Diagnostic value of serum TSI levels in Graves' disease and direct comparison of diagnostic performance with TRAb: A systematic review and meta-analysis.

The aim of this study was to assess the sensitivity and accuracy of magnetic resonance imaging-guided targeted biopsy (MRI-TB) in patients undergoing active surveillance (AS) procedure. We searched databases to identify relevant studies which compared MRI-TB with systemic biopsy for diagnosing prostate cancer in patients on AS. Outcomes included sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), area under the curve (AUC) and publication bias of AS group, confirmatory biopsy group and follow-up biopsy group. Fourteen articles involving 1693 patients were included. In AS group, the sensitivity was 0.62 (95% confidence interval [CI], 0.57-0.68), specificity was 0.89 (95% CI, 0.87-0.90), NLR was 0.43 (0.31-0.60), PLR was 4.90 (3.50-6.86), DOR was 12.75 (7.22-22.51), and AUC was 0.8645. In confirmatory biopsy group, the sensitivity was 0.67 (0.59-0.74), specificity was 0.89 (0.86-0.91), NLR was 0.42 (0.27-0.65), PLR was 4.94 (3.88-6.30), DOR was 14.54 (9.60-22.02), and AUC was 0.8812. In follow-up biopsy group, the sensitivity was 0.35 (0.22-0.51), specificity was 0.88 (0.82-0.92), NLR was 0.76 (0.52-1.11), PLR was 3.06 (1.71-5.50), DOR was 4.41 (2.15-9.03), and AUC was 0.8367. MRI-TB has a moderate-to-high diagnostic accuracy for diagnosing and reclassifying patients on AS with high specificity and AUC value under the SROC curve.

Bacterial meningitis is a serious infection leading to increased morbidity and mortality every year due to delayed diagnosis and treatment. Previous literatures had shown that cerebrospinal fluid (CSF) procalcitonin outweighs serum procalcitonin to diagnose bacterial infections of the central nervous system. Current meta-analysis aims to find the diagnostic accuracy of serum and CSF C-reactive protein (CRP) to diagnose bacterial meningitis. PubMed, Google Scholar, Cochrane Library and Google databases were searched from 1st January 1980 to 30th June 2022. Observational studies, prospective or retrospective focusing on C-reactive protein as a biomarker for bacterial meningitis in adult patients were searched. The articles related to serum and CSF CRP for diagnosing bacterial meningitis were explored and retrieved separately, by two independent experts from the published studies available in the electronic search engines. The risk of bias and scholarly quality of studies were evaluated by QUADAS-2. Altogether 637 articles were recognized, out of which 22 studies selected. CSF CRP has shown better diagnostic value than serum CRP. Pooled sensitivity of CSF CRP was 0.89 (95% confidence interval [CI], 0.81-0.94), specificity 0.96 (95% CI, 0.92-0.97), area under the curve (AUC) 0.98 (95% CI, 0.96-0.99), diagnostic odds ratio (DOR) 175 (95% CI, 74-410), positive likelihood ratio (PLR) 20 (95% CI, 11.5-34.1) and negative likelihood ratio (NLR) 0.11 (95% CI, 0.06-0.21). While, pooled sensitivity of serum CRP was 0.80 (95% CI, 0.69-0.88), specificity 0.86 (95% CI, 0.74-0.93), AUC 0.89 (95% CI, 0.86-0.92), DOR 24 (95% CI, 9-62), PLR 6 (95% CI, 2.9-10.7) and NLR 0.23 (95% CI, 0.15-0.37). Heterogeneity was higher for serum CRP than CSF CRP. Our meta-analysis shows that CSF CRP had higher pooled sensitivity, specificity and PLR along with higher AUC and DOR for confirming bacterial meningitis in adults than serum CRP.

Paper 27; The Diagnostic Accuracy of Clinical Tests in Identifying Those with Deep Gluteal Nerve Entrapment

The accuracy of obstructive sleep apnea (OSA) screening instruments in seniors may change as the predictive role of sex, age, and body mass index (BMI) changes with aging. We investigated the diagnostic performance of the STOP-BANG questionnaire in older individuals with aging-adapted scores and thresholds. Independent community-dwelling adults aged 65 years or older were screened for OSA. The STOP-BANG questionnaire was tested with different configurations and compared to the apnea-hypopnea index (AHI) obtained from home sleep apnea testing (HSAT). Epworth Sleepiness Scale (ESS) and Athens Insomnia Scale (AIS) were tested as possible supplementary screening criteria. We recruited 458 individuals with a mean age of 71 ± 5 years, 41% men, BMI of 28.5 ± 4.6 kg/m². Mild, moderate, and severe OSA were present in, respectively, 34%, 30%, and 19% of the sample. The STOP questions had an area under the curve (AUC) of the receiver operating characteristic curve significantly lower than the STOP-BANG and the STOP+BMI > 28 kg/m² (STOP-B28). Both STOP-BANG and STOP-B28 had high sensitivity and low specificity in all OSA levels with similar AUC to predict AHI ≥ 5 events/h, 0.64. ESS and AIS were nonsignificant as adjunctive instruments. Novel modifications of a standard instrument created the STOP-B28, a simpler-to-obtain and similarly performing variation of the STOP-BANG using fewer inputs, and useful to exclude OSA. Screening seniors via questionnaires to detect OSA is problematic. Considering the 83% OSA prevalence in this age group, it may be a sensible option to indicate objective tests, oximetry, HSAT, or even polysomnography, as a first step in OSA investigation.

Barrett's oesophagus is a precursor to the development of oesophageal adenocarcinoma. This study sought to clarify the role of genetic, chromosomal and proliferation biomarkers that have been the subjects of multiple studies through meta-analysis. MEDLINE, Embase, PubMed and the Cochrane Library were searched for clinical studies assessing the value of p53, p16, Ki-67 and DNA content abnormalities in Barrett's oesophagus. The main outcome measure was the risk of development of high-grade dysplasia (HGD) or oesophageal adenocarcinoma. Some 102 studies, with 12 353 samples, were identified. Mutation (diagnostic odds ratio (DOR) 10·91, sensitivity 47 per cent, specificity 92 per cent, positive likelihood ratio (PLR) 4·71, negative likelihood ratio (NLR) 0·65, area under the curve (AUC) 0·792) and loss (DOR 16·16, sensitivity 31 per cent, specificity 98 per cent, PLR 6·66, NLR 0·41, AUC 0·923) of p53 were found to be superior to the other p53 abnormalities (loss of heterozygosity (LOH) and overexpression). Ki-67 had high sensitivity in identifying high-risk patients (DOR 5·54, sensitivity 82 per cent, specificity 48 per cent, PLR 1·59, NLR 0·42, AUC 0·761). Aneuploidy (DOR 12·08, sensitivity 53 per cent, specificity 87 per cent, PLR 4·26, NLR 0·42, AUC 0·846), tetraploidy (DOR 5·87, sensitivity 46 per cent, specificity 85 per cent, PLR 3·47, NLR 0·65, AUC 0·793) and loss of Y chromosome (DOR 9·23, sensitivity 68 per cent, specificity 80 per cent, PLR 2·67, NLR 0·49, AUC 0·807) also predicted malignant development, but p16 aberrations (hypermethylation, LOH, mutation and loss) failed to demonstrate any advantage over the other biomarkers studied. Loss and mutation of p53, and raised level of Ki-67 predicted malignant progression in Barrett's oesophagus.

BackgroundThis meta-analysis assessed the efficacy of dual-energy computed tomography (DECT) in the diagnosis of anterior cruciate ligament (ACL) injuries.MethodsThe literature search was performed up to December 8, 2023, and included a comprehensive examination of several databases: PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang, and VIP. Diagnostic metrics sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and a summary receiver operating characteristic (SROC) were determined using a bivariate model analysis. Heterogeneity within the data was explored through subgroup analyses, which considered variables including geographical region, use of magnetic resonance imaging (MRI), arthroscopy, and study design.ResultsThe analysis included ten studies encompassing 544 patients. DECT demonstrated substantial diagnostic utility for ACL injuries of the knee, with a sensitivity of 0.91 (95% confidence interval [CI]: 0.88–0.94), a specificity of 0.90 (95% CI: 0.81–0.95), a PLR of 9.20 (95% CI: 4.50–19.00), a NLR of 0.10 (95% CI: 0.06–0.14), a DOR of 97.00 (95% CI: 35.00–268.00), and an area under the curve (AUC) of 0.95 (95% CI: 0.93–0.97). The subgroup analyses consistently showed high diagnostic precision for ACL injuries across Asian population (sensitivity: 0.91, specificity: 0.91, PLR: 9.90, NLR: 0.09, DOR: 105.00, AUC: 0.96), in MRI subgroup (sensitivity: 0.85, specificity: 0.94, PLR: 9.57, NLR: 0.18, DOR: 56.00, AUC: 0.93), in arthroscopy subgroup (sensitivity: 0.92, specificity: 0.89, PLR: 8.40, NLR: 0.09, DOR: 94.00, AUC: 0.95), for prospective studies (sensitivity: 0.92, specificity: 0.88, PLR: 7.40, NLR: 0.09, DOR: 78.00, AUC: 0.95), and for retrospective studies (sensitivity: 0.91, specificity: 0.93, AUC: 0.93).ConclusionDECT exhibits a high value in diagnosing ACL injuries. The significant diagnostic value of DECT provides clinicians with a powerful tool that enhances the accuracy and efficiency of diagnosis and optimizes patient management and treatment outcomes.

ObjectiveTo evaluate thyroid‐stimulating immunoglobulin (TSI) and thyrotropin receptor antibodies (TRAb) diagnostic performance for Graves' disease (GD) and determine clinical cut‐off value for diagnosing GD.MethodsOf 1369 retrospectively enrolled subjects, 1364 had a definitive diagnosis of untreated GD (GD‐UT, n = 87); treated GD (GD‐T, n = 206); autoimmune thyroid disease (AIT, n = 241); thyroid nodules (TN, n = 677); subacute thyroiditis (ST, n = 28); healthy subjects (HS, n = 125); other diseases with serological hyperthyroidism (n = 5) and were grouped into the following: UT‐GD and control groups (AIT, TN, ST, and HS); and UT‐GD and non‐GD hyperthyroidism groups. Diagnostic performance of TSI and TRAb was evaluated using area under the curve (AUC) of receiver‐operating characteristic (ROC) curve, and optimal clinical cut‐off value was determined using maximization of Youden index.ResultsTRAb AUC and clinical cut‐off value for diagnosing GD were 0.981 and 1.245 IU/L (sensitivity, 96.6%; specificity, 97.1%; positive predictive value [PPV], 71.8%; negative predictive value [NPV], 99.9%; positive likelihood ratio [PLR], 33.31; negative likelihood ratio [NLR, 0.035), respectively, for the GD‐UT and control groups. Those for TSI were 0.992 and 0.467 IU/L (sensitivity 98.8%; specificity, 96.4%; PPV, 68.8%; NPV, 99.9%; PLR, 27.472; NLR, 0.011). Those for TRAb in GD‐UT and non‐GD hyperthyroidism groups were 0.923 and 1.78 IU/L (sensitivity, 92.0%; specificity, 89.1%; PPV, 93%; NPV, 87.5%; PLR, 8.44; NLR, 0.089), respectively. For TSI, these were 0.92 and 0.545 IU/L (sensitivity, 97.7%; specificity, 83.6%; PPV, 90.4%; NPV, 95.8%; PLR27.472, NLR, 0.011), respectively.ConclusionTSI diagnostic performance for GD was excellent and had better sensitivity than TRAb.

Objective To evaluate the diagnostic value of endoscopic ultrasonography (EUS) on preoperative invasive depth of early esophageal cancer. Methods A systematic retrieval was performed in PubMed, CNKI and Wangfang databases. Studies on diagnosis of EUS on invasion depth or T1a/T1b stage of early esophageal cancer were retrieved, and related literatures were selected for meta-analysis based on inclusion criteria. The sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic advantage were calculated, and the receiver operating characteristic curve was drawn to calculate the area under the curve (AUC). Results A total of 20 articles with 1 336 cases were included in the meta-analysis. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio and AUC of EUS for T1m staging of early esophageal cancer were 0.86(95%CI: 0.83-0.88), 0.81(95%CI: 0.78-0.85), 4.92(95%CI: 3.02-8.00), 0.19(95%CI: 0.14-0.27), 32.54(95%CI: 15.52-68.25) and 0.923, respectively. For T1sm staging, these results were 0.81(95%CI: 0.78-0.85), 0.86(95%CI: 0.83-0.88), 5.17(95%CI: 3.66-7.32), 0.20(95%CI: 0.13-0.33), 32.02(95%CI: 15.31-66.99) and 0.922, respectively. Conclusion The diagnostic value of EUS is good for early esophageal cancer, and it has a relatively high sensitivity, specificity and AUC for the T1m and T1sm staging. Key words: Endoscopic ultrasonography; Early esophageal carcinoma; Depth; Meta-analysis

Circulating microRNAs (miRNA) have emerged as promising diagnostic biomarkers for several diseases, including cancer. However, the diagnostic accuracy of miRNA panels in colorectal cancer (CRC) remains inconsistent and there is still lack of meta-analyses to determine whether miRNA panels can serve as robust biomarkers for CRC diagnosis. This study performed a systematic review and meta-analysis to evaluate the clinical utility of miRNA panels as potential biomarkers for the diagnosis of CRC. The investigation systematically searched PubMed, Medline, Web of Science, Cochrane Library, and Google Scholar (21-year span, between 2000 and 2021) to retrieve articles reporting the diagnostic role of miRNA panels in detecting CRC. Diagnostic meta-analysis of miRNA panels used diverse evaluation indicators, including sensitivity, specificity, Positive Likelihood Ratio (PLR), Negative Likelihood Ratio (NLR), Diagnostic Odds Ratio (DOR), and the area under the curve (AUC) values. Among the 313 articles identified, 20 studies met the inclusion criteria. The pooled estimates of miRNA panels for the diagnosis of CRC were 0.85 (95% CI: 0.84-0.86), 0.79 (95% CI: 0.78-0.80), 4.06 (95% CI: 3.89-4.23), 0.20 (95% CI: 0.19-0.20), 22.50 (95% CI: 20.81-24.32) for sensitivity, specificity, PLR, NLR, and DOR, respectively. Moreover, the summary receiver operating characteristics (SROC) curve revealed an AUC value of 0.915 (95% CI: 0.914-0.916), suggesting an outstanding diagnostic accuracy for overall miRNA panels. Subgroup and meta-regression analyses demonstrated that miRNA panels have the highest diagnostic accuracy within serum samples, rather than in other sample-types - with a sensitivity, specificity, PLR, NLR, DOR, and AUC of 0.87, 0.86, 7.33, 0.13, 55.29, and 0.943, respectively. Sensitivity analysis revealed that DOR values did not differ markedly, which indicates that the meta-analysis had strong reliability. Furthermore, this study demonstrated no proof of publication bias for DOR values analyzed using Egger's regression test (P > 0.05) and funnel plot. Interestingly, miR-15b, miR-21 and miR-31 presented the best diagnostic accuracy values for CRC with sensitivity, specificity, PLR, NLR, DOR, and AUC values of 0.95, 0.94, 17.19, 0.05, 324.81, and 0.948, respectively. This study's findings indicated that miRNA panels, particularly serum-derived miRNA panels, can serve as powerful and promising biomarkers for early CRC screening. [www.crd.york.ac.uk/prospero], identifier [CRD42021268172].

The aim of the present study was to evaluate the diagnostic value of the ImmunoCyt test compared with urine cytology in detecting bladder cancer. A systematic literature search was performed to locate all publications reporting on the diagnostic accuracy of the ImmunoCyt test for bladder cancer. Data were extracted from 2×2 tables or calculated from reported accuracy data. Collected data were meta-analyzed for sensitivity, specificity, positive likelihood ratio (LR), negative LR, diagnostic odds ratio (DOR), and summary receiver operator characteristic (sROC) curve analysis. We applied the Meta-DiSc 1.4 and STATA 13.0 software to the meta-analysis. Seven separate studies consisting of 1,602 patients with bladder cancer were considered in the meta-analysis. We found that the ImmunoCyt test had a higher sensitivity than the urine cytology test [0.725, 95% confidence interval (CI) 0.683–0.765 vs. 0.566, 95% CI, 0.521–0.611], but the specificity, positive LR, negative LR, DOR, area under the curve (AUC) and Q index of the ImmunoCyt test were lower compared with the urine cytology test. In addition, the pooled sensitivity, specificity, positive LR, negative LR, DOR, AUC, and Q index of the combined method (combination of ImmunoCyt and cytology) were 0.833, 0.644, 2.804, 0.228, 13.50, 0.8554 and 0.7863, respectively. The results of the Eggers test showed no publication bias (P>0.05). In conclusion, specificity, positive LR, negative LR, DOR, the AUC, and the Q index of the urine cytology test may be superior to the ImmunoCyt test, but the ImmunoCyt test has greater sensitivity than the urine cytology test. Use of ImmunoCyt and cytology in combination has the potential to improve the sensitivity and promises to be an alternative in the detection of bladder cancer.

To evaluate the diagnostic accuracy of machine learning models incorporating multimodal features for predicting radiation pneumonitis in lung cancer through a systematic review and meta-analysis. Relevant studies were identified through a systematic search of PubMed, Web of Science, Embase, and the Cochrane Library from October 2003 to December 2023. Additional studies were located by reviewing bibliographies and relevant websites. Two independent researchers screened titles, abstracts, and full-text articles according to predefined inclusion and exclusion criteria. Data extraction was performed using standardized forms, and study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. The primary outcomes, including combined sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC), were calculated using STATA MP-64 software(Stata Corporation LLC, College Station, USA) with a random-effects model. Meta-analysis was conducted to synthesize diagnostic accuracy measures, and analyses of heterogeneity and publication bias were performed. A total of 1,406 patients with primary lung cancer were included in this systematic review, drawing data from 9 studies. The pooled analysis revealed a sensitivity of 0.74 [0.58-0.85] and a specificity of 0.91 [0.87-0.95] for machine learning models in diagnosing radiation pneumonitis. The positive likelihood ratio (PLR) was 8.69 [5.21-14.50], the negative likelihood ratio (NLR) was 0.28 [0.16-0.49], and the diagnostic odds ratio (DOR) was 30.73 [11.96-78.97]. The area under the curve (AUC) was 0.93 [0.90-0.95], indicating excellent diagnostic performance. Meta-regression analysis identified that the number of machine learning models, year of publication, and study design contributed to heterogeneity among studies. No evidence of publication bias was found. Overall, machine learning models incorporating multimodal characteristics demonstrated 75% accuracy in predicting moderate to severe radiation pneumonitis. In conclusion, by integrating the current machine learning (ML) algorithm's ability in big data mining, a predictive model can be constructed by combining multi-modal features such as genetics, imaging, and cell factors. By selecting multiple machine learning algorithm frameworks and competing for the best combination model based on research goals, the reliability and accuracy of the radiation pneumonitis prediction model can be greatly improved. PROSPERO (CRD42024497599).

Objective To evaluate the diagnostic accuracy of miniprobe endoscopic ultrasonography(EUS)in assessment of tumor invasion depth in early gastric cancer. Methods We searched on the PubMed, Cochrane Library, Embase, CNKI, WanFang data, VIP data for relevant studies published.Stata 14.2 software was used to perform the Meta-analysis for sensitivity, specificity, positive likelihood ratio(LR), and negative LR, diagnostic odds ratio and 95% CI.A summary receiver-operating characteristic(SROC)curve was constructed, the area under the curve(AUC)was calculated, and the diagnostic value was evaluated.Furthermore, to explore the potential sources of heterogeneity, we used meta-regression to estimate the effect of the characteristics of the studies on the diagnostic accuracy of miniprobe EUS, and a subgroup analysis was performed.We assessed the publication bias using Deeks′Funnel plot. Results Sixteen studies with a total of 3 168 tumors were included in the analysis.The pooled sensitivity, specificity, positive likelihood ratio(LR), negative LR, diagnostic odds ratio and 95% CI and area under curve(AUC)were 0.85(95% CI: 0.78-0.90), 0.73(95% CI: 0.65-0.80), 3.2(95% CI: 2.4-4.1), 0.20(95% CI: 0.14-0.30), 16(95% CI: 9-26). The AUC of SROC curve was 0.85.No significant publication bias was found with Deeks′Funnel plot. Conclusion Miniprobe EUS can not accurately diagnose or exclude the M/SM1 layer invasion in early gastric cancer, but it still can greatly improve the diagnostic accuracy of invasion depth in early gastric cancer. Key words: Miniprobe endoscopic ultrasonography; Early gastric cancer; Invasion depth; Meta-analysis

TSH-receptor antibodies (TRAb) directed against the TSH receptor (TSH-R) induce hyperthyroidism in patients with Graves' disease (GD). TRAb detected by previous radioimmunoassay only reflects the presence of autoantibodies, but not the function of such antibodies. Thyroid stimulating immunoglobulins (TSI) is a relatively new method for assessing TSH-receptor antibodies function. The aim of this study was to investigate the role of TSI in the diagnosis and management of GD. Patients with newly diagnosed GD (n=140, age 38.00 ± 11.99 years, 106 women) received pharmacological therapy (methimazole) up to 18 months in the outpatient or inpatient department of the Second People's Hospital of Foshan City from January 2013 to December 2018. GD was identified by clinical signs and symptoms and relevant laboratory tests. Blood samples for TSI and TRAb and other thyroidal biomarkers were obtained at baseline and at three times during the follow-up. All patients with GD were followed up for at least 5 years to see if the patient was cured or had relapsed. TSI and TRAb in GD patients were significantly higher than those in the normal control group (P<0.001), and there was a strong correlation between TSI and TRAb in GD patients (P<0.001). After treatment, TSI and TRAb significantly decreased (P<0.05), TSI and TRAb in patients with disease course more than 2 years were significantly higher than those in patients with disease course less than 2 years (P<0.05), There was no statistically significant difference in TSI and TRAb at initial diagnosis between patients with a disease duration of more than 2 years and less than 5 years and those with a disease duration of more than 5 years (P>0.05); if the patients were still positive for TSI or TRAb antibodies at 5 years of follow-up after treatment with anti-hyperthyroidism medication, the patients were at a higher risk of relapse (P<0.001). The higher TSI at the initial diagnosis of GD, the longer duration of treatment with anti-hyperthyroid drugs and the higher risk of relapse. Compared with TRAb, serum TSI level is also important in the clinical diagnosis and prognosis of GD, but which one is superior to the other needs further study.

To establish the diagnostic accuracy of RASSF1A (Ras association domain family 1 isoform) methylation using bronchial aspirates as an auxiliary method for diagnosing lung cancer through a systematic review and meta-analysis. Studies published prior to October 30, 2022, were retrieved from the Embase, PubMed, Web of Science, and Wan Fang databases using the keywords "lung cancer", "RASSF1A", "methylation", and "bronchial aspirates". A fixed or random effect model was used to calculate the combined sensitivity, specificity, positive likelihood ratios (LR), negative LR, diagnostic odds ratio (DOR), along with the respective 95% confidence intervals (CIs) and the area under the curve (AUC) with Q index. The threshold effect was defined by using the Spearman correlation coefficient, and the Deeks funnel plot was generated to evaluate publication bias. Among the 12 trials that met the inclusion criteria, a total of 2388 participants were involved. The pooled results for the diagnosis of lung cancer were as follows, when compared to the pathological diagnosis: sensitivity of 0.47 (95% CI: 0.45-0.50), specificity of 0.96 (95% CI: 0.95-0.97), positive LR of 12.18 (95% CI: 8.96-16.55), negative LR of 0.56 (95% CI: 0.52-0.61), DOR of 24.05 (95% CI: 17.29-33.47), and AUC of 0.78 (Q index = 0.72), respectively. The sensitivity of the RASSF1A methylation assay was relatively low in a detailed subgroup analysis, fluctuating between 0.39 and 0.90, indicating a limitation in its diagnostic value for lung cancer. The RASSF1A methylation assay, on the other hand, demonstrated excellent specificity, suggesting a high exclusion value. Of note, the diagnostic sensitivity, specificity, DOR, and AUC for small cell lung cancer were 0.90 (0.84-0.94), 0.95 (0.94-0.97), 249.5 (103.94-598.8), and 0.98, respectively, showing that RASSF1A methylation was a promising biomarker for diagnosing small cell lung cancer with both high diagnostic and exclusion value. Furthermore, RASSF1A methylation using bronchial washings and bronchial aspirates showed a high AUC of 0.998 and 0.93, respectively, indicating excellent diagnostic performance. The methylation of RASSF1A in bronchial aspirates demonstrated a high level of diagnostic accuracy and has the potential to be a valuable supplementary diagnostic method, especially for identifying small cell lung cancer.

Many studies have shown that human telomerase activity could play potential role as a diagnostic biomarker of pancreatic cancer (PaC). The aim of this meta-analysis is to summarize the clinical value of human telomerase activity in the diagnosis of PaC. Eligible studies from PubMed, Embase, the Cochrane Library, Web of Science, Ovid, Sci Verse, Science Direct, Scopus, BioMed Central, Biosis previews, Chinese Biomedical Literature Database (CBM), Chinese National Knowledge Infrastructure (CNKI), Technology of Chongqing (VIP), and Wan Fang databases were searched concerning the diagnostic value of human telomerase activity in PaC without language restriction. The quality of each study was scored with the Quality Assessment of Diagnostic Accuracy Studies (QUADAS). Sensitivity, specificity, positive and negative likelihood ratios (PLR and NLR, respectively), and diagnostic odds ratio (DOR) for human telomerase activity in the diagnosis of PaC were pooled. Summary receiver operating characteristic (SROC) curve analysis and the area under the curve (AUC) were used to estimate the overall test performance. Evidence of heterogeneity was evaluated using the Chi-square and I (2) test. Meta-Disc 1.4 and Stata 12.0 software were used to analyze the data. Nine studies with a total 186 PaC patients and 132 control individuals were included in this meta-analysis. All of the included studies are of high quality (QUADAS score ≥10). The summary estimate was 0.83 (95 % confidence interval (CI), 95 % CI = 0.77-0.88) for sensitivity and 0.72 (95 % CI = 0.64-0.79) for specificity. The positive likelihood (PLR), negative likelihood (NLR), and diagnostic odds (DOR) ratios were 3 (95 % CI = 1.67-5.41), 0.25 (95 % CI = 0.13-0.46), and 3 (95 % CI = 4.91-43.23), respectively. The area under the summary ROC curve (AUC) and Q* index for the diagnosis of PaC were 0.88 and 0.81, respectively. Our study demonstrates that telomerase could be a useful tumor marker for PaC diagnosis. Although more studies are needed to highlight the theoretical strengths, these results will provide theoretical basis for bringing telomerase activity detection into PaC screening plan.