Pub Date : 2020-09-16eCollection Date: 2020-01-01DOI: 10.1177/1177271920958704
Deborah Jo Levine, David J Ross, Edward Sako
{"title":"Single Center \"Snapshot\" Experience With Donor-Derived Cell-Free DNA After Lung Transplantation.","authors":"Deborah Jo Levine, David J Ross, Edward Sako","doi":"10.1177/1177271920958704","DOIUrl":"10.1177/1177271920958704","url":null,"abstract":"","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":"15 ","pages":"1177271920958704"},"PeriodicalIF":3.8,"publicationDate":"2020-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/69/06/10.1177_1177271920958704.PMC7498978.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38424744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-09-09eCollection Date: 2020-01-01DOI: 10.1177/1177271920954828
Ignacio I Álvarez-Rodríguez, Eduardo Castaño-Tostado, David G García-Gutiérrez, Rosalía Reynoso-Camacho, Juana E Elton-Puente, Alicia Barajas-Pozos, Iza F Pérez-Ramírez
Diabetic foot ulcer (DFU) is a common complication of type 2 diabetes mellitus (T2DM) characterized by ulcer formation, which can lead to the amputation of lower extremities. However, the metabolic alterations related to this complication are not completely elucidated. Therefore, we carried out a metabolomic analysis of serum samples obtained from T2DM adult patients diagnosed with diabetic foot ulcer in a cross-sectional, observational, and comparative study. Eighty-four volunteers were classified into the following groups: without T2DM (control group, n = 30) and with T2DM and different stages of diabetic foot ulcer according to Wagner-Meggitt classification system: DFU G0 (n = 11), DFU G1 (n = 14), DFU G2 (n = 16), and DFU G3 (n = 13). The non-target metabolomic profile followed by chemometric analysis revealed that lysophosphatidylethanolamine (16:1) could be proposed as key metabolite related to the onset of diabetic foot ulcer; however, this phospholipid was not affected by diabetic foot ulcer progression. Therefore, further studies are necessary to validate these phospholipids as biomarker candidates for the early diagnosis of diabetic foot ulcer in T2DM patients.
{"title":"Non-Targeted Metabolomic Analysis Reveals Serum Phospholipid Alterations in Patients with Early Stages of Diabetic Foot Ulcer.","authors":"Ignacio I Álvarez-Rodríguez, Eduardo Castaño-Tostado, David G García-Gutiérrez, Rosalía Reynoso-Camacho, Juana E Elton-Puente, Alicia Barajas-Pozos, Iza F Pérez-Ramírez","doi":"10.1177/1177271920954828","DOIUrl":"https://doi.org/10.1177/1177271920954828","url":null,"abstract":"<p><p>Diabetic foot ulcer (DFU) is a common complication of type 2 diabetes mellitus (T2DM) characterized by ulcer formation, which can lead to the amputation of lower extremities. However, the metabolic alterations related to this complication are not completely elucidated. Therefore, we carried out a metabolomic analysis of serum samples obtained from T2DM adult patients diagnosed with diabetic foot ulcer in a cross-sectional, observational, and comparative study. Eighty-four volunteers were classified into the following groups: without T2DM (control group, n = 30) and with T2DM and different stages of diabetic foot ulcer according to Wagner-Meggitt classification system: DFU G0 (n = 11), DFU G1 (n = 14), DFU G2 (n = 16), and DFU G3 (n = 13). The non-target metabolomic profile followed by chemometric analysis revealed that lysophosphatidylethanolamine (16:1) could be proposed as key metabolite related to the onset of diabetic foot ulcer; however, this phospholipid was not affected by diabetic foot ulcer progression. Therefore, further studies are necessary to validate these phospholipids as biomarker candidates for the early diagnosis of diabetic foot ulcer in T2DM patients.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":"15 ","pages":"1177271920954828"},"PeriodicalIF":3.8,"publicationDate":"2020-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1177271920954828","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38496160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-08-21eCollection Date: 2020-01-01DOI: 10.1177/1177271920950319
Elena Camporesi, Johanna Nilsson, Ann Brinkmalm, Bruno Becker, Nicholas J Ashton, Kaj Blennow, Henrik Zetterberg
Synapses are the site for brain communication where information is transmitted between neurons and stored for memory formation. Synaptic degeneration is a global and early pathogenic event in neurodegenerative disorders with reduced levels of pre- and postsynaptic proteins being recognized as a core feature of Alzheimer’s disease (AD) pathophysiology. Together with AD, other neurodegenerative and neurodevelopmental disorders show altered synaptic homeostasis as an important pathogenic event, and due to that, they are commonly referred to as synaptopathies. The exact mechanisms of synapse dysfunction in the different diseases are not well understood and their study would help understanding the pathogenic role of synaptic degeneration, as well as differences and commonalities among them and highlight candidate synaptic biomarkers for specific disorders. The assessment of synaptic proteins in cerebrospinal fluid (CSF), which can reflect synaptic dysfunction in patients with cognitive disorders, is a keen area of interest. Substantial research efforts are now directed toward the investigation of CSF synaptic pathology to improve the diagnosis of neurodegenerative disorders at an early stage as well as to monitor clinical progression. In this review, we will first summarize the pathological events that lead to synapse loss and then discuss the available data on established (eg, neurogranin, SNAP-25, synaptotagmin-1, GAP-43, and α-syn) and emerging (eg, synaptic vesicle glycoprotein 2A and neuronal pentraxins) CSF biomarkers for synapse dysfunction, while highlighting possible utilities, disease specificity, and technical challenges for their detection.
{"title":"Fluid Biomarkers for Synaptic Dysfunction and Loss.","authors":"Elena Camporesi, Johanna Nilsson, Ann Brinkmalm, Bruno Becker, Nicholas J Ashton, Kaj Blennow, Henrik Zetterberg","doi":"10.1177/1177271920950319","DOIUrl":"10.1177/1177271920950319","url":null,"abstract":"Synapses are the site for brain communication where information is transmitted between neurons and stored for memory formation. Synaptic degeneration is a global and early pathogenic event in neurodegenerative disorders with reduced levels of pre- and postsynaptic proteins being recognized as a core feature of Alzheimer’s disease (AD) pathophysiology. Together with AD, other neurodegenerative and neurodevelopmental disorders show altered synaptic homeostasis as an important pathogenic event, and due to that, they are commonly referred to as synaptopathies. The exact mechanisms of synapse dysfunction in the different diseases are not well understood and their study would help understanding the pathogenic role of synaptic degeneration, as well as differences and commonalities among them and highlight candidate synaptic biomarkers for specific disorders. The assessment of synaptic proteins in cerebrospinal fluid (CSF), which can reflect synaptic dysfunction in patients with cognitive disorders, is a keen area of interest. Substantial research efforts are now directed toward the investigation of CSF synaptic pathology to improve the diagnosis of neurodegenerative disorders at an early stage as well as to monitor clinical progression. In this review, we will first summarize the pathological events that lead to synapse loss and then discuss the available data on established (eg, neurogranin, SNAP-25, synaptotagmin-1, GAP-43, and α-syn) and emerging (eg, synaptic vesicle glycoprotein 2A and neuronal pentraxins) CSF biomarkers for synapse dysfunction, while highlighting possible utilities, disease specificity, and technical challenges for their detection.","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":"15 ","pages":"1177271920950319"},"PeriodicalIF":3.8,"publicationDate":"2020-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1177271920950319","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38368135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-08-04eCollection Date: 2020-01-01DOI: 10.1177/1177271920946715
Stuart G Baker, Barnett S Kramer
We review simple methods for evaluating 4 types of biomarkers. First, we discuss the evaluation of surrogate endpoint biomarkers (to shorten a randomized trial) using 2 statistical and 3 biological criteria. Second, we discuss the evaluation of prognostic biomarkers (to predict the risk of disease) by comparing data collection costs with the anticipated net benefit of risk prediction. Third, we discuss the evaluation of predictive markers (to search for a promising subgroup in a randomized trial) using a multivariate subpopulation treatment effect pattern plot involving a risk difference or responders-only benefit function. Fourth, we discuss the evaluation of cancer screening biomarkers (to predict cancer in asymptomatic persons) using methodology to substantially reduce the sample size with stored specimens.
{"title":"Simple Methods for Evaluating 4 Types of Biomarkers: Surrogate Endpoint, Prognostic, Predictive, and Cancer Screening.","authors":"Stuart G Baker, Barnett S Kramer","doi":"10.1177/1177271920946715","DOIUrl":"https://doi.org/10.1177/1177271920946715","url":null,"abstract":"<p><p>We review simple methods for evaluating 4 types of biomarkers. First, we discuss the evaluation of surrogate endpoint biomarkers (to shorten a randomized trial) using 2 statistical and 3 biological criteria. Second, we discuss the evaluation of prognostic biomarkers (to predict the risk of disease) by comparing data collection costs with the anticipated net benefit of risk prediction. Third, we discuss the evaluation of predictive markers (to search for a promising subgroup in a randomized trial) using a multivariate subpopulation treatment effect pattern plot involving a risk difference or responders-only benefit function. Fourth, we discuss the evaluation of cancer screening biomarkers (to predict cancer in asymptomatic persons) using methodology to substantially reduce the sample size with stored specimens.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":"15 ","pages":"1177271920946715"},"PeriodicalIF":3.8,"publicationDate":"2020-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1177271920946715","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38294326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chronic pruritus of unknown origin (CPUO) is a refractory condition. The expression of Interleukin-31 (IL-31), a major pruritogenic cytokine, in CPUO patients has not been investigated. This study aimed to investigate the potential association of IL-31 with CPUO. This was a cross-sectional, analytical study. Patients diagnosed with CPUO and healthy subjects were included at a ratio of 1:2. Serum IL-31 levels were measured in both groups and compared. There were 10 CPUO and 20 healthy subjects who participated in this study. The median IL-31 level in the CPUO group was significantly higher than in the healthy group (127.3 vs 34.4 pg/mL; P < .001). The presence of CPUO was independently associated with IL-31 levels with a coefficient of 89.678 (P < .001). The serum IL-31 cutoff point for CPUO was 56.8 pg/mL, with an area under the receiver operating characteristic curve (ROC) of 100%. Chronic pruritus of unknown origin was significantly and independently associated with higher IL-31 levels. Further clinical trials of IL-31-related treatment may be justified in CPUO patients.
来源不明的慢性瘙痒症(CPUO)是一种难治性疾病。白细胞介素-31 (IL-31),一种主要的致瘙痒细胞因子,在CPUO患者中的表达尚未被研究。本研究旨在探讨IL-31与CPUO的潜在关联。这是一项横断面分析研究。诊断为CPUO的患者与健康受试者按1:2的比例入组。测定两组患者血清IL-31水平并进行比较。共有10名CPUO受试者和20名健康受试者参加本研究。CPUO组IL-31的中位水平显著高于健康组(127.3 vs 34.4 pg/mL;P P
{"title":"Interleukin-31 and Chronic Pruritus of Unknown Origin.","authors":"Kanin Salao, Kittisak Sawanyawisuth, Kengkart Winaikosol, Charoen Choonhakarn, Suteeraporn Chaowattanapanit","doi":"10.1177/1177271920940712","DOIUrl":"https://doi.org/10.1177/1177271920940712","url":null,"abstract":"<p><p>Chronic pruritus of unknown origin (CPUO) is a refractory condition. The expression of Interleukin-31 (IL-31), a major pruritogenic cytokine, in CPUO patients has not been investigated. This study aimed to investigate the potential association of IL-31 with CPUO. This was a cross-sectional, analytical study. Patients diagnosed with CPUO and healthy subjects were included at a ratio of 1:2. Serum IL-31 levels were measured in both groups and compared. There were 10 CPUO and 20 healthy subjects who participated in this study. The median IL-31 level in the CPUO group was significantly higher than in the healthy group (127.3 vs 34.4 pg/mL; <i>P</i> < .001). The presence of CPUO was independently associated with IL-31 levels with a coefficient of 89.678 (<i>P</i> < .001). The serum IL-31 cutoff point for CPUO was 56.8 pg/mL, with an area under the receiver operating characteristic curve (ROC) of 100%. Chronic pruritus of unknown origin was significantly and independently associated with higher IL-31 levels. Further clinical trials of IL-31-related treatment may be justified in CPUO patients.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":"15 ","pages":"1177271920940712"},"PeriodicalIF":3.8,"publicationDate":"2020-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1177271920940712","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38171845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-06-08eCollection Date: 2020-01-01DOI: 10.1177/1177271920929705
Vaibhav Gandhi, Mara H O'Brien, Sumit Yadav
Background: Human saliva has been identified as a novel, practical, and noninvasive source of biomarkers and genetic materials. However, it is equally challenging due to the availability of an abundance of impurities in the form of microbes and other proteinaceous compounds. The objective of this study was to develop a robust, reproducible, and economic method of extracting high-yield and high-quality RNA from whole human saliva.
Methods: The modified TRIzol protocol was developed to extract RNA from saliva (n = 14), followed by complementary DNA synthesis and reverse transcription quantitative polymerase chain reaction analyses for the genes encoding IL1B, ALPL, RUNX2, and ACTB. To compare our protocol with the spin column-based method, we used Qiagen Salivary Protect Micro-RNA spin columns (n = 6). To evaluate and compare the yields and quality of extracted RNAs from both methods, we used (1) Experion Bioanalyzer, (2) QuantiFluor RNA dye, and (3) NanoDrop 2000 Spectrometer.
Results: With the modified TRIzol lysis protocol, a high yield of total RNA, on average 12.34 μg, from saliva was extracted compared with on average 0.2 μg with a spin column-based method. The average RQI (RNA quality index) with the TRIzol method was 7.86, which is also comparable with that of the spin column-based method (RQI = 7.58). QuantiFluor dye used for RNA quantification showed a 16-fold higher yield of RNA concentration using our TRIzol protocol.
Conclusions: Our modified TRIzol protocol is a reproducible method to extract RNA from whole human saliva which can be used for gene expression analysis. This method allows also ensures the quality of RNA required for specific applications such as RNA sequencing.
{"title":"High-Quality and High-Yield RNA Extraction Method From Whole Human Saliva.","authors":"Vaibhav Gandhi, Mara H O'Brien, Sumit Yadav","doi":"10.1177/1177271920929705","DOIUrl":"https://doi.org/10.1177/1177271920929705","url":null,"abstract":"<p><strong>Background: </strong>Human saliva has been identified as a novel, practical, and noninvasive source of biomarkers and genetic materials. However, it is equally challenging due to the availability of an abundance of impurities in the form of microbes and other proteinaceous compounds. The objective of this study was to develop a robust, reproducible, and economic method of extracting high-yield and high-quality RNA from whole human saliva.</p><p><strong>Methods: </strong>The modified TRIzol protocol was developed to extract RNA from saliva (n = 14), followed by complementary DNA synthesis and reverse transcription quantitative polymerase chain reaction analyses for the genes encoding <i>IL1B, ALPL, RUNX2</i>, and <i>ACTB.</i> To compare our protocol with the spin column-based method, we used Qiagen Salivary Protect Micro-RNA spin columns (n = 6). To evaluate and compare the yields and quality of extracted RNAs from both methods, we used (1) Experion Bioanalyzer, (2) QuantiFluor RNA dye, and (3) NanoDrop 2000 Spectrometer.</p><p><strong>Results: </strong>With the modified TRIzol lysis protocol, a high yield of total RNA, on average 12.34 μg, from saliva was extracted compared with on average 0.2 μg with a spin column-based method. The average RQI (RNA quality index) with the TRIzol method was 7.86, which is also comparable with that of the spin column-based method (RQI = 7.58). QuantiFluor dye used for RNA quantification showed a 16-fold higher yield of RNA concentration using our TRIzol protocol.</p><p><strong>Conclusions: </strong>Our modified TRIzol protocol is a reproducible method to extract RNA from whole human saliva which can be used for gene expression analysis. This method allows also ensures the quality of RNA required for specific applications such as RNA sequencing.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":"15 ","pages":"1177271920929705"},"PeriodicalIF":3.8,"publicationDate":"2020-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1177271920929705","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38059630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-06-05eCollection Date: 2020-01-01DOI: 10.1177/1177271920928923
Luisa Veiga, Miguel Brito, Carina Silva, José Silva-Nunes
Introduction: Unacylated ghrelin (UAG) is the major form of circulating ghrelin. Initially considered as a nonfunctional peptide, soon after, UAG has been associated to an insulin sensitizing action and to a negative action on energy balance. The aim of this study was to analyze the association between the serum levels of UAG and glucose metabolism parameters in obese women, independently from eventual influence of anthropometrics.
Methods: One hundred lean and 254 obese Caucasian women were studied. Each woman was characterized for anthropometrics, fasting glucose, insulin, HbA1c, and UAG. In addition, obese women were subjected to a classic oral glucose tolerance test (oGTT) to assess glucose and insulin at 120 minutes. Insulin resistance was assessed by the homeostasis model assessment (HOMA-IR). Obese women were classified in 3 glycemic status subgroups (normoglycemia, prediabetes, and diabetes) according to HbA1c and to fasting and oGTT glucose values.
Results: In comparison with the lean group, significantly lower levels of UAG were observed in obese women. However, no significant difference was observed through obesity classes I to III. UAG levels were not significantly different among glycemic status subgroups and did not show any association with glucose, insulin, HOMA-IR, or HbA1c.
Conclusions: Although anthropometry can influence the level of the unacylated form of ghrelin, UAG plasma levels do not associate to glucose homeostasis parameters.
{"title":"Glucose Homeostasis in Obese Women Is Not Associated to Unacylated Ghrelin Plasma Levels.","authors":"Luisa Veiga, Miguel Brito, Carina Silva, José Silva-Nunes","doi":"10.1177/1177271920928923","DOIUrl":"https://doi.org/10.1177/1177271920928923","url":null,"abstract":"<p><strong>Introduction: </strong>Unacylated ghrelin (UAG) is the major form of circulating ghrelin. Initially considered as a nonfunctional peptide, soon after, UAG has been associated to an insulin sensitizing action and to a negative action on energy balance. The aim of this study was to analyze the association between the serum levels of UAG and glucose metabolism parameters in obese women, independently from eventual influence of anthropometrics.</p><p><strong>Methods: </strong>One hundred lean and 254 obese Caucasian women were studied. Each woman was characterized for anthropometrics, fasting glucose, insulin, HbA1c, and UAG. In addition, obese women were subjected to a classic oral glucose tolerance test (oGTT) to assess glucose and insulin at 120 minutes. Insulin resistance was assessed by the homeostasis model assessment (HOMA-IR). Obese women were classified in 3 glycemic status subgroups (normoglycemia, prediabetes, and diabetes) according to HbA1c and to fasting and oGTT glucose values.</p><p><strong>Results: </strong>In comparison with the lean group, significantly lower levels of UAG were observed in obese women. However, no significant difference was observed through obesity classes I to III. UAG levels were not significantly different among glycemic status subgroups and did not show any association with glucose, insulin, HOMA-IR, or HbA1c.</p><p><strong>Conclusions: </strong>Although anthropometry can influence the level of the unacylated form of ghrelin, UAG plasma levels do not associate to glucose homeostasis parameters.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":"15 ","pages":"1177271920928923"},"PeriodicalIF":3.8,"publicationDate":"2020-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1177271920928923","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38059629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-05-15eCollection Date: 2020-01-01DOI: 10.1177/1177271920917941
Richard J Durrance, Tofura Ullah, Harsh Patel, Grace Martinez, Kelly Cervellione, Veronica B Zafonte, Khalid Gafoor, Farshad Bagheri
Background: Bacteremia and sepsis are significant contributors to the morbidity, mortality, and economic burden of health care systems worldwide. Procalcitonin has been identified as a potentially useful marker of disease and severity in sepsis. However, the assumption that greater procalcitonin levels correlate with greater burden of disease has not been adequately studied.
Methods: A retrospective chart review of adult patients admitted to an urban teaching hospital with suspected sepsis was undertaken to test the association of elevated procalcitonin (>30 ng/mL) with other markers of sepsis (lactic acid, white blood cell count, percent bands), severity of disease (Sequential Organ Failure Assessment [SOFA] and Acute Physiology and Chronic Health Evaluation-II [APACHE II] scores), and mortality.
Results: In total, 168 patients were identified over 18 months (42% ward, 11% Stepdown, 44% medical intensive care unit [MICU], 2% surgical intensive care unit (STICU), 1% gynecology [GYN]). The Spearman correlation analysis showed that serum procalcitonin level did not correlate with SOFA (P = .238) or APACHE II (P = .918) scores on admission, and did not correlate with survival (Kruskal-Wallis test, P = .937). However, higher serum procalcitonin levels were associated with patients who had positive blood cultures (Kruskal-Wallis test, P = .0016 for Gram-positive and P = .0007 for Gram-negative bacteria). Lactic acid levels on admission strongly correlated with SOFA APACHE II (the Spearman correlation, P < .0001 for both) and mortality (P = .0001 for both).
Conclusions: Higher serum procalcitonin levels above 30 ng/mL failed to correlate with indicators of sepsis, severity of disease (SOFA and APACHE II scores), and mortality but were associated with positive blood cultures. Lactic acid levels did show correlation to both severity of disease and mortality. Serum procalcitonin levels >30 ng/mL do not appear to correlate with the severity of disease in a sample of patients with markedly elevated initial procalcitonin levels.
{"title":"Marked Elevation in Serum Procalcitonin Levels Do Not Correlate With Severity of Disease or Mortality in Hospitalized Patients: A Retrospective Study.","authors":"Richard J Durrance, Tofura Ullah, Harsh Patel, Grace Martinez, Kelly Cervellione, Veronica B Zafonte, Khalid Gafoor, Farshad Bagheri","doi":"10.1177/1177271920917941","DOIUrl":"https://doi.org/10.1177/1177271920917941","url":null,"abstract":"<p><strong>Background: </strong>Bacteremia and sepsis are significant contributors to the morbidity, mortality, and economic burden of health care systems worldwide. Procalcitonin has been identified as a potentially useful marker of disease and severity in sepsis. However, the assumption that greater procalcitonin levels correlate with greater burden of disease has not been adequately studied.</p><p><strong>Methods: </strong>A retrospective chart review of adult patients admitted to an urban teaching hospital with suspected sepsis was undertaken to test the association of elevated procalcitonin (>30 ng/mL) with other markers of sepsis (lactic acid, white blood cell count, percent bands), severity of disease (Sequential Organ Failure Assessment [SOFA] and Acute Physiology and Chronic Health Evaluation-II [APACHE II] scores), and mortality.</p><p><strong>Results: </strong>In total, 168 patients were identified over 18 months (42% ward, 11% Stepdown, 44% medical intensive care unit [MICU], 2% surgical intensive care unit (STICU), 1% gynecology [GYN]). The Spearman correlation analysis showed that serum procalcitonin level did not correlate with SOFA (<i>P</i> = .238) or APACHE II (<i>P</i> = .918) scores on admission, and did not correlate with survival (Kruskal-Wallis test, <i>P</i> = .937). However, higher serum procalcitonin levels were associated with patients who had positive blood cultures (Kruskal-Wallis test, <i>P</i> = .0016 for Gram-positive and <i>P</i> = .0007 for Gram-negative bacteria). Lactic acid levels on admission strongly correlated with SOFA APACHE II (the Spearman correlation, <i>P</i> < .0001 for both) and mortality (<i>P</i> = .0001 for both).</p><p><strong>Conclusions: </strong>Higher serum procalcitonin levels above 30 ng/mL failed to correlate with indicators of sepsis, severity of disease (SOFA and APACHE II scores), and mortality but were associated with positive blood cultures. Lactic acid levels did show correlation to both severity of disease and mortality. Serum procalcitonin levels >30 ng/mL do not appear to correlate with the severity of disease in a sample of patients with markedly elevated initial procalcitonin levels.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":"15 ","pages":"1177271920917941"},"PeriodicalIF":3.8,"publicationDate":"2020-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1177271920917941","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37992278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-05-03eCollection Date: 2020-01-01DOI: 10.1177/1177271920914585
Ashley N Edes, Katie L Edwards, Barbara A Wolfe, Janine L Brown, Douglas E Crews
Allostatic load, or the physiological dysregulation accumulated due to senescence and stress, is an established predictor of human morbidity and mortality and has been proposed as a tool for monitoring health and welfare in captive wildlife. It is estimated by combining biomarkers from multiple somatic systems into allostatic load indices (ALIs), providing a score representing overall physiological dysregulation. Such ALIs have been shown to predict disease and mortality risk in western lowland gorillas. In these prior analyses, we were unable to include lipid markers, a potential limitation as they are key biomarkers in human models. Recently, we were able to assay serum cholesterol and triglycerides and add them to our previous ALI. We then re-examined associations with health outcomes using binomial generalized linear models. We constructed ALIs using 2 pooling strategies and 2 methods. By itself, a 1-unit increase in allostatic load was associated with higher odds of all-cause morbidity and mortality, but results were mixed for cardiac disease. However, the best fit models for all-cause morbidity and cardiac disease included only age and sex. Allostatic load was retained alongside age in the best fit models for mortality, with a 1-unit increase associated with 23% to 45% higher odds of death. Compared with previous results, ALIs containing cholesterol and triglycerides better predict disease risk in zoo-housed western lowland gorillas, as evidenced by larger effect sizes for some models and better goodness of fit for all ALIs. Based on these results, we address methodology for future allostatic load research on wildlife.
{"title":"Allostatic Load Indices With Cholesterol and Triglycerides Predict Disease and Mortality Risk in Zoo-Housed Western Lowland Gorillas (<i>Gorilla gorilla gorilla</i>).","authors":"Ashley N Edes, Katie L Edwards, Barbara A Wolfe, Janine L Brown, Douglas E Crews","doi":"10.1177/1177271920914585","DOIUrl":"10.1177/1177271920914585","url":null,"abstract":"<p><p>Allostatic load, or the physiological dysregulation accumulated due to senescence and stress, is an established predictor of human morbidity and mortality and has been proposed as a tool for monitoring health and welfare in captive wildlife. It is estimated by combining biomarkers from multiple somatic systems into allostatic load indices (ALIs), providing a score representing overall physiological dysregulation. Such ALIs have been shown to predict disease and mortality risk in western lowland gorillas. In these prior analyses, we were unable to include lipid markers, a potential limitation as they are key biomarkers in human models. Recently, we were able to assay serum cholesterol and triglycerides and add them to our previous ALI. We then re-examined associations with health outcomes using binomial generalized linear models. We constructed ALIs using 2 pooling strategies and 2 methods. By itself, a 1-unit increase in allostatic load was associated with higher odds of all-cause morbidity and mortality, but results were mixed for cardiac disease. However, the best fit models for all-cause morbidity and cardiac disease included only age and sex. Allostatic load was retained alongside age in the best fit models for mortality, with a 1-unit increase associated with 23% to 45% higher odds of death. Compared with previous results, ALIs containing cholesterol and triglycerides better predict disease risk in zoo-housed western lowland gorillas, as evidenced by larger effect sizes for some models and better goodness of fit for all ALIs. Based on these results, we address methodology for future allostatic load research on wildlife.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":"15 ","pages":"1177271920914585"},"PeriodicalIF":3.8,"publicationDate":"2020-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/57/65/10.1177_1177271920914585.PMC7218307.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37949885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-04-17eCollection Date: 2020-01-01DOI: 10.1177/1177271920913320
George A Dominguez, Alexander T Polo, John Roop, Anthony J Campisi, Robert A Somer, Adam D Perzin, Dmitry I Gabrilovich, Amit Kumar
Current screening methods for prostate cancer (PCa) result in a large number of false positives making it difficult for clinicians to assess disease status, thus warranting advancements in screening and early detection methods. The goal of this study was to design a liquid biopsy test that uses flow cytometry-based immunophenotyping and artificial neural network (ANN) analysis to detect PCa. Numerous myeloid and lymphoid cell populations, including myeloid-derived suppressor cells, were measured from 156 patients with PCa, 123 with benign prostatic hyperplasia (BPH), and 99 male healthy donor (HD) controls. Using pattern recognition neural network (PRNN) analysis, a type of ANN, PCa detection compared against HD resulted in 96.6% sensitivity, 87.5% specificity, and an area under the curve (AUC) value of 0.97. Detecting patients with higher risk disease (⩾Gleason 7) against lower risk disease (BPH/Gleason 6) resulted in 92.0% sensitivity, 42.7% specificity, and an AUC of 0.72. This study suggests that analyzing flow cytometry immunophenotyping data with PRNNs may prove to be a useful tool to improve PCa detection and reduce the number of unnecessary prostate biopsies performed each year.
{"title":"Detecting Prostate Cancer Using Pattern Recognition Neural Networks With Flow Cytometry-Based Immunophenotyping in At-Risk Men.","authors":"George A Dominguez, Alexander T Polo, John Roop, Anthony J Campisi, Robert A Somer, Adam D Perzin, Dmitry I Gabrilovich, Amit Kumar","doi":"10.1177/1177271920913320","DOIUrl":"10.1177/1177271920913320","url":null,"abstract":"<p><p>Current screening methods for prostate cancer (PCa) result in a large number of false positives making it difficult for clinicians to assess disease status, thus warranting advancements in screening and early detection methods. The goal of this study was to design a liquid biopsy test that uses flow cytometry-based immunophenotyping and artificial neural network (ANN) analysis to detect PCa. Numerous myeloid and lymphoid cell populations, including myeloid-derived suppressor cells, were measured from 156 patients with PCa, 123 with benign prostatic hyperplasia (BPH), and 99 male healthy donor (HD) controls. Using pattern recognition neural network (PRNN) analysis, a type of ANN, PCa detection compared against HD resulted in 96.6% sensitivity, 87.5% specificity, and an area under the curve (AUC) value of 0.97. Detecting patients with higher risk disease (⩾Gleason 7) against lower risk disease (BPH/Gleason 6) resulted in 92.0% sensitivity, 42.7% specificity, and an AUC of 0.72. This study suggests that analyzing flow cytometry immunophenotyping data with PRNNs may prove to be a useful tool to improve PCa detection and reduce the number of unnecessary prostate biopsies performed each year.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":"15 ","pages":"1177271920913320"},"PeriodicalIF":3.4,"publicationDate":"2020-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/48/90/10.1177_1177271920913320.PMC7169353.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37878097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}