Elevated troponin levels are often indicative of various cardiac diseases; however, analytical interference can lead to false positive troponin concentrations. We present the case of a 48-year-old female patient with persistently falsely elevated high sensitivity troponin I (hsTnI) probably caused by the presence of macrotroponin. Laboratory testing included determination of hsTnI using various analytical methods, serial dilutions and determination of heterophilic antibodies and other autoimmune antibodies. Only precipitation with polyethylene glycol (PEG) indicated the presence of an interference by causing a significant decrease in hsTnI concentration.
Our results suggest that the falsely elevated hsTnI concentration could be due to interference with the macrotroponin complex.
{"title":"Long term false positive hsTnI on Alinity I probably caused by macrotroponin complex: Case report","authors":"Tamara Sušić , Marijana Miler , Nora Nikolac Gabaj , Andrea Tešija Kuna , Krešimir Kordić , Vedrana Ilić , Ozren Vinter","doi":"10.1016/j.clinbiochem.2024.110802","DOIUrl":"10.1016/j.clinbiochem.2024.110802","url":null,"abstract":"<div><p>Elevated troponin levels are often indicative of various cardiac diseases; however, analytical interference can lead to false positive troponin concentrations. We present the case of a 48-year-old female patient with persistently falsely elevated high sensitivity troponin I (hsTnI) probably caused by the presence of macrotroponin. Laboratory testing included determination of hsTnI using various analytical methods, serial dilutions and determination of heterophilic antibodies and other autoimmune antibodies. Only precipitation with polyethylene glycol (PEG) indicated the presence of an interference by causing a significant decrease in hsTnI concentration.</p><p>Our results suggest that the falsely elevated hsTnI concentration could be due to interference with the macrotroponin complex.</p></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"131 ","pages":"Article 110802"},"PeriodicalIF":2.5,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141765667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-24DOI: 10.1016/j.clinbiochem.2024.110807
Midori Awazu, Kazuya Matsumura
Background
Fractional excretion of magnesium (FEMg) is commonly used to diagnose of renal magnesium (Mg) wasting, but it can be affected by serum Mg (SMg) and serum creatinine concentration (SCr). We investigated the sensitivity and specificity of FEMg to diagnose Mg wasting in subgroups with different SMg and eGFR (estimated glomerular filtration rate) in pediatric nephrology practice.
Methods
One hundred and nineteen patients (59 males and 60 females, median 15 years) seen in our pediatric clinic were investigated for FEMg, SMg, eGFR, and urine Mg-to-creatinine ratio (Mg/Cr). Normal eGFR was defined as ≥ 90 ml/min/1.73 m2 or for infants SCr < chronic kidney disease stage 2. Urine Mg/Cr was compared with age-specific reference values.
Results
Sixteen of all patients (13 %) had hypomagnesemia. All had FEMg greater than the cut-off value of 2 %. Only 4 patients had elevated urine Mg/Cr. Of 65 patients with normal SMg and eGFR, 19 had FEMg above the cut-off value of 4 %. Of these, 13 patients had elevated urine Mg/Cr i.e. Mg wasting (sensitivity and specificity of FEMg, 93 % and 88 %, respectively). Among 38 patients with normal SMg and low eGFR, 30 had FEMg > 4 %, but only 6 had elevated urine Mg/Cr (sensitivity 100 % and specificity 25 %). Overall, hypomagnesemic patients and normomagnesemic patients with elevated urine Mg/Cr were diagnosed with Mg wasting (36/119, 30 %).
Conclusions
FEMg has variable sensitivity and specificity depending on SMg and eGFR in the diagnosis of Mg wasting. Mg wasting is not uncommon in pediatric nephrology practice.
{"title":"Utility of fractional excretion of magnesium in diagnosing renal magnesium wasting in pediatric nephrology practice","authors":"Midori Awazu, Kazuya Matsumura","doi":"10.1016/j.clinbiochem.2024.110807","DOIUrl":"10.1016/j.clinbiochem.2024.110807","url":null,"abstract":"<div><h3>Background</h3><p>Fractional excretion of magnesium (FE<sub>Mg</sub>) is commonly used to diagnose of renal magnesium (Mg) wasting, but it can be affected by serum Mg (SMg) and serum creatinine concentration (SCr). We investigated the sensitivity and specificity of FE<sub>Mg</sub> to diagnose Mg wasting in subgroups with different SMg and eGFR (estimated glomerular filtration rate) in pediatric nephrology practice.</p></div><div><h3>Methods</h3><p>One hundred and nineteen patients (59 males and 60 females, median 15 years) seen in our pediatric clinic were investigated for FE<sub>Mg</sub>, SMg, eGFR, and urine Mg-to-creatinine ratio (Mg/Cr). Normal eGFR was defined as ≥ 90 ml/min/1.73 m<sup>2</sup> or for infants SCr < chronic kidney disease stage 2. Urine Mg/Cr was compared with age-specific reference values.</p></div><div><h3>Results</h3><p>Sixteen of all patients (13 %) had hypomagnesemia. All had FE<sub>Mg</sub> greater than the cut-off value of 2 %. Only 4 patients had elevated urine Mg/Cr. Of 65 patients with normal SMg and eGFR, 19 had FE<sub>Mg</sub> above the cut-off value of 4 %. Of these, 13 patients had elevated urine Mg/Cr i.e. Mg wasting (sensitivity and specificity of FE<sub>Mg</sub>, 93 % and 88 %, respectively). Among 38 patients with normal SMg and low eGFR, 30 had FE<sub>Mg</sub> > 4 %, but only 6 had elevated urine Mg/Cr (sensitivity 100 % and specificity 25 %). Overall, hypomagnesemic patients and normomagnesemic patients with elevated urine Mg/Cr were diagnosed with Mg wasting (36/119, 30 %).</p></div><div><h3>Conclusions</h3><p>FE<sub>Mg</sub> has variable sensitivity and specificity depending on SMg and eGFR in the diagnosis of Mg wasting. Mg wasting is not uncommon in pediatric nephrology practice.</p></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"131 ","pages":"Article 110807"},"PeriodicalIF":2.5,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141765668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-23DOI: 10.1016/j.clinbiochem.2024.110803
Rachel K. Vanderschelden , Nicholas L. Benjamin , Michael R. Shurin , Levi Shelton , Sarah E. Wheeler
Background
Criteria developed for the diagnosis of multiple sclerosis (MS) in adults are also used in the pediatric setting. However, differential diagnosis in pediatric-onset MS (POMS) is distinct from that of adult-onset MS. There is little literature characterizing the utility of oligoclonal bands (OCB) and IgG index in differentiating POMS from other childhood diseases with overlapping clinical presentation which can require immediate treatment.
Methods
A retrospective review of all MS panels resulted between March 2022 and May 2023 on patients age ≤ 18 years at one tertiary care pediatric hospital in the northeastern United States was performed with pediatric neurology collaboration to characterize clinical utility (n = 85 cases).
Results
Demyelinating diseases accounted for 31 of 85 total cases (36.5%), 12 of these cases were POMS (14%). Other diagnoses consisted of psychiatric etiologies (17.6%), infectious meningitis/encephalitis (5.9%), and migraine (5.9%). Elevated IgG index was seen in 67% of those with demyelinating diseases, versus only 13% of those with other conditions. Unique OCBs were found in 41% of those with demyelinating diseases, versus only 9% of those with other conditions. Fourteen of 15 patients (93.3%) with psychiatric conditions had normal MS panels.
Conclusions
Patients with demyelinating diseases were more likely to have elevated IgG index and unique OCBs versus patients with other conditions. For pediatric hospitals without in-house OCB evaluation, implementation of an in-house IgG index may serve as a rapid screen for differentials that include demyelinating diseases while awaiting OCB results, in the appropriate clinical context.
Impact statement
IgG index and CSF oligoclonal bands are important tools in the diagnosis of patients with suspected Multiple Sclerosis (MS). In the pediatric population, these markers are used to differentiate pediatric-onset MS (POMS) from other neurologic, psychiatric, and inflammatory diseases that display clinical overlap. The use of these markers in differentiating these conditions has not been thoroughly investigated. We examined the associations between abnormal markers and final diagnoses in pediatric patients undergoing testing for POMS in order to identify trends that may enhance ordering and reporting practices.
{"title":"Clinical laboratory test utilization of CSF oligoclonal bands and IgG index in a tertiary pediatric hospital","authors":"Rachel K. Vanderschelden , Nicholas L. Benjamin , Michael R. Shurin , Levi Shelton , Sarah E. Wheeler","doi":"10.1016/j.clinbiochem.2024.110803","DOIUrl":"10.1016/j.clinbiochem.2024.110803","url":null,"abstract":"<div><h3>Background</h3><p>Criteria developed for the diagnosis of multiple sclerosis (MS) in adults are also used in the pediatric setting. However, differential diagnosis in pediatric-onset MS (POMS) is distinct from that of adult-onset MS. There is little literature characterizing the utility of oligoclonal bands (OCB) and IgG index in differentiating POMS from other childhood diseases with overlapping clinical presentation which can require immediate treatment.</p></div><div><h3>Methods</h3><p>A retrospective review of all MS panels resulted between March 2022 and May 2023 on patients age ≤ 18 years at one tertiary care pediatric hospital in the northeastern United States was performed with pediatric neurology collaboration to characterize clinical utility (n = 85 cases).</p></div><div><h3>Results</h3><p>Demyelinating diseases accounted for 31 of 85 total cases (36.5%), 12 of these cases were POMS (14%). Other diagnoses consisted of psychiatric etiologies (17.6%), infectious meningitis/encephalitis (5.9%), and migraine (5.9%). Elevated IgG index was seen in 67% of those with demyelinating diseases, versus only 13% of those with other conditions. Unique OCBs were found in 41% of those with demyelinating diseases, versus only 9% of those with other conditions. Fourteen of 15 patients (93.3%) with psychiatric conditions had normal MS panels.</p></div><div><h3>Conclusions</h3><p>Patients with demyelinating diseases were more likely to have elevated IgG index and unique OCBs versus patients with other conditions. For pediatric hospitals without in-house OCB evaluation, implementation of an in-house IgG index may serve as a rapid screen for differentials that include demyelinating diseases while awaiting OCB results, in the appropriate clinical context.</p></div><div><h3>Impact statement</h3><p>IgG index and CSF oligoclonal bands are important tools in the diagnosis of patients with suspected Multiple Sclerosis (MS). In the pediatric population, these markers are used to differentiate pediatric-onset MS (POMS) from other neurologic, psychiatric, and inflammatory diseases that display clinical overlap. The use of these markers in differentiating these conditions has not been thoroughly investigated. We examined the associations between abnormal markers and final diagnoses in pediatric patients undergoing testing for POMS in order to identify trends that may enhance ordering and reporting practices.</p></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"131 ","pages":"Article 110803"},"PeriodicalIF":2.5,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0009912024000973/pdfft?md5=e1642a4f678b4f5481b5a575c36e4fb8&pid=1-s2.0-S0009912024000973-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141757435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-17DOI: 10.1016/j.clinbiochem.2024.110801
Li Liu, Daniel Y. Chang, Kent B. Lewandrowski, Anand S. Dighe
Objective
Estimated glomerular filtration rate (eGFR) calculated by cystatin C (cysC) has been recommended for broader adoption. This study assessed the discrepancy between eGFR calculated by cysC (eGFRcys) and creatinine (eGFRcr) in different patient care settings and explored potential contributing factors to such discrepancies.
Methods
This retrospective study included 2072 patients with paired cysC and creatinine results in different patient care settings. Delta eGFRcr-cys (eGFRcr − eGFRcys) was analyzed in relationship to patient care settings and the Elixhauser Comorbidity index. The 90-day survival in patients with different delta eGFR was assessed by Kaplan-Meier analysis, univariate and multivariate Cox proportional hazard models. In addition, discrepancy between eGFRcys and eGFRcr was analyzed in 50 ambulatory patients with systemic inflammation but normal kidney function.
Results
Inpatients had higher cysC (median 1.91 mg/L), lower eGFRcys (median 31 mL/min/1.73 m2), and larger delta eGFRcr-cys (median 18 mL/min/1.73 m2) than outpatients (cysC median 1.53 mg/L, p < 0.0001, eGFRcys median 41 mL/min/1.73 m2, p < 0.0001, delta eGFRcr-cys median 4 mL/min/1.73 m2, p < 0.0001). Higher Elixhauser Comorbidity index correlated with lower eGFRcys and larger delta eGFRcr-cys, with median delta eGFRcr-cys 11 and 6 mL/min/1.73 m2 in patients with a Comorbidity index > 15 and ≤ 15, respectively (p < 0.0001). Increased delta eGFRcr-cys was associated with worse 90-day survival. Patients with systemic inflammation but normal kidney function had lower eGFRcys (median 77.5 mL/min/1.73 m2) than eGFRcr (median 97 mL/min/1.73 m2, p < 0.001), with red blood cell abnormalities as associated factors.
Conclusion
Inflammation and comorbidities are associated with decreased eGFRcys and large discrepancies between eGFRcr and eGFRcys independent of kidney function and are most apparent in inpatients. Creatinine-cysC combined eGFR reduces this discrepancy and should be broadly adopted.
{"title":"Discrepancy between estimated glomerular filtration rate by creatinine versus cystatin C in different patient care settings","authors":"Li Liu, Daniel Y. Chang, Kent B. Lewandrowski, Anand S. Dighe","doi":"10.1016/j.clinbiochem.2024.110801","DOIUrl":"10.1016/j.clinbiochem.2024.110801","url":null,"abstract":"<div><h3>Objective</h3><p>Estimated glomerular filtration rate (eGFR) calculated by cystatin C (cysC) has been recommended for broader adoption. This study assessed the discrepancy between eGFR calculated by cysC (eGFRcys) and creatinine (eGFRcr) in different patient care settings and explored potential contributing factors to such discrepancies.</p></div><div><h3>Methods</h3><p>This retrospective study included 2072 patients with paired cysC and creatinine results in different patient care settings. Delta eGFRcr-cys (eGFRcr − eGFRcys) was analyzed in relationship to patient care settings and the Elixhauser Comorbidity index. The 90-day survival in patients with different delta eGFR was assessed by Kaplan-Meier analysis, univariate and multivariate Cox proportional hazard models. In addition, discrepancy between eGFRcys and eGFRcr was analyzed in 50 ambulatory patients with systemic inflammation but normal kidney function.</p></div><div><h3>Results</h3><p>Inpatients had higher cysC (median 1.91 mg/L), lower eGFRcys (median 31 mL/min/1.73 m<sup>2</sup>), and larger delta eGFRcr-cys (median 18 mL/min/1.73 m<sup>2</sup>) than outpatients (cysC median 1.53 mg/L, p < 0.0001, eGFRcys median 41 mL/min/1.73 m<sup>2</sup>, p < 0.0001, delta eGFRcr-cys median 4 mL/min/1.73 m<sup>2</sup>, p < 0.0001). Higher Elixhauser Comorbidity index correlated with lower eGFRcys and larger delta eGFRcr-cys, with median delta eGFRcr-cys 11 and 6 mL/min/1.73 m<sup>2</sup> in patients with a Comorbidity index > 15 and ≤ 15, respectively (p < 0.0001). Increased delta eGFRcr-cys was associated with worse 90-day survival. Patients with systemic inflammation but normal kidney function had lower eGFRcys (median 77.5 mL/min/1.73 m<sup>2</sup>) than eGFRcr (median 97 mL/min/1.73 m<sup>2</sup>, p < 0.001), with red blood cell abnormalities as associated factors.</p></div><div><h3>Conclusion</h3><p>Inflammation and comorbidities are associated with decreased eGFRcys and large discrepancies between eGFRcr and eGFRcys independent of kidney function and are most apparent in inpatients. Creatinine-cysC combined eGFR reduces this discrepancy and should be broadly adopted.</p></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"131 ","pages":"Article 110801"},"PeriodicalIF":2.5,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141726978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-10DOI: 10.1016/j.clinbiochem.2024.110793
Background and aims
Insulin resistance (IR) is a risk factor for several cardiometabolic disorders; however, there is conflicting evidence about the reliability of certain IR markers. In this context, the triglyceride-glucose index (TyG) has been proposed as a surrogate marker for IR. This study aimed to compare the TyG index and homeostasis model assessment of insulin resistance (HOMA-IR).
Methods and results
A cross-sectional analysis was conducted using baseline data from 11,314 adults (aged 35–74 years) from the ELSA-Brasil study. The correlation between TyG and HOMA-IR, their interrater reliability, and their predictive value in identifying metabolic syndrome (MetS) were assessed. The mean TyG and HOMA-IR in our sample were 8.81 ± 0.52 and 2.78 ± 1.58 for men, and 8.53 ± 0.48 and 2.49 ± 1.38 for women, respectively. TyG and HOMA-IR showed a weak to moderate correlation with each other (Pearson’s r for men: 0.395 and 0.409 for women, p-value <0.05) and other markers of glycemic metabolism. Additionally, the area under the curve for the prediction of MetS was greater for TyG than HOMA-IR, regardless of sex (TyG: 0.836 for men and 0.826 for women; HOMA-IR: 0.775 for men and 0.787 for women). The concordance between these markers was low (Coheńs kappa coefficient: 0.307 for men and 0.306 for women). Individuals with increased TyG exhibited mainly anthropometrical and glycemic metabolic alterations, whereas those with elevated HOMA-IR displayed mostly lipid-associated metabolic alterations.
Conclusion
TyG and HOMA-IR might indicate different profiles of cardiometabolic disorders, showing poor agreement in classifying individuals (normal vs. altered) and a weak correlation. Therefore, further studies are needed to investigate the role of TyG as a surrogate marker of IR.
{"title":"High triglyceride-glucose index and HOMA-IR are associated with different cardiometabolic profile in adults from the ELSA-Brasil study","authors":"","doi":"10.1016/j.clinbiochem.2024.110793","DOIUrl":"10.1016/j.clinbiochem.2024.110793","url":null,"abstract":"<div><h3>Background and aims</h3><p>Insulin resistance (IR) is a risk factor for several cardiometabolic disorders; however, there is conflicting evidence about the reliability of certain IR markers. In this context, the triglyceride-glucose index (TyG) has been proposed as a surrogate marker for IR. This study aimed to compare the TyG index and homeostasis model assessment of insulin resistance (HOMA-IR).</p></div><div><h3>Methods and results</h3><p>A cross-sectional analysis was conducted using baseline data from 11,314 adults (aged 35–74 years) from the ELSA-Brasil study. The correlation between TyG and HOMA-IR, their interrater reliability, and their predictive value in identifying metabolic syndrome (MetS) were assessed. The mean TyG and HOMA-IR in our sample were 8.81 ± 0.52 and 2.78 ± 1.58 for men, and 8.53 ± 0.48 and 2.49 ± 1.38 for women, respectively. TyG and HOMA-IR showed a weak to moderate correlation with each other (Pearson’s r for men: 0.395 and 0.409 for women, p-value <0.05) and other markers of glycemic metabolism. Additionally, the area under the curve for the prediction of MetS was greater for TyG than HOMA-IR, regardless of sex (TyG: 0.836 for men and 0.826 for women; HOMA-IR: 0.775 for men and 0.787 for women). The concordance between these markers was low (Coheńs kappa coefficient: 0.307 for men and 0.306 for women). Individuals with increased TyG exhibited mainly anthropometrical and glycemic metabolic alterations, whereas those with elevated HOMA-IR displayed mostly lipid-associated metabolic alterations.</p></div><div><h3>Conclusion</h3><p>TyG and HOMA-IR might indicate different profiles of cardiometabolic disorders, showing poor agreement in classifying individuals (normal vs. altered) and a weak correlation. Therefore, further studies are needed to investigate the role of TyG as a surrogate marker of IR.</p></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"131 ","pages":"Article 110793"},"PeriodicalIF":2.5,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141598770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-09DOI: 10.1016/j.clinbiochem.2024.110792
Acute hepatic porphyrias (AHP) comprise four rare monogenic autosomal conditions. Each is linked to a deficiency of heme metabolizing enzymes. Common manifestations include severe abdominal pain, nausea, confusion, hyponatremia, hypertension, tachycardia, and neuropathy. Diagnosis is challenging due to a non-specific, variable presentation with symptoms mimicking other common conditions. Initial diagnosis of AHP can be made with a test for urinary porphobilinogen, δ-aminolevulinic acid and porphyrins using a single random (spot) sample. However, many patients have complications due to delays in diagnosis and management. A novel small interfering RNA-based agent, givosiran, has demonstrated efficacy in reducing acute attacks in a recent Phase III trial, leading to its approval for the management of AHP. Early diagnosis is crucial for the timely introduction of disease-modifying treatments that reduce impairments, enhance quality of life, and extend survival. In this guidance, we aim to improve awareness and outcomes of AHP by making recommendations about diagnosis, monitoring, and treatment in Canada.
{"title":"Canadian guidance for diagnosis and management of acute hepatic porphyrias","authors":"","doi":"10.1016/j.clinbiochem.2024.110792","DOIUrl":"10.1016/j.clinbiochem.2024.110792","url":null,"abstract":"<div><p>Acute hepatic porphyrias (AHP) comprise four rare monogenic autosomal conditions. Each is linked to a deficiency of heme metabolizing enzymes. Common manifestations include severe abdominal pain, nausea, confusion, hyponatremia, hypertension, tachycardia, and neuropathy. Diagnosis is challenging due to a non-specific, variable presentation with symptoms mimicking other common conditions. Initial diagnosis of AHP can be made with a test for urinary porphobilinogen, δ-aminolevulinic acid and porphyrins using a single random (spot) sample. However, many patients have complications due to delays in diagnosis and management. A novel small interfering RNA-based agent, givosiran, has demonstrated efficacy in reducing acute attacks in a recent Phase III trial, leading to its approval for the management of AHP. Early diagnosis is crucial for the timely introduction of disease-modifying treatments that reduce impairments, enhance quality of life, and extend survival. In this guidance, we aim to improve awareness and outcomes of AHP by making recommendations about diagnosis, monitoring, and treatment in Canada.</p></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"131 ","pages":"Article 110792"},"PeriodicalIF":2.5,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0009912024000869/pdfft?md5=4dd4a8d1d397846dbb32fc95c33e933f&pid=1-s2.0-S0009912024000869-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141589758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-06DOI: 10.1016/j.clinbiochem.2024.110791
Sevilay Sezer , Ali Oter , Betul Ersoz , Canan Topcuoglu , Halil İbrahim Bulbul , Seref Sagiroglu , Murat Akin , Gulsen Yilmaz
Introduction
Monitoring LDL-C levels is essential in clinical practice because there is a direct relation between low-density lipoprotein cholesterol (LDL-C) levels and atherosclerotic heart disease risk. Therefore, measurement or estimate of LDL-C is critical. The present study aims to evaluate Artificial Intelligence (AI) and Explainable AI (XAI) methodologies in predicting LDL-C levels while emphasizing the interpretability of these predictions.
Materials and methods
We retrospectively reviewed data from the Laboratory Information System (LIS) of Ankara Etlik City Hospital (AECH). We included 60.217 patients with standard lipid profiles (total cholesterol [TC], high-density lipoprotein cholesterol, and triglycerides) paired with same-day direct LDL-C results. AI methodologies, such as Gradient Boosting (GB), Random Forests (RF), Support Vector Machines (SVM), and Decision Trees (DT), were used to predict LDL-C and compared directly measured and calculated LDL-C with formulas. XAI techniques such as Shapley additive annotation (SHAP) and locally interpretable model-agnostic explanation (LIME) were used to interpret AI models and improve their explainability.
Results
Predicted LDL-C values using AI, especially RF or GB, showed a stronger correlation with direct measurement LDL-C values than calculated LDL-C values with formulas. TC was shown to be the most influential factor in LDL-C prediction using SHAP and LIME. The agreement between the treatment groups based on NCEP ATPIII guidelines according to measured LDL-C and the LDL-C groups obtained with AI was higher than that obtained with formulas.
Conclusions
It can be concluded that AI is not only a reliable method but also an explainable method for LDL-C estimation and classification.
{"title":"Explainable artificial intelligence for LDL cholesterol prediction and classification","authors":"Sevilay Sezer , Ali Oter , Betul Ersoz , Canan Topcuoglu , Halil İbrahim Bulbul , Seref Sagiroglu , Murat Akin , Gulsen Yilmaz","doi":"10.1016/j.clinbiochem.2024.110791","DOIUrl":"10.1016/j.clinbiochem.2024.110791","url":null,"abstract":"<div><h3>Introduction</h3><p>Monitoring LDL-C levels is essential in clinical practice because there is a direct relation between low-density lipoprotein cholesterol (LDL-C) levels and atherosclerotic heart disease risk. Therefore, measurement or estimate of LDL-C is critical. The present study aims to evaluate Artificial Intelligence (AI) and Explainable AI (XAI) methodologies in predicting LDL-C levels while emphasizing the interpretability of these predictions.</p></div><div><h3>Materials and methods</h3><p>We retrospectively reviewed data from the Laboratory Information System (LIS) of Ankara Etlik City Hospital (AECH). We included 60.217 patients with standard lipid profiles (total cholesterol [TC], high-density lipoprotein cholesterol, and triglycerides) paired with same-day direct LDL-C results. AI methodologies, such as Gradient Boosting (GB), Random Forests (RF), Support Vector Machines (SVM), and Decision Trees (DT), were used to predict LDL-C and compared directly measured and calculated LDL-C with formulas. XAI techniques such as Shapley additive annotation (SHAP) and locally interpretable model-agnostic explanation (LIME) were used to interpret AI models and improve their explainability.</p></div><div><h3>Results</h3><p>Predicted LDL-C values using AI, especially RF or GB, showed a stronger correlation with direct measurement LDL-C values than calculated LDL-C values with formulas. TC was shown to be the most influential factor in LDL-C prediction using SHAP and LIME. The agreement between the treatment groups based on NCEP ATPIII guidelines according to measured LDL-C and the LDL-C groups obtained with AI was higher than that obtained with formulas.</p></div><div><h3>Conclusions</h3><p>It can be concluded that AI is not only a reliable method but also an explainable method for LDL-C estimation and classification.</p></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"130 ","pages":"Article 110791"},"PeriodicalIF":2.5,"publicationDate":"2024-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141558192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-06DOI: 10.1016/j.clinbiochem.2024.110789
Gorkem Berna Koyun , Serdar Berk , Omer Tamer Dogan
Introduction
Quick and simple parameters are needed to predict mortality in patients with idiopathic pulmonary fibrosis (IPF). In this way, risky patients will have the opportunity to receive early and effective treatment. In this study, we examined whether the Fibrosis-4 index (FIB-4) and systemic immune inflammation index (SII) are associated with mortality in IPF patients.
Materials and methods
The study was designed retrospectively. 100 patients diagnosed with IPF were included in the study. Variables between living patients and deceased patients were examined.
Results
Out of a total of 100 patients, 67 were divided into the surviving group and 33 into the non-surviving group. In multivariate analysis, high FIB-4 and SII values were significantly associated with an increased risk of death.
Conclusion
FIB-4 and SII are parameters that can predict mortality in IPF patients. In this way, IPF patients with high mortality risk will be identified earlier and more effective methods will be used in follow-up and treatment.
{"title":"The importance of SII and FIB-4 scores in predicting mortality in idiopathic pulmonary fibrosis patients","authors":"Gorkem Berna Koyun , Serdar Berk , Omer Tamer Dogan","doi":"10.1016/j.clinbiochem.2024.110789","DOIUrl":"10.1016/j.clinbiochem.2024.110789","url":null,"abstract":"<div><h3>Introduction</h3><p>Quick and simple parameters are needed to predict mortality in patients with idiopathic pulmonary fibrosis (IPF). In this way, risky patients will have the opportunity to receive early and effective treatment. In this study, we examined whether the Fibrosis-4 index (FIB-4) and systemic immune inflammation index (SII) are associated with mortality in IPF patients.</p></div><div><h3>Materials and methods</h3><p>The study was designed retrospectively. 100 patients diagnosed with IPF were included in the study. Variables between living patients and deceased patients were examined.</p></div><div><h3>Results</h3><p>Out of a total of 100 patients, 67 were divided into the surviving group and 33 into the non-surviving group. In multivariate analysis, high FIB-4 and SII values were significantly associated with an increased risk of death.</p></div><div><h3>Conclusion</h3><p>FIB-4 and SII are parameters that can predict mortality in IPF patients. In this way, IPF patients with high mortality risk will be identified earlier and more effective methods will be used in follow-up and treatment.</p></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"131 ","pages":"Article 110789"},"PeriodicalIF":2.5,"publicationDate":"2024-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141558193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-03DOI: 10.1016/j.clinbiochem.2024.110788
F.J. Lievanos-Ruiz, B. Fenton-Navarro
Oxidative stress (OS) results from the imbalance between the production of reactive oxygen species and the body’s antioxidant mechanisms and is associated with various diseases, including depression. Antioxidants protect cells by neutralizing free radicals and include enzymatic components such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), glutathione reductase (GR), and glutathione S-transferase (GST). The concentration of these biomarkers can quantify OS. This research aimed to gather available information published in the last ten years about the concentration of enzymatic OS biomarkers in samples from patients with depressive disorders. Method: A systematic review was conducted following the PRISMA guidelines, including original scientific articles that evaluated enzymatic OS biomarkers in participants with depressive disorders, using the keywords and boolean operators “superoxide dismutase” OR “catalase” OR “glutathione” AND “depress*” in the databases PubMed, SAGE Journals, DOAJ, Scielo, Dialnet, and Redalyc. Results: The initial search showed 614 results, with only 28 articles meeting the selection criteria. It was observed that all evaluated oxidative stress enzymatic markers showed a significant increase or decrease in patients with depressive disorders, due to a wide variability in the depressive disorders studied, the type of biological sample analyzed, and the techniques used. Conclusion: There is evidence of the relationship between enzymatic OS biomarkers and depressive disorders, but additional studies are needed to clarify the nature of this relationship, particularly considering the different types of depressive disorders.
{"title":"Enzymatic biomarkers of oxidative stress in patients with depressive disorders. A systematic review","authors":"F.J. Lievanos-Ruiz, B. Fenton-Navarro","doi":"10.1016/j.clinbiochem.2024.110788","DOIUrl":"10.1016/j.clinbiochem.2024.110788","url":null,"abstract":"<div><p>Oxidative stress (OS) results from the imbalance between the production of reactive oxygen species and the body’s antioxidant mechanisms and is associated with various diseases, including depression. Antioxidants protect cells by neutralizing free radicals and include enzymatic components such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), glutathione reductase (GR), and glutathione S-transferase (GST). The concentration of these biomarkers can quantify OS. This research aimed to gather available information published in the last ten years about the concentration of enzymatic OS biomarkers in samples from patients with depressive disorders. Method: A systematic review was conducted following the PRISMA guidelines, including original scientific articles that evaluated enzymatic OS biomarkers in participants with depressive disorders, using the keywords and boolean operators “superoxide dismutase” OR “catalase” OR “glutathione” AND “depress*” in the databases PubMed, SAGE Journals, DOAJ, Scielo, Dialnet, and Redalyc. Results: The initial search showed 614 results, with only 28 articles meeting the selection criteria. It was observed that all evaluated oxidative stress enzymatic markers showed a significant increase or decrease in patients with depressive disorders, due to a wide variability in the depressive disorders studied, the type of biological sample analyzed, and the techniques used. Conclusion: There is evidence of the relationship between enzymatic OS biomarkers and depressive disorders, but additional studies are needed to clarify the nature of this relationship, particularly considering the different types of depressive disorders.</p></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"130 ","pages":"Article 110788"},"PeriodicalIF":2.5,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141537608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This study aims to investigate the alteration of salivary biomarker profiling in the development of oral submucous fibrosis (OSMF) and to explore the influence of saliva in the diagnosis of OSMF. A systematic search of published articles using the PRISMA guidelines was conducted to identify relevant studies on OSMF and saliva. All eligible studies, including case-control, cross-sectional studies, cohort, and pilot studies, contained the evaluation of salivary biomarker profiling in patients with OSMF. Salivary biomarker data from 28 selected articles were categorized into nine groups, and their mean values were determined. A three-step meta-analysis was performed by grouping salivary biomarker profiling into more heterogeneous categories based on OSMF classification, considering functional, histological, and clinical grading. The salivary biomarker profiling analysis revealed significant alterations in all markers, indicating their efficacy in OSMF diagnosis. Subgroup analyses highlighted significant associations in oxidative stress and protein with increased mean values, particularly emphasizing lipid peroxidase (LPO), malondialdehyde (MDA), and lactate dehydrogenase (LDH). Conversely, decreased mean values were observed in glutathione, glutathione peroxidase (GPx), superoxide dismutase (SOD), and vitamins. Notably, OSMF grading analysis demonstrated a significant difference in weighted effect sizes for histological grading, particularly in stage IV. The study underscores the alteration of specific salivary biomarkers, particularly those associated with LPO, MDA, LDH, glutathione, GPx, SOD, and vitamins, in diagnosing and grading OSMF.
本研究旨在调查唾液生物标志物图谱在口腔黏膜下纤维化(OSMF)发病过程中的变化,并探讨唾液在诊断口腔黏膜下纤维化中的影响。研究人员按照PRISMA指南对已发表的文章进行了系统检索,以确定与口腔黏膜下纤维化和唾液相关的研究。所有符合条件的研究,包括病例对照研究、横断面研究、队列研究和试点研究,都包含了对OSMF患者唾液生物标志物分析的评估。28 篇入选文章的唾液生物标志物数据被分为九组,并确定了其平均值。根据OSMF的分类,考虑功能、组织学和临床分级,将唾液生物标志物分析分为更多的异质性类别,从而进行了三步荟萃分析。唾液生物标志物分析显示,所有标志物都发生了显著变化,这表明它们在OSMF诊断中的功效。亚组分析显示,氧化应激和蛋白质与平均值升高有明显关联,尤其是脂质过氧化物酶(LPO)、丙二醛(MDA)和乳酸脱氢酶(LDH)。相反,谷胱甘肽、谷胱甘肽过氧化物酶(GPx)、超氧化物歧化酶(SOD)和维生素的平均值则有所下降。值得注意的是,OSMF 分级分析表明,组织学分级的加权效应大小存在显著差异,尤其是在 IV 期。该研究强调了在诊断和分级 OSMF 时,特定唾液生物标志物的变化,尤其是与 LPO、MDA、LDH、谷胱甘肽、GPx、SOD 和维生素相关的生物标志物的变化。
{"title":"Alteration of salivary LPO, MDA, LDH, glutathione, GPx, SOD and vitamins in oral submucous fibrosis: A three-level meta-analysis study","authors":"Meircurius Dwi Condro Surboyo , Rizky Merdietio Boedi , Fatma Yasmin Mahdani , Nurina Febriyanti Ayuningtyas , Basher Shalgm , Dimas Bayu Paramananda , Ina Indriyani","doi":"10.1016/j.clinbiochem.2024.110790","DOIUrl":"10.1016/j.clinbiochem.2024.110790","url":null,"abstract":"<div><p>This study aims to investigate the alteration of salivary biomarker profiling in the development of oral submucous fibrosis (OSMF) and to explore the influence of saliva in the diagnosis of OSMF. A systematic search of published articles using the PRISMA guidelines was conducted to identify relevant studies on OSMF and saliva. All eligible studies, including case-control, cross-sectional studies, cohort, and pilot studies, contained the evaluation of salivary biomarker profiling in patients with OSMF. Salivary biomarker data from 28 selected articles were categorized into nine groups, and their mean values were determined. A three-step <em>meta</em>-analysis was performed by grouping salivary biomarker profiling into more heterogeneous categories based on OSMF classification, considering functional, histological, and clinical grading. The salivary biomarker profiling analysis revealed significant alterations in all markers, indicating their efficacy in OSMF diagnosis. Subgroup analyses highlighted significant associations in oxidative stress and protein with increased mean values, particularly emphasizing lipid peroxidase (LPO), malondialdehyde (MDA), and lactate dehydrogenase (LDH). Conversely, decreased mean values were observed in glutathione, glutathione peroxidase (GPx), superoxide dismutase (SOD), and vitamins. Notably, OSMF grading analysis demonstrated a significant difference in weighted effect sizes for histological grading, particularly in stage IV. The study underscores the alteration of specific salivary biomarkers, particularly those associated with LPO, MDA, LDH, glutathione, GPx, SOD, and vitamins, in diagnosing and grading OSMF.</p></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"130 ","pages":"Article 110790"},"PeriodicalIF":2.5,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141537607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}