Diagnostic Performance In Patients Research Articles

Diagnostic Accuracy of 18 F-FES PET/CT for the Detection of Recurrent and Metastatic Breast Cancer.

To evaluate the diagnostic value of 16α- 18 F-fluoro-17β-fluoroestradiol ( 18 F-FES) PET/CT for distant metastasis or recurrence in patients with estrogen receptor (ER)-positive breast cancer. Patients with ER-positive breast cancer and suspected of de novo metastasis or recurrence were retrospectively identified from a prospective cohort enrolled for a postmarketing surveillance study of 18 F-FES at our institution. Per-patient diagnostic accuracy was assessed using pathology or 2 or more standard-of-care imaging procedures with a minimum of 6 months of follow-up as the reference standard. The per-region detection rate of 18 F-FES PET/CT was evaluated and compared with that of standard-of-care imaging. Of the 162 included patients, 104 and 58 were suspected to have recurrence or de novo metastasis, respectively. The overall sensitivity and specificity of 18 F-FES PET/CT were 95% (95% confidence interval [CI], 89%-98%) and 89% (95% CI, 76%-96%), respectively. When stratified according to clinical settings, the sensitivity and specificity were 95% (95% CI, 88%-99%) and 96% (95% CI, 78%-100%), respectively, for detecting recurrence, and 94% (95% CI, 81%-99%) and 82% (95% CI, 60%-95%) for detecting distant metastasis. In region-based analysis, the overall detection rate of 18 F-FES PET/CT was significantly higher than that of standard-of-care imaging (92% [95% CI, 89%-94%] vs 83% [95% CI, 79%-87%], P < 0.001). 18 F-FES PET/CT showed excellent diagnostic performance in patients with ER-positive breast cancer suspected of de novo metastasis or recurrence.

Impact of Baseline Renal Insufficiency on Piflufolastat F-18 Performance and Investigation of Changes in Renal Function Following Piflufolastat F-18 Administration: Results From the OSPREY Trial

IntroductionPiflufolastat F-18, a prostate-specific membrane antigen (PSMA)-targeted radiopharmaceutical, is predominantly eliminated via urinary excretion, and the kidneys have one of the highest absorbed doses. Therefore, this subgroup analysis aimed to investigate the impact of piflufolastat F-18 on renal function and its diagnostic performance in patients stratified by baseline renal function. Patients and MethodsThe OSPREY clinical trial enrolled 2 cohorts: A—high-risk patients undergoing radical prostatectomy with pelvic lymphadenectomy, and B—patients with suspected recurrent/metastatic prostate cancer on conventional imaging. Baseline estimated glomerular filtration rates were calculated, and patients were stratified by baseline chronic kidney disease (CKD) stage. Changes in serum creatinine within 28 days postdose and diagnostic performance of piflufolastat F-18 were assessed for each CKD stage group in both cohorts. Results385 patients (cohort A, n = 268; cohort B, n = 117) underwent piflufolastat F-18-PET/CT. Baseline and postpiflufolastat F-18 median creatinine levels (mg/dL) were similar for patients in cohort A (0.95 [n = 264] vs. 0.95 [n = 252], respectively) and cohort B (0.93 [n = 116] vs. 0.96 [n = 84], respectively). Among 332 men (cohort A, n = 249; cohort B, n = 83) with baseline and postpiflufolastat creatinine measurements, there were minimal changes in creatinine across all baseline CKD stage groups (median change ranged from -0.02 to 0.023 in groups with >1 patient). The diagnostic performance of piflufolastat F-18 showed no meaningful differences when stratified by baseline CKD stage. ConclusionPiflufolastat F-18 appears to be safe and effective for imaging prostate cancer, including men with mild/moderate renal insufficiency.

Diagnostic performance of 2-[18F]FDG PET/CT in recurrent differentiated thyroid cancer and elevated antithyroglobulin antibodies: an updated systematic review and bivariate meta-analysis.

This updated systematic review and bivariate meta-analysis aimed to investigate the diagnostic performance of 2-[18F]FDG PET/CT for the detection of recurrent disease in patients with differentiated thyroid cancer (DTC) who have negative 131I whole body scintigraphy and increased antithyroglobulin antibodies (TgAb) levels. The current systematic review was carried out following a preset protocol, and the "Preferred Reporting Items for a Systematic Review and Meta-Analysis" served as a guideline for its development and reporting. A comprehensive research of the PubMed/MEDLINE, Embase and Cochrane library databases was conducted until June 2024. Between 2002 and 2023, 13 studies (608 patients) published on this topic were selected. The pooled sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 2-[18F]FDG PET or PET/CT were 84% (95%CI: 78-87%), 82% (95%CI: 78-86%), 72% (95%CI: 67-76%), 90% (95%CI: 87-93%) and 83% (95%CI: 79%-86%) respectively. The pooled positive and negative likelihood ratios (LR+ and LR - ) and the diagnostic odds ratio (DOR) were 0.180 (95%CI: 0.128-0.253), 3.214 (95%CI: 2.357-4.383), and 17.863 (95%CI: 10.475-30.462), respectively. No statistically significant heterogeneity among the studies was found for all the metrics evaluated (I2 < 50%). 2-[18F]FDG PET/CT demonstrated a good diagnostic performance in patients with DTC and increased TgAb. Although more studies are warranted, the provided evidence-based data should support the integration of 2-[18F]FDG PET/CT in clinical and diagnostic guidelines on DTC patients with increased TgAb.

Syndrome de Sjögren et anticorps anti-cN1A

AbstractSince their discovery in 2013, anti-5’nucleotidase 1A (anti-cN1A) antibodies have been the subject of numerous publications to assess their sensitivity and diagnostic specificity. Currently used as an aid in the diagnosis of inclusion body myositis for which their specificity is good, they can be detected in other autoimmune diseases and in particular in Sjögren’s Syndrome. Their prevalence, which is significant during this disease, decreases diagnostic performance in patients with both myositis and Sjögren’s Syndrome. Anti-cN1A antibodies may also have a prognostic role during SGS.

Diagnostic performance of the 0/2 hours ESC algorithm with high-sensitivity cardiac troponin T in an unselected community United States cohort

Abstract Background There are no robust data addressing the United States (US) experience with the 0/2 hours (h) European Society of Cardiology (ESC) algorithm using high-sensitivity cardiac troponin T (hs-cTnT). Purpose To evaluate the diagnostic performance of the 0/2h ESC-recommended absolute deltas in a US population. Methods Observational US cohort study of ED patients undergoing 0 and 2 h hs-cTnT measurements. The 99th percentiles upper reference limits (URL) used were 10 ng/L for women and 15 ng/L for men. Diagnostic outcomes were the adjudicated diagnoses of acute myocardial infarction (MI, type 1 or 2). Results A total of 1084 patients met inclusion criteria, amongst which 49% were women. Chest discomfort was reported in 521 (48%) patients. Among patients with a baseline hs-cTnT≤99th URL (n=434), 4 MIs occurred. To rule-out MI, an absolute 0-2h delta change &amp;lt;4 ng/L resulted in a sensitivity of 100% (95% CI: 39.8, 100) and a negative predictive value (NPV) of 100% (95% CI: 99.1, 100). To rule-in MI, an absolute 0-2h delta ≥10 ng/L had a specificity of 99.8 % (95% CI: 98.7, 99.9) and positive predictive value (PPV) of 75% (95% CI: 19.4, 99.4). Among patients with a baseline hs-cTnT &amp;gt;99th URL (n=650), 110 MIs occurred. In these patients, both rule-out (sensitivity 65%, NPV 91%) and rule-in (specificity 7.2%, PPV 11%) were poor using the ESC-recommended absolute deltas. Among patients with modest hs-cTnT increases (99th URL to 100 ng/L) neither the ESC-recommended absolute nor the Fourth Universal Definition of MI (UDMI)-recommended relative deltas provided acceptable performance. Among patients with marked hs-cTnT increases at presentation (&amp;gt;100 ng/L), a relative delta change &amp;gt;20% as recommended by the UDMI resulted in a superior rule-in performance, with a specificity of 92.0% (95% CI 74.0, 99.0) and PPV of 84.6% (57.4, 95.7). Conclusions In our unselected US-cohort of patients undergoing hs-cTnT, the 0/2h ESC algorithm had a good diagnostic performance in patients without myocardial injury at presentation. Conversely, in patients with myocardial injury at baseline, the ESC-recommended absolute deltas performed poorly to determine who had MI. In patients with marked hs-cTnT increases &amp;gt;100 ng/L at presentation, the UDMI recommended 20% relative change showed good rule-in performance.

Methods of the PivotaL triAl of the Atellica VTLi point of care emergencY dePartment high sensitivity troponin evalUationS

BackgroundThe Atellica® VTLi point-of-care (POC) High Sensitivity Cardiac Troponin-I (hs-cTnI) assay is intended for use as an aid in the diagnosis of myocardial infarction (MI). Our primary objective is to assess its diagnostic performance in patients presenting with suspected acute coronary syndrome (ACS). MethodsThis prospective observational study will enrol ∼1500 patients at ∼20 U.S. Emergency Departments. After informed consent, adults (>21 years of age) with suspected ACS, and no prior enrollment in this study, will provide a fingerstick and venous blood sample within 2 h of ED presentation, >2 to ≤4 h, and >4 to ≤9 h (max. blood draw = 60 mL). HEART and EDACS scores will be prospectively documented. Patients without the first blood draw may be enrolled if the second draw was obtained. Capillary and venous whole blood will undergo Atellica VTLi assay testing, with remaining venous sample processed to plasma and run. All results will be blinded to the clinical care team. Site operators will undergo a 3-day familiarization period. Quality control testing will be performed daily. At 30 ± 3 days, patient mortality status, major adverse cardiac events, and rehospitalizations will be determined. A clinical endpoint adjudication committee, blinded to hs-cTnI VTLi result, will define the final diagnosis. Sensitivity, specificity, and predictive values will describe the assay performance. ResultsWe expect study completion within 114 weeks of enrollment of the first patient. ConclusionsIt is anticipated that the Atellica VTLi hs-cTnI assay validation study will define a performance equivalent to lab-based hs-cTnI, with results within ∼8 min at the point of care.

Predictive value of myocardial performance indices for the detection of significant coronary artery disease in patients with a positive ischemia test

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Echocardiography using conventional global or segmental function evaluation has low diagnostic value in detecting subclinical coronary artery disease (CAD). Deformation parameters are more informative but load-dependent. Myocardial Work (MW) based on non-invasive LV pressure-strain loops has been suggested as a new alternative tool for the early detection of CAD. Purpose This study aimed to determine MW diagnostic performance in patients with a positive ischemia test. Methods Fifty-four patients referred for a coronary angiography secondary to a positive ischemia test were included (43 men (79.6%), mean age: 64.3 ± 9.7 years). Patients were divided into two groups according to the presence (SCAD) or absence (NCAD) of significant CAD requiring revascularization. Global and segmental MW parameters were measured on top of conventional echo parameters. Territorial myocardial work index (TWI) and constructive work (TCW) were analyzed according to coronary angiogram results. Results All patients had normal wall motion and left ventricular ejection fraction. There were no significant differences between the two groups regarding conventional echocardiographic parameters and global myocardial deformation. Patients with SCAD had a significantly reduced Global Constructive Work (GCW) compared to NCAD group (2316 mmHg% vs. 2565 mmHg%; p = 0.012). Territorial analysis confirmed a significant decrease in TCW in myocardial segments related to SCAD. GCW is the parameter with the largest AUC to predict a SCAD (AUC = 0.706; CI 95% (0.56 – 0.84)) with a high positive predictive value (73.9%). Conclusion Patients with SCAD had significantly impaired global and territorial MW parameters. MW quantification allows better discrimination of patients with confirmed SCAD. The routine addition of those parameters should improve the predictive value of ischemic tests.

Heart failure-related genes associated with oxidative stress and the immune landscape in lung cancer.

Lung cancer is a common comorbidity of heart failure (HF). The early identification of the risk factors for lung cancer in patients with HF is crucial to early diagnosis and prognosis. Furthermore, oxidative stress and immune responses are the two critical biological processes shared by HF and lung cancer. Therefore, our study aimed to select the core genes in HF and then investigate the potential mechanisms underlying HF and lung cancer, including oxidative stress and immune responses through the selected genes. Differentially expressed genes (DEGs) were analyzed for HF using datasets extracted from the Gene Expression Omnibus database. Functional enrichment analysis was subsequently performed. Next, weighted gene co-expression network analysis was performed to select the core gene modules. Support vector machine models, the random forest method, and the least absolute shrinkage and selection operator (LASSO) algorithm were applied to construct a multigene signature. The diagnostic values of the signature genes were measured using receiver operating characteristic curves. Functional analysis of the signature genes and immune landscape was performed using single-sample gene set enrichment analysis. Finally, the oxidative stress-related genes in these signature genes were identified and validated in vitro in lung cancer cell lines. The DEGs in the GSE57338 dataset were screened, and this dataset was then clustered into six modules using weighted gene co-expression network analysis; MEblue was significantly associated with HF (cor = -0.72, p < 0.001). Signature genes including extracellular matrix protein 2 (ECM2), methyltransferase-like 7B (METTL7B), meiosis-specific nuclear structural 1 (MNS1), and secreted frizzled-related protein 4 (SFRP4) were selected using support vector machine models, the LASSO algorithm, and the random forest method. The respective areas under the curve of the receiver operating characteristic curves of ECM2, METTL7B, MNS1, and SFRP4 were 0.939, 0.854, 0.941, and 0.926, respectively. Single-sample gene set enrichment analysis revealed significant differences in the immune landscape of the patients with HF and healthy subjects. Functional analysis also suggested that these signature genes may be involved in oxidative stress. In particular, METTL7B was highly expressed in lung cancer cell lines. Meanwhile, the correlation between METTL7B and oxidative stress was further verified using flow cytometry. We identified that ECM2, METTL7B, MNS1, and SFRP4 exhibit remarkable diagnostic performance in patients with HF. Of note, METTL7B may be involved in the co-occurrence of HF and lung cancer by affecting the oxidative stress immune responses.

Comparison of Computed Tomography Scoring Systems in Patients with COVID-19 and Hematological Malignancies.

Numerous computed tomography (CT) scales have been proposed to assess lung involvement in COVID-19 pneumonia as well as correlate radiological findings with patient outcomes. Comparison of different CT scoring systems in terms of time consumption and diagnostic performance in patients with hematological malignancies and COVID-19 infection. Retrospective analysis included hematological patients with COVID-19 and CT performed within 10 days of diagnosis of infection. CT scans were analyzed in three different semi-quantitative scoring systems, Chest CT Severity Score (CT-SS), Chest CT Score(CT-S), amd Total Severity Score (TSS), as well as qualitative modified Total Severity Score (m-TSS). Time consumption and diagnostic performance were analyzed. Fifty hematological patients were included. Based on the ICC values, excellent inter-observer reliability was found among the three semi-quantitative methods with ICC > 0.9 (p < 0.001). The inter-observer concordance was at the level of perfect agreement (kappa value = 1) for the mTSS method (p < 0.001). The three-receiver operating characteristic (ROC) curves revealed excellent and very good diagnostic accuracy for the three quantitative scoring systems. The AUC values were excellent (0.902), very good (0.899), and very good (0.881) in the CT-SS, CT-S and TSS scoring systems, respectively. Sensitivity showed high levels at 72.7%, 75%, and 65.9%, respectively, and specificity was recorded at 98.2%, 100%, 94.6% for the CT-SS, CT-S, and TSS scoring systems, respectively. Time consumption was the same for Chest CT Severity Score and TSS and was longer for Chest CT Score (p < 0.001). Chest CT score and chest CT severity score have very high sensitivity and specificity in terms of diagnostic accuracy. The highest AUC values and the shortest median time of analysis in chest CT severity score indicate this method as preferred for semi-quantitative assessment of chest CT in hematological patients with COVID-19.

Enhancing Clinical Diagnosis for Patients With Persistent Pulmonary Abnormalities After COVID-19 Infection: The Potential Benefit of 68 Ga-FAPI PET/CT.

Six post COVID-19 patients suspected for pulmonary fibrosis were scheduled for dual-tracer PET/CT with 18 F-FDG and 68 Ga-fibroblast activation protein inhibitor (FAPI)-46. The uptake of 68 Ga-FAPI-46 in the involved lung was compared with a control group of 9 non-COVID-19 patients. Clinical data and PET/CT imaging were collected and analyzed. PET/CT revealed in all 6 pulmonary impaired patients the reduced glucose avidity on 18 F-FDG and clear positivity on 68 Ga-FAPI-46 PET/CT in comparison to the control group. Enhancing fibrotic repair mechanisms, 68 Ga-FAPI PET/CT may improve noninvasive clinical diagnostic performance in patients with long-term CT abnormalities after severe COVID-19. Although this study shows promising results, additional studies in larger populations are required to establish a general diagnostic guideline.

Performance of the Newly Proposed Peguero-Lo Presti Criterion in Adults with Hypertrophic Cardiomyopathy.

The classic electrocardiogram (ECG) criteria have been applied to left ventricular hypertrophy (LVH) screening but have low sensitivity. Recently, the newly proposed Peguero-Lo Presti criterion has been proven to be more sensitive in detecting LVH in patients with hypertension than several current ECG criteria. The diagnostic value of the Peguero-Lo Presti criterion in hypertrophic cardiomyopathy (HCM) patients has not been fully evaluated. This study aims to test whether the new Peguero-Lo Presti criterion can improve the diagnostic performance in patients with HCM. This study included HCM patients and sex-and age-matched healthy control subjects. The diagnostic performance of the Peguero-Lo Presti criterion was evaluated along with the Sokolow-Lyon criterion, Cornell criterion, and total 12-lead voltage criterion. Overall, 63 HCM patients and 63 controls were enrolled. The diagnostic accuracy, sensitivity and specificity of Peguero-Lo Presti criterion were 74.6%, 73.0% and 76.2%, respectively. The Peguero-Lo Presti criterion had the highest sensitivity, while the Cornell criterion and Sokolow-Lyon criterion had the highest specificity (96.8%). The area under the curve (AUC) showed that the Peguero-Lo Presti criterion was 0.809 (95% CI, 0.730-0.874; p 0.0001), Sokolow-Lyon criterion was 0.841 (95% CI, 0.766-0.900) and total 12-lead voltage criterion was 0.814 (95% CI, 0.735-0.878). There was no significant difference in AUC between Peguero-Lo Presti criterion and Sokolow-Lyon criterion (p = 0.533), or Peguero-Lo Presti criterion and total 12-lead voltage criterion (p = 0.908). Receiver operator characteristic curve analysis of the Peguero-Lo Presti criterion showed an optimal cutoff of 3.15 mV for men (sensitivity: 63.9%; specificity: 80.0%) and 2.29 mV for women (sensitivity: 78.6%; specificity: 85.7%). The Peguero-Lo Presti criterion provides high sensitivity for ECG diagnosis of HCM patients and can be considered when applicable but this needs to be verified in a larger population.

Correlation and validity of imputed PaO2/FiO2 and SpO2/FiO2 in patients with invasive mechanical ventilation at 2600m above sea level.

To establish the correlation and validity between PaO2/FiO2 obtained on arterial gases versus noninvasive methods (linear, nonlinear, logarithmic imputation of PaO2/FiO2 and SpO2/FiO2) in patients under mechanical ventilation living at high altitude. Ambispective descriptive multicenter cohort study. Two intensive care units (ICU) from Colombia at 2600m a.s.l. Consecutive critically ill patients older than 18 years with at least 24h of mechanical ventilation were included from June 2016 to June 2019. None. Variables analyzed were demographic, physiological messures, laboratory findings, oxygenation index and clinical condition. Nonlinear, linear and logarithmic imputation formulas were used to calculate PaO2 from SpO2, and at the same time the SpO2/FiO2 by severe hypoxemia diagnosis. The intraclass correlation coefficient, area under the ROC curve, sensitivity, specificity, positive predictive value, negative predictive value, positive and negative likelihood ratio were calculated. The correlation between PaO2/FiO2 obtained from arterial gases, PaO2/FiO2 derived from one of the proposed methods (linear, non-linear, and logarithmic formula), and SpO2/FiO2 measured by the intraclass correlation coefficient was high (greater than 0.77, p<0.001). The different imputation methods and SpO2/FiO2 have a similar diagnostic performance in patients with severe hypoxemia (PaO2/FiO2 <150). PaO2/FiO2 linear imputation AUC ROC 0,84 (IC 0.81-0.87, p<0.001), PaO2/FiO2 logarithmic imputation AUC ROC 0.84 (IC 0.80-0.87, p<0.001), PaO2/FiO2 non-linear imputation AUC ROC 0.82 (IC 0.79-0.85, p<0.001), SpO2/FiO2 oximetry AUC ROC 0.84 (IC 0.81-0.87, p<0.001). At high altitude, the SaO2/FiO2 ratio and the imputed PaO2/FiO2 ratio have similar diagnostic performance in patients with severe hypoxemia ventilated by various pathological conditions.

Correlation and validity of imputed PaO2/FiO2 and SpO2/FiO2 in patients with invasive mechanical ventilation at 2600 m above sea level

ObjectiveTo establish the correlation and validity between PaO2/FiO2 obtained on arterial gases versus noninvasive methods (linear, nonlinear, logarithmic imputation of PaO2/FiO2 and SpO2/FiO2) in patients under mechanical ventilation living at high altitude. DesignAmbispective descriptive multicenter cohort study. SettingTwo intensive care units (ICU) from Colombia at 2600m a.s.l. Patients or participantsConsecutive critically ill patients older than 18 years with at least 24h of mechanical ventilation were included from June 2016 to June 2019. InterventionsNone. VariablesVariables analyzed were demographic, physiological messures, laboratory findings, oxygenation index and clinical condition. Nonlinear, linear and logarithmic imputation formulas were used to calculate PaO2 from SpO2, and at the same time the SpO2/FiO2 by severe hypoxemia diagnosis. The intraclass correlation coefficient, area under the ROC curve, sensitivity, specificity, positive predictive value, negative predictive value, positive and negative likelihood ratio were calculated. ResultsThe correlation between PaO2/FiO2 obtained from arterial gases, PaO2/FiO2 derived from one of the proposed methods (linear, non-linear, and logarithmic formula), and SpO2/FiO2 measured by the intraclass correlation coefficient was high (greater than 0.77, p<0.001). The different imputation methods and SpO2/FiO2 have a similar diagnostic performance in patients with severe hypoxemia (PaO2/FiO2 <150). PaO2/FiO2 linear imputation AUC ROC 0,84 (IC 0.81–0.87, p<0.001), PaO2/FiO2 logarithmic imputation AUC ROC 0.84 (IC 0.80–0.87, p<0.001), PaO2/FiO2 non-linear imputation AUC ROC 0.82 (IC 0.79–0.85, p<0.001), SpO2/FiO2 oximetry AUC ROC 0.84 (IC 0.81–0.87, p<0.001). ConclusionsAt high altitude, the SaO2/FiO2 ratio and the imputed PaO2/FiO2 ratio have similar diagnostic performance in patients with severe hypoxemia ventilated by various pathological conditions.

Aberrant Circulating SNHG1 Serves as a Biomarker to Distinguish Acute Myocardial Infarction and Construction of a Risk Model for Secondary Heart Failure.

Abstract: Acute myocardial infarction (AMI) is a severe condition observed in patients with coronary heart disease, and heart failure (HF) often occurs after AMI. This study aimed to evaluate the clinical significance of long noncoding RNA (lncRNA) small nucleolar RNA host gene 1 (SNHG1) in the diagnosis and prognosis of AMI and to construct a logistic predict model to determine the risk of post-AMI HF. This study analyzed the data of 229 patients with AMI. Serum SNHG1 levels were examined using quantitative real-time PCR, and its diagnostic value was evaluated using receiver operating characteristic analysis. The predictive value of SNHG1 for HF onset was evaluated using the Kaplan–Meier method and Cox regression analysis. The risk factors and predictive parameters included in the predictive model of post-AMI HF were determined using multivariate logistic regression analysis. In this study, we found that reduced serum SNHG1 was negatively correlated with the Gensini score of patients with AMI. The diagnostic performance of combining cardiac troponin I (cTnI) and creatine kinase (CK)-MB and SNHG1 was the best. Lower SNHG1 expression served as an independent indicator for HF secondary to AMI. A logistic risk model was constructed with the following equation: , and the predictive accuracy of this model was relatively high with an area under the curve of 0.890. Taken together, our results revealed that reduced SNHG1 combining cTnI and CK-MB had the best diagnostic performance in patients with AMI. A logistic risk model based on SNHG1, age, cTnI, CK-MB, left ventricular ejection fraction, and Gensini score may help to determine the development of HF in patients with AMI.

Diagnostic performance of minichromosome maintenance 5 (MCM5) in bladder cancer: A systematic review and meta-analysis.

Primary objective of this study was to determine diagnostic accuracy of minichromosome maintenance 5 (MCM5) protein in patients with bladder cancer (BC). In this review, we searched electronic databases to identify studies on the diagnostic accuracy of MCM5 in patients with BC. We pooled sensitivity and specificities using DerSimonian-Laird random-effect analysis and followed PRISMA guidelines while conducting this review (CRD42021255609). In this meta-analysis, eight prospective studies with 5,114 patients were included. Pooled sensitivity and specificity for MCM5 in predicting BC were 0.66 (0.56-0.75) and 0.72 (0.61-0.81). Subgroup analysis of five studies with 3,000 patients using ADXBLADDER revealed sensitivity and specificity of 0.61 (0.49-0.71) and 0.67 (0.51-0.80). Pooled sensitivity and specificity for primary diagnosis of BC were 0.74 (0.64-0.82) and 0.78 (0.67-0.86), respectively. For BC surveillance, pooled sensitivity and specificity were 0.58 (0.45-0.69) and 0.61 (0.48-0.73), respectively. Pooled sensitivities for low and high-grade tumors were 0.50 (0.36-0.64) and 0.79 (0.68-0.87), respectively. Pooled specificities for low and high-grade tumors were 0.79 (0.63-0.90) and 0.82 (0.65-0.92). MCM5 has an overall moderate diagnostic accuracy for detecting BC. Subgroup analysis revealed good diagnostic performance in patients with high-grade tumors and primary diagnosis of symptomatic patients.

Diagnostic performance of quantitative flow ratio, non-hyperaemic pressure indices and fractional flow reserve for the assessment of coronary lesions in severe aortic stenosis.

Quantitative flow ratio (QFR) may be used to assess the functional significance of coronary lesions. Only limited validation exists for this technology in the setting of severe aortic stenosis. A prospective study was performed on patients who were being considered for transcatheter aortic valve implantation. QFR analysis was performed (Medis Medical Imaging System, Leiden, The Netherlands) and compared to invasive measurements of haemodynamic assessment [fractional flow reserve (FFR), instantaneous wave-free ratio (iFR), diastolic pressure ratio during the wave-free period (dPR) and distal arterial pressure/arterial pressure (Pd/Pa)]. A total of 35 patients were included in the study. Mean age was 75.5±6.5 and mean aortic valve gradient was 44.3±11.8 mmHg. There were 57 vessels analysed. The mean FFR was 0.83±0.10 and 22 vessels (39%) had a functionally significant FFR ≤0.80. QFR demonstrated a discriminatory power to predict functionally significant FFR [area under the receiver operating characteristic curve (AUC), 0.92; 95% confidence interval (CI): 0.84 to 1.00], representing a sensitivity of 73%, specificity of 91%, positive predictive value of 84%, negative predictive value of 84% and an accuracy of 84%. QFR also demonstrated a discriminatory power to predict functionally significant iFR ≤0.89 (AUC =0.92; 95% CI: 0.85 to 0.99), dPR ≤0.89 (AUC =0.90; 95% CI: 0.83 to 0.98) and Pd/Pa ≤0.92 (AUC =0.89; 95% CI: 0.80 to 0.97). QFR demonstrates acceptable diagnostic performance in patients with severe aortic stenosis when both FFR and non-hyperaemic pressure indices are used as reference standards.

The macular inner plexiform layer thickness as an early diagnostic indicator for Parkinson’s disease

Whether structural alterations of intraretinal layers are indicators for the early diagnosis of Parkinson’s disease (PD) remains unclear. We assessed the retinal layer thickness in different stages of PD and explored whether it can be an early diagnostic indicator for PD. In total, 397 [131, 146, and 120 with Hoehn-Yahr I (H-Y I), H-Y II, and H-Y III stages, respectively] patients with PD and 427 healthy controls (HCs) were enrolled. The peripapillary retinal nerve fiber layer (pRNFL), total macular retinal thickness (MRT), and macular volume (TMV) were measured by high-definition optical coherence tomography, and the macular intraretinal thickness was analyzed by the Iowa Reference Algorithms. As a result, the PD group had a significantly lower average, temporal quadrant pRNFL, MRT, and TMV than the HCs group (all p < 0.001). Moreover, the ganglion cell layer (GCL), inner plexiform layer (IPL), and outer nuclear layer were thinner in patients with PD with H-Y I, and significantly decreased as the H-Y stage increased. In addition, we observed that GCL and IPL thicknesses were both correlated with Movement Disorder Society-Unified Parkinson’s Disease Rating Scale III (MDS-UPDRS III) scores and non-motor symptoms assessment scores. Furthermore, macular IPL thickness in the superior inner (SI) quadrant (IPL-SI) had the best diagnostic performance in patients with PD with H-Y I versus HCs, with a sensitivity and specificity of 75.06% and 81.67%, respectively. In conclusion, we confirmed the retinal structure was significantly altered in patients with PD in different clinical stages, and that GCL and IPL changes occurred during early PD disease and were correlated with MDS-UPDRS III scores and non-motor symptoms assessment scores. Furthermore, macular IPL-SI thickness might be performed as an early diagnostic indicator for PD.

Diagnostic performance of coronary computed tomography angiography-derived fractional flow reverse in lesion-specific ischemia patients with different Gensini score levels.

BackgroundCoronary pressure-derived fractional flow reverse (FFR) is the standard of the functional assessment of lesion severity. In spite of its strengths in determining ischemia-related coronary stenosis, the invasive operation involved still limits its clinical application. Coronary computed tomography angiography-derived FFR (CCTA-FFR) or computed tomography-derived FFR (CT-FFR) has been indicated as an effective and non-invasive index to evaluate lesion-specific ischemia. However, its diagnostic performance, especially in patients with different severity of coronary stenosis, remains unknown. The current research attempted to demonstrate this problem and provided the foundation for extensive clinical application of CCTA-FFR.MethodsThe design of this study was a diagnostic test. A total of 97 vessels from 91 patients who performed CCTA and coronary angiography (CAG) during a hospitalization collected from two research centers were included in this study. CCTA-FFR and FFR were obtained by CCTA and CAG separately. The Gensini score was calculated according to the CAG in each patient. FFR was indicated as the golden diagnosis of lesion-specific ischemia with a cut-off value of 0.80, which was consistent with most contemporary studies. A receiver-operating characteristic (ROC) curve, simple linear analysis, and Bland-Altman plot were performed to determine the diagnostic performance of CCTA-FFR.ResultsCCTA-FFR was well correlated with invasive FFR (R2=0.745, P<0.001) and the area under the curve (AUC) was 0.976. The sensitivity was 94.6% and the specificity was 95.1%. The mean difference between FFR and CT-FFR was 0.011, and the 95% confidence interval was −0.173 to 0.196. The AUCs were 0.989 and 0.928 in the low and high Gensini groups, respectively, and there was no significant difference in the diagnostic accuracies between these two groups (Z=0.003, P>0.500). CT-FFR still exhibited a good correlation with FFR (R2=0.713, P<0.001 in the low Gensini group and R2=0.743, P<0.001 in the high Gensini group). The systematic differences were calculated, and the mean difference between FFR and CT-FFR was −0.005 and 0.025, respectively, in these two groups.ConclusionsCCTA-FFR exhibited good diagnostic performance in patients with different Gensini score levels. Our results indicate that CCTA-FFR could be an effective tool to screen lesion-specific ischemia in patients with coronary artery disease.

Quantitative myocardial perfusion 82Rb-PET assessed by hybrid PET/coronary-CT: Normal values and diagnostic performance

PurposeWe aimed to assess normal values for quantified myocardial blood flow (MBF) on a hybrid PET/coronary-CT scanner and to test their diagnostic performance in patients with suspected CAD. Materials and MethodsPatients underwent 82Rb-PET/CT and integrated CT-based coronary angiography (CCTA) and were classified as normal (no stenosis), with non-obstructive stenosis (< 50%) and with CAD (≥ 50%). Global and regional stress MBF (sMBF), rest MBF and myocardial flow reserve (MFR) were calculated. Ischemia was defined as SDS ≥ 2, severe ischemia as SDS ≥ 7. Results357 consecutive patients were included. Global sMBF and MFR were higher in normal patients than in patients with CAD (3.61 ± 0.71 vs 3.04 ± 0.77, P < 0.0001; 3.08 ± 0.84 vs 2.68 ± 0.79, P = 0.0001), but not different compared to patients with non-obstructive stenosis (3.61 ± 0.71 vs 3.43 ± 0.69, P = 0.052; 3.08 ± 0.84 vs 2.99 ± 0.82, P = 0.45). sMBF yielded superior accuracy over MFR in identifying both ischemia (AUC 0.74 vs 0.62, P = 0.003) and severe ischemia (AUC 0.88 vs 0.78, P = 0.012). Optimal threshold for global sMBF to rule out myocardial ischemia was 3.5 mL g−1 min−1. ConclusionsNormal quantitative values are provided. Global sMBF provided higher diagnostic accuracy than MFR. Using sMBF-threshold of 3.5 mL·g−1·min−1 on 82Rb-PET/CT yielded similar NPV (96%) as CCTA to rule out CAD. Hence, resting scan could be omitted in patients with sMBF values above reference.

Diagnostic performance of automated, streamlined, daily updated exome analysis in patients with neurodevelopmental delay

BackgroundThe diagnostic yield of whole-exome sequencing (WES) varies from 30%–50% among patients with mild to severe neurodevelopmental delay (NDD)/intellectual disability (ID). Routine retrospective reanalysis of undiagnosed patients has increased the total diagnostic yield by 10–15%. Here, we performed proband-only WES of 1065 patients with NDD/ID and applied a prospective, daily reanalysis automated pipeline to patients without clinically significant variants to facilitate diagnoses.MethodsThe study included 1065 consecutive patients from 1056 nonconsanguineous unrelated families from 10 multimedical centers in South Korea between April 2018 and August 2021. WES data were analyzed daily using automatically updated databases with variant classification and symptom similarity scoring systems.ResultsAt the initial analysis, 402 patients from 1056 unrelated families (38.0%, 402/1,056 families) had a positive genetic diagnosis. Daily prospective, automated reanalysis resulted in the identification of 34 additional diagnostic variants in 31 patients (3%), which increased our molecular diagnostic yield to 41% (433/1056 families). Among these 31 patients, 26 were diagnosed with 23 different diseases that were newly discovered after 2019. The time interval between the first analysis and the molecular diagnosis by reanalysis was 1.2 ± 0.9 years, which was shorter in the patients enrolled during the latter part of the study period.ConclusionDaily updated databases and reanalysis systems enhance the diagnostic performance in patients with NDD/ID, contributing to the rapid diagnosis of undiagnosed patients by applying the latest molecular genetic information.