various infectious diseases. This review is structured around several key aspects of IgG avidity in clinical diagnosis, including: (i) a detailed exposition of the IgG affinity maturation process; (ii) a thorough discussion of the IgG avidity assays, including the recently emerged biosensor-based approaches; and (iii) an examination of the applications of IgG avidity in clinical diagnosis. This review is intended to contribute toward the development of enhanced diagnostic tools through critical assessment of the present landscape of avidity-based testing, which allows us to identify the existing knowledge gaps and highlight areas for future investigation.
{"title":"The significance of antigen-antibody-binding avidity in clinical diagnosis.","authors":"Yaxin Li, He S Yang, P J Klasse, Zhen Zhao","doi":"10.1080/10408363.2024.2379286","DOIUrl":"10.1080/10408363.2024.2379286","url":null,"abstract":"<p><p>Immunoglobulin G (IgG) and immunoglobulin M (IgM) testing are commonly used to determine infection status. Typically, the detection of IgM indicates an acute or recent infection, while the presence of IgG alone suggests a chronic or past infection. However, relying solely on IgG and IgM antibody positivity may not be sufficient to differentiate acute from chronic infections. This limitation arises from several factors. The prolonged presence of IgM can complicate diagnostic interpretations, and false positive IgM results often arise from antibody cross-reactivity with various antigens. Additionally, IgM may remain undetectable in prematurely collected samples or in individuals who are immunocompromised, further complicating accurate diagnosis. As a result, additional diagnostic tools are required to confirm infection status. Avidity is a measure of the strength of the binding between an antigen and antibody. Avidity-based assays have been developed for various infectious agents, including toxoplasma, cytomegalovirus (CMV), SARS-CoV-2, and avian influenza, and are promising tools in clinical diagnostics. By measuring the strength of antibody binding, they offer critical insights into the maturity of the immune response. These assays are instrumental in distinguishing between acute and chronic or past infections, monitoring disease progression, and guiding treatment decisions. The development of automated platforms has optimized the testing process by enhancing efficiency and minimizing the risk of manual errors. Additionally, the recent advent of real-time biosensor immunoassays, including the label-free immunoassays (LFIA), has further amplified the capabilities of these assays. These advances have expanded the clinical applications of avidity-based assays, making them useful tools for the diagnosis and management of various infectious diseases. This review is structured around several key aspects of IgG avidity in clinical diagnosis, including: (i) a detailed exposition of the IgG affinity maturation process; (ii) a thorough discussion of the IgG avidity assays, including the recently emerged biosensor-based approaches; and (iii) an examination of the applications of IgG avidity in clinical diagnosis. This review is intended to contribute toward the development of enhanced diagnostic tools through critical assessment of the present landscape of avidity-based testing, which allows us to identify the existing knowledge gaps and highlight areas for future investigation.</p>","PeriodicalId":10760,"journal":{"name":"Critical reviews in clinical laboratory sciences","volume":" ","pages":"9-23"},"PeriodicalIF":6.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141747618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01Epub Date: 2024-07-31DOI: 10.1080/10408363.2024.2383899
Kay Weng Choy, Nilika Wijeratne, Cherie Chiang, Andrew Don-Wauchope
<p><p>Copeptin is a 39-amino-acid long glycosylated peptide with a leucine-rich core segment in the C-terminal part of pre-pro-vasopressin. It exhibits a rapid response comparable to arginine vasopressin (AVP) in response to osmotic, hemodynamic, and nonspecific stress-related stimuli. This similarity can be attributed to equimolar production of copeptin alongside AVP. However, there are markedly different decay kinetics for both peptides, with an estimated initial half-life of copeptin being approximately two times longer than that of AVP. Like AVP, copeptin correlates strongly over a wide osmolality range in healthy individuals, making it a useful alternative to AVP measurement. While copeptin does not appear to be significantly affected by food intake, small amounts of oral fluid intake may result in a significant decrease in copeptin levels. Compared to AVP, copeptin is considerably more stable <i>in vitro</i>. An automated immunofluorescent assay is now available and has been used in recent landmark trials. However, separate validation studies are required before copeptin thresholds from these studies are applied to other assays. The biological variation of copeptin in presumably healthy subjects has been recently reported, which could assist in defining analytical performance specifications for this measurand. An established diagnostic utility of copeptin is in the investigation of polyuria-polydipsia syndrome and copeptin-based testing protocols have been explored in recent years. A single baseline plasma copeptin >21.4 pmol/L differentiates AVP resistance (formerly known as nephrogenic diabetes insipidus) from other causes with 100% sensitivity and specificity, rendering water deprivation testing unnecessary in such cases. In a recent study among adult patients with polyuria-polydipsia syndrome, AVP deficiency (formerly known as central diabetes insipidus) was more accurately diagnosed with hypertonic saline-stimulated copeptin than with arginine-stimulated copeptin. Glucagon-stimulated copeptin has been proposed as a potentially safe and precise test in the investigation of polyuria-polydipsia syndrome. Furthermore, copeptin could reliably identify those with AVP deficiency among patients with severe hypernatremia, though its diagnostic utility is reportedly limited in the differential diagnosis of profound hyponatremia. Copeptin measurement may be a useful tool for early goal-directed management of post-operative AVP deficiency. Additionally, the potential prognostic utility of copeptin has been explored in other diseases. There is an interest in examining the role of the AVP system (with copeptin as a marker) in the pathogenesis of insulin resistance and diabetes mellitus. Copeptin has been found to be independently associated with an increased risk of incident stroke and cardiovascular disease mortality in men with diabetes mellitus. Increased levels of copeptin have been reported to be independently predictive of a decline in estimat
{"title":"Copeptin as a surrogate marker for arginine vasopressin: analytical insights, current utility, and emerging applications.","authors":"Kay Weng Choy, Nilika Wijeratne, Cherie Chiang, Andrew Don-Wauchope","doi":"10.1080/10408363.2024.2383899","DOIUrl":"10.1080/10408363.2024.2383899","url":null,"abstract":"<p><p>Copeptin is a 39-amino-acid long glycosylated peptide with a leucine-rich core segment in the C-terminal part of pre-pro-vasopressin. It exhibits a rapid response comparable to arginine vasopressin (AVP) in response to osmotic, hemodynamic, and nonspecific stress-related stimuli. This similarity can be attributed to equimolar production of copeptin alongside AVP. However, there are markedly different decay kinetics for both peptides, with an estimated initial half-life of copeptin being approximately two times longer than that of AVP. Like AVP, copeptin correlates strongly over a wide osmolality range in healthy individuals, making it a useful alternative to AVP measurement. While copeptin does not appear to be significantly affected by food intake, small amounts of oral fluid intake may result in a significant decrease in copeptin levels. Compared to AVP, copeptin is considerably more stable <i>in vitro</i>. An automated immunofluorescent assay is now available and has been used in recent landmark trials. However, separate validation studies are required before copeptin thresholds from these studies are applied to other assays. The biological variation of copeptin in presumably healthy subjects has been recently reported, which could assist in defining analytical performance specifications for this measurand. An established diagnostic utility of copeptin is in the investigation of polyuria-polydipsia syndrome and copeptin-based testing protocols have been explored in recent years. A single baseline plasma copeptin >21.4 pmol/L differentiates AVP resistance (formerly known as nephrogenic diabetes insipidus) from other causes with 100% sensitivity and specificity, rendering water deprivation testing unnecessary in such cases. In a recent study among adult patients with polyuria-polydipsia syndrome, AVP deficiency (formerly known as central diabetes insipidus) was more accurately diagnosed with hypertonic saline-stimulated copeptin than with arginine-stimulated copeptin. Glucagon-stimulated copeptin has been proposed as a potentially safe and precise test in the investigation of polyuria-polydipsia syndrome. Furthermore, copeptin could reliably identify those with AVP deficiency among patients with severe hypernatremia, though its diagnostic utility is reportedly limited in the differential diagnosis of profound hyponatremia. Copeptin measurement may be a useful tool for early goal-directed management of post-operative AVP deficiency. Additionally, the potential prognostic utility of copeptin has been explored in other diseases. There is an interest in examining the role of the AVP system (with copeptin as a marker) in the pathogenesis of insulin resistance and diabetes mellitus. Copeptin has been found to be independently associated with an increased risk of incident stroke and cardiovascular disease mortality in men with diabetes mellitus. Increased levels of copeptin have been reported to be independently predictive of a decline in estimat","PeriodicalId":10760,"journal":{"name":"Critical reviews in clinical laboratory sciences","volume":" ","pages":"24-44"},"PeriodicalIF":6.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141859257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01Epub Date: 2024-06-07DOI: 10.1080/10408363.2024.2361012
Jiang-Shan Tan, Yixiao Wei, Lingtao Chong, Yanmin Yang, Song Hu, Yimeng Wang
Pulmonary arterial hypertension (PAH), one subtype of pulmonary hypertension (PH), is a life-threatening condition characterized by pulmonary arterial remodeling, elevated pulmonary vascular resistance, and blood pressure in the pulmonary arteries, leading to right heart failure and increased mortality. The disease is marked by endothelial dysfunction, vasoconstriction, and vascular remodeling. The role of Sodium-Glucose Co-Transporter-2 (SGLT2) inhibitors, a class of medications originally developed for diabetes management, is increasingly being explored in the context of cardiovascular diseases, including PAH, due to their potential to modulate these pathophysiological processes. In this review, we systematically examine the burgeoning evidence from both basic and clinical studies that describe the effects of SGLT2 inhibitors on cardiovascular health, with a special emphasis on PAH. By delving into the complex interactions between these drugs and the potential pathobiology that underpins PH, this study seeks to uncover the mechanistic underpinnings that could justify the use of SGLT2 inhibitors as a novel therapeutic approach for PAH. We collate findings that illustrate how SGLT2 inhibitors may influence the normal function of pulmonary arteries, possibly alleviating the pathological hallmarks of PAH such as inflammation, oxidative stress, aberrant cellular proliferation, and so on. Our review thereby outlines a potential paradigm shift in PAH management, suggesting that these inhibitors could play a crucial role in modulating the disease's progression by targeting the potential dysfunctions that drive it. This comprehensive synthesis of existing research underscores the imperative need for further clinical trials to validate the efficacy of SGLT2 inhibitors in PAH and to integrate them into the therapeutic agents used against this challenging disease.
{"title":"SGLT2 inhibitors as a potential therapeutic option for pulmonary hypertension: mechanisms and clinical perspectives.","authors":"Jiang-Shan Tan, Yixiao Wei, Lingtao Chong, Yanmin Yang, Song Hu, Yimeng Wang","doi":"10.1080/10408363.2024.2361012","DOIUrl":"10.1080/10408363.2024.2361012","url":null,"abstract":"<p><p>Pulmonary arterial hypertension (PAH), one subtype of pulmonary hypertension (PH), is a life-threatening condition characterized by pulmonary arterial remodeling, elevated pulmonary vascular resistance, and blood pressure in the pulmonary arteries, leading to right heart failure and increased mortality. The disease is marked by endothelial dysfunction, vasoconstriction, and vascular remodeling. The role of Sodium-Glucose Co-Transporter-2 (SGLT2) inhibitors, a class of medications originally developed for diabetes management, is increasingly being explored in the context of cardiovascular diseases, including PAH, due to their potential to modulate these pathophysiological processes. In this review, we systematically examine the burgeoning evidence from both basic and clinical studies that describe the effects of SGLT2 inhibitors on cardiovascular health, with a special emphasis on PAH. By delving into the complex interactions between these drugs and the potential pathobiology that underpins PH, this study seeks to uncover the mechanistic underpinnings that could justify the use of SGLT2 inhibitors as a novel therapeutic approach for PAH. We collate findings that illustrate how SGLT2 inhibitors may influence the normal function of pulmonary arteries, possibly alleviating the pathological hallmarks of PAH such as inflammation, oxidative stress, aberrant cellular proliferation, and so on. Our review thereby outlines a potential paradigm shift in PAH management, suggesting that these inhibitors could play a crucial role in modulating the disease's progression by targeting the potential dysfunctions that drive it. This comprehensive synthesis of existing research underscores the imperative need for further clinical trials to validate the efficacy of SGLT2 inhibitors in PAH and to integrate them into the therapeutic agents used against this challenging disease.</p>","PeriodicalId":10760,"journal":{"name":"Critical reviews in clinical laboratory sciences","volume":" ","pages":"709-725"},"PeriodicalIF":6.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141283267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01Epub Date: 2024-08-09DOI: 10.1080/10408363.2024.2358304
Miles D Thompson, David Reiner-Link, Alessandro Berghella, Brinda K Rana, G Enrico Rovati, Valerie Capra, Caroline M Gorvin, Alexander S Hauser
The field of pharmacogenetics, the investigation of the influence of one or more sequence variants on drug response phenotypes, is a special case of pharmacogenomics, a discipline that takes a genome-wide approach. Massively parallel, next generation sequencing (NGS), has allowed pharmacogenetics to be subsumed by pharmacogenomics with respect to the identification of variants associated with responders and non-responders, optimal drug response, and adverse drug reactions. A plethora of rare and common naturally-occurring GPCR variants must be considered in the context of signals from across the genome. Many fundamentals of pharmacogenetics were established for G protein-coupled receptor (GPCR) genes because they are primary targets for a large number of therapeutic drugs. Functional studies, demonstrating likely-pathogenic and pathogenic GPCR variants, have been integral to establishing models used for in silico analysis. Variants in GPCR genes include both coding and non-coding single nucleotide variants and insertion or deletions (indels) that affect cell surface expression (trafficking, dimerization, and desensitization/downregulation), ligand binding and G protein coupling, and variants that result in alternate splicing encoding isoforms/variable expression. As the breadth of data on the GPCR genome increases, we may expect an increase in the use of drug labels that note variants that significantly impact the clinical use of GPCR-targeting agents. We discuss the implications of GPCR pharmacogenomic data derived from the genomes available from individuals who have been well-phenotyped for receptor structure and function and receptor-ligand interactions, and the potential benefits to patients of optimized drug selection. Examples discussed include the renin-angiotensin system in SARS-CoV-2 (COVID-19) infection, the probable role of chemokine receptors in the cytokine storm, and potential protease activating receptor (PAR) interventions. Resources dedicated to GPCRs, including publicly available computational tools, are also discussed.
{"title":"G protein-coupled receptor (GPCR) pharmacogenomics.","authors":"Miles D Thompson, David Reiner-Link, Alessandro Berghella, Brinda K Rana, G Enrico Rovati, Valerie Capra, Caroline M Gorvin, Alexander S Hauser","doi":"10.1080/10408363.2024.2358304","DOIUrl":"10.1080/10408363.2024.2358304","url":null,"abstract":"<p><p>The field of pharmacogenetics, the investigation of the influence of one or more sequence variants on drug response phenotypes, is a special case of pharmacogenomics, a discipline that takes a genome-wide approach. Massively parallel, next generation sequencing (NGS), has allowed pharmacogenetics to be subsumed by pharmacogenomics with respect to the identification of variants associated with responders and non-responders, optimal drug response, and adverse drug reactions. A plethora of rare and common naturally-occurring GPCR variants must be considered in the context of signals from across the genome. Many fundamentals of pharmacogenetics were established for G protein-coupled receptor (GPCR) genes because they are primary targets for a large number of therapeutic drugs. Functional studies, demonstrating likely-pathogenic and pathogenic GPCR variants, have been integral to establishing models used for <i>in silico</i> analysis. Variants in GPCR genes include both coding and non-coding single nucleotide variants and insertion or deletions (indels) that affect cell surface expression (trafficking, dimerization, and desensitization/downregulation), ligand binding and G protein coupling, and variants that result in alternate splicing encoding isoforms/variable expression. As the breadth of data on the GPCR genome increases, we may expect an increase in the use of drug labels that note variants that significantly impact the clinical use of GPCR-targeting agents. We discuss the implications of GPCR pharmacogenomic data derived from the genomes available from individuals who have been well-phenotyped for receptor structure and function and receptor-ligand interactions, and the potential benefits to patients of optimized drug selection. Examples discussed include the renin-angiotensin system in SARS-CoV-2 (COVID-19) infection, the probable role of chemokine receptors in the cytokine storm, and potential protease activating receptor (PAR) interventions. Resources dedicated to GPCRs, including publicly available computational tools, are also discussed.</p>","PeriodicalId":10760,"journal":{"name":"Critical reviews in clinical laboratory sciences","volume":" ","pages":"641-684"},"PeriodicalIF":6.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141906140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01Epub Date: 2024-07-03DOI: 10.1080/10408363.2024.2370267
Siyi Liu, Yunshan Cao, Yan Zhang
RNA methylation is a widespread regulatory mechanism that controls gene expression in physiological processes. In recent years, the mechanisms and functions of RNA methylation under diseased conditions have been increasingly unveiled by RNA sequencing technologies with large scale and high resolution. In this review, the fundamental concept of RNA methylation is introduced, and the common types of transcript methylation and their machineries are described. Then, the regulatory roles of RNA methylation, particularly N6-methyladenosine and 5-methylcytosine, in the vascular lesions of ocular and cardiopulmonary diseases are discussed and compared. The ocular diseases include corneal neovascularization, retinopathy of prematurity, diabetic retinopathy, and pathologic myopia; whereas the cardiopulmonary ailments involve atherosclerosis and pulmonary hypertension. This review hopes to shed light on the common regulatory mechanisms underlying the vascular lesions in these ocular and cardiopulmonary diseases, which may be conducive to developing therapeutic strategies in clinical practice.
{"title":"Regulatory roles of RNA methylation in vascular lesions in ocular and cardiopulmonary diseases.","authors":"Siyi Liu, Yunshan Cao, Yan Zhang","doi":"10.1080/10408363.2024.2370267","DOIUrl":"10.1080/10408363.2024.2370267","url":null,"abstract":"<p><p>RNA methylation is a widespread regulatory mechanism that controls gene expression in physiological processes. In recent years, the mechanisms and functions of RNA methylation under diseased conditions have been increasingly unveiled by RNA sequencing technologies with large scale and high resolution. In this review, the fundamental concept of RNA methylation is introduced, and the common types of transcript methylation and their machineries are described. Then, the regulatory roles of RNA methylation, particularly N6-methyladenosine and 5-methylcytosine, in the vascular lesions of ocular and cardiopulmonary diseases are discussed and compared. The ocular diseases include corneal neovascularization, retinopathy of prematurity, diabetic retinopathy, and pathologic myopia; whereas the cardiopulmonary ailments involve atherosclerosis and pulmonary hypertension. This review hopes to shed light on the common regulatory mechanisms underlying the vascular lesions in these ocular and cardiopulmonary diseases, which may be conducive to developing therapeutic strategies in clinical practice.</p>","PeriodicalId":10760,"journal":{"name":"Critical reviews in clinical laboratory sciences","volume":" ","pages":"726-740"},"PeriodicalIF":6.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141491223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01Epub Date: 2024-06-10DOI: 10.1080/10408363.2024.2360996
Jordan Canning, Rona J Strawbridge, Zosia Miedzybrodzka, Riccardo E Marioni, Mads Melbye, David J Porteous, Matthew E Hurles, Naveed Sattar, Cathie L M Sudlow, Rory Collins, Sandosh Padmanabhan, Jill P Pell
This scoping review aimed to synthesize the analytical techniques used and methodological limitations encountered when undertaking secondary research using residual neonatal dried blood spot (DBS) samples. Studies that used residual neonatal DBS samples for secondary research (i.e. research not related to newborn screening for inherited genetic and metabolic disorders) were identified from six electronic databases: Cochrane Library, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Embase, Medline, PubMed and Scopus. Inclusion was restricted to studies published from 1973 and written in or translated into English that reported the storage, extraction and testing of neonatal DBS samples. Sixty-seven studies were eligible for inclusion. Included studies were predominantly methodological in nature and measured various analytes, including nucleic acids, proteins, metabolites, environmental pollutants, markers of prenatal substance use and medications. Neonatal DBS samples were stored over a range of temperatures (ambient temperature, cold storage or frozen) and durations (two weeks to 40.5 years), both of which impacted the recovery of some analytes, particularly amino acids, antibodies and environmental pollutants. The size of DBS sample used and potential contamination were also cited as methodological limitations. Residual neonatal DBS samples retained by newborn screening programs are a promising resource for secondary research purposes, with many studies reporting the successful measurement of analytes even from neonatal DBS samples stored for long periods of time in suboptimal temperatures and conditions.
本范围综述旨在总结利用残留新生儿干血斑(DBS)样本进行二次研究时所使用的分析技术和遇到的方法限制。从六个电子数据库中找出了使用新生儿残留干血斑样本进行二次研究(即与新生儿遗传和代谢疾病筛查无关的研究)的研究:Cochrane Library、Cumulative Index to Nursing and Allied Health Literature (CINAHL)、Embase、Medline、PubMed 和 Scopus。纳入的研究仅限于 1973 年以来发表的、用英语撰写或翻译成英语的、报告新生儿 DBS 样本的储存、提取和测试的研究。共有 67 项研究符合纳入条件。所纳入的研究主要是方法学性质的,测量了各种分析物,包括核酸、蛋白质、代谢物、环境污染物、产前药物使用标记物和药物。新生儿 DBS 样本的保存温度(环境温度、冷藏或冷冻)和保存时间(两周到 40.5 年)各不相同,这都会影响某些分析物的回收率,尤其是氨基酸、抗体和环境污染物。使用的 DBS 样本的大小和潜在的污染也被认为是方法学上的局限性。新生儿筛查项目保留的残留新生儿 DBS 样本是一种很有希望用于二次研究的资源,许多研究报告称,即使是在不理想的温度和条件下长期储存的新生儿 DBS 样本也能成功测量出分析物。
{"title":"Methods applied to neonatal dried blood spot samples for secondary research purposes: a scoping review.","authors":"Jordan Canning, Rona J Strawbridge, Zosia Miedzybrodzka, Riccardo E Marioni, Mads Melbye, David J Porteous, Matthew E Hurles, Naveed Sattar, Cathie L M Sudlow, Rory Collins, Sandosh Padmanabhan, Jill P Pell","doi":"10.1080/10408363.2024.2360996","DOIUrl":"10.1080/10408363.2024.2360996","url":null,"abstract":"<p><p>This scoping review aimed to synthesize the analytical techniques used and methodological limitations encountered when undertaking secondary research using residual neonatal dried blood spot (DBS) samples. Studies that used residual neonatal DBS samples for secondary research (i.e. research not related to newborn screening for inherited genetic and metabolic disorders) were identified from six electronic databases: Cochrane Library, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Embase, Medline, PubMed and Scopus. Inclusion was restricted to studies published from 1973 and written in or translated into English that reported the storage, extraction and testing of neonatal DBS samples. Sixty-seven studies were eligible for inclusion. Included studies were predominantly methodological in nature and measured various analytes, including nucleic acids, proteins, metabolites, environmental pollutants, markers of prenatal substance use and medications. Neonatal DBS samples were stored over a range of temperatures (ambient temperature, cold storage or frozen) and durations (two weeks to 40.5 years), both of which impacted the recovery of some analytes, particularly amino acids, antibodies and environmental pollutants. The size of DBS sample used and potential contamination were also cited as methodological limitations. Residual neonatal DBS samples retained by newborn screening programs are a promising resource for secondary research purposes, with many studies reporting the successful measurement of analytes even from neonatal DBS samples stored for long periods of time in suboptimal temperatures and conditions.</p>","PeriodicalId":10760,"journal":{"name":"Critical reviews in clinical laboratory sciences","volume":" ","pages":"685-708"},"PeriodicalIF":6.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141295721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}