scholarly journals Urine Cellular DNA Point Mutation and Methylation as Potential Biomarkers for Early Detection of Urothelial Carcinoma

2021 ◽  
Author(s):  
Junjie Zhang ◽  
Ran Xu ◽  
qiang lu ◽  
zhenzhou Xu ◽  
jianye Liu ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Early Detection ◽  
Sensitivity And Specificity ◽  
External Validation ◽  
Point Mutations ◽  
Test Group ◽  
Training Group ◽  
Clinical Trial Registry ◽  
Urine Sediment ◽  
Cellular Dna

Abstract Background: Previously, our team identified a seven-gene mutation panel in urine sediment to discriminate UBC from benign urological diseases. In the present study, we aimed to validate the panel in an expanded and close to natural population cohort of hematuria. Also, we tried to optimize the panel by incorporating methylation biomarkers. We performed external validation to investigate the robustness and stability of the novel panel. Methods: Patients with urothelial carcinomas and controls were prospectively recruited in clinical trial ChiCTR2000029980. The mutation panel was validated in the expanded cohort(n=333) from Hunan multicenter. Several UBC-specific methylation biomarkers were identified by comprehensive analyses of a series of TCGA, GEO and an independent cohorts, and examined in the expanded cohort. Random Forest algorithm was used to construct an optimal panel. External validation of the optimal panel was carried out in Beijing single center cohort(n=89). NGS technique was used to analyze the DNA point mutations and MS-PCR for methylation.Results: The AUC, sensitivity and specificity of the mutation panel in expanded cohort were 0.81, 0.67 and 0.90, respectively. After screening, only cg16966315, cg17945976 and cg24720571 were left for further analysis. The optimal panel consisted of cg24720571 and 8 point mutations, including TERT 228(G_A), FGFR3 568(C_T), TERT 250(G_A), FGFR3 099(A_G), PIK3CA 091(G_A), PIK3CA 085(A_G), PIK3CA 082 (G_A) and HRAS 874(T_C). The AUC, sensitivity and specificity of the optimal panel in training group were 0.89, 0.84 and 0.79, respectively, and in test group were 0.95, 0.91 and 0.95, respectively. In the external validation, the AUC, sensitivity and specificity were 0.98, 0.93 and 0.93, respectively.Conclusions: The optimal panel was obviously superior to previous mutation panel and showed a highly specific and robust performance. The optimal panel may be used as a replaceable approach for early detection of UC.Trial registration: This research was registered in Chinese Clinical Trial Registry(ChiCTR2000029980).

scholarly journals Urine Cellular DNA Point Mutation and Methylation as Potential Biomarkers for the Detection of Urothelial Carcinoma

2021 ◽  
Author(s):  
Junjie Zhang ◽  
Ran Xu ◽  
Qiang Lu ◽  
Zhenzhou Xu ◽  
Jianye Liu ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Sensitivity And Specificity ◽  
External Validation ◽  
Point Mutations ◽  
Test Group ◽  
Training Group ◽  
The Novel ◽  
Clinical Trial Registry ◽  
Urine Sediment ◽  
Cellular Dna

Abstract BackgroundPreviously, our team identified a seven-gene mutation panel in urine sediment to discriminate UBC from benign urological diseases. In the present study, we aimed to validate the panel in an expanded and close to natural population cohort of hematuria. Also, we tried to optimize the panel by incorporating methylation biomarkers. We performed external validation to investigate the robustness and stability of the novel panel.MethodsPatients with urothelial carcinomas and controls were prospectively recruited in clinical trial ChiCTR2000029980. The mutation panel was validated in the expanded cohort(n=333) from Hunan multicenter. Several UBC-specific methylation biomarkers were identified by comprehensive analyses of a series of TCGA, GEO and an independent cohorts, and examined in the expanded cohort. Random Forest algorithm was used to construct an optimal panel. External validation of the optimal panel was carried out in Beijing single center cohort(n=89). NGS technique was used to analyze the DNA point mutations and MS-PCR for methylation.ResultsThe AUC, sensitivity and specificity of the mutation panel in expanded cohort were 0.81, 0.67 and 0.90, respectively. After screening, only cg16966315, cg17945976 and cg24720571 were left for further analysis. The optimal panel consisted of cg24720571 and 8 point mutations, including TERT.chr5_1295228 G_A (TERT 228), FGFR3.chr4_1803568 C_G (FGFR3 568), TERT.chr5_1295250 G_A (TERT 250), FGFR3.chr4_1806099 A_G (FGFR3 099), PIK3CA.chr3_178936091 G_A (PIK3CA 091), PIK3CA.chr3_178952085 A_G (PIK3CA 085), PIK3CA.chr3_178936082 G_A (PIK3CA 082), HRAS.chr11_533874 T_C (HRAS 874). The AUC, sensitivity and specificity of the optimal panel in training group were 0.89, 0.84 and 0.79, respectively, and in test group were 0.95, 0.91 and 0.95, respectively. In the external validation, the AUC, sensitivity and specificity were 0.98, 0.93 and 0.93, respectively.ConclusionsThe optimal panel was obviously superior to previous mutation panel and showed a highly specific and robust performance. The optimal panel may be used as a replaceable approach for early detection of UC.Trial registrationThis research was registered in Chinese Clinical Trial Registry(ChiCTR2000029980).

scholarly journals Effect of a Vibration System on Pain Reduction during Injection of Dental Anesthesia in Children: A Randomized Clinical Trial

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Muhanad AlHareky ◽  
Jehan AlHumaid ◽  
Sumit Bedi ◽  
Maha El Tantawi ◽  
Mazin AlGahtani ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Test Group ◽  
The United States ◽  
Nerve Fibers ◽  
T Test ◽  
Control Group ◽  
Controlled Clinical Trial ◽  
Clinical Trial Registry ◽  
Dental Anesthesia ◽  
Gate Control Theory

Background. The ‘‘gate control’’ theory suggests pain can be reduced by simultaneous activation of larger diameter nerve fibers using appropriate coldness, warmth, rubbing, pressure, or vibration. This study investigated the efficacy of a device combining cold and vibration, for needle-related procedural pain in children. Methodology. A total of 51 children aged 5–12 years participated in this randomized controlled clinical trial. Half of the children were in the control group and received maxillary buccal infiltration, by injecting 1.8 ml of 2% lidocaine with 1 : 100,000 adrenaline using topical anesthesia 20% benzocaine gel for 15 seconds, while the other half were in the test group and received the same anesthesia using a commercially available external cold and a vibrating device. A face version of Visual Analogue Scale (VAS) was used as a subjective measure to assess the child’s pain experience. The parents were requested to evaluate the child’s ability to tolerate pain using a behavioral/observational pain scale. Sound, Eyes, and Motor (SEM) scale and Faces, Legs, Activity, Cry, and Consolability (FLACC) scale were used to record the child’s pain as perceived by the external evaluator. T-test or Mann–Whitney U-test was used for scale variables, paired sample T-test or Wilcoxon rank t-test was used for before and after data, and chi-square was used for categorical variable, based on the results of normality test. Results. The results showed a statistically significant reduction in pain after the injection for the test group compared with control using VAS scale (mean = 6.68 (1.09) and 8.42 (0.50); p = 0.001 ) and FLACC scale (mean = 5.92 (1.05) and 8.16 (0.54); p = 0.002 ), but not when using SEM scale (mean 3.22 (0.42) and 4.24 (2.74); p = 0.08 ). Conclusions. Combined external cold and vibrating devices can be an effective alternative in reducing experienced pain and fear in children undergoing infiltration dental anesthesia. This study was registered with clinical trial registry of the United States National Institutes of Health (NIH) at ClinicalTrials.gov (NCT03953001).

scholarly journals Radiomics-Based Distinction of s-HCC and Precancerous Lesion Based on Precontrast MRI

2021 ◽  
Author(s):  
JiaWen Luo ◽  
Kun Guo ◽  
XiaoNing Gao ◽  
Hao Liu ◽  
Yue Xiang ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Sensitivity And Specificity ◽  
Precancerous Lesion ◽  
Test Group ◽  
Training Group ◽  
Accurate Diagnosis ◽  
Fat Suppression ◽  
Model Based

Abstract Background: To assess the feasibility of radiomics based on precontrast MRI for the distinguish of s-HCC and pre-HCC.Method: We retrospectively analyzed 146 nodules from 78 patients, with pathological confirmed. Each nodule was segment on precontrast MRI sequence(TIWI and fat-suppression T2WI), retrospectively. 1223radiomics features were extracted and the optimal 10 features were selected by LASSO to establish the logistic regression radiomics model. Result: The AUC, sensitivity and specificity of the training group and test group were 0.757 (95% CI 0.638 -0.853), 83.02% , 66.67% and 0.789 (95% CI 0.643-0.895), 88.89% and 80.00%, respectively. The AUC, sensitivity and specificity of the training group and test group were 0.903 (95% CI 0.807-0.962), 86.79% , 86.67% and 0.778 (95% CI 0.632-0.887), 75.00%, 80.00%, respectively. Delong test has proved that, the diagnositic performances of radiomics model based on T2WI were higher than that of radiomics model based on T1WI (p = 0.0379).Conclusion: Radiomics model can classify s-HCC and pre-HCC based on precontrast MRI. And may serve as an adjunct tool for accurate diagnosis of s-HCC.

Detector-C: A Blood-based IVD with High Sensitivity and Specificity for Early Detection and Screening of Colorectal Cancer

2010 ◽  
Vol 48 (08) ◽  
Author(s):  
A Rosenthal ◽  
H Köppen ◽  
R Musikowski ◽  
R Schwanitz ◽  
J Behrendt ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Early Detection ◽  
Sensitivity And Specificity ◽  
High Sensitivity

scholarly journals Calling for improved quality in the registration of traditional Chinese medicine during the public health emergency: a survey of trial registries for COVID-19, H1N1, and SARS

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Zhuoran Kuang ◽  
◽  
Xiaoyan Li ◽  
Jianxiong Cai ◽  
Yaolong Chen ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Secondary Outcome ◽  
Specific Information ◽  
Clinical Trial Registry ◽  
Data Set ◽  
Diagnosis Criteria

Abstract Objective To assess the registration quality of traditional Chinese medicine (TCM) clinical trials for COVID-19, H1N1, and SARS. Method We searched for clinical trial registrations of TCM in the WHO International Clinical Trials Registry Platform (ICTRP) and Chinese Clinical Trial Registry (ChiCTR) on April 30, 2020. The registration quality assessment is based on the WHO Trial Registration Data Set (Version 1.3.1) and extra items for TCM information, including TCM background, theoretical origin, specific diagnosis criteria, description of intervention, and outcomes. Results A total of 136 records were examined, including 129 severe acute respiratory syndrome coronavirus 2 (COVID-19) and 7 H1N1 influenza (H1N1) patients. The deficiencies in the registration of TCM clinical trials (CTs) mainly focus on a low percentage reporting detailed information about interventions (46.6%), primary outcome(s) (37.7%), and key secondary outcome(s) (18.4%) and a lack of summary result (0%). For the TCM items, none of the clinical trial registrations reported the TCM background and rationale; only 6.6% provided the TCM diagnosis criteria or a description of the TCM intervention; and 27.9% provided TCM outcome(s). Conclusion Overall, although the number of registrations of TCM CTs increased, the registration quality was low. The registration quality of TCM CTs should be improved by more detailed reporting of interventions and outcomes, TCM-specific information, and sharing of the result data.

Impact of copeptin, miRNA-499 and miRNA-208 as new biomarkers for early detection of acute coronary syndrome

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
S El-Deek ◽  
A.R Meki ◽  
A Hassan ◽  
M Gaber ◽  
O Mohamed
Keyword(s):  
Acute Coronary Syndrome ◽  
Early Detection ◽  
Sensitivity And Specificity ◽  
Cardiac Troponin ◽  
Roc Curve Analysis ◽  
Major Drawback ◽  
Expression Levels ◽  
Positive Correlation ◽  
Coronary Syndrome ◽  
Novel Biomarkers

Abstract Introduction Acute coronary syndrome (ACS) is a leading cause of mortality and morbidity worldwide. Despite being the gold standard biomarkers, cTn and CK-MB have a major drawback as they are less sensitive in the first 3 hours of the onset of symptom. So, there is still a need for novel biomarkers, which can reliably rule in or rule out this disease immediately on admission. Aim of the work To evaluate the role of copeptin, miRNA-499 and miRNA-208 as novel biomarkers for early detection of unstable angina (UA) and non-ST-segment elevation myocardial infarction (NSTEMI) Patients and Methods: A total of 65 patients presenting within 4 h of onset of chest pain suggestive of ACS were enrolled in the study. They included 23 UA, 42 NSTEMI. Also 25 apparently healthy controls were included. Blood samples (first set within the first 3 hours and second set at 6 hours) were taken for estimation of copeptin by ELISA and miRNA-499 and miRNA-208 expression levels by real time PCR. Results Copeptin, miRNA-499 and miRNA-208 expression levels were significantly increased in UA and NSTEMI patients compared to controls (P<0.001 each). Also these biomarkers were significantly increased in NSTEMT compared to UA (P<0.001 each). They also significantly elevated in UA and NSTEMI patient in the first 3 hours who had negative cardiac troponin (p<0.001 each). ROC curve analysis revealed that the area under curve (AUC) for prediction of ACS was 0.96 for copeptin, 0.97 for miRNA-499 and 0.0.97 for miRNA-208. Interestingly, combining copeptin with miRNA-499 and miRNA-210 significantly improved the diagnostic value by increasing the AUC to 0.98, P<0.001. The sensitivity and specificity within the first 3 hours were 90%, 86% for copeptin, 95%, 94% for miRNA-499 and 93%, 98% for miRNA-208. The sensitivity and specificity were 81% and 86% for cardiac troponin within 6 hours. There was a positive correlation between copeptin and miRNA-499 and miRNA-208 (r=0.75, P<0.001 and r=0.76, P<0.001 respectively) Also, there was a positive correlation between these biomarkers and cTn (r=0.7. P<0.001, r=0.64, P<0.001 and r=0.68, P<0.001 respectively). Conclusions Copeptin, miRNA-499 and miRNA-208 expression might be novel biomarkers as they are associated with UA and NSTEMI presented in the first 3 hours of onset of pain. The combination of copeptin and miRNA with cTn accelerate the diagnosis of ACS and avoiding the gray zone of cTn. Copeptin and miRNAs representing a potential aid in early diagnosis as they have different pathogenesis and site of liberation. Funding Acknowledgement Type of funding source: None

scholarly journals Primary success of electrical cardioversion for new-onset atrial fibrillation and its association with clinical course in non-cardiac critically ill patients: sub-analysis of a multicenter observational study

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Nozomu Shima ◽  
Kyohei Miyamoto ◽  
Seiya Kato ◽  
Takuo Yoshida ◽  
Shigehiko Uchino ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Clinical Trial ◽  
Sinus Rhythm ◽  
Trial Registry ◽  
Clinical Trial Registry ◽  
Icu Discharge ◽  
Primary Success ◽  
Success Group ◽  
Onset Atrial Fibrillation ◽  
New Onset

Abstract Background Electrical cardioversion (ECV) is widely used to restore sinus rhythm in critically ill adult patients with atrial fibrillation, although its prognostic value is uncertain. This study aims to elucidate the clinical meaning of successful ECV. Methods This is a sub-analysis of the AFTER-ICU study, a multicenter prospective study with a cohort of 423 adult non-cardiac patients with new-onset atrial fibrillation (AF). Patients that underwent ECV within 7 days after initial onset of AF were included in the sub-analysis. We compared intensive care unit (ICU) and overall hospital mortality, survival time within 30 days, cardiac rhythm at ICU discharge, and the length of ICU and overall hospital stay between patients whose sinus rhythm was restored immediately after the first ECV session (primary success group) and those in whom it was not restored (unsuccessful group). To find the factors related to the primary success of ECV, we also compared patient characteristics, the delivered energy, and pretreatment. Results Sixty-five patients received ECV and were included in this study. Although 35 patients (54%) had primary success, recurrence of AF occurred in 24 of these patients (69%). At ICU discharge, three patients still had AF in the unsuccessful group, but no patients in the primary success group still had AF. ICU mortality was 34% in the primary success group and 17% in the unsuccessful group (P = 0.10). Survival time within 30 days did not differ between the groups. Delivered energy and pretreatment were not associated with primary success of ECV. Conclusions The primary success rate of ECV for new-onset AF in adult non-cardiac ICU population was low, and even if it succeeded, the subsequent recurrence rate was high. Primary success of ECV did not affect the rate of mortality. Pretreatment and delivered energy were not associated with the primary success of ECV. Trial registration UMIN clinical trial registry, the Japanese clinical trial registry (registration number: UMIN000026401, March 31, 2017).

scholarly journals Expression of inflammatory mediators in biofilm samples and clinical association in inflammatory bowel disease patients—a preliminary study

2021 ◽  
Author(s):  
Mayte Buchbender ◽  
Jakob Fehlhofer ◽  
Peter Proff ◽  
Tobias Möst ◽  
Jutta Ries ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Inflammatory Bowel Disease ◽  
Oral Cavity ◽  
Bowel Disease ◽  
Trial Registry ◽  
Clinical Trial Registry ◽  
Clinical Trial Registration ◽  
Expression Levels ◽  
Inflammatory Bowel ◽  
Group 2

Abstract Objectives Inflammatory bowel disease (IBD) has multiple impacts on soft and hard tissues in the oral cavity. The aim of this study was to analyze the expression of cytokines in biofilm samples from patients suffering from IBD and compare them to healthy patients. It was hypothesized that different cytokine expression levels and clinical associations might be drawn. Material and methods A total of 56 biofilm samples from three different patient cohorts (group 0 = healthy, HC n = 30; group 1 = Crohn’s disease, CD, n = 19; group 2 = ulcerative colitis, UC, n = 7) were examined for the expression levels of the cytokine interleukins IL-2, -6, and -10; matrix metalloproteinases 7 and 9; and surface antigens CD90/CD11a by quantitative real-time PCR and according to clinical parameters (plaque index, BOP, PD, DMFT, CAL). Relative gene expression was determined using the ∆∆CT method. Results The mean BOP values (p = 0.001) and PD (p = 0.000) were significantly higher in the CD group compared to controls. Expression of IL-10 was significantly higher in the CD (p = 0.004) and UC groups (p = 0.022). Expression of MMP-7 was significantly higher in the CD group (p = 0.032). IBD patients treated with TNF inhibitors (p = 0.007) or other immunosuppressants (p = 0.014) showed significant overexpression of IL-10 compared to controls. Conclusion Different expression levels of IL-10 and MMP-7 were detected in plaque samples from IBD patients. As only BOP was significantly increased, we conclude that no clinical impairment of periodontal tissue occurred in IBD patients. Clinical relevance With the worldwide increasing incidence of IBD, it is important to obtain insights into the effects of the disease on the oral cavity. The study was registered (01.09.2020) at the German clinical trial registry (DRKS00022956). Clinical trial registration The study is registered at the German clinical trial registry (DRKS00022956).

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