A Novel Liquid Biopsy (NETest) identifies Paragangliomas and Pheochromocytomas with High Accuracy

2021 ◽  
Author(s):  
Karel Pacak ◽  
Mark Kidd ◽  
Leah Meuter ◽  
Irvin M. Modlin
Keyword(s):  
Clinical Utility ◽  
Roc Analysis ◽  
Pediatric Patients ◽  
Marker Gene ◽  
Receiver Operating Curve ◽  
Growth Factor Signaling ◽  
Transcript Analysis ◽  
Regulatory Pathway ◽  
Blood Assay ◽  
Cluster 2

Pheochromocytomas and paragangliomas (PHEOs/PGLs) represent diagnostically challenging and complex neuroendocrine tumors (NETs). Current biomarker tests for PHEOs/PGLs are technically complex or limited. We assessed the diagnostic utility of a NET-specific 51-marker gene blood assay (NETest) in patients with PHEOs/PGLs (n=81), including 10 pediatric patients, and age-/gender-matched controls (n=142) using a prospective case:control (1:2) analysis. mRNA was measured (qPCR) and results scaled 0-100 (ULN<20). Receiver Operating Curve (ROC) and non-parametric (Mann-Whitney) were used for analyses (2-tailed). All data is presented as mean±SEM. NETest accuracy for PHEO/PGL diagnosis was 100%. PHEO/PGL scores were 70±3 versus 8.5±1 in controls (p<0.0001) and ROC analysis was 0.99±0.004 (p<0.0001). Diagnostic metrics were 94% accurate, 100% sensitive, and 92% specific. Imaging correlation with 68Ga-PET-SSA was 100%. NETest levels in PHEOs (n=26) were significantly (p<0.0001) elevated (83±4) versus 66±4 in PGLs (n=40) and mixed PHEOs/PGLs (n=5: 37±3). Adrenal-derived tumors (n=30) exhibited higher scores (76±5) than extra-adrenal-derived tumors (66±4, p<0.05). Cluster 2 tumors exhibited significantly (p=0.034) elevated NETest levels (n=4: 92±2) versus Cluster 1 tumors (n=35: 69±4). Regulatory pathway analysis identified elevated RAS-RAF, metastatic, pluripotential, neural and secretory gene cluster levels (p<0.05) in PHEOs compared to PGLs. Cluster 2 PPGLs exhibited elevated (p=0.046) levels of growth-factor signaling genes compared to cluster 1. The PHEOs/PGLs in the pediatric cohort (n=10) were all NETest-positive (81±8) and exhibited a gene expression profile spectrum analogous to adults. Circulating NET transcript analysis identifies PHEOs/PGLs with 100% efficacy and is likely to have clinical utility in the diagnosis and management of PHEO/PGL patients.

scholarly journals Use of endocytoscopy for identification of sessile serrated adenoma/polyps and hyperplastic polyps by quantitative image analysis of the luminal areas

2017 ◽  
Vol 05 (08) ◽  
pp. E769-E774 ◽  
Author(s):  
Yushi Ogawa ◽  
Shin-ei Kudo ◽  
Yuichi Mori ◽  
Nobunao Ikehara ◽  
Yasuharu Maeda ◽  
...  
Keyword(s):  
Roc Analysis ◽  
Normal Mucosa ◽  
Receiver Operating Curve ◽  
Hyperplastic Polyps ◽  
Sessile Serrated Adenoma ◽  
Serrated Adenoma ◽  
Important Indicator ◽  
Cutoff Value ◽  
Luminal Area ◽  
Magnifying Chromoendoscopy

Abstract Background and study aims Recent studies that used magnifying chromoendoscopy and endocytoscopy (EC) to investigate endoscopic features of sessile serrated adenoma/polyps (SSA/Ps) suggested that a dilated crypt opening was an important indicator of SSA/Ps. However, no studies to date have measured the actual extent of dilatation. Hence, we investigated retrospectively the luminal areas using EC to determine a cutoff value for differentiating SSA/Ps from hyperplastic polyps (HPs). Patients and methods A total of 101 lesions, including 25 SSA/Ps, 66 HPs, and 10 normal mucosal samples, assessed by an integrated-type EC were collected. For each lesion, 1 image that showed the widest lumen was selected and the average area of the contiguous 3 lumens were calculated. The cutoff value differentiating SSAPs from HPs was determined by receiver operating curve (ROC) analysis. Results The mean luminal areas of SSA/Ps and HPs were 4152 μm2 and 2117 μm2, respectively. ROC analysis found that a luminal area cutoff of 3068 μm2 had a sensitivity of 80.0 %, a specificity of 77.3 %, an accuracy of 78.0 %, and an area under the ROC curve of 0.865. Furthermore, a cutoff of ≥ 556 μm2 was found to accurately distinguish between HPs and normal mucosa (sensitivity 98.5 %, specificity 100 %, accuracy 98.7 %, and AUC 0.998). Conclusions EC analysis of the luminal area is useful for differentiating between SSAPs and HPs. This approach could be adapted for computer-aided diagnosis of SSA/P.

scholarly journals Determining Postoperative Thrombocyte Reduction Cut Off to Predict 30-Day Mortality in Patients Undergo Coronary Artery Bypass Graft Surgery

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4914-4914
Author(s):  
Ikhwan Rinaldi ◽  
Arif Mansjoer
Keyword(s):  
Sensitivity And Specificity ◽  
Roc Analysis ◽  
Conflicts Of Interest ◽  
Artery Bypass ◽  
Bypass Graft ◽  
Area Under The Curve ◽  
Early Mortality ◽  
Receiver Operating Curve ◽  
Thrombocyte Count ◽  
Cabg Surgery

Background There are many factors associated with early mortality after CABG, including postoperative thrombocytopenia (Kertai, 2016). Many factors during CABG surgery, such as administration of heparin or cardio pulmonary bypass during surgery are related to thrombocyte count reduction (Hamid, Akhtar, Naqvi, & Ahsan, 2017; Arepally, 2017). However, it is possible for a post-CABG patient to suffer a significant thrombocyte reduction without reaching the thrombocytopenic state (thrombocyte count <150000/µL). Up to this time, there is still lack of study about association between thrombocyte reduction after surgery and 30-day mortality in patients undergo CABG. This study aim to determine cut off point for postoperative thrombocyte reduction as a predictor of 30-day mortality after CABG surgery. Method This is a retrospective cohort study using medical record of 263 adult patients who underwent CABG surgery in dr. Ciptomangunkusumo National Hospital on 2012-2015. Thrombocyte reduction was determined by substracting preoperative thrombocyte count from postoperative thrombocyte count. Receiver operating curve (ROC) analysis between percentage of thrombocyte reduction and 30-day mortality after surgery was done to obtain the sensitivity and specificity value of a particular degree of thrombocyte reduction. Cut off point was obtained from intersection between sensitivity and specificity value. Result Thirty-day mortality rate after CABG surgery in this study was 11.9%. Cut off point obtained from ROC analysis was 30% with area under the curve (AUC) 0.671. The sensitivity of this cut off point to predict early mortality after CABG surgery was 64.5%, while the specificity was 64.7% Conclusion Thrombocyte reduction more than or equal to 30% can be used as a predictor of 30-day mortality after CABG surgery. Figure Disclosures No relevant conflicts of interest to declare.

scholarly journals Evaluating the diagnostic accuracy of gene xpert analysis in pediatric pulmonary tuberculosis: a prospective clinical study in North-Western India

2021 ◽  
Vol 8 (4) ◽  
pp. 716
Author(s):  
Venkatesh Karthik S. ◽  
Jigisha Patadiya
Keyword(s):  
Diagnostic Accuracy ◽  
Predictive Value ◽  
Roc Analysis ◽  
Gastric Lavage ◽  
Control Program ◽  
Tuberculin Test ◽  
Receiver Operating Curve ◽  
Prospective Clinical Study ◽  
Western India ◽  
X Rays

Background: The diagnosis of tuberculosis (TB) by microbiological tests is a major challenge particularly in children. The use of Xpert analysis, a rapid genetic testing modality is not widely reported in our locality. The aim of the study to evaluate the diagnostic accuracy of Gene xpert analysis in diagnosis of pediatric Pulmonary TB.Methods: A prospective hospital-based study was conducted among 140 participants with symptomatology pertaining to pulmonary TB as per Revised national tuberculosis control program (RNTCP, India) criteria. The Xpert testing (GXT) was performed as per standards and was compared with erythrocyte sedimentation rate (ESR), tuberculin test (TT) and chest X-rays (CXR). The obtained results were reported in terms of Sensitivity %, Specificity %, Positive Predictive Value % (PPV) and Negative Predictive Value % (NPV) for comparisons. The receiver operating curve (ROC) analysis was employed to evaluate the accuracy of diagnosis.Results: The GXT was positive (10.71 %) in suspected TB patients. TT has significantly (10 %) with a73.33% sensitivity, 93.60% specificity and a PPV of 57.89 % when compared with xpert. The ESR showed a sensitivity of 53.33% and a specificity of 56%. The CXR showed sensitivity of 93.33%. The ROC analysis showed that TT had a higher confidence interval (0.699-0.970) t5`han other methods. The Rifampicin resistance was found 7.5% (n=2) of 15 GXT positive cases.Conclusions: The xpert based diagnosis of gastric lavage samples after a tuberculin test (TT) had high sensitivity and specificity, followed by chest X ray while the ESR had lower clinical accuracy. The ‘gene xpert analysis’ is highly useful rapid tool for diagnosis of children with TB. 

26917 Clinical utility of imaging for evaluation of cellulitis in hospitalized pediatric patients

2021 ◽  
Vol 85 (3) ◽  
pp. AB26
Author(s):  
Sidharth Chand ◽  
Renajd Rrapi ◽  
Sarah Song ◽  
Colleen Gabel ◽  
Daniela Kroshinsky
Keyword(s):  
Clinical Utility ◽  
Pediatric Patients

Clinical Utility of Striational Antibodies in Paraneoplastic and Myasthenia Gravis Paraneoplastic Panels

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000012050
Author(s):  
Shahar Shelly ◽  
John R Mills ◽  
Divyansu Dubey ◽  
Andrew McKeon ◽  
Anastasia Zekeridou ◽  
...  
Keyword(s):  
Diagnostic Accuracy ◽  
Myasthenia Gravis ◽  
Clinical Utility ◽  
Roc Analysis ◽  
Thymic Cancer ◽  
Diagnostic Characteristics ◽  
Data Platform ◽  
Neurological Phenotype ◽  
Antibody Positivity

Objective:To critically assess the clinical utility of striational antibodies (StrAbs) within paraneoplastic and myasthenia gravis serological evaluations.Methods:All Mayo Clinic patients tested for StrAbs from January 1st 2012-December 31st 2018 utilizing Mayo’s Unified Data Platform (UDP) were reviewed for neurological diagnosis and cancer.Results:38,502 unique paraneoplastic and 1,899 MG patients were tested. In paraneoplastic evaluations, the StrAbs positivity rate was higher in cancer vs without cancer (5% [321/6775] vs 4% [1154/31727]; p<0.0001; OR 1.35; CI=1.19-1.53) but ROC analysis indicated no diagnostic accuracy in cancer (AUC=0.505). No neurological phenotype was significantly associated with StrAbs in the paraneoplastic group. Positivity was more common in all MG cancers compared to paraneoplastic cancers (p<0.0001). In MG evaluations, the StrAbs positivity rate was higher in those with cancer vs without (46% [217/474] vs 26% [372/1425]; p<0.0001; OR 2.39, CI 1.9-2.96) with ROC analysis indicating poor diagnostic accuracy for thymic cancer (AUC 0.634, recommended cutoff=1:60, sensitivity=56%, specificity=71%), with worse accuracy for extrathymic cancers (AUC 0.543). In paraneoplastic or MG evaluations, the value of antibody positivity did not improve cancer predictions. Paraneoplastic evaluated patients were more likely with positive StrAbs to obtain computed tomography (CT) (p=0.0001) with 3% (12/468) cancer found.Conclusion:Despite a statistically significant association with cancer, an expansive review of performance in clinical service demonstrates that StrAbs are neither specific nor sensitive in predicting malignancy or neurological phenotypes. CT imaging is over utilized with positive StrAbs results. Removal of StrAbs from paraneoplastic or MG evaluations will improve the diagnostic characteristics of the current MG test.Classification of Evidence:This study provides Class II evidence that the presence of StrAbs do not accurately identify patients with malignancy or neurological phenotypes.

scholarly journals Myoglobin for Detection of High-Risk Patients with Acute Myocarditis

2020 ◽  
Vol 13 (5) ◽  
pp. 853-863 ◽  
Author(s):  
Jan Kottwitz ◽  
Katelyn A. Bruno ◽  
Jan Berg ◽  
Gary R. Salomon ◽  
DeLisa Fairweather ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Cardiac Magnetic Resonance ◽  
Late Gadolinium Enhancement ◽  
Roc Analysis ◽  
Acute Myocarditis ◽  
Unmet Need ◽  
Receiver Operating Curve ◽  
Resonance Imaging ◽  
Gadolinium Enhancement ◽  
Risk Patients

Abstract There is an unmet need for accurate and practical screening to detect myocarditis. We sought to test the hypothesis that the extent of acute myocarditis, measured by late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging (CMR), can be estimated based on routine blood markers. A total of 44 patients were diagnosed with acute myocarditis and included in this study. There was strong correlation between myoglobin and LGE (rs = 0.73 [95% CI 0.51; 0.87], p < 0.001), while correlation was weak between LGE and TnT-hs (rs = 0.37 [95% CI 0.09; 0.61], p = 0.01). Receiver operating curve (ROC) analysis determined myoglobin ≥ 87 μg/L as cutoff to identify myocarditis (92% sensitivity, 80% specificity). The data were reproduced in an established model of coxsackievirus B3 myocarditis in mice (n = 26). These data suggest that myoglobin is an accurate marker of acute myocarditis.

scholarly journals The clinical utility of circulating neuroendocrine gene transcript analysis in well-differentiated paragangliomas and pheochromocytomas

2017 ◽  
Vol 176 (2) ◽  
pp. 143-157 ◽  
Author(s):  
M Pęczkowska ◽  
J Cwikla ◽  
M Kidd ◽  
A Lewczuk ◽  
A Kolasinska-Ćwikła ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multivariate Analysis ◽  
Clinical Utility ◽  
Progressive Disease ◽  
Somatostatin Receptor ◽  
Blood Analysis ◽  
Receptor Expression ◽  
Gene Transcript ◽  
Transcript Analysis ◽  
Well Differentiated

Context Paragangliomas and pheochromocytomas (PPGLs) exhibit variable malignancy, which is difficult to determine by histopathology, amine measurements or tissue genetic analyses. Objective To evaluate whether a 51-neuroendocrine gene blood analysis has clinical utility as a diagnostic and prognostic marker. Design Prospective cohort study. Well-differentiated PPGLs (n = 32), metastatic (n = 4); SDHx mutation (n = 25); 12 biochemically active, Lanreotide treated (n = 4). Nine patients had multiple sampling. Age- and gender-matched controls and GEP-NETs (comparators). Methods Circulating neuroendocrine tumor mRNA measured (qPCR) with multianalyte algorithmic analysis. Metabolic, epigenomic and proliferative genes as well as somatostatin receptor expression were assessed (averaged, normalized gene expression: mean ± s.e.m.). Amines were measured by HPLC and chromogranin A by ELISA. Analyses (2-tailed): Fisher’s test, non-parametric (Mann–Whitney), receiver-operator curve (ROC) and multivariate analysis (MVA). All data are presented as mean ± s.e.m. Results PPGL were NETest positive (100%). All exhibited higher scores than controls (55 ± 5% vs 8 ± 1%, P = 0.0001), similar to GEP-NETs (47 ± 5%). ROC analysis area under curve was 0.98 for differentiating PPGLs/controls (cut-off for normal: 26.7%). Mutation status was not directly linked to NETest. Genetic and molecular clustering was associated (P < 0.04) with NETest scores. Metastatic (80 ± 9%) and multicentric (64 ± 9%) disease had significantly (P < 0.04) higher scores than localized disease (43 ± 7%). Progressive disease (PD) had the highest scores (86 ± 2%) vs stable (SD, 41 ± 2%) (P < 0.0001). The area under the curve for PD from SD was 0.93 (cut-off for PD: 53%). Proliferation, epigenetic and somatostatin receptor gene expression was elevated (P < 0.03) in PD. Metabolic gene expression was decreased in SDHx mutations. Repeat NETest measurements defined clinical status in the 9 patients (6 SD and 3 PD). Amine measurement was non-informative. Multivariate analysis identified NETest >53% as an independent prognostic factor. Conclusion Circulating NET transcript analysis is positive (100% diagnostic) in well-differentiated PCC/PGL, scores were elevated in progressive disease irrespective of mutation or biochemical activity and elevated levels were prognostic.

Reliability, validity and factor structure of the GHQ-28 used among elderly Iranians

2006 ◽  
Vol 19 (4) ◽  
pp. 623-634 ◽  
Author(s):  
Seyed Kazem Malakouti ◽  
Paridokht Fatollahi ◽  
Arash Mirabzadeh ◽  
Taher Zandi
Keyword(s):  
Urban Areas ◽  
Roc Analysis ◽  
Short Form ◽  
General Health Questionnaire ◽  
Composite International Diagnostic Interview ◽  
Diagnostic Interview ◽  
Face Validity ◽  
Receiver Operating Curve ◽  
Elderly Subjects ◽  
Cutoff Score

Background: The object of this study was to develop an Iranian version of the General Health Questionnaire-28 (GHQ-28) for use with elderly subjects.Methods: The GHQ-28 Farsi version was evaluated for face validity among 204 elderly subjects aged 59 years or older, chosen randomly from residents of Tehran. The Composite International Diagnostic Interview (CIDI) was used to establish a gold standard diagnosis of mental disorders.Results: The GHQ-28 was an internally consistent measure. Cronbach's α, split-half coefficients and test-retest reliability were 0.9, 0.89 and 0.58 respectively. Four factors were extracted using factor analysis: “depression,” “psychosocial activity,” “anxiety,” and “somatic.” Using receiver operating curve (ROC) analysis, the optimum cutoff score for the GHQ-28 in this group was 19/20 (sensitivity 0.83, specificity 0.76). Using a loading of 0.6 or greater, a short form of the instrument (GHQ-15) (α = 0.9) was derived and correlated well with the longer form of the scale (r = 0.97). Using ROC analysis, the optimum cutoff score was 10/11 (sensitivity 0.83, specificity 0.69).Conclusions: The short and long forms of the GHQ-28 are suitable screening instruments for elderly Iranian residents, particularly those living in urban areas.

scholarly journals PROKALSITONIN SEBAGAI PENANDA PEMBEDA INFEKSI BAKTERI DAN NON BAKTERI

2018 ◽  
Vol 17 (2) ◽  
pp. 76
Author(s):  
Bastiana Bastiana ◽  
Aryati Aryati ◽  
Dominicus Husada ◽  
M.Y. Probohoesodo
Keyword(s):  
Bacterial Infection ◽  
Roc Analysis ◽  
Final Diagnosis ◽  
Receiver Operating Curve ◽  
Fluorescent Assay ◽  
Infection Group ◽  
Cross Sectional ◽  
Predictive Values ◽  
Significant Difference ◽  
Sensitivity Specificity

Early diagnosis of an infection and prompt administration of an antibiotic can dramatically reduce morbidity and mortality.Procalcitonin (PCT), a precursor of calcitonin, has been proposed as a marker of bacterial infection. The aim of this study is to assess theefficiency of procalcitonin in children for the diagnosis of bacterial vs. non bacterial infection. This was a prospective, cross-sectional study.The subjects were enrolled consecutively, consisting of feverish children (temperature ³38.5° C) admitted to the Pediatric EmergencyDepartment with ages up to 12 years old. The subjects were divided into two groups according to their final diagnosis, bacterial and nonbacterial infection. Serum PCT concentration was measured by enzyme linked fluorescent assay (ELFA) method. Sensitivity, specificity,positive predictive and negative predictive values, and receiver operating curve (ROC) of PCT were calculated. Out of 54 patients,24 (44.4%) had a final diagnosis of bacterial infection. PCT showed a wide concentration range in the bacterial infection group (median:1.09 ng/mL, lower (L)=0.05 ng/mL, upper (U)=128.7 ng/mL) compared with non bacterial infection group (0.21 ng/mL; L=0.05ng/mL; U=12.15 ng/mL). There was a significant difference in PCT between the 2 groups (p=0.020). ROC analysis demonstrated anarea under curve (AUC) of 0.686 (95% CI, 0.534 to 0.838). Using a cut-off point of 0.5 ng/mL, the sensitivity, and specificity, positivepredictive and negative predictive values of PCT were 66.7%, 76.7%, 69.6%, 74.2%, respectively. In this study, PCT may be useful fordifferentiation of bacterial vs. non bacterial infection in children.

scholarly journals The Investigation of the Relation Between Expansion Strategy and Outcomes of Two-Stage Expander-Implant Breast Reconstruction

2021 ◽  
Author(s):  
min JI kim ◽  
Woo beom Lee ◽  
Il Jae Lee ◽  
Hyung Min Hahn ◽  
Duy Quang Thai ◽  
...  
Keyword(s):  
Breast Reconstruction ◽  
Roc Analysis ◽  
Negative Relationship ◽  
Multivariate Logistic Regression Analysis ◽  
Receiver Operating Curve ◽  
Breast Size ◽  
Expansion Velocity ◽  
Two Stage ◽  
The Impact ◽  
Expansion Volume

Abstract Numerous risk factors for the complications of two-stage, immediate implant-based breast reconstruction have been identified, although few studies have directly examined the impact of breast size and expansion protocols on the surgical outcomes of breast reconstruction. This study aimed to evaluate the impact of breast size, expansion velocity, and volume-related variables on postoperative complications of breast reconstruction. The cohort involved patients who underwent immediate breast expander reconstruction at a single center between 2017 and 2019. The breast size was classified into three categories according to the weight of the mastectomy specimen as small (< 300 g), medium (≥ 300 g, ≤ 500 g), or large (> 500 g). Multifactorial logistic regressions were used to assess the impact of variables, and receiver operating curve (ROC) analysis was used to determine the optimal cut-off value for predicting the complication event. Of the 174 breasts (168 patients), 51 (29.3%), 66 (37.9%), and 57 (32.6%) breasts were classified as small, medium, and large, respectively. The rate of infection (p = 0.014) and expander/implant failure (p = 0.007) significantly differed according to breast size, with the rate being the highest in large breasts. Multivariate logistic regression analysis showed that body mass index (odds ratio [OR]: 1.25, p = 0.003), nipple-sparing mastectomy (OR: 2.82, p = 0.036), sentinel biopsy (OR: 5.10, p = 0.016), final expansion volume (OR: 0.99, p = 0.022), and expansion velocity (OR: 0.703, p = 0.024) were significant independent predictors of any complication. In the ROC analysis, breast weight > 696 g could predict the possibility of revision surgery, with a sensitivity of 42.9% and specificity of 81.8%. The final expansion volume and expansion velocity have a significant negative relationship with overall complications in breast reconstruction. A standard expansion protocol needs to be established to ensure the success of two-stage breast reconstruction.

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