Diagnostic accuracy of intrathecal kappa free light chains compared with OCBs in MS

ObjectiveTo determine what kappa free light chain (KFLC) metric has the highest capacity to separate healthy patients from patients with MS, we evaluated the sensitivity, specificity, and the overall diagnostic accuracy of 4 different KFLC metrics. To assess the usefulness of KFLC in the diagnostics of MS, we compared the different KFLC metrics with oligoclonal bands (OCBs), the current gold standard biochemical method to demonstrate intrathecal antibody production.MethodsCSF and plasma were collected from patients with confirmed or suspected MS, other neurological diseases, as well as symptomatic and healthy controls between May 2017 and May 2018 (n = 335) at the Department of Neurology, Karolinska University Hospital, as part of routine diagnostic workup. KFLC analysis and isoelectric focusing for the detection of oligoclonal bands (OCB) were determined and correlated with diagnosis. Receiver operating characteristic (ROC) curve analysis was used to determine accuracy.ResultsOCBs yielded a sensitivity of 87% and a specificity of 100%. All KFLC metrics showed a high sensitivity (89%–95%) and specificity (95%–100%). Using the optimal cutoff according to the Youden Index resulted for the KFLC intrathecal fraction in a cutoff of −0.41 with a sensitivity of 95% and a specificity of 97% and for CSF KFLC/CSF albumin with a cutoff of 1.93 × 10−3 with a sensitivity of 94% and specificity of 100%.ConclusionAll evaluated KFLC metrics have excellent accuracy, and both KFLC intrathecal fraction and CSF KFLC/CSF albumin are at least as good as OCB in separating patients with MS from a control group.Classification of evidenceThis study provides Class III evidence that CSF KFLC accurately distinguishes patients with MS from healthy controls.

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The Relevant Hormonal Levels and Diagnostic Features of Polycystic Ovary Syndrome in Adolescents

Journal of Clinical Medicine ◽

10.3390/jcm9061831 ◽

2020 ◽

Vol 9 (6) ◽

pp. 1831

Author(s):

Elena Khashchenko ◽

Elena Uvarova ◽

Mikhail Vysokikh ◽

Tatyana Ivanets ◽

Lyubov Krechetova ◽

...

Keyword(s):

Logistic Regression ◽

Polycystic Ovary Syndrome ◽

Diagnostic Accuracy ◽

Polycystic Ovary ◽

Regression Function ◽

High Sensitivity ◽

Sex Hormone Binding Globulin ◽

Control Group ◽

Ovary Syndrome ◽

Diagnostic Features

Relevance: The clinical picture of polycystic ovary syndrome (PCOS) is extremely polymorphic, especially in adolescence. At the same time, the diagnostic criteria of PCOS in adolescence are still under discussion, and the hormonal parameters, including anti-Mullerian hormone range and hyperandrogenism, are not determined. The aim of the present study was to characterize the pivotal clinical and hormonal features of PCOS in adolescents and to establish the age-specific thresholds of the most essential hormonal parameters. Design: A case-control study. Methods: The study included 130 girls with PCOS according to the complete Rotterdam criteria, aged 15 to 17 years. The control group consisted of 30 healthy girls with a regular menstrual cycle of the same age. A complete clinical and laboratory examination, hormonal assays, and ultrasound of the pelvic organs were performed. The serums anti-Mullerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), LH/FSH, prolactin, estradiol, 17α-OH progesterone (17α-OHP), androstenedione, testosterone (T), dehydroepiandrosterone sulfate (DHEAS), sex hormone-binding globulin (SHBG), leptin, and free androgen index (FAI) were analyzed. The diagnostic accuracy of AMH, FAI, LH/FSH, T, and androstenedione levels in predicting PCOS in adolescents was established using a logistic regression model and calculating area under the receiver operator characteristic (ROC) curve (AUC). Results: The serum levels of LH (9.0 (5.4–13.8) vs. 3.7 (2.5–4.7) IU/L; p < 0.0001), LH/FSH (1.6 (1.0–2.3) vs. 0.7 (0.5–1.1); p < 0.0001), 17α–OHP (4.1 (3.2–5.1) vs. 3.4 (2.7–3.8) nmol/L; p = 0.0071), cortisol (464.0 ± 147.6 vs. 284.0 ± 129.7 nmol/L; p < 0.0001), prolactin (266.0 (175.0–405.0) vs. 189.0 (142.0–269.0) mIU/L; p = 0.0141), T (1.9 (1.2–2.5) vs. 0.8 (0.7–1.1) nmol/L; p < 0.0001), androstenedione (15.8 (11.6–23.2) vs. 8.3 (6.5–10.8) ng/mL; p < 0.0001), AMH (9.5 (7.5–14.9) vs. 5.8 (3.8–6.9) ng/mL; p < 0.0001), FAI (5.5 (2.8–7.0) vs. 1.6 (1.1–2.3); p < 0.0001), SHBG (37.0 (24.7–55.5) vs. 52.9 (39.0–67.6) nmol/L; p = 0.0136), DHEAS (6.8 ± 3.2 vs. 5.1 ± 1.5 μmol/L; p = 0.0039), and leptin (38.7 ± 27.1 vs. 23.7 ± 14.0 ng/mL; p = 0.0178) were significantly altered in the PCOS patients compared to the controls. Multivariate analysis of all studied hormonal and instrumental parameters of PCOS in adolescents revealed as the most essential: AMH level > 7.20 ng/mL, FAI > 2.75, androstenedione > 11.45 ng/mL, total T > 1.15 nmol/L, LH/FSH ratio > 1.23, and the volume of each ovary > 10.70 cm3 (for each criterion sensitivity ≥ 75.0–93.0%, specificity ≥ 83.0–93.0%). The diagnostic accuracy of PCOS determination was 90.2–91.6% with the combined use of either four detected indexes, which was significantly higher than the use of each index separately. The accuracy of PCOS diagnostics reached 92% using AMH and leptin concentrations when the value of the logistic regression function [85.73 − (1.73 × AMH) − (0.12 × Leptin)] was less than 70.72. Conclusions: The results of the study estimate the threshold for AMH, FAI, androstenedione, testosterone, LH/FSH, and ovarian volume, which could be suggested for use in the PCOS diagnostics in adolescents with a high sensitivity and specificity. Moreover, the combination of either four determined indexes improved the diagnostic accuracy for the PCOS detection in adolescents.

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Is suicidal ideation associated with allergic asthma and allergic rhinitis?

Jornal Brasileiro de Pneumologia ◽

10.1590/s1806-37562017000000129 ◽

2018 ◽

Vol 44 (1) ◽

pp. 31-35 ◽

Cited By ~ 2

Author(s):

Martín Bedolla-Barajas ◽

Norma Angélica Pulido-Guillén ◽

Bolívar Vivar-Aburto ◽

Jaime Morales-Romero ◽

José Raúl Ortiz-Peregrina ◽

...

Keyword(s):

Allergic Rhinitis ◽

Suicidal Ideation ◽

Allergic Asthma ◽

Allergic Diseases ◽

Cross Sectional Study ◽

University Hospital ◽

Control Group ◽

Healthy Controls ◽

Cross Sectional ◽

And Control

ABSTRACT Objective: To investigate whether there is an association between suicidal ideation (SI) and allergic diseases in adults. Methods: This was a comparative cross-sectional study involving individuals ranging from 20 to 50 years of age recruited from a university hospital in the city of Guadalajara, Mexico. We included patients with a confirmed diagnosis of allergic asthma, those with a confirmed diagnosis of allergic rhinitis, and healthy controls. All subjects completed the Beck Depression Inventory-II (BDI-II), which includes an item that evaluates the presence of suicidal thoughts or desires within the last two weeks, in order to identify SI. Results: The sample comprised 115 patients with allergic asthma, 111 patients with allergic rhinitis, and 96 healthy controls. The number of individuals identified with SI in the three groups were, respectively, 17 (14.8%), 13 (11.7%), and 8 (8.3%). Regarding the presence of SI, no statistically significant association was found in the allergic asthma group (OR = 1.98; 95% CI: 0.78-4.64; p = 0.154) or in the allergic rhinitis group (OR = 1.46; 95% CI: 0.58-3.68; p = 0.424) when they were compared with the control group. However, the presence of depression was associated with SI in the three groups: allergic asthma (OR = 12.36; 95% CI: 2.67-57.15; p = 0.001); allergic rhinitis (OR = 6.20; 95% CI: 1.66-23.14; p = 0.006); and control (OR = 21.0; 95% CI: 3.75-117.36; p < 0,001). Conclusions: In comparison with the control group, no association was found between SI and the groups with allergic diseases. In contrast, there was association between SI and depression in the three groups.

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Abstract 15928: Relative Sparing of Apical Longitudinal Strain for Detection of Cardiac Amyloidosis: Intervendor Variation

Circulation ◽

10.1161/circ.142.suppl_3.15928 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Julia M Simkowski ◽

Michael Jiang ◽

NADIA El HANGOUCHE ◽

Jeesoo Lee ◽

Milica Marion ◽

...

Keyword(s):

Cardiac Amyloidosis ◽

Longitudinal Strain ◽

Global Longitudinal Strain ◽

High Sensitivity ◽

High Specificity ◽

Left Ventricular ◽

Control Group ◽

Lower Sensitivity ◽

Medical Systems ◽

Roc Curve Analysis

Introduction: Relative apical longitudinal strain (RALS) is defined as (average apical LS/(average basal & mid-ventricular LS)). A threshold of 2 has been found to have high sensitivity and specificity for differentiating cardiac amyloidosis (CA) from other causes of left ventricular hypertrophy (LVH). This threshold was developed using General Electric (GE) software, and its reproducibility among different software vendors is unknown. Hypothesis: In patients with CA, regional segmental LS patterns and relative apical longitudinal strain will vary among software vendors. Methods: Speckle-tracking echocardiography was retroactively performed by an experienced technician on two patient cohorts, CA (n=52) and LVH (n=52), using software from two independent vendors: EchoPAC (GE Medical Systems) and TomTEC (TOMTEC Imaging Systems GMBH). For each vendor and patient, strain values for the basal, mid, and apical segments were averaged to obtain three regional LS values which were then used to calculate global longitudinal strain (GLS) and RALS. Results: EchoPAC demonstrated greater average apical LS (-16.5±5.7 vs -13.1±6.6, p<0.001) and RALS (2.1±0.9 vs 1.7±0.7, p<0.001) compared to TomTEC. Bland-Altman analysis yielded a mean bias of -0.4 with limit of agreement 2.2 (p<0.001) in RALS between the two vendors. ROC curve analysis using a RALS cutoff of 2 to differentiate CA from the overall control group showed similarly high specificity (EchoPAC 85%, TomTEC 83%) between vendors but lower sensitivity for TomTEC (23% vs 45%) (Figure 1). LVH subgroup analysis showed similar comparisons. Overall difference in area-under-curve (AUC) was significant (AUC = 0.78 EchoPAC vs AUC = 0.52 TomTEC, p < 0.001). Conclusions: Software measurements of regional LS and thus RALS vary between vendors. Further efforts are needed for intervendor regional strain fidelity. For now, different RALS thresholds to diagnose CA may be needed for various vendors.

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Evidence for potential involvement of pro-inflammatory adipokines in the pathogenesis of idiopathic intracranial hypertension

Cephalalgia ◽

10.1177/0333102416650705 ◽

2016 ◽

Vol 37 (6) ◽

pp. 525-531 ◽

Cited By ~ 10

Author(s):

Bedia Samancı ◽

Yavuz Samancı ◽

Erdem Tüzün ◽

Güneş Altıokka-Uzun ◽

Esme Ekizoğlu ◽

...

Keyword(s):

Intracranial Hypertension ◽

Idiopathic Intracranial Hypertension ◽

Oligoclonal Bands ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

Healthy Controls ◽

Childbearing Age ◽

Serum Samples ◽

Necrosis Factor Alpha ◽

Tnf Α

Background Although specific role players are currently unknown, contribution of inflammatory mediators has been suggested in the pathophysiology of idiopathic intracranial hypertension (IIH), which is a disease more prevalent in obese female individuals of childbearing age. We aimed to investigate the levels of adipokines and cytokines to demonstrate possible markers for inflammation that participate in IIH pathophysiology and their association with clinical features of IIH. Methods IIH patients, diagnosed according to the revised criteria, and age-, gender- and body mass index (BMI)-matched healthy controls were enrolled in this study. Serum samples were evaluated for insulin-like growth factor 1, insulin, nesfatin, adiponectin, interleukin (IL)-1β, IL-6, IL-8, leptin, plasminogen activator inhibitor type-1, resistin, tumour necrosis factor-alpha (TNF-α) and monocyte chemotactic protein 1 via enzyme-linked immunosorbent assay or multiplex immunoassays. Results IL-1β level was significantly higher ( p = 0.012), and IL-8 and TNF-α levels were significantly lower in the IIH group ( p < 0.001 and p = 0.008, respectively) compared to the control group. There were no correlations between the cytokine/adipokine levels and age, BMI, disease duration, and cerebrospinal fluid oligoclonal bands. There were also no significant differences in cytokine and adipokine levels between IIH patients regarding visual impairment. However, statistically significant differences were found between IIH patients with relapse versus healthy controls regarding IL-1β ( p = 0.007), IL-8 ( p = 0.001) and TNF-α ( p = 0.017) levels. Other investigated cytokines and adipokines showed no significant alterations in IIH patients investigated in the remission period. Conclusion Altered serum levels of IL-1β, IL-8 and TNF-α seem to be associated with IIH pathogenesis, and these cytokines may be used as prognostic markers in IIH to predict relapse.

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Evaluation of a novel immunoassay to detect p-tau Thr217 in the CSF to distinguish Alzheimer disease from other dementias

Neurology ◽

10.1212/wnl.0000000000010814 ◽

2020 ◽

Vol 95 (22) ◽

pp. e3026-e3035

Author(s):

Jozef Hanes ◽

Andrej Kovac ◽

Hlin Kvartsberg ◽

Eva Kontsekova ◽

Lubica Fialova ◽

...

Keyword(s):

Alzheimer Disease ◽

Positive Predictive Value ◽

Diagnostic Accuracy ◽

Predictive Value ◽

Healthy Controls ◽

Class Iii ◽

Total Tau ◽

Β Amyloid ◽

Healthy Participants

ObjectiveTo investigate whether tau phosphorylated at Thr217 (p-tau T217) assay in CSF can distinguish patients with Alzheimer disease (AD) from patients with other dementias and healthy controls.MethodsWe developed and validated a novel Simoa immunoassay to detect p-tau T217 in CSF. There was a total of 190 participants from 3 cohorts with AD (n = 77) and other neurodegenerative diseases (n = 69) as well as healthy participants (n = 44).ResultsThe p-tau T217 assay (cutoff 242 pg/mL) identified patients with AD with accuracy of 90%, with 78% positive predictive value (PPV), 97% negative predictive value (NPV), 93% sensitivity, and 88% specificity, compared favorably with p-tau T181 ELISA (52 pg/mL), showing 78% accuracy, 58% PPV, 98% NPV, 71% specificity, and 97% sensitivity. The assay distinguished patients with AD from age-matched healthy controls (cutoff 163 pg/mL, 98% sensitivity, 93% specificity), similarly to p-tau T181 ELISA (cutoff 60 pg/mL, 96% sensitivity, 86% specificity). In patients with AD, we found a strong correlation between p-tau T217 and p-tau T181, total tau and β-amyloid 40, but not β-amyloid 42.ConclusionsThis study demonstrates that p-tau T217 displayed better diagnostic accuracy than p-tau T181. The data suggest that the new p-tau T217 assay has potential as an AD diagnostic test in clinical evaluation.Classification of evidenceThis study provides Class III evidence that a CSF immunoassay for p-tau T217 distinguishes patients with AD from patients with other dementias and healthy controls.

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Blood-based NfL

Neurology ◽

10.1212/wnl.0000000000003680 ◽

2017 ◽

Vol 88 (10) ◽

pp. 930-937 ◽

Cited By ~ 156

Author(s):

Oskar Hansson ◽

Shorena Janelidze ◽

Sara Hall ◽

Nadia Magdalinou ◽

Andrew J. Lees ◽

...

Keyword(s):

Diagnostic Accuracy ◽

Single Molecule ◽

Area Under The Curve ◽

Diagnostic Workup ◽

Healthy Controls ◽

Class Iii ◽

Early Disease ◽

Neurofilament Light Chain ◽

Neurofilament Light ◽

Parkinsonian Disorders

Objective:To determine if blood neurofilament light chain (NfL) protein can discriminate between Parkinson disease (PD) and atypical parkinsonian disorders (APD) with equally high diagnostic accuracy as CSF NfL, and can therefore improve the diagnostic workup of parkinsonian disorders.Methods:The study included 3 independent prospective cohorts: the Lund (n = 278) and London (n = 117) cohorts, comprising healthy controls and patients with PD, progressive supranuclear palsy (PSP), corticobasal syndrome (CBS), and multiple system atrophy (MSA), as well as an early disease cohort (n = 109) of patients with PD, PSP, MSA, or CBS with disease duration ≤3 years. Blood NfL concentration was measured using an ultrasensitive single molecule array (Simoa) method, and the diagnostic accuracy to distinguish PD from APD was investigated.Results:We found strong correlations between blood and CSF concentrations of NfL (ρ ≥ 0.73–0.84, p ≤ 0.001). Blood NfL was increased in patients with MSA, PSP, and CBS (i.e., all APD groups) when compared to patients with PD as well as healthy controls in all cohorts (p < 0.001). Furthermore, in the Lund cohort, blood NfL could accurately distinguish PD from APD (area under the curve [AUC] 0.91) with similar results in both the London cohort (AUC 0.85) and the early disease cohort (AUC 0.81).Conclusions:Quantification of blood NfL concentration can be used to distinguish PD from APD. Blood-based NfL might consequently be included in the diagnostic workup of patients with parkinsonian symptoms in both primary care and specialized clinics.Classification of evidence:This study provides Class III evidence that blood NfL levels discriminate between PD and APD.

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Effect of implementing epilepsy educational guidelines on nurses’ performance and patients’ outcomes

Clinical Nursing Studies ◽

10.5430/cns.v9n2p20 ◽

2021 ◽

Vol 9 (2) ◽

pp. 20

Author(s):

Walaa El-khanany Zahran ◽

Wafaa Ismail Sherif ◽

Hanan Abo-Bakr Mohamed

Keyword(s):

Neurological Diseases ◽

Active Role ◽

University Hospital ◽

Self Management ◽

Control Group ◽

Quasi Experimental ◽

Knowledge And Practice ◽

Nursing Guidelines ◽

Patients With Epilepsy ◽

Nurses Knowledge

Objective: Epilepsy is considered one of the most common neurological diseases affecting 65 people worldwide. People with epilepsy are more likely to get injured and die prematurely than the general population. Nurses must acquire professional knowledge related to epilepsy and should strengthen patients to play a more active role in their care to improve their understanding of their diseases. The study aimed to evaluate implementing epilepsy educational guidelines on nurses’ performance and patients’ outcomes.Methods: A quasi-experimental research design was conducted at the Neurology department in Mansoura University Hospital. This study sample is a convenient sample of 28 nurses and a purposive sample of 60 adult patients with epilepsy who attend the neurological department in Mansoura University Hospital.Results: The results indicate a significant improvement in nurses’ knowledge and practice regarding epilepsy. Also, it helped to improve patients’ knowledge and thus promoted epilepsy self-management behaviors in the study group.Conclusions: The designed nursing guidelines have achieved their objectives by improving nurses’ knowledge and practice regarding epileptic patient care, in addition to improving patients’ knowledge and epilepsy self-management scale for the study group compared with the control group.

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Expression and clinical significance of IL7R, NFATc2, and RNF213 in familial and sporadic multiple sclerosis

Scientific Reports ◽

10.1038/s41598-021-98691-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Seyedeh Zahra Hosseini Imani ◽

Zohreh Hojati ◽

Sheyda Khalilian ◽

Fariba Dehghanian ◽

Majid Kheirollahi ◽

...

Keyword(s):

Multiple Sclerosis ◽

Family History ◽

Area Under The Curve ◽

Group Versus ◽

Expression Level ◽

Inflammatory Factors ◽

Control Group ◽

Healthy Controls ◽

Roc Curve Analysis ◽

Axonal Dysfunction

AbstractMultiple sclerosis (MS) is a chronic inflammatory and autoimmune disorder of the central nervous system characterized by myelin loss and axonal dysfunction. Increased production of inflammatory factors such as cytokines has been implicated in axon destruction. In the present study, we compared the expression level of IL7R, NFATc2, and RNF213 genes in the peripheral blood of 72 MS patients (37 familial MS, 35 sporadic MS) and 74 healthy controls (34 individuals with a family history of the disease, 40 healthy controls without a family history) via Real-time PCR. Our results showed that the expression level of IL7R was decreased in the sporadic patients in comparison with other groups. Additionally, there was an increased NFATc2 expression level in MS patients versus healthy controls. Increased expression of NFATc2 in sporadic and familial groups compared to the controls, and familial group versus FDR was also seen. Our results also represented an increased expression level of RNF213 in familial patients as compared to the control group. The similar RNF213 expression between sporadic and control group, as well as FDR and familial group was also seen. Diagnostic evaluation was performed by receiver operating characteristic (ROC) curve analysis and area under the curve (AUC) calculation. The correlation of clinical parameters including onset age and Expanded Disability Status Scale (EDSS) with our gene expression levels were also assessed. Overall, decreased expression level of IL7R in the sporadic cases and increased expression level of NFATc2 may be associated with the pathogenesis of MS disease. Confirmation of the effects of differential expression of RNF213 gene requires further studies in the wider statistical populations.

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Clinical Evaluation of the Diagnostic Role of MicroRNA-155 in Breast Cancer

International Journal of Genomics ◽

10.1155/2020/9514831 ◽

2020 ◽

Vol 2020 ◽

pp. 1-13

Author(s):

Fatemeh Hosseini Mojahed ◽

Amir Hossein Aalami ◽

Vahid Pouresmaeil ◽

Amir Amirabadi ◽

Mahdi Qasemi Rad ◽

...

Keyword(s):

Breast Cancer ◽

Rna Extraction ◽

Tumor Grade ◽

Breast Cancer Diagnosis ◽

Tumor Stage ◽

Lymph Node Involvement ◽

Youden Index ◽

Control Group ◽

Roc Curve Analysis ◽

Ki 67

Aim. Biochemical markers, including microRNAs (miRs), may facilitate the diagnosis and prognosis of breast cancer. This study was aimed at assessing serum miR-155 expression in patients with breast cancer and receptors. Methods. This case-control study was conducted on 36 patients with breast cancer and 36 healthy individuals. After RNA extraction from the patient’s serum, cDNA was synthesized. The expression of miR-155 was measured using RT-qPCR. Demographic and histochemical data were extracted from patient documents. Data were analyzed using the Statistical Package for the Social Sciences (SPSS) software. Results. The mean age of subjects in breast cancer and control groups was 47.64±8.19 and 47.36±7.52 years, respectively. The serum miR-155 expression was higher in the cancer group (1.68±0.66) compared to the control group (p<0.0001). There was a significant relationship between serum miR-155 expression and the tumor grade (p<0.001), tumor stage (p<0.001), and tumor size (p<0.001) of the patients. However, no relationship between miR-155 expression and the presence of lymph node involvement (p=0.15), HER2 (p=0.79), Ki-67 (p=0.9), progesterone receptor (p=0.54), and estrogen receptors (p=0.84) was found. The ROC curve analysis showed that the AUC was 0.89 (77.78% sensitivity and 88.89% specificity), and the cutoff was 1.4 (Youden index: 0.6667) for detecting breast cancer. Conclusion. The findings of this study revealed that serum miR-155 may serve as a potential noninvasive molecular biomarker for breast cancer diagnosis and can help predict the grade of the disease.

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Early detection of pancreatic ductal adenocarcinoma using abnormal urinary fragmentation ratio of a liver-originated protein.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.4_suppl.214 ◽

2019 ◽

Vol 37 (4_suppl) ◽

pp. 214-214

Author(s):

Motoyasu Kan ◽

Shuichi Mitsunaga ◽

Masafumi Ikeda ◽

Izumi Ohno ◽

Hironobu Tsubouchi ◽

...

Keyword(s):

Roc Curve ◽

Curve Analysis ◽

Control Group ◽

Healthy Controls ◽

Roc Curve Analysis ◽

Protein Fragments ◽

Abnormal Protein ◽

Pdac Tissue ◽

Healthy Control ◽

Fragmentation Ratio

214 Background: Non PDAC tissue-originated proteins are cleaved by proteases derived from PDAC, which can result in abnormal cleavage patterns in the urine of PDAC patients. Urinary proteomic analysis for quantifying the ratios of the abnormal protein fragments to the non-fragmented protein levels in the urine may be useful to distinguish early PDAC from healthy controls. This proof-of-concept study was planned to determine the usefulness of measuring the protein fragments from non PDAC tissue-originated proteins in the urine using the multiple-reaction-monitoring technique (MRM) for discriminating resectable PDAC from healthy controls. Methods: Urinary proteins were digested with trypsin, and resultant peptides were measured by MRM analysis and the ratio of the level of each fragment to the non-fragmented protein level (fragmentation ratio) was calculated. Fragments for which the fragmentation ratios were higher in the PDAC group than those in the healthy group were defined as abnormal protein fragments. The diagnostic capability of each abnormal protein fragment for discriminating cases of PDAC from healthy controls was evaluated by receiver operating characteristic (ROC) curve analysis. Results: A total of 21 patients with resectable PDAC and 30 healthy control subjects were enrolled in this study. All the PDAC patients were treated by pancreatic resection. Urine samples for this study were collected prior to the surgery from the PDAC patients. The non PDAC tissue-originated protein was determined as a liver-originated protein. The fragmentation ratios for six fragments were found to be higher in the PDAC group as compared to those in the healthy control group, and these fragments were determined as abnormal protein fragments. ROC curve analysis was performed for each of the abnormal fragments to determine the areas under the curve (AUCs) for discriminating cases of PDAC from healthy controls. The best AUC was 0.81 (95% CI, 0.68-0.91). Conclusions: The urinary fragmentation ratios showed the ability to discriminate cases of resectable PDAC from a healthy control group; abnormal fragmentation ratios may be promising, noninvasively measurable biomarkers of early PDAC.

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