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Objectives:In December 2019, a new type of coronavirus, called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), appeared in Wuhan, China. Serious outbreaks of coronavirus disease 2019 (COVID-19), related to the SARS-CoV-2 virus, have occurred throughout China and the world. Therefore, we intend to shed light on its potential clinical and epidemiological characteristics.Methods:In this retrospective study, we included 50 confirmed fatal cases of SARS-CoV-2 reported on Chinese official media networks from January 16, 2020, to February 5, 2020. All the cases were confirmed by local qualified medical and health institutions. Specific information has been released through official channels. According to the contents of the reports, we recorded in detail the gender, age, first symptom date, death date, primary symptoms, chronic fundamental diseases, and other data of the patients, and carried out analyses and discussion.Results:In total, 50 fatal cases were reported: median age was 70 y old, and males were 2.33 times more likely to die than females. The median number of days from the first symptom to death was 13, and that length of time tended to be shorter among people aged 65 and older compared with those younger than 65 (12 days vs 17 days;P= 0.046). Therefore, the older patients had fewer number of days from the first symptom to death (r = -0.40;P= 0.012).Conclusions:In our study, we found that most of the deaths were elderly men with chronic fundamental diseases, and their COVID-19 progression to death time was shorter. At the same time, we demonstrated that older men are more likely to become infected with COVID-19, and the risk of death is positively correlated with age.

The aim of the work described here was to investigate the value of point-of-care ultrasound (POCUS) in the early assessment of the severity of pulmonary edema in rabbits. A rabbit oleic acid (OA)-induced pulmonary edema model was used. Thirty-two New Zealand rabbits were randomly divided into four groups: a control group and three pulmonary edema groups (mild, moderate and severe). Features of transthoracic B-line artifacts (BLA), blood pH, PaO2 and PaCO2, serum inflammatory factors, lung coefficient (LC), lung wet-to-dry weight ratio (W/D) and lung histopathology were assessed. BLA features and severity of pulmonary edema were semiquantitatively scored. Correlations between the number of BLA and PaO2, PaCO2, serum inflammatory factors, LC and W/D were analyzed. An additional 8 rabbits with severe pulmonary edema were used as the verified group, in which the lung was divided into ex vivo BLA (BLA-ev)-free (BLA-ev-free) and BLA-ev-clustered subregions depending on the features of BLA-ev recorded by ex vivo lung ultrasound. Lung specimens from each subregion were collected for histopathological examination. Relationships between features of BLA-ev and lung histopathological abnormalities were analyzed. With increasing doses of OA, number of BLA, W/D and levels of serum inflammatory factors decreased. Meanwhile, lung pathologic abnormalities were aggravated. In addition, time of appearance of BLA, blood pH and PaO2, and PaCO2 decreased dose dependently on OA (p

Background: The clinical benefit of chemotherapy or endocrine therapy maintenance in patients with metastatic breast cancer (MBC) after first-line chemotherapy, specifically hormone receptor (HR) positive MBC patients remain inconclusive. This study aims to comprehensively evaluate the clinical efficacy of chemotherapy or endocrine therapy maintenance in MBC patients. Methods: The meta-analysis of randomized clinical trials (RCTs) and propensity score matched analysis of multicentre cohort study in China were evaluated MBC patients who underwent first-line chemotherapy or endocrine therapy maintenance. The GRADE approach was used to assess quality of evidence in meta-analysis. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Findings: A total of 2,867 patients from 15 RCTs and 760 patients from multicentre cohort were included. The results from meta-analysis showed that chemotherapy maintenance significantly improved PFS (hazard ratio [HR], 0·63; 95% confidence interval (CI) 0·54-0·73; P 0·05). Additionally, treatment effect sizes were greater for OS than for PFS, and a moderate correlation between PFS and OS was identified. Interpretation: This study provided a high evidence for PFS and OS benefits of longer first-line chemotherapy and endocrine therapy maintenance in MBC patients, and there were no difference efficacy between chemotherapy and endocrine therapy maintenance for HR-positive patients. We also suggested that both PFS and OS should be evaluated to determine the effectiveness of maintenance therapy in future clinical trials. Trial Registration: This study is registered with PROSPERO Identifier: CRD42017071858, and ClinicalTrials.gov Identifier: NCT04258163. Funding Statement: This study was supported by grant 2020ZX09201021 from the National Science and Technology Major Project, grant YXRGZN201902 from the Medical Artificial Intelligence Project of Sun Yat-Sen Memorial Hospital, grants 81572596, 81972471, U1601223, 82073408, 81802656, and 82071754 from the National Natural Science Foundation of China, grant 2017A030313828 from the Natural Science Foundation of Guangdong Province, grant 201704020131 from the Guangzhou Science and Technology Major Program, grant 2017B030314026 from the Guangdong Science and Technology Department, grant 2018007 from the Sun Yat-Sen University Clinical Research 5010 Program, grant SYS-C-201801 from the Sun Yat-Sen Clinical Research Cultivating Program, and A2020558 from the Medical Scientific Research Foundation of Guangdong Province. Declaration of Interests: The authors have no conflicts of interest to declare. Ethics Approval Statement: The study protocol was approved by the ethics committee of the Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China and was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines.

Glioma accounts for the highest proportion of primary intracranial malignant tumors. Microenvironment enormously influences the process of glioma progression. Our study is to establish an individualized prognostic nomogram for glioma patients with microenvironment signature. Glioma samples of Chinese Glioma Genome Atlas (CGGA) were grouped by the immune and stromal score based on ESTIMATE algorithm. Microenvironment-related genes (MRGs) in glioma were analyzed by R. To determine the best prognostic correlation genes, univariate and multivariate Cox regression analysis were used to analyze MRGs. Use the selected genes (CHI3L1, SOCS3, SLC47A2, COL3A1, SRPX2 and SERPINA3), we established the prognostic risk score model (microenvironment signature) and validated it. Gene Set Enrichment Analysis (GSEA) showed that the high-risk group was mainly enriched in immune and stromal function KEGG pathways. Finally, the nomogram was constructed and evaluated. The receiver operating characteristic (ROC) curve, Calibration plots and decision curve analysis (DCA) of training and validation set indicated the excellent predictive performance of nomogram. In conclusion, the 6-gene microenvironment signature can not only provide directions for the basic research of glioma, but also can be included as an independent prognostic index in nomogram for individual prediction to guide clinical treatment.

In current clinical practice, the standard evaluation for axillary lymph node (ALN) status in breast cancer is based on the invasive procedure and many patients will suffer from operative associated complications. Hence, a novel signature incorporated tumor and lymph node magnetic resonance imaging (MRI) radiomics, clinical and pathological characteristics, and molecular subtypes based on the machine learning approach was established to accurately identify ALN metastasis in early-stage invasive breast cancer patients. Although the misjudgment of ALN status by clinicians according to preoperative MRI are common during clinical practice and even the senior radiologists make mistakes sometimes, this multiomic radiomic signature showed the superiority over clinicians and could precisely discriminate ALN metastasis among different molecular subtype patients. Furthermore, the association between MRI radiomic features and tumor-microenvironment features including immune cells, long non-coding RNAs, and types of methylated sites were found, which revealed the potential biological underpinning of MRI radiomics.

There are no satisfying approaches to identify high- and low-risk recurrence patients with early-stage breast cancer in current clinical practice. Patients might be overtreated or undertreated due to the inaccurate prediction of recurrence risk. Herein, machine learning magnetic resonance imaging radiomic-based signature that integrates the intratumoral and peritumoral radiomic signatures, and clinicopathological characteristics was developed to classify high- and low-risk recurrence patients and predict recurrence within multicentre cohorts. The radiomic-clinical signature could also discriminate high- from low-risk recurrence patients among different breast cancer molecular subtype, and HR+/Her2-, T1N0M0 stage patients. Furthermore, it was observed that the neoadjuvant chemotherapy improved survival in high-risk Luminal subtype patients compared with the adjuvant chemotherapy. The survival-associated radiomic features also showed the correlation with the immune microenvironment. The radiomic-clinical signature presented the feasibility of predicting recurrence risk and assisting clinical decision-making in early-stage invasive breast cancer patients.

Aims Here, we explored the potential application and selection of neuroendocrine biomarkers in the diagnosis and treatment of small cell lung cancer. Methods We retrospectively analyzed 118 patients with small cell lung cancer (SCLC), 166 patients with non-small cell lung cancer (NSCLC), 33 patients with benign lung disease (BLD), and 200 healthy individuals admitted to Zhejiang Provincial People’s Hospital between January 1, 2015 and May 31, 2019. All the patients were newly diagnosed with either SCLC, NSCLC, or BLD and previously untreated. Peripheral blood levels of ProGRP, NSE, CEA, and CYFRA21-1 were analyzed during the follow-up treatment, and 2-fold upper limit of reference intervals were defined as effective elevation. We used paired results to analyze the diagnostic efficiency of proGRP and NSE on SCLC. Results In the 118 SCLC patients, proGRP levels were significantly higher compared with NSE levels. The diagnostic efficiencies of NSE and ProGRP for SCLC were 0.8554 and 0.9053, respectively. The combined diagnostic efficiency (0.9426) was higher relative to NSE, but there was no significant difference compared with proGRP. The effective elevation rate of proGRP was 45.3% higher than that of NSE in the limited stage of SCLC. In the extensive disease of SCLC patients, 70.7% cases had more than 10-fold increase in proGRP value, whereas 56.9% cases had less than 5-fold increase in NSE value. Compared with pre-treatment, the median concentrations of proGRP increased by 204.0% higher than that of NSE (71.3%) in the progressive group. Besides, the dynamic change in imaging characteristics and tumor size had a strong correlation with the levels of proGRP. Significance ProGRP is a reliable neuroendocrine biomarker in SCLC. The effective elevation of proGRP has a potential diagnostic and efficacy value in the evaluation of SCLC. However, the combined detection of proGRP and NSE does not significantly improve the diagnosis of lung cancer.

Purpose The purpose of this study was to investigate the predictive capability of neutrophil-to-apolipoprotein A1 ratio (NAR) for predicting overall survival (OS) among patients with hepatocellular carcinoma (HCC) receiving transarterial chemoembolization (TACE). Patients and Methods We investigated the clinical features of 554 patients with HCC receiving TACE and assessed NAR's predictive value for OS with 222 patients (the discovery cohort) and 332 patients (the validation cohort). The association of NAR with circulation lectin-type oxidized low-density lipoprotein receptor-1–positive (LOX-1+) polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) was illustrated. Results Multivariate Cox regression revealed that lymphocyte count; Tumor, Node, Metastasis (TNM) stage; and NAR were independent prognostic factors in the discovery cohort. The validation cohort confirmed the independent prognostic value of TNM stage and NAR. Patients with low NAR ( Conclusion This study identified NAR as an independent predictor for OS among patients with HCC receiving TACE. NAR reflected circulation LOX-1+ PMN-MDSC level. Implications for Practice The present study identified neutrophil-to-apolipoprotein A1 ratio (NAR) as an independent predictor for overall survival among patients with hepatocellular carcinoma receiving transarterial chemoembolization. NAR reflected circulation level of lectin-type oxidized low-density lipoprotein receptor-1–positive polymorphonuclear myeloid-derived suppressor cells.

We performed a meta-analysis to assess whether corticosteroids (C) plus (+) doublet immunosuppressive therapy (IT) is superior to the classical combination of C with single-agent IT in active proliferative lupus nephritis (LN).Randomized trials evaluating the benefits and risks of C+doublet versus single-agent IT in active proliferative LN were obtained by searching PubMed, EMBASE, and Cochrane Central Register. The primary outcome was overall response rate (ORR). The secondary outcomes were the change from baseline in Systemic Lupus Erythematosus Disease Activity Index (SLE-DAI) score, negative conversion ratio of anti-double-stranded DNA (anti-dsDNA), and adverse events. The PROSPERO registry number is CRD42017068491.Eleven trials with 1855 patients were included. Compared with C+single-agent IT, C+doublet IT had a significantly higher ORR (relative risk [RR], 1.22; 95% confidence interval [CI], 1.09 to 1.35; P 0.01). In a subgroup analysis, C+doublet IT without biologics had a significantly higher ORR than C+single-agent IT (RR, 1.30; 95% CI, 1.13 to 1.50; P 0.01), while C+doublet IT including biologics improved ORR only for refractory severe LN (RR, 1.46; 95% CI, 1.09 to 1.96; P = 0.012). A larger change from baseline in SLE-DAI scores (standardized mean difference, - 0.49; 95% CI, - 0.68 to - 0.30; P 0.01) and a higher negative conversion ratio of anti-dsDNA (RR, 1.34; 95% CI, 1.06 to 1.69; P = 0.014) were observed with C+doublet IT than with C+single-agent IT. The rates of adverse events were similar between the two regimens.Compared with single-agent IT, the combination of C and doublet IT without biologics improved clinical outcomes in active proliferative LN. Key Points • Compared with corticosteroids + single-agent immunosuppressive therapy, corticosteroids + doublet immunosuppressive therapy without biologics had a significantly higher overall response rate in active proliferative lupus nephritis. • Compared with corticosteroids + single-agent immunosuppressive therapy, corticosteroids + doublet immunosuppressive therapy including biologics improved overall response rate only for refractory severe lupus nephritis. • A larger change from baseline in SLE-DAI scores and a higher negative conversion ratio of anti-dsDNA were observed with corticosteroids + doublet immunosuppressive therapy than with corticosteroids + single-agent immunosuppressive therapy.

Key Points Question Can multiparametric magnetic resonance imaging (MRI) radiomic profiles be used to predict axillary lymph node metastasis (ALNM) and disease-free survival (DFS) in patients with early-stage breast cancer? Findings In this prognostic study that included 1214 patients, 2 clinical-radiomic nomograms were developed that accurately predicted ALNM and stratified patients into low-risk and high-risk groups for DFS. Meaning In this study, clinical-radiomic nomograms were useful in clinical decision-making associated with personalized selection of surgical interventions and therapeutic regimens for patients with early-stage breast cancer., This prognostic study develops and validates dynamic contrast–enhanced magnetic resonance imaging (DCE-MRI) radiomic signatures for preoperative identification of axillary lymph node metastasis and to assess individual disease-free survival in patients with early-stage breast cancer., Importance Axillary lymph node metastasis (ALNM) status, typically estimated using an invasive procedure with a high false-negative rate, strongly affects the prognosis of recurrence in breast cancer. However, preoperative noninvasive tools to accurately predict ALNM status and disease-free survival (DFS) are lacking. Objective To develop and validate dynamic contrast–enhanced magnetic resonance imaging (DCE-MRI) radiomic signatures for preoperative identification of ALNM and to assess individual DFS in patients with early-stage breast cancer. Design, Setting, and Participants This retrospective prognostic study included patients with histologically confirmed early-stage breast cancer diagnosed at 4 hospitals in China from July 3, 2007, to September 21, 2019, randomly divided (7:3) into development and vaidation cohorts. All patients underwent preoperative MRI scans, were treated with surgery and sentinel lymph node biopsy or ALN dissection, and were pathologically examined to determine the ALNM status. Data analysis was conducted from February 15, 2019, to March 20, 2020. Exposure Clinical and DCE-MRI radiomic signatures. Main Outcomes and Measures The primary end points were ALNM and DFS. Results This study included 1214 women (median [IQR] age, 47 [42-55] years), split into development (849 [69.9%]) and validation (365 [30.1%]) cohorts. The radiomic signature identified ALNM in the development and validation cohorts with areas under the curve (AUCs) of 0.88 and 0.85, respectively, and the clinical-radiomic nomogram accurately predicted ALNM in the development and validation cohorts (AUC, 0.92 and 0.90, respectively) based on a least absolute shrinkage and selection operator (LASSO)–logistic regression model. The radiomic signature predicted 3-year DFS in the development and validation cohorts (AUC, 0.81 and 0.73, respectively), and the clinical-radiomic nomogram could discriminate high-risk from low-risk patients in the development cohort (hazard ratio [HR], 0.04; 95% CI, 0.01-0.11; P

Three-dimensional (3D) imaging instead of two-dimensional (2D) computed tomography (CT) for diagnosis and preoperative planning in infants and young children with complex liver tumors is a promising technique for precision hepatectomy. This study was a retrospective analysis of 26 infants and young children with giant liver tumors involving the hepatic hilum who underwent precise hepatectomy at the Affiliated Hospital of Qingdao University between February 2012 and January 2015. All patients received upper abdominal contrast-enhanced CT scanning before surgery. 16 patients used Hisense CAS system for 3D reconstruction as the reconstruction group. While ten patients underwent 3D CT reconstruction by the CT Workstation as the control group. The clinical outcomes were analyzed and compared between the two groups. The 3D reconstruction of abdominal organs and blood vessels was generated using the Hisense CAS system. Diagnosis and preoperative planning assisted by the system was used for preoperative and intraoperative decision-making for precise hepatectomy. All patients underwent successful surgery. The 3D models clearly demonstrated the association of liver tumors with the intrahepatic vascular system and provided a preoperative assessment of resectability, assisting surgeons in preoperative procedural planning. Anatomic hepatectomy was successfully completed in the reconstruction group. The mean operation time was shorter in the reconstruction group (137.81 ± 17.51 min) than in the control group (192 ± 34.66 min) (P

Background The efficacy and safety of neoadjuvant treatment over surgery alone and that of neoadjuvant chemoradiotherapy (NCRT) over neoadjuvant chemotherapy (NCT) in resectable esophageal carcinoma remains inconclusive. This study (NewEC) used global data to comprehensively evaluate these comparisons and to provide a preferable strategy for patient subsets. Methods This study included a meta-analysis of randomized controlled trials (RCTs) identified from inception to May 2019 from PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and congresses and a registry-based cohort study with patients from Massachusetts General Hospital (Massachusetts, USA) and Guangdong Provincial People's Hospital (Guangzhou, China) recruited from November 2000 and June 2017, to cross-validate the comparisons among NCRT versus NCT versus surgery. The GRADE approach was used to assessed quality of evidence in meta-analysis. Neural network machine learning propensity score–matched analysis was used to account for confounding by patient-level characteristics in the cohort study. The primary endpoint was overall survival (OS). The study was registered with PROSPERO CRD42017072242 and ClinicalTrials.gov NCT04027543. Findings Of 22,070 studies assessed, there were 38 (n = 6,993 patients) eligible RCTs. Additionally, 423 out of 467 screened patients were included in the cohort study. The results from trials showed that NCT had a better OS than surgery alone (hazard ratio [HR] 0·88, 95% confidence interval [CI] 0·79–0·98; high quality) and was only favorable for adenocarcinoma (HR 0·83, 95% CI 0·72–0·96; moderate quality). High-quality evidence showed a significantly better OS for NCRT than surgery alone (HR 0·74, 95% CI 0·66–0·82) for both adenocarcinoma (HR 0·73, 95% CI 0·62–0·86) and squamous cell carcinoma (SCC) (HR 0·73, 95% CI 0·65–0·83). The OS benefit of NCRT over NCT was seen in the pairwise (HR 0·78, 95% CI 0·62–0·99; high quality) and network (HR 0·82, 95% CI 0·72–0·93; high quality) meta-analyses, with similar results before (HR 0·60, 95% CI 0·40–0·91) and after (HR 0·44, 95% CI 0·25–0·77) matching in the cohort study, leading to a significantly increased 5-year OS rate in both adenocarcinoma and SCC before and after matching. The increased benefits from NCT or NCRT were not associated with the risk of 30-day or in-hospital mortality. Interpretation NewEC Study provided high-quality evidence supporting the survival benefits of NCRT or NCT over surgery alone, with NCRT presenting the greatest benefit for resectable esophageal carcinoma. Funding National Science and Technology Major Project, the National Natural Science Foundation of China, the Natural Science Foundation of Guangdong Province, the Guangzhou Science and Technology Major Program, the Medical artificial intelligence project of Sun Yat-Sen Memorial Hospital, the Guangdong Science and Technology Department, the Guangdong Province Medical Scientific Research Foundation, and Guangdong Provincial People's Hospital Intermural Program.

e16637 Background: Current guidelines lack definitive evidences about the predictive capability of clinical parameters for transcatheter arterial chemoembolization (TACE). The aim of this study was to comprehensively investigate the predictive factor among stage I-IV liver hepatocellular carcinoma (LIHC) patients after TACE. Methods: We investigated the clinical features of 211 stage I-IV patients with LIHC in discover group and 341 patients in validation group. Overall survival (OS) was estimated using the Kaplan-Meier method and the log-rank test. Results: Univariate Cox regression revealed that Monocyte count, TNM stage and AST-to-APOA ratio (AAR) were associated with unfavorable OS. AAR was identified as an independent predictor of OS using multivariate analysis. Kaplan-Meier curve demonstrated that patients with AAR < 50 displayed better prognosis. The median follow-up time was 17.1 (95%CI, 14.4 to 19.3) months, 3-year overall survival was 55.9% in the low AAR group versus 28.6% in the high AAR group, and there was significant difference in OS (Hazard ratio [HR] 0.47, 95%CI 0.33 to 0.67, P < 0.001). The AAR showed predictive ability for OS (12-month, AUC = 0.707). These findings were successfully validated in validation group (HR 0.62, 95%CI 0.46 to 0.84, P = 0.002; 12-month AUC = 0.636). Conclusions: AAR was an independent predictor among LIHC patients after TACE. Patients with lower AAR were optimal candidates for TACE.

This cohort study explores long noncoding RNA–based immune subtypes associated with survival and response to cancer immunotherapy and presents a novel long noncoding RNA score for immunotherapy prediction using computational algorithms., Key Points Question Are long noncoding RNAs (lncRNAs) associated with immune molecular classification and clinical outcomes of cancer immunotherapy? Findings This cohort study of 348 patients with bladder cancer from the IMvigor210 trial and 71 patients with melanoma from The Cancer Genome Analysis identified 4 distinct classes with different immunotherapeutic overall survival and response. An lncRNA score was developed that also was associated with survival and immunotherapy response. Meaning This study identifies novel lncRNA-based immune classes in cancer immunotherapy and provides an lncRNA score for integration into multiomic panels for precision immunotherapy., Importance Long noncoding RNAs (lncRNAs) are involved in innate and adaptive immunity in cancer by mediating the functional state of immunologic cells, pathways, and genes. However, whether lncRNAs are associated with immune molecular classification and clinical outcomes of cancer immunotherapy is largely unknown. Objectives To explore lncRNA-based immune subtypes associated with survival and response to cancer immunotherapy and to present a novel lncRNA score for immunotherapy prediction using computational algorithms. Design, Setting, and Participants In this cohort study, an individual patient analysis based on a phase 2, single-arm clinical trial and multicohort was performed from June 25 through September 30, 2019. Data are from the phase 2 IMvigor210 trial and from The Cancer Genome Atlas (TCGA). The study analyzed lncRNA and genomic data of 348 patients with bladder cancer from the IMvigor210 trial and 71 patients with melanoma from TCGA who were treated with immunotherapy. In addition, a pancancer multicohort that included 2951 patients was obtained from TCGA. Main Outcomes and Measures The primary end point was overall survival (OS). Results Among 348 patients from the IMvigor210 trial (272 [78.2%] male) and 71 patients with melanoma from TCGA (mean [SD] age, 58.3 [13.4] years; 37 [52.1%] female), 4 distinct classes with statistically significant differences in OS (median months, not reached vs 9.6 vs 8.1 vs 6.7 months; P = .002) were identified. The greatest OS benefit was obtained in the immune-active class, as characterized by the immune-functional lncRNA signature and high CTL infiltration. Patients with low vs high lncRNA scores had statistically significantly longer OS (hazard ratio, 0.32; 95% CI, 0.24-0.42; P

Background In this study, images of 2450 benign thyroid nodules and 2557 malignant thyroid nodules were collected and labeled, and an automatic image recognition and diagnosis system was established by deep learning using the YOLOv2 neural network. The performance of the system in the diagnosis of thyroid nodules was evaluated, and the application value of artificial intelligence in clinical practice was investigated. Methods The ultrasound images of 276 patients were retrospectively selected. The diagnoses of the radiologists were determined according to the Thyroid Imaging Reporting and Data System; the images were automatically recognized and diagnosed by the established artificial intelligence system. Pathological diagnosis was the gold standard for the final diagnosis. The performances of the established system and the radiologists in diagnosing the benign and malignant thyroid nodules were compared. Results The artificial intelligence diagnosis system correctly identified the lesion area, with an area under the receiver operating characteristic (ROC) curve of 0.902, which is higher than that of the radiologists (0.859). This finding indicates a higher diagnostic accuracy (p = 0.0434). The sensitivity, positive predictive value, negative predictive value, and accuracy of the artificial intelligence diagnosis system for the diagnosis of malignant thyroid nodules were 90.5%, 95.22%, 80.99%, and 90.31%, respectively, and the performance did not significantly differ from that of the radiologists (p > 0.05). The artificial intelligence diagnosis system had a higher specificity (89.91% vs 77.98%, p = 0.026). Conclusions Compared with the performance of experienced radiologists, the artificial intelligence system has comparable sensitivity and accuracy for the diagnosis of malignant thyroid nodules and better diagnostic ability for benign thyroid nodules. As an auxiliary tool, this artificial intelligence diagnosis system can provide radiologists with sufficient assistance in the diagnosis of benign and malignant thyroid nodules.

In recent years, the research on the pathogenesis of systemic lupus erythematosus (SLE) has been deepened, from the level of histopathology to the cellular and molecular biology, thus promoting the progress of SLE drug therapeutics. In March 2011, the United States Food and Drug Administration (FDA) approved the humanized monoclonal antibody, Belimumab for the treatment of SLE and put an end to the dilemma of no new drug available to SLE for more than half a century. On the other hand, the continuous evidence-based medical information has enabled rheumatologists to have a more comprehensive and depth understanding of the application of SLE traditional therapies, further improve the treatment strategy of SLE and put forward higher requirements for treatment goals. At the same time, advances in therapies have significantly improved survival rate of the patients, and the importance of long-term complications such as early-onset atherosclerosis and cardiovascular events has become increasingly apparent as a new challenge. In view of the hot issues of SLE clinical treatment, this paper introduces the research progress in recent years.

This meta-analysis examines whether differences in biomarkers, such as programmed cell death ligand 1 (PD-L1) expression and tumor mutation burden, are associated with improved response to immunotherapy and survival in patients with advanced non–small cell lung cancer (NSCLC)., Key Points Question Is immunotherapy associated with beneficial outcomes for advanced non–small cell lung cancer and how can combination strategies and biomarkers be deployed to produce the best benefit? Findings In this meta-analysis including 14 395 patients and individual patient–level analysis including 1833 patients, immunotherapy was associated with improved survival, and pembrolizumab with platinum-based chemotherapy was identified as the best first-line checkpoint blockade strategy. Programmed cell death ligand 1 expression and tumor mutation burden jointly exhibited promising predictive and prognostic associations, and CD8+ T-cell tumor-infiltrating lymphocytes score further synergized with these 2 biomarkers. Meaning Integrated tumor microenvironment-based biomarkers may be an effective means to predict responsiveness to immunotherapy for patients with advanced non–small cell lung cancer., Importance The beneficial role of immunotherapy and the clinical relevance of current biomarkers in non–small cell lung cancer (NSCLC) remain inconclusive; thus, appropriate strategies and reliable predictors need further definition. Objectives To evaluate the association of clinical outcomes with immune checkpoint inhibitors, tumor vaccines, and cellular immunotherapy in patients with advanced NSCLC and to explore appropriate strategies, candidates, and predictors. Data Sources The PubMed, EMBASE, and Cochrane Central Register of Controlled Trials databases were searched from inception to June 2018, using relevant search keywords and Medical Subject Headings (MeSH) terms, including tumor vaccine, cellular immunotherapy, immune checkpoint inhibitor, cytotoxic T-lymphocyte-associated protein 4, programmed death-ligand 1, programmed death receptor 1, and non-small cell lung carcinoma. Systematic reviews, meta-analyses, references, and conference proceedings were manually searched. Study Selection English-language randomized clinical trials with available data that measured overall survival (OS), progression-free survival (PFS), or objective response rate comparing immune checkpoint inhibitors, tumor vaccines, or cellular immunotherapy with conventional therapy for patients with advanced or metastatic NSCLC were included. Thirty-one immunotherapy randomized clinical trials were included, and multicohort data included next-generation sequencing data from patients with advanced NCSLC. Data Extraction and Synthesis Hazard ratios and 95% CIs were pooled to estimate the survival increases in OS and PFS. Dichotomous data, such as object response rate data, were analyzed using the risk ratio. Mantel-Haenszel random-effects model was used. I2 was used to assess the heterogeneity between trials; an I2 value exceeding 50% indicated the existence of substantial heterogeneity. Analyses took place from February 1, 2018, to August 31, 2018. Main Outcomes and Measures Primary outcomes were OS and PFS. Results In total, 14 395 patients (9500 [66.0%] men) were included in the meta-analysis, and 1833 patients (mean [SD], 65.2 [9.9] years; 1063 [58.0%] men) were included in the individual patient–level study. Compared with conventional therapy, immunotherapy was associated with significantly longer OS (hazard ratio, 0.76; 95% CI, 0.71-0.82; P

2573 Background: Atezolizumab, a programmed death ligand 1 (PD-L1) inhibitor, prolonged overall survival (OS) compared with docetaxel among patients with previously treated advanced non–small-cell lung cancer (NSCLC) in two independent multicentre, randomized trials (POPLAR and OAK). We conducted a combined analysis of the two trials to evaluate its efficacy and genomic biomarkers, and to further developed a novel predictive clinicopathologic-genomic nomogram of immunotherapy in NSCLC. Methods: Patients (N = 1,137) with stage IIIB/IV NSCLC and disease progression after previously platinum-based chemotherapy were randomly assigned (1:1) to receive atezolizumab (1200 mg/kg every 3 weeks) or docetaxel (75 mg/m2 every 3 weeks). The primary endpoint was OS. We applied a two-stage meta-analysis of pooled individual patient data in the intention-to-treat population. In OAK trial, patients treated with atezolizumab were randomly assigned (1:1) to the training group or the validation group to develop a predictive clinicopathologic-genomic nomogram of immunotherapy. POPLAR and OAK were registered with ClinicalTrials.gov, numbers NCT02008227 and NCT01903993. Results: In the pooled analysis, the median overall survival was 13.49 months (95% confidence interval [CI], 11.95 to 15.22) with atezolizumab versus 9.66 months (95% CI, 8.73 to 10.70) with docetaxel. The risk of death was 28% lower with atezolizumab than with docetaxel (hazard ratio [HR], 0.72; 95% CI, 0.62 to 0.83; P < 0.001). The race, sex, tumor histology, eastern cooperative oncology group performance status, PD-L1 expression, and especially pretreatment mutation (TP53, DNMT3A and KEAP1) were significantly associated with OS, and were used for the development of the predictive nomogram. The clinical use of the nomogram showed a closer association with 3-year OS than the blood-based tumor mutational burden (bTMB) or PD-L1 expression alone (nomogram, AUC = 0.818; bTMB, AUC = 0.701; PD-L1, AUC = 0.526) among NSCLC patients who had received atezolizumab. The superior predictability of the nomogram was further confirmed in the validation and entire OAK cohorts. Conclusions: Among patients with advanced, previously treated NSCLC, OS was significantly better with atezolizumab than with docetaxel. Furthermore, we constructed a novel and powerful clinicopathologic-genomic nomogram for personalized immunotherapy options.

e14122 Background: Our objective was to evaluate progression-free survival (PFS) and objective response rate (ORR) as surrogate end points for overall survival (OS) among patients with advanced non-small-cell lung cancer (NSCLC) in randomized trials of immunotherapy. Methods: Individual patient data (total N = 569 patients) were available from two multicentre, randomized, phase II/III trials (POPLAR and OAK). Analysis of OS, PFS and ORR were computed using the Kaplan-Meier estimates method and compared with the log-rank test, hazard ratios [HRs] and 95% confidence intervals [CIs] were calculated by using the Cox regression model. The surrogacy was evaluated using Spearman’s correlation coefficient (ρ) and coefficient of determination ( R²) between treatment effects on the surrogate end point and OS. We further validated the surrogacy in trial-level analysis with 26 NSCLC immunotherapy trials (total N = 12,094 patients) published prior to June 2018. Results: In the patient-level analyses, patients who achieved a response had better OS compared with nonresponders (HR 0.18; 95% CI, 0.11 to 0.29; P < 0.001). Greater OS was also observed in landmark anlyses at 6-month PFS (HR 0.21; 95% CI 0.11 to 0.39; P < 0.001) and 12-month PFS (HR 0.16; 95% CI 0.11 to 0.24; P < 0.001). PFS correlated with OS at the individual level (Spearman ρ = 0.37; P < 0.001). In the trial-level analysis, PFS moderately correlated with OS (Spearman ρ = 0.64; P < 0.001), and the R² was 0.50 (95% CI 0.39 to 0.64). Conclusions: In NSCLC immunotherapy trials, responders and patients with longer PFS had better OS. ORR and PFS are acceptable surrogates for OS in trials of immunotherapy, but caution must be taken when interpreting efficacy in the absence of OS data.

1094 Background: Breast cancer treatment with immunotherapy can improve clinical benefits, but the majority of patients did not respond to the treatment. To understand tumor–immune interactions in breast cancer, we identified novel microenvironment-based immune molecular subtypes. Methods: A training cohort of 1,394 breast cancer patients from the Molecular Taxonomy of Breast Cancer International Consortium profiled by RNA and DNA sequencing data were analyzed to calculate immune-related gene biomarkers and to assign prognostic categories using LASSO Cox regression model. Additionally, 969 patients from The Cancer Genome Atlas data set was used as an independent validation cohort. We further compared tumor mutation burden (TMB) and cytolytic activity (CYT) levels between different immune molecular subtypes. Results: Using the LASSO model, we established an immune molecular classifier based on following 5 features: IFN-γ signature, ICOSLG, TNFRSF14, Mast.cells.resting, and T.cells. CD4.memory.resting. Then we found that it contained two distinct microenvironment-based subtypes (immune class and non-immune class), characterized by significant differences in overall survival in the training cohort (hazard ratio [HR] 0.71; 95% confidence interval [CI] 0.61 to 0.81; P < 0.001) and in the validation cohort (HR 0.34; 95% CI 0.22 to 0.54; P < 0.001). We found an inverse association between immune gene expression and TMB levels (ρ = 0.096, P < 0.001). Immune class subtype patients with good prognosis had significantly lower TMB and higher CYT than did non-immune class subtype patients with poor prognosis (all, P < 0.05). The clinical use of the immune molecular subtypes showed a closer association with survival than did IFN-γ signature or PD-L1 expression (all, P < 0.05). The robustness of the immune molecular subtypes was confirmed in the validation cohort. Conclusions: We revealed novel immune molecular subtypes, which represented better utility in predicting breast cancer patients’ survival compared with IFN-γ signature or PD-L1, and could be an important guide for precision immunotherapy.

1082Background: Current guidelines lack definitive evidences about the relative benefits of locoregional surgery for the primary tumor in de novo stage IV breast cancer. The aim of this study was t...

Objective To explore the embryo development characteristics in Robertsonian translocations (RTs) in their preimplantation genetic diagnosis (PGD) cycles. Method A total of 37 RT carrier couples underwent 41 blastomere PGD cycles from August 2005 to September 2008. The development of 272 embryos was analyzed in their PGD cycles. Result(s) At D3, there were 161 high-grade embryos, including 59 normal/balanced embryos and 102 abnormal embryos. There was no difference between the normal/balanced embryo group and the abnormal embryo group in terms of the high-grade embryo percentage (64.84% vs 56.35%, p = 0.179). However, at D5–D6, the blastocyst percentage in the normal/balanced embryo group was significantly higher than that in the abnormal embryo group (43.96% vs 20.44%, p = 0.000). Conclusion(s) Normal/balanced embryos developed better and a self-selective mechanism may exist in the RTs' embryos at the blastocyst formation stage. Copyright © 2009 John Wiley & Sons, Ltd.

Objective To evaluate the effect of growth differentiation factor-9 (GDF-9) and bone morphogenetic protein-15 (BMP-15) on the development of follicles among patients with polycystic ovary syndrome (PCOS). Design Case-control study. Setting University Hospital. Patient(s) Twenty-two oocytes were obtained from 15 patients with PCOS and 67 oocytes from 58 controls. Cumulus granulosa cells (GC) were obtained from 16 patients with PCOS and controls treated with intracytoplasmic sperm injection. Intervention(s) Immunofluorescence combined with laser scanning confocal microscopy and immunocytochemistry were used to analyze the expression of GDF-9 and BMP-15 in oocytes and cumulus GCs. Main Outcome Measure(s) To detect the protein expression levels. Result(s) No significant difference was found in the expression of GDF-9 and BMP-15 in the oocytes and BMP-15 in the cumulus GCs of patients with PCOS and controls. However, the expression of GDF-9 in cumulus GCs of patients with PCOS was decreased significantly compared with controls (8.88 ± 1.52 vs. 5.01 ± 0.83). Conclusion(s) The expression of GDF-9 and BMP-15 in the oocytes of patients with PCOS who received ovulation induction treatment was in the normal range, but the GDF-9 expression in cumulus GCs from patients with PCOS was significantly lower than the normal. Reduced GDF-9 expression in cumulus GCs of patients with PCOS appears to be associated with decreased long-term developmental potential of the oocytes of patients with PCOS.

Bone morphogenetic protein-15 is expressed in ooctytes and cumulus granulosa cells. It may play an important role in the hCG-induced oocyte final maturation and corpus luteum (CL) formation.

Surface-enhanced Raman scattering (SERS) is proved to be a powerful analytical tool for investigation of biological tissue. In this study, SERS based on Ag nanoparticles was used to investigate the normal and cancerous thyroid tissue. Preliminary results indicated that Raman peaks and the spectra profile from both normal and cancerous tissues showed a basic similarity, obvious differences are that, first, Raman peaks 563cm−1, 1449cm−1 and 1587cm−1 in cancerous tissue decreased obviously compared with the normal thyroid tissue. Besides, Raman peaks 1004cm−1 and 1128cm−1 might be specific peaks for normal thyroid tissue, whereas 1294cm−1 might attribute to specific peak for cancerous thyroid tissue. In addition, some peaks in normal thyroid tissue appeared to have shifted in cancerous tissue. Intensity ratio of 656cm−1 vs. 725cm−1 in normal tissue are significantly different from cancerous tissue (P