GFAP as a biomarker in frontotemporal dementia and primary psychiatric disorders: diagnostic and prognostic performance

2021 ◽  
pp. jnnp-2021-326487
Author(s):  
Kasper Katisko ◽  
Antti Cajanus ◽  
Nadine Huber ◽  
Olli Jääskeläinen ◽  
Tarja Kokkola ◽  
...  
Keyword(s):  
Psychiatric Disorders ◽  
Brain Atrophy ◽  
Temporal Cortex ◽  
Area Under The Curve ◽  
Repeat Expansion ◽  
Differential Diagnostics ◽  
Characteristic Analysis ◽  
Atrophy Rate ◽  
First Time ◽  
Glial Fibrillar Acidic Protein

BackgroundFrontotemporal lobar degeneration (FTLD) and primary psychiatric disorders (PPD) are characterised by overlapping clinical features but different aetiologies. Here, we assessed for the first time the potential of blood glial fibrillar acidic protein (GFAP), marker of astrogliosis, as a discriminative and prognostic tool in FTLD and PPD.MethodsThe levels of GFAP in serum (sGFAP) of patients with FTLD (N=107) and PPD (N=44) and GFAP in whole blood samples (bGFAP) from FTLD (N=10), PPD (N=10) and healthy controls (N=18) were measured. We evaluated whether the sGFAP levels associate with C9orf72 repeat expansion, survival of FTLD and PPD patients, and brain atrophy assessed cross-sectionally and longitudinally by structural T1W MRI. We also examined the correlation between sGFAP and bGFAP levels in a subset of patients.ResultssGFAP and bGFAP levels were elevated in the FTLD group compared with the PPD or control groups. Receiver operating characteristic analysis indicated an excellent diagnostic performance between FTLD and PPD (the area under the curve (AUC)=0.820, 95% CI 0.745 to 0.896). sGFAP and bGFAP levels showed a strong correlation and elevated sGFAP levels significantly associated with atrophy rate in the temporal cortex and predicted shorter survival time in patients with FTLD. No association with C9orf72 repeat expansion was detected.ConclusionssGFAP enabled differentiation of patients with FTLD and PPD and associated with shorter survival and more severe brain atrophy rate in patients with FTLD. These results suggest that blood-based GFAP represents a minimally invasive and useful biomarker in the differential diagnostics between patients with FTLD and PPD and in evaluating disease progression and astrogliosis in FTLD.

scholarly journals Measles Virus IgG Avidity Assay for Use in Classification of Measles Vaccine Failure in Measles Elimination Settings

2012 ◽  
Vol 19 (11) ◽  
pp. 1810-1817 ◽  
Author(s):  
Sara Mercader ◽  
Philip Garcia ◽  
William J. Bellini
Keyword(s):  
Measles Virus ◽  
Area Under The Curve ◽  
Epidemiological Data ◽  
Diagnostic Tools ◽  
High Avidity ◽  
Characteristic Analysis ◽  
Vaccine Failure ◽  
Avidity Assay ◽  
Igg Avidity

ABSTRACTIn regions where endemic measles virus has been eliminated, diagnostic assays are needed to assist in correctly classifying measles cases irrespective of vaccination status. A measles IgG avidity assay was configured using a commercially available measles-specific IgG enzyme immunoassay by modifying the protocol to include three 5-min washes with diethylamine (60 mM; pH 10.25) following serum incubation; serum was serially diluted, and the results were expressed as the end titer avidity index. Receiver operating characteristic analysis was used for evaluation and validation and to establish low (≤30%) and high (≥70%) end titer avidity thresholds. Analysis of 319 serum specimens expected to contain either high- or low-avidity antibodies according to clinical and epidemiological data indicated that the assay is highly accurate, with an area under the curve of 0.998 (95% confidence interval [CI], 0.978 to 1.000), sensitivity of 91.9% (95% CI, 83.2% to 97.0%), and specificity of 98.4% (95% CI, 91.6% to 100%). The assay is rapid (<2 h) and precise (standard deviation [SD], 4% to 7%). In 18 samples from an elimination setting outbreak, the assay identified 2 acute measles cases with low-avidity results; both were IgM-positive samples. Additionally, 11 patients (15 samples) with modified measles who were found to have high-avidity IgG results were classified as secondary vaccine failures; one sample with an intermediate-avidity result was not interpretable. In elimination settings, measles IgG avidity assays can complement existing diagnostic tools in confirming unvaccinated acute cases and, in conjunction with adequate clinical and epidemiologic investigation, aid in the classification of vaccine failure cases.

scholarly journals Head-to-Head Comparison of Two Nomograms Predicting Probability of Lymph Node Invasion in Prostate Cancer and the Therapeutic Impact of Higher Nomogram Threshold

2021 ◽  
Vol 10 (5) ◽  
pp. 999
Author(s):  
Zilvinas Venclovas ◽  
Tim Muilwijk ◽  
Aivaras J. Matjosaitis ◽  
Mindaugas Jievaltas ◽  
Steven Joniau ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Lymph Node ◽  
Area Under The Curve ◽  
Pelvic Lymph Node ◽  
Cancer Center ◽  
Study Cohort ◽  
Net Benefit ◽  
Characteristic Analysis ◽  
Therapeutic Impact ◽  
Mskcc Nomogram

Introduction: The aim of the study was to compare the performance of the 2012 Briganti and Memorial Sloan Kettering Cancer Center (MSKCC) nomograms as a predictor for pelvic lymph node invasion (LNI) in men who underwent radical prostatectomy (RP) with pelvic lymph node dissection (PLND), to examine their performance and to analyse the therapeutic impact of using 7% nomogram cut-off. Materials and Methods: The study cohort consisted of 807 men with clinically localised prostate cancer (PCa) who underwent open RP with PLND between 2001 and 2019. The area under the curve (AUC) of the receiver operator characteristic analysis was used to quantify the accuracy of the 2012 Briganti and MSKCC nomograms to predict LNI. Calibration plots were used to visualise over or underestimation by the models and a decision curve analysis (DCA) was performed to evaluate the net benefit associated with the used nomograms. Results: A total of 97 of 807 patients had LNI (12%). The AUC of 2012 Briganti and MSKCC nomogram was 80.6 and 79.2, respectively. For the Briganti nomogram using the cut-off value of 7% would lead to reduce PLND in 47% (379/807), while missing 3.96% (15/379) cases with LNI. For the MSKCC nomogram using the cut-off value of 7% a PLND would be omitted in 44.5% (359/807), while missing 3.62% (13/359) of cases with LNI. Conclusions: Both analysed nomograms demonstrated high accuracy for prediction of LNI. Using a 7% nomogram cut-off would allow the avoidance up to 47% of PLNDs, while missing less than 4% of patients with LNI.

scholarly journals Red cell distribution width as a predictor for bronchopulmonary dysplasia in premature infants

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hayato Go ◽  
Hitoshi Ohto ◽  
Kenneth E. Nollet ◽  
Kenichi Sato ◽  
Hirotaka Ichikawa ◽  
...  
Keyword(s):  
Blood Cell ◽  
Bronchopulmonary Dysplasia ◽  
Gestational Age ◽  
Red Blood Cell ◽  
Area Under The Curve ◽  
Cell Distribution ◽  
Characteristic Analysis ◽  
Distribution Width ◽  
Potential Biomarker ◽  
Rbc Transfusion

AbstractBronchopulmonary dysplasia (BPD) is the most common morbidity complicating preterm birth. Red blood cell distribution width (RDW), a measure of the variation red blood cell size, could reflect oxidative stress and chronic inflammation in many diseases such as cardiovascular, pulmonary, and other diseases. The objectives of the present study were to evaluate perinatal factors affecting RDW and to validate whether RDW could be a potential biomarker for BPD. A total of 176 preterm infants born at < 30 weeks were included in this study. They were categorized into BPD (n = 85) and non-BPD (n = 91) infants. RDW at birth and 14 days and 28 days of life (DOL 14, DOL 28) were measured. Clinical data were obtained from all subjects at Fukushima Medical University (Fukushima, Japan). The mean RDW at birth, DOL 14 and DOL 28 were 16.1%, 18.6%, 20.1%, respectively. Small for gestational age (SGA), chorioamnionitis (CAM), hypertensive disorders of pregnancy (HDP), gestational age and birth weight were significantly associated with RDW at birth. SGA, BPD and red blood cell (RBC) transfusion before DOL 14 were associated with RDW at DOL 14. BPD and RBC transfusion before DOL 14 were associated with RDW at DOL 28. Compared with non-BPD infants, mean RDW at birth DOL 14 (21.1% vs. 17.6%, P < 0.001) and DOL 28 (22.2% vs. 18.2%, P < 0.001) were significantly higher in BPD infants. Multivariate analysis revealed that RDW at DOL 28 was significantly higher in BPD infants (P = 0.001, odds ratio 1.63; 95% CI 1.22–2.19). Receiver operating characteristic analysis for RDW at DOL 28 in infants with and without BPD yielded an area under the curve of 0.87 (95% CI 0.78–0.91, P < 0.001). RDW at DOL 28 with mild BPD (18.3% vs. 21.2%, P < 0.001), moderate BPD (18.3% vs. 21.2%, P < 0.001), and severe BPD (18.3% vs. 23.9%, P < 0.001) were significantly higher than those with non-BPD, respectively. Furthermore, there are significant differences of RDW at DOL 28 between mild, moderate, and severe BPD. In summary, we conclude that RDW at DOL 28 could serve as a biomarker for predicting BPD and its severity. The mechanism by which RDW at DOL 28 is associated with the pathogenesis of BPD needs further elucidation.

scholarly journals Identification of an optimal prolactin threshold to determine prolactinoma size using receiver operating characteristic analysis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Bianca M. Leca ◽  
Maria Mytilinaiou ◽  
Marina Tsoli ◽  
Andreea Epure ◽  
Simon J. B. Aylwin ◽  
...  
Keyword(s):  
Receiver Operating Characteristic ◽  
Operating Characteristic ◽  
Tumour Size ◽  
Area Under The Curve ◽  
Serum Prolactin ◽  
Pituitary Neoplasms ◽  
Characteristic Analysis ◽  
Roc Curve Analysis ◽  
Baseline Serum ◽  
Receiver Operating

AbstractProlactinomas represent the most common type of secretory pituitary neoplasms, with a therapeutic management that varies considerably based on tumour size and degree of hyperprolactinemia. The aim of the current study was to evaluate the relationship between serum prolactin (PRL) concentrations and prolactinoma size, and to determine a cut-off PRL value that could differentiate micro- from macro-prolactinomas. A retrospective cohort study of 114 patients diagnosed with prolactinomas between 2007 and 2017 was conducted. All patients underwent gadolinium enhanced pituitary MRI and receiver operating characteristic (ROC) analyses were performed. 51.8% of patients in this study were men, with a mean age at the time of diagnosis of 42.32 ± 15.04 years. 48.2% of the total cohort were found to have microadenomas. Baseline serum PRL concentrations were strongly correlated to tumour dimension (r = 0.750, p = 0.001). When performing the ROC curve analysis, the area under the curve was 0.976, indicating an excellent accuracy of the diagnostic method. For a value of 204 μg/L (4338 mU/L), sensitivity and specificity were calculated at 0.932 and 0.891, respectively. When a cut off value of 204 μg/L (4338 mU/L) was used, specificity was 93.2%, and sensitivity 89.1%, acceptable to reliably differentiate between micro- and macro- adenomas.

scholarly journals Psychiatric comorbid disorders of cognition: a machine learning approach using 1175 UK Biobank participants

2020 ◽  
Vol 23 (4) ◽  
pp. 140-145
Author(s):  
Chenlu Li ◽  
Delia A Gheorghe ◽  
John E Gallacher ◽  
Sarah Bauermeister
Keyword(s):  
Machine Learning ◽  
Cognitive Decline ◽  
Psychiatric Disorders ◽  
Characteristic Curve ◽  
Area Under The Curve ◽  
Imaging Study ◽  
Cognitive Change ◽  
Poor Mental Health ◽  
Uk Biobank

BackgroundConceptualising comorbidity is complex and the term is used variously. Here, it is the coexistence of two or more diagnoses which might be defined as ‘chronic’ and, although they may be pathologically related, they may also act independently. Of interest here is the comorbidity of common psychiatric disorders and impaired cognition.ObjectivesTo examine whether anxiety and/or depression are/is important longitudinal predictors of cognitive change.MethodsUK Biobank participants used at three time points (n=502 664): baseline, first follow-up (n=20 257) and first imaging study (n=40 199). Participants with no missing data were 1175 participants aged 40–70 years, 41% women. Machine learning was applied and the main outcome measure of reaction time intraindividual variability (cognition) was used.FindingsUsing the area under the receiver operating characteristic curve, the anxiety model achieves the best performance with an area under the curve (AUC) of 0.68, followed by the depression model with an AUC of 0.63. The cardiovascular and diabetes model, and the covariates model have weaker performance in predicting cognition, with an AUC of 0.60 and 0.56, respectively.ConclusionsOutcomes suggest that psychiatric disorders are more important comorbidities of long-term cognitive change than diabetes and cardiovascular disease, and demographic factors. Findings suggest that psychiatric disorders (anxiety and depression) may have a deleterious effect on long-term cognition and should be considered as an important comorbid disorder of cognitive decline.Clinical implicationsImportant predictive effects of poor mental health on longitudinal cognitive decline should be considered in secondary and also primary care.

scholarly journals Mean Platelet Volume: Is It a Predictive Parameter in Diagnosis of Acute Mesenteric Ischemia?

2015 ◽  
Vol 100 (5) ◽  
pp. 962-965 ◽  
Author(s):  
Ahmet Türkoğlu ◽  
Mesut Gül ◽  
Abdullah Oğuz ◽  
Zübeyir Bozdağ ◽  
Burak Veli Ülger ◽  
...  
Keyword(s):  
Early Diagnosis ◽  
Mean Platelet Volume ◽  
Mesenteric Ischemia ◽  
Area Under The Curve ◽  
Acute Mesenteric Ischemia ◽  
The Elderly ◽  
Control Group ◽  
Characteristic Analysis ◽  
Platelet Volume ◽  
Cell Counts

Our objective for this study was to discuss the usability of mean platelet volume, which is associated with numerous vascular pathologies, in the early diagnosis of acute mesenteric ischemia. Acute mesenteric ischemia is an uncommon, life-threatening clinical condition mostly seen in the elderly. Early diagnosis of acute mesenteric ischemia and correction of blood circulation before necrosis occurs are important factors affecting prognosis. A total of 95 patients who underwent emergency surgery for acute mesenteric ischemia and 90 healthy volunteers as control group were included in this study. Age, gender, hemoglobin values, white blood cell counts, mean platelet volume, and platelet counts are recorded for evaluation. The mean platelet volume values were significantly higher in patients with acute mesenteric ischemia than in the controls (9.4 ± 1.1 fL and 7.4 ± 1.4 fL, respectively; P &lt; 0.001). Receiver-operating characteristic analysis demonstrated a cutoff value of mean platelet volume as 8.1 fL (area under the curve, 0.862), a sensitivity of 83.2%, and a specificity of 80%. As a result, in the patients who are admitted to the hospital with acute nonspecific abdominal pain and suspected of having acute mesenteric ischemia, high mean platelet volume values in routine hemograms support the diagnosis of acute mesenteric ischemia.

P2-007: Automating the BSI brain atrophy rate calculation: Comparison of using automated and semi-automated brain regions

2008 ◽  
Vol 4 ◽  
pp. T367-T368
Author(s):  
Matthew C. Evans ◽  
Casper Nielsen ◽  
Abdel Douiri ◽  
Josephine Barnes ◽  
Shona L. Clegg ◽  
...  
Keyword(s):  
Brain Atrophy ◽  
Brain Regions ◽  
Atrophy Rate ◽  
Rate Calculation

Abstract 15293: Increased Level of Cardiac Troponin T is a Clue of Cardiac Amyloidosis in Patients With Myocardial Hypertrophy

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Seiji Takashio ◽  
Megumi Yamamuro ◽  
Toshihisa Anzai ◽  
Hisao Ogawa
Keyword(s):  
Endomyocardial Biopsy ◽  
Cardiac Troponin ◽  
Cardiac Amyloidosis ◽  
Myocardial Hypertrophy ◽  
Troponin T ◽  
Area Under The Curve ◽  
Al Amyloidosis ◽  
Cardiac Troponin T ◽  
Characteristic Analysis ◽  
Precise Diagnosis

Background: Cardiac amyloidosis (CA) is an important differential diagnosis in patients with myocardial hypertrophy. The precise diagnosis of CA requires endomyocardial biopsy to demonstrate amyloid deposition, but this procedure is relatively invasive and cannot be performed routinely. Therefore, it is important to increase pretest probability of CA in patients with myocardial hypertrophy by noninvasive modalities. Because it is well known that cardiac troponin level is elevated in patients with CA, we hypothesized that increased level of cardiac troponin T contributes to diagnosis of CA in patients with myocardial hypertrophy using high sensitive assay (hs-TnT). Methods and Results: Among nonischemic patients with myocardial hypertrophy (interventricular septal thickness≧ 12 mm), hs-TnT level was measured in 28 CA patients (senile systemic amyloidosis: 13, AL amyloidosis: 14, familial amyloidosis: 1) proven amyloidosis pathologically and 29 non-CA patients proven by endomyocardial biopsy. It was significantly higher in CA patients than non-CA patients (0.075 [0.047-0.116] ng/ml vs. 0.013 [0.009-0.019] ng/ml; p<0.001: Figure). Receiver operating characteristic analysis selected 0.030 ng/ml as the best cutoff value of diagnosis for CA, with a sensitivity and specificity of 96% and 93%, respectively and area under the curve of 0.98 (95% confidence interval 0.94 to 1.00, p<0.001). Conclusions: Increased level of hs-TnT (>0.030 ng/ml) is highly suggestive of CA in patients with myocardial hypertrophy. These patients need additional diagnostic approach for CA.

Elevated serum sortilin is related to carotid plaque concomitant with calcification

2020 ◽  
Vol 14 (5) ◽  
pp. 381-389
Author(s):  
Shanshan Huang ◽  
Xingxing Yu ◽  
Haiqing Wang ◽  
Jianlei Zheng
Keyword(s):  
Ischemic Stroke ◽  
Carotid Plaque ◽  
Elevated Serum ◽  
Area Under The Curve ◽  
Plaque Burden ◽  
Multivariable Logistic Regression Analysis ◽  
Characteristic Analysis ◽  
Plaque Score ◽  
Carotid Calcification

Aim: To explore whether elevated serum sortilin was associated with calcified carotid plaque and ischemic stroke. Methods: A total of 171 patients with cardiovascular risk factors were enrolled. Ultrasonography was performed to evaluate calcified plaques and noncalcified plaques. Serum sortilin concentration was measured by ELISA. Results: Serum sortilin level was higher in patients with calcified carotid plaque and positively related to carotid plaque burden, but not with ischemic stroke during the follow-up. Multivariable logistic regression analysis revealed serum sortilin level was an independent determinant for calcified carotid plaque (p = 0.001). Receiving operating characteristic analysis showed an area under the curve of sortilin for carotid calcification was 0.759. Conclusion: Higher serum sortilin level was associated with carotid calcification and severe carotid plaque score.

scholarly journals Diagnosing and quantifying a common deficit in multiple sclerosis

Neurology ◽  
2019 ◽  
Vol 92 (20) ◽  
pp. e2299-e2308 ◽  
Author(s):  
J.A. Nij Bijvank ◽  
L.J. van Rijn ◽  
L.J. Balk ◽  
H.S. Tan ◽  
B.M.J. Uitdehaag ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Multiple Sclerosis ◽  
Diagnostic Accuracy ◽  
Peak Velocity ◽  
Area Under The Curve ◽  
Interquartile Range ◽  
Characteristic Analysis ◽  
Related Quality ◽  
Definition Of

ObjectiveWe present an objective and quantitative approach for diagnosing internuclear ophthalmoplegia (INO) in multiple sclerosis (MS).MethodsA validated standardized infrared oculography protocol (DEMoNS [Demonstrate Eye Movement Networks with Saccades]) was used for quantifying prosaccades in patients with MS and healthy controls (HCs). The versional dysconjugacy index (VDI) was calculated, which describes the ratio between the abducting and adducting eye. The VDI was determined for peak velocity, peak acceleration, peak velocity divided by amplitude, and area under the curve (AUC) of the saccadic trajectory. We calculated the diagnostic accuracy for the several VDI parameters by a receiver operating characteristic analysis comparing HCs and patients with MS. The National Eye Institute Visual Function Questionnaire–25 was used to investigate vision-related quality of life of MS patients with INO.ResultsTwo hundred ten patients with MS and 58 HCs were included. The highest diagnostic accuracy was achieved by the VDI AUC of 15° horizontal prosaccades. Based on a combined VDI AUC and peak velocity divided by amplitude detection, the prevalence of an INO in MS calculated to 34%. In the INO group, 35.2% of the patients with MS reported any complaints of double vision, compared to 18.4% in the non-INO group (p = 0.010). MS patients with an INO had a lower overall vision-related quality of life (median 89.9, interquartile range 12.8) compared to patients without an INO (median 91.8, interquartile range 9.3, p = 0.011).ConclusionsThis study provides an accurate quantitative and clinically relevant definition of an INO in MS. This infrared oculography-based INO standard will require prospective validation. The high prevalence of INO in MS provides an anatomically well described and accurately quantifiable model for treatment trials in MS.

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