SROC Curve Research Articles

The interferon-gamma (IFN-y) signature from baseline tumor material predicts pathologic response after neoadjuvant ipilimumab (IPI) + nivolumab (NIVO) in stage III melanoma.

9539 Background: Neoadjuvant IPI + NIVO induces high pathologic response rates (pRR) of 74-78% in macroscopic stage III melanoma. Pathologic response ( < 50% viable tumor) is strongly associated with improved relapse-free survival (RFS); the previous OpACIN-neo study demonstrated a 2-year RFS of 96.9% in patients (pts) with pathologic response, whereas the 2-year RFS in non-responders was 35.5%. These data highlight the need for baseline biomarkers predictive for response and survival. Here, we present the predictive value of the 10-gene IFN-y expression signature algorithm (based on Ayers et al.) for pathologic response and relapse in a cohort of melanoma pts treated with neoadjuvant IPI + NIVO. Methods: Baseline tumor biopsies from lymph node metastases of stage III melanoma pts were used for IFN-y signature assessment. Pts were treated with a maximum of two cycles of neoadjuvant IPI 1mg/kg + NIVO 3mg/kg in the OpACIN-neo (arm B) and PRADO studies. RNA expression analysis was conducted using the nCounter® PanCancer Immune Profiling panel on the NanoString Flex machine (NanoString Technologies), which is clinically applicable due to its fast turn-around-time (two days). An IFN-y signature gene expression score (IFN-y score) was calculated using a NKI-developed algorithm. Association between IFN-y score and pathologic response or event-free survival (EFS) was examined by logistic regression and Cox analyses. The optimal cutoff between a high and low IFN-y score was defined based on a summary receiver operating characteristic (sROC) curve. Results: In total, 103 pts treated in the OpACIN-neo and PRADO studies had baseline tumor material available. Median age was 56 years, 62% was male, and 52% had a high baseline IFN-y score. The pRR of the total cohort was 70% (72/103 pts), including 56% (58/103) major pathologic response (MPR, 0-≤10% viable tumor) and 14% (14/103) partial responses (pPR, 10-≤50% viable tumor). 30% (31/103 pts) had no pathologic response. After a median follow-up of 25.2 months, 26 pts (25.2%) developed a melanoma relapse. The IFN-y score was significantly associated with response (OR 1.061, p < 0.001) and relapse (OR 0. 974, p = 0.029). The pRR was 89% (48/54) in pts with a high IFN-y score versus 49% (24/49) in those with a low IFN-y score (p < 0.001). Pts with a high IFN-y score were also less likely to develop a relapse (11% [6/54] versus 41% [20/49], p = 0.001). Conclusions: Pts with a high IFN-y score in pre-treatment biopsies are more likely to respond to neoadjuvant IPI + NIVO with favorable EFS. A rapid gene expression analysis enables the IFN-y score to be used in daily clinical practice to identify pts who might qualify for treatment escalation or de-escalation. The DONIMI study [NCT04133948] currently investigates different neoadjuvant treatment combinations in stage III melanoma pts based on their intratumoral IFN-y score.

993-P: Cell-Free DNA Methylation as a Biomarker of Islet-Cell Death in Youth with Type 2 Diabetes

Type 2 diabetes (T2D) in youth is diagnosed after irreparable islet damage. Cell-free DNA methylation can be used as a marker of islet cell death after islet transplantation. We assessed the performance of cell-free (cf) DNA in the discrimination of T2D and as a circulating biomarker of islet cell death. Methods: We recruited 72 youth 10-20 years old through provider networks in Atlanta, Georgia. Participant groups were (a) new onset T2D (n=21, within 16 weeks of diagnosis) ; (b) healthy, normal weight (n=23, no family history of diabetes) ; and (c) High Risk (HR, n=31, BMI ≥ 95th %ile or acanthosis nigricans; with family history) . All participants had an oral glucose tolerance test. Based on genes uniquely unmethylated in islets, plasma was analyzed at 9 CpG sites across 3 genes (INS, GCK, IADD) using bisulfite conversion and next generation sequencing. T2D and HR were grouped and compared to Healthy by (a) linear regression of % methylation on group, and (b) area under the curve (AUC) ROC analysis, adjusted for age and BMI %ile. Results: Mean age was higher among healthy participants (17yr SD±3) vs. T2D+HR (14±2) . Age- & BMI %ile- adjusted methylation of INS GRCh38 CpG Chr11:2160843 was highest in T2D+HR (94.8%, 95%CI: 93.5, 96.1) and lowest in Healthy (90.0%, 95%CI: 87.7, 92.2) , p=0.0051. Secondly, at CpG Chr11:2160806, methylation was highest in T2D+HR (85.6%, 95%CI: 83.3, 87.8) vs. Healthy (83.1%, 95%CI: 79.1, 87.1) , p=0.0409. Cell-free INS methylation improved the AUC for T2D or severe prediabetes (i.e., combined impaired fasting glucose + impaired glucose tolerance, per ADA cutpoints) from 0.72 in models of age and BMI %ile to 0.81 in models also including cfINS methylation. Conclusions: Higher % methylated cfINS was found in T2D+HR youth, rather than hypothesized lower levels. It is possible that during T2D onset, non-islet apoptosis occurs in larger concentration than islet cell apoptosis. Methylated cfINS improved discrimination of T2D and severe prediabetes by nearly 10% beyond age and BMI. Disclosure L.R.Staimez: None. J.Ham: None. T.Daley: None. P.Vellanki: n/a. A.K.Smith: None. K.Narayan: n/a. A.Baccarelli: None. K.Conneely: None. Funding Georgia CTSA UL1 (UL1TR002378) and KL2 (KL2TR002381) ; Emory University Woodruff Health Sciences Center Foundation

A nomogram to predict the prognosis of advanced soft tissue sarcoma patients treated with anlotinib: A real-world population-based study.

e23550 Background: The ALTER0203 randomized controlled trial proved the antitumor activity of anlotinib, a multitargeted tyrosine kinase inhibitor, in 8 subtypes of advanced refractory soft tissue sarcoma (STS). Our previous studies have shown that anlotinib showed antitumor activity in more than 30 STS pathological subtypes in the real world. This study further constructed a nomogram to predict the prognosis of advanced STS patients treated with anlotinib based on real-world data. Methods: We retrospectively analyzed the data of patients with unresectable locally advanced or metastatic STS who received at least one dose of anlotinib from June 2018 to March 2021. A nomogram was developed to predict the survival probability based on the multivariate analysis. The performance of the nomogram was evaluated by concordance index, bootstrap resampling calibration curve and time-dependent ROC curve. Results: A total of 209 patients were included in this study. The median age was 48 years (range 11-85 years), and the median follow-up time was 18.7 months. Based on five independent prognostic factors including ECOG performance status, FNCLCC grade G2-3, poor nutrition, increased neutrophil count, and treatment patterns according to the multivariate analysis, we constructed a nomogram to predict the prognosis of advanced STS patients treated with anlotinib. The concordance index was 0.780. For the prediction of 1-year and 2-year overall survival probability according to the nomogram, the area under the receiver operating characteristic curve was 0.833 and 0.829, respectively. Conclusions: The nomogram based on ECOG performance status, FNCLCC grade, nutritional status, neutrophil count, and treatment patterns can accurately predict the 1-year and 2-year OS probability for advanced STS patients treated with anlotinib.

Which of the Cornell Scale for Depression in Dementia or the Geriatric Depression Scale is more useful to screen for depression in older adults?

Depression in older adults is a major disorder that can be triggering, exacerbating, or co-occurring with dementia symptoms. This study compared the diagnostic accuracy of the Cornell Scale for Depression in Dementia (CSDD) and the Geriatric Depression Scale (GDS), a depression screening tool developed for older adults. Electronic searches were performed on the MEDLINE, EMBASE, CINAHL, and PsycINFO databases using the following keywords: dementia, depression, and CSDD. The pooled sensitivity of the CSDD and the GDS was 0.89 and 0.82, the pooled specificity was 0.88 and 0.85, and the summary receiver operating characteristic (SROC) curve was 0.94 and 0.91, respectively. In the subgroup analysis, the CSDD had the highest accuracy in the pooled sensitivity of 0.91, the pooled specificity of 0.87, and the sROC curve of 0.95 in the dementia group, and the GDS was the best in the non-dementia group at 0.88, 0.82, and 0.93, respectively. The CSDD showed high diagnostic accuracy in older adults with dementia, and the GDS in older adults without dementia.

BepFAMN: A Method for Linear B-Cell Epitope Predictions Based on Fuzzy-ARTMAP Artificial Neural Network.

The public health system is extremely dependent on the use of vaccines to immunize the population from a series of infectious and dangerous diseases, preventing the system from collapsing and millions of people dying every year. However, to develop these vaccines and effectively monitor these diseases, it is necessary to use accurate diagnostic methods capable of identifying highly immunogenic regions within a given pathogenic protein. Existing experimental methods are expensive, time-consuming, and require arduous laboratory work, as they require the screening of a large number of potential candidate epitopes, making the methods extremely laborious, especially for application to larger microorganisms. In the last decades, researchers have developed in silico prediction methods, based on machine learning, to identify these markers, to drastically reduce the list of potential candidate epitopes for experimental tests, and, consequently, to reduce the laborious task associated with their mapping. Despite these efforts, the tools and methods still have low accuracy, slow diagnosis, and offline training. Thus, we develop a method to predict B-cell linear epitopes which are based on a Fuzzy-ARTMAP neural network architecture, called BepFAMN (B Epitope Prediction Fuzzy ARTMAP Artificial Neural Network). This was trained using a linear averaging scheme on 15 properties that include an amino acid ratio scale and a set of 14 physicochemical scales. The database used was obtained from the IEDB website, from which the amino acid sequences with the annotations of their positive and negative epitopes were taken. To train and validate the knowledge models, five-fold cross-validation and competition techniques were used. The BepiPred-2.0 database, an independent database, was used for the tests. In our experiment, the validation dataset reached sensitivity = 91.50%, specificity = 91.49%, accuracy = 91.49%, MCC = 0.83, and an area under the curve (AUC) ROC of approximately 0.9289. The result in the testing dataset achieves a significant improvement, with sensitivity = 81.87%, specificity = 74.75%, accuracy = 78.27%, MCC = 0.56, and AOC = 0.7831. These achieved values demonstrate that BepFAMN outperforms all other linear B-cell epitope prediction tools currently used. In addition, the architecture provides mechanisms for online training, which allow the user to find a new B-cell linear epitope, and to improve the model without need to re-train itself with the whole dataset. This fact contributes to a considerable reduction in the number of potential linear epitopes to be experimentally validated, reducing laboratory time and accelerating the development of diagnostic tests, vaccines, and immunotherapeutic approaches.

Performance of adding hepatobiliary phase image in magnetic resonance imaging for detection of hepatocellular carcinoma: a meta-analysis.

To determine the performance of diagnostic algorithm of adding hepatobiliary phase (HBP) images in Gd-EOB-DTPA-enhanced MRI for the detection of hepatocellular carcinoma (HCC) measuring up to 3 cm in patients with chronic liver disease. We searched multiple databases from inception to April 10, 2020, to identify studies on using Gd-EOB-DTPA-enhanced MRI for the diagnostic accuracy of HCC (≤ 3 cm) in patients with chronic liver disease. The diagnostic algorithm of Gd-EOB-DTPA-enhanced MRI with HBP for HCC was defined as a nodule showing hyperintensity during arterial phase and hypointensity during the portal venous, delayed, or hepatobiliary phases. For gadoxetic acid-enhanced MRI without HBP, the diagnostic criteria were a nodule showing arterial enhancement and hypointensity on the portal venous or delayed phases. The data were extracted to calculate summary estimates of sensitivity, specificity, diagnostic odds ratio, likelihood ratio, and summary receiver operating characteristic (sROC) by using a bivariate random-effects model. Twenty-nine studies with 2696 HCC lesions were included. Overall Gd-EOB-DTPA-enhanced MRI with HBP had a sensitivity of 87%, specificity of 92%, and the area under the sROC curve of 95%. The summary sensitivity of Gd-EOB-DTPA-enhanced MRI with HBP was significantly higher than that without HBP (84% vs 68%, p = 0.01). Gd-EOB-DTPA-enhanced MRI with HBP showed higher sensitivity than that without HBP and had comparable specificity for diagnosis of HCC in patients with chronic liver disease. • Hypointensity on HBP is a major feature for diagnosis of HCC. • Extending washout appearance to the transitional or hepatobiliary phase on Gd-EOB-DTPA provides favorable sensitivity and comparable specificity for diagnosis HCC. • The summary sensitivity of gadoxetic acid-enhanced MRI with HBP was significantly higher than that without HBP (84% vs 68%, p = 0.01) for diagnosis of HCC in patients with chronic liver disease.

MicroRNA-21 as a diagnostic and prognostic biomarker of lung cancer: a systematic review and meta-analysis.

Background: The relationship between microRNA-21 (miRNA-21) and pathogenesis of lung cancer is a considerable focus of research interest. However, to our knowledge, no in-depth meta-analyses based on existing evidence to ascertain the value of miRNA-21 in diagnosis and clinical prognosis of lung cancer have been documented.Methods: We comprehensively searched all the literature pertaining to ‘miRNA-21’ and ‘lung cancer’ from four databases from the period of inception of each database until May 2020. Using specific inclusion and exclusion criteria, the literature for inclusion was identified and the necessary data extracted.Results: In total, 46 articles were included in the meta-analysis, among which 31 focused on diagnostic value and 15 on prognostic value. Combined sensitivity (SEN) of miRNA-21 in diagnosis of lung cancer was 0.77 (95% confidence interval (CI): 0.72–0.81), specificity (SPE) was 0.86 (95% CI: 0.80–0.90), diagnostic odds ratio (DOR) was (95% CI: 12–33), and area under the SROC curve (AUC) was 0.87 (95% CI: 0.84–0.90). No significant correlations were observed between abnormal expression of miRNA-21 and gender, smoking habits, pathological type and clinical stage of lung cancer (P>0.05). In terms of overall survival (OS), univariate analysis (hazards ratio (HR) = 1.49, 95% CI: 1.22–1.82) revealed high expression of miRNA-21 as an influencing factor for lung cancer. MiRNA-21 was confirmed as an independent risk factor for poor prognosis in multivariate analysis (HR = 1.65, 95% CI: 1.24–2.19).Conclusion: MiRNA-21 has potential clinical value in the diagnosis and prognosis of lung cancer and may serve as an effective diagnostic marker and therapeutic target in the future.

Single-cell transcriptome highlights a multilayer regulatory network on an invasive trajectory within colorectal cancer progression

PurposeColorectal cancer (CRC) is one of the most common and fatal gastrointestinal malignancies, in which cancer stem cells (CSCs) were identified to enable tumor heterogeneity and initiate tumor formation. However, the process from CSCs to invasion cells is unconfirmed.MethodsSeveral bioinformatics methods, including clustering, pseudotime analysis, gene set variation analysis and gene ontology enrichment, were used to construct a path of gradual transformation of CSCs to invasive cells, called “stem-to-invasion path”. A large amount of signaling interactions were collated to build the multilayer regulatory network. Kaplan–Meier curve and time-dependent ROC method were applied to reveal prognostic values.ResultsWe validated the heterogeneity of cells in the tumor microenvironment and revealed the presence of malignant epithelial cells with high invasive potential within primary colonic carcinomas. Next, the “stem-to-invasion path” was identified through constructing a branching trajectory with cancer cells arranged in order. A multilayer regulatory network considered as the vital factor involved in acquiring invasion characteristics underlying the path was built to elucidate the interactions between tumor cell and tumor-associated microenvironment. Then we further identified a novel combinatorial biomarker that can be used to assess the prognosis for CRC patients, and validated its predictive robustness on the independent dataset.ConclusionOur work provides new insights into the acquisition of invasive potential in primary tumor cells, as well as potential therapeutic targets for CRC invasiveness, which may be useful for the cancer research and clinical treatment.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00432-022-04020-2.

Diagnostic accuracy of probe-based confocal laser endomicroscopy and tissue sampling by endoscopic retrograde cholangiopancreatography in indeterminate biliary strictures: a meta‑analysis

Probe-based confocal laser endomicroscopy (pCLE), also known as optical biopsy, is a new endoscopic technique that provides real-time magnification of 1000 × microscopic tissue information to diagnose indeterminate biliary strictures. Tissue sampling by endoscopic retrograde cholangiopancreatography (ERCP) is routinely performed to evaluate indeterminate biliary strictures. To evaluate the accuracy of pCLE and tissue sampling by ERCP in the diagnosis of indeterminate biliary strictures, 18 articles were included from 2008 to 2021 through Embase, PubMed, Web of Science, and Cochrane library databases. The summary estimates for the pCLE diagnosis of indeterminate biliary strictures were: sensitivity 0.88 (95% confidence interval (CI), 0.84–0.91); specificity 0.79 (95% CI 0.74–0.83); and Diagnostic Odds Ratio (DOR) 24.63 (95% CI 15.76–38.48). The summary estimates for tissue sampling by ERCP diagnosis for indeterminate biliary strictures were: sensitivity 0.54 (95% CI 0.49–0.59); specificity 0.96 (95% CI 0.94–0.98); and DOR 11.31 (95% CI 3.90–32.82). The area under the sROC curve of pCLE diagnosis of indeterminate biliary strictures is 0.90 higher than 0.65 of tissue sampling by ERCP. The pCLE is a better approach than tissue sampling by ERCP for the diagnosis of indeterminate biliary strictures by providing real-time microscopic images of the bile ducts.

Diagnostic accuracy of red blood cell distribution width for neonatal sepsis.

Red blood cell distribution width (RDW) is a biomarker for the diagnosis and prognosis of many diseases. However, the relevance between RDW and neonatal sepsis (NS) have not reached a consensus yet; the perform of RDW in the diagnosis of neonatal sepsis is still not clear. The aim of this meta-analysis was to estimate the significance of RDW in neonatal sepsis and the perform of RDW in diagnosis of neonatal sepsis. We used Pubmed, Embase, Web of science, CNKI and Google academic database to find all articles that met the inclusion criteria until July 1, 2020. Fifteen eligible studies involving 1362 newborns were included in the meta-analysis after two independent investigators read the title, abstract and full text in detail. The pooled result of this meta-analysis showed that RDW was significantly higher in the NS group than in the control group (WMD=3.224; 95%CI: 2.359-4.090, P<0.001). In addition, the overall pooled sensitivity, specificity, PLR, NLR and DOR were 0.88 (95%CI:0.66-0.96), 0.90 (95%CI:0.65-0.98), 9.2 (95%CI:2.1-40.3), 0.14(95%CI:0.04-0.43) and 66.9 (95%CI:8.73-513.26), respectively. The area under the SROC curve (AUC) was 0.95 (95%CI:0.93-0.96). The meta-analysis demonstrated that newborns with sepsis had an elevated RDW level than healthy controls. RDW levels have significant correlated with neonatal sepsis; and RDW can be used as a cheap and satisfactory diagnostic biomarker for neonatal sepsis with a relatively high performance.

Predictive validity of the Edinburgh postnatal depression scale and other tools for screening depression in pregnant and postpartum women: a systematic review and meta-analysis.

To compare the predictive validity of the Edinburgh Postnatal Depression Scale (EPDS) and other tools for screening depression in pregnant and postpartum women through a systematic review and meta-analysis. An electronic search of MEDLINE, EMBASE, CINAHL, and PsycArticles databases was conducted using the following keywords: depression, perinatal-related terms, and EPDS. Quality Assessment of Diagnostic Accuracy Studies-2 was used to assess the risk of bias in diagnostic studies. The search identified 823 articles, of which 17 studies met the inclusion criteria. In 1831 pregnant women from nine studies, pooled sensitivity and specificity of the EPDS were 0.81 and 0.87, respectively, with summary receiver operating characteristic (sROC) curve of 0.90. In 515 postpartum women from six studies, pooled sensitivity, specificity, and sROC were 0.79, 0.92, and 0.90, respectively. We then compared the EPDS with other tools using three or more studies. The sROC curve of the Patient Health Questionnaire-9 was 0.74, which was lower than that (0.86) of the EPDS. The sROC curve of the Beck Depression Inventory and the ten-item Kessler Psychological Distress Scale was 0.91, similar to that of the EPDS (0.90 and 0.87). However, in comparison with the Postpartum Depression Screening Scale (0.98), the sROC curve of the EPDS was 0.54. As a tool specialized for screening depression in pregnant and postpartum women, the EPDS showed excellent performance. Thus, the EPDS can be used in preference to other tools to screen for depression in perinatal women at a primary care setting or a midwifery center.

Pleural Fluid Soluble Interleukin-2 Receptor as a Biomarker for the Diagnosis of Tuberculosis Pleural Effusion: A Systematic Review and Meta-Analysis.

Background Several studies have assessed the diagnostic accuracy of pleural fluid soluble interleukin-2 receptor (sIL-2R) for tuberculous pleural effusion (TPE) but with varied results. Therefore, we conducted this systematic review and meta-analysis to evaluate the accuracy of sIL-2R for TPE. Methods PubMed, Ovid, and Web of Science databases were searched from inception to 23 March 2021 to identify eligible studies concerning the diagnostic accuracy of fluid sIL-2R for TPE. The sensitivity and specificity of sIL-2R for TPE were pooled with a bivariate model. We estimated the global diagnostic accuracy of PE sIL-2R with a summary receiver operating characteristic (sROC) curve. The revised Quality Assessment for Diagnostic Accuracy Studies tool (QUADAS-2) was used to assess the quality of eligible studies. Results A total of nine studies with 270 TPEs and 586 non-TPEs were included in the final analysis. The pooled sensitivity and specificity were 0.81 (95% CI: 0.76–0.86) and 0.92 (95% CI: 0.77–0.98), respectively. The area under the sROC curve (AUC) was 0.82 (95% CI: 0.79–0.86). No significant publication bias was observed. Conclusions Pleural fluid sIL-2R is a useful diagnostic marker for TPE. However, the diagnostic accuracies of already available biomarkers such as pleural fluid adenosine deaminase, interferon-γ, and interleukin-27 appear to be superior relative to sIL-2R. Therefore, it might not be preferable to use sIL-2R for diagnosing TPE.

Diagnostic Accuracy of Wireless Capsule Endoscopy in Polyp Recognition Using Deep Learning: A Meta-Analysis.

Aim As the completed studies have small sample sizes and different algorithms, a meta-analysis was conducted to assess the accuracy of WCE in identifying polyps using deep learning. Method Two independent reviewers searched PubMed, Embase, the Web of Science, and the Cochrane Library for potentially eligible studies published up to December 8, 2021, which were analysed on a per-image basis. STATA RevMan and Meta-DiSc were used to conduct this meta-analysis. A random effects model was used, and a subgroup and regression analysis was performed to explore sources of heterogeneity. Results Eight studies published between 2017 and 2021 included 819 patients, and 18,414 frames were eventually included in the meta-analysis. The summary estimates for the WCE in identifying polyps by deep learning were sensitivity 0.97 (95% confidence interval (CI), 0.95–0.98); specificity 0.97 (95% CI, 0.94–0.98); positive likelihood ratio 27.19 (95% CI, 15.32–50.42); negative likelihood ratio 0.03 (95% CI 0.02–0.05); diagnostic odds ratio 873.69 (95% CI, 387.34–1970.74); and the area under the sROC curve 0.99. Conclusion WCE uses deep learning to identify polyps with high accuracy, but multicentre prospective randomized controlled studies are needed in the future.

Prognostic role of elevated lactate in acute pulmonary embolism: A systematic review and meta-analysis

Background Previous studies have shown elevated lactate was a good predictor for the prognosis of pulmonary embolism (PE). However, due to low number of patients and different expression of blood lactate in separate study, these results are inconsistent. Therefore, the aim of this meta-analysis is to evaluate the relationship between increased lactate levels and adverse outcome in acute PE. Method The literatures search was conducted in PubMed, Web of Science, and EMBASE until May 29, 2021. Results Finally, 6 studies with 1706 patients were included in our meta-analysis. High lactate levels were markedly associated with overall mortality both in unselected PE patients (OR 5.13, 95% CI: 3.36–7.86, p &lt; .00,001) and normotensive PE patients (OR 4.54, 95% CI: 2.64–7.80, p &lt; .00,001), and PE-related short-term mortality in patients with elevated lactate was significantly higher than that in patients with normal levels (OR 9.05, 95% CI :4.08–20.10, p &lt; .00,001). The pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of lactate for predicting overall mortality in patients with acute PE were 0.67 (95% CI: 0.43–0.85), 0.73 (95% CI: 0.60–0.83), 2.5 (95% CI: 2.0–3.1), and 0.45 (95% CI: 0.26–0.78), respectively. The area under SROC curve (AUC) was 0.76 (95% CI: 0.73–0.80). Conclusion The result of our meta-analysis indicate that elevated blood lactate is a good predictor for overall mortality and short-term mortality in patients with acute PE, and can be routinely measured in risk stratification, but its prognostic role in patients with different risk classes still need to be verified.

An exploratory analysis of forme fruste keratoconus sensitivity diagnostic parameters.

To secondary statistical analysis of the Pentacam or Corvis ST parameters from literatures, and to obtain more sensitive diagnostic parameters for clinical keratoconus (CKC) and forme fruste keratoconus (FFKC), respectively. The parameters and the corresponding area of ROC curve (AUC) in previous studies were extracted and screened to obtain the database of CKC (Data-CKC) and FFKC (Data-FFKC), respectively. Two different importance evaluation methods (%IncMSE and IncNodePurity) of random forest were used to preliminary select the important parameters. Then, based on the partial dependency analysis, the sensitive diagnostic parameters that had promotion to the diagnostic performance were obtained. Data-FFKC was analyzed in the same way. Finally, a diagnostic test meta-analysis on the sensitive parameter of interest was conducted to verify the reliability of the above analysis methods. There were 88 parameters with 766 records in Data-CKC, 57 parameters with 346 records in Data-FFKC. Based on two importance evaluation methods, 60 important parameters were obtained, of which 20 were further screened as sensitive parameters of keratoconus, and most of these parameters were related to the thinnest point of cornea. The stiffness parameter at first applanation (SPA1) was the only Corvis ST output parameter sensitive to FFKC except the Tomographic and Biomechanical Index and the Corvis Biomechanical Parameter (CBI). A total of 4 records were included in the meta-analysis of diagnostic tests on SPA1. The results showed that there was threshold effect, but no significant heterogeneity (I2 = 33%), and the area under the SROC curve was 0.87 (95% CI, 0.84-0.90). For the diagnosis of FFKC, the sensitivity of SPA1 is not inferior to the well-known CBI, and may be the earliest Corvis ST output parameter to reflect the changes of corneal biomechanics during keratoconus progression. The elevation parameters based on the typical position of the thinnest point of corneal thickness are of great significance for the diagnosis of keratoconus.

Risk stratification for hepatocellular carcinoma of contrast-enhanced ultrasound Liver Imaging Reporting and Data System (LI-RADS) and the diagnostic performance of LR-5 and LR-M: a systematic review and meta-analysis

To evaluate the risk stratification of hepatocellular carcinoma (HCC) and overall malignancies in different contrast-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System (LI-RADS) categories, and to explore the diagnostic performance of LR-5 for HCC and LR-M for non-HCC malignancies. The PubMed, Embase, and Cochrane Central databases were searched from 2016 to February 2021 for studies on CEUS LI-RADS v2016 and v2017. The proportion of HCC and overall malignancy in each LI-RADS category and the sensitivity, specificity, accuracy, diagnostic odds ratio (DOR) and area under the receiver operating characteristic curve (AUC) of LR-5 and LR-M categories were determined using a random effects model. A total of 113 studies were retrieved and 10 studies were included. A total of 5,543 patients with 6,124 lesions were included, including 4,492 HCC. There was no HCC in LR-1, and the proportion of HCC in LR-2-5 increased with the increase of category. The proportion of HCC in LR-5 was 97%, and that in LR-M was 44%. The sensitivity, specificity, and accuracy of CEUS LR-5 for HCC were 0.76, 0.95, and 0.82, respectively, and the area under the SROC curve was 0.83. The sensitivity, specificity, and accuracy of CEUS LR-M for non-HCC malignancies were 0.81, 0.92, and 0.91, and the area under the SROC curve was 0.89. The risk of HCC increases gradually from LR-1 to LR-5, in which there was no HCC lesion in LR-1 and the proportion of HCC in LR-3 was 22%, lower than that reported in earlier studies. The proportion of HCC in LR-5 was 97% and that in LR-M was 44%. LR-5 has a high specificity of 95% for the diagnosis of HCC.

Diagnostic accuracy of immunohistochemistry compared with molecular tests for detection of BRAF V600E mutation in ameloblastomas: Systematic review and meta-analysis.

The objective of this systematic review with meta-analysis was to critically evaluate the available data on sensitivity and specificity of IHC compared with molecular tests in the detection of BRAF V600E mutation in ameloblastomas. This systematic review was performed based on the PRISMA statement and registered in Prospero (CRD42021259117). PubMed, Web of Science, Scopus, and Cochrane Library databases were searched for observational studies to answer the question "What is the diagnostic accuracy of immunohistochemistry compared with molecular tests for the diagnosis of BRAF V600E mutation in ameloblastomas?". Methodological quality and risk of bias assessment of the selected studies were based on the QUADAS-2. Meta-analysis based on hierarchical SROC curve model and summary measures for sensitivity and specificity were computed. A total of 226 records were found, but only 05 articles met the inclusion criteria, with 277 FFPE specimens of ameloblastoma included in the quantitative analysis. The sensitivity of the IHC compared to molecular tests ranged from 0.71 to 1.00, while all of the included studies showed perfect specificity (1.00). Pooled measures for sensitivity and specificity were 0.95 [95% CI 0.89, 1.00] and 1.00 [95% CI 0.95, 1.00], respectively. The diagnostic odds ratio was 4.05, and the AUC for SROC curve was calculated as 0.979. BRAF V600E-specific IHC using VE1 antibody showed extremely high sensitivity and specificity when compared with molecular tests in the detection of the mutation in ameloblastomas.

Potential diagnostic and prognostic value of the long non-coding RNA SNHG3 in human cancers: A systematic review and meta-analysis.

Small nucleolar RNA host gene 3 (SNHG3), as a novel long non-coding RNA (lncRNA) participates in the oncogenic processes of various cancers. We combined a systematic review and a meta-analysis to assess the potential role of SNHG3 as a pan-cancer marker for cancer diagnosis and prognosis. Our study comprehensively searched for SNHG3 expression profiling studies from PubMed, Web of Science, Excerpta Medica Database (EMBASE), Cochrane Library, Google Scholar, and The Cancer Genome Atlas (TCGA). The diagnostic capacity of SNHG3 for all cancers in TCGA database was evaluated from the perspective of pooled sensitivity, specificity, diagnostic odds ratio (DOR), area under the curve (AUC) of the summary receiver operating characteristic (sROC) curve. Also, this research studied the correlation of SNHG3 expression and the overall survival to access its prognostic value. A sum total of 11,888 cancer patients and 730 controls from 44 eligible studies were enrolled in this integrated analysis. In TCGA database, SNHG3 was significantly upregulated in most types of cancers (16/33, 48%). The pooled sensitivity, specificity, and DOR with 95% CIs was 0.72 (95% CI: 0.60-0.82), 0.87 (95% CI: 0.84-0.90), and 18 (95% CI: 11-30), respectively. Similarly, the AUC of the sROC curve was 0.89 (95% CI: 0.86-0.92), indicating SNHG3 was highly conserved as a diagnosis biomarker. Additionally, SNHG3 overexpression significantly deteriorated the overall survival of cancer patients (pooled HR = 1.28, 95% CI:1.11-1.48; P < 0.05). These findings suggest that the lncRNA SNHG3 could serve as a promising diagnostic and prognostic biomarker.

Systematic review and meta-analysis of diagnostic test accuracy (DTA) studies: the role of cerebral perfusion imaging in prognosis evaluation of mild cognitive impairment.

The application value of cerebral perfusion imaging, such as fluorodeoxyglucose-positron-emission computed tomography (FDG-PET), single-photon emission computed tomography (SPECT), and structural magnetic resonance imaging (MRI), in the prognostic assessment of mild cognitive impairment (MCI) remains unclear. Thus, it was the focus of this meta-analysis, which aimed to provide a theoretical basis for early diagnosis of neurological diseases. The Boolean logic retrieval method was used to retrieve related literature, with "cognitive disorder", "cerebral perfusion imaging", "cerebral imaging", "mild cognitive impairment", and "prognostic assessment" as search terms. The PubMed, Medline, CNKI (China National Knowledge Infrastructure), and other databases were searched from the date of establishment of the database to December 30, 2020 for literature on the prognostic assessment of MCI using FDG-PET, SPECT, and MRI imaging. Meta-analysis was performed using Review Manager software. A total of 16 references were identified, most of which had a low risk of bias (i.e. medium and high-quality). The meta-analysis results showed that the sensitivity and specificity of FDG-PET imaging was significantly higher than those of SPECT and MRI imaging, and the differences were statistically significant (P<0.05). The summary receiver operating characteristic (sROC) curves for the sensitivity and specificity of FDG-PET, SPECT, and MRI imaging did not present a "shoulder arm" distribution, and there was no threshold effect. Cerebral perfusion imaging has good prognostic value for patients with MCI, and FDG-PET imaging has better predictive ability of the prognosis for patients with MCI.

Predictive validity of the functional capacity of the CUPAX questionnaire in older adults with hip fracture

Background and objectivesOsteoporotic hip fracture is a relevant pathology due to its prevalence and social and health impact. The aim of this study is to explore the predictive validity of the CUPAX questionnaire on mortality, place of residence and post-fracture functionality. Materials and methodsProspective observational study. Two hundred and six patients older than 65 years were included, admitted after a hip fracture. The CUPAX questionnaire score was collected before fracture and one year later, and the place of residence and survival at hospital discharge, and after 6 and 12 months. The statistical analysis was carried out with the SAS®9.4 and Stata®13.1 programmes. ResultsThe median age of the sample was 87.0 years (80.1% women). The in-hospital and one-year mortality rate were 5.8% and 19.1%, respectively. Most of the patients were admitted from home (71.4%), and the most frequent discharge destination was a social health centre (48.2%). The percentage of retention of previous functional level in the total sample was 50%, being higher in the younger patients. The area under the curve ROC for mortality one year later was .697 (95% CI .626–.760) and 0.659 (95%CI .576–.741) for the discharge destination of patients admitted from home. Evaluation of functional retention one year after the fracture, identified three groups of patients based on the pre-fracture CUPAX value. ConclusionsThese findings support the clinical utility of the CUPAX questionnaire as a predictive functional tool in elderly patients with hip fracture.