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Purpose: The tumor immune microenvironment (TME) plays a vital role in tumorigenesis, progression, and treatment. Macrophages, as an important component of the tumor microenvironment, play an essential role in antitumor immunity and TME remodeling. In this study, we aimed to explore the different functions of different origins macrophages in TME and their value as potential predictive markers of prognosis and treatment. Methods: We performed single-cell analysis using 21 lung adenocarcinoma (LUAD), 12 normal, and four peripheral blood samples from our data and public databases. A prognostic prediction model was then constructed using 502 TCGA patients and explored the potential factors affecting prognosis. The model was validated using data from 4 different GEO datasets with 544 patients after integration. Results: According to the source of macrophages, we classified macrophages into alveolar macrophages (AMs) and interstitial macrophages (IMs). AMs mainly infiltrated in normal lung tissue and expressed proliferative, antigen-presenting, scavenger receptors genes, while IMs occupied the majority in TME and expressed anti-inflammatory, lipid metabolism-related genes. Trajectory analysis revealed that AMs rely on self-renew, whereas IMs originated from monocytes in the blood. Cell-to-cell communication showed that AMs interacted mainly with T cells through the MHC I/II signaling pathway, while IMs mostly interacted with tumor-associated fibrocytes and tumor cells. We then constructed a risk model based on macrophage infiltration and showed an excellent predictive power. We further revealed the possible reasons for its potential prognosis prediction by differential genes, immune cell infiltration, and mutational differences. Conclusion: In conclusion, we investigated the composition, expression differences, and phenotypic changes of macrophages from different origins in lung adenocarcinoma. In addition, we developed a prognostic prediction model based on different macrophage subtype infiltration, which can be used as a valid prognostic biomarker. New insights were provided into the role of macrophages in the prognosis and potential treatment of LUAD patients. [ABSTRACT FROM AUTHOR]

Objectives: To identify factors affecting the development of drug‐resistant epilepsy (DRE), and establish a reliable nomogram to predict DRE development in post‐traumatic epilepsy (PTE) patients. Methods: This study conducted a retrospective clinical analysis in patients with PTE who visited the Epilepsy Center, Beijing Tiantan Hospital from January 2013 to December 2018. All participants were followed up for at least 3 years, and the development of DRE was assessed. Data from January 2013 to December 2017 were used as development dataset for model building. Those independent predictors of DRE were included in the final multivariable logistic regression, and a derived nomogram was built. Data from January 2018 to December 2018 were used as validation dataset for internal validation. Results: Complete clinical information was available for 2830 PTE patients (development dataset: 2023; validation dataset: 807), of which 21.06% (n = 596) developed DRE. Among all parameters of interest including gender, age at PTE, family history, severity of traumatic brain injury (TBI), single or multiple injuries, lesion location, post‐TBI treatments, acute seizures, PTE latency, seizure type, status epilepticus (SE), and electroencephalogram (EEG) findings, four predictors showed independent effect on DRE, they were age at PTE, seizure type, SE, and EEG findings. A model incorporating these four variables was created, and a nomogram to calculate the probability of DRE using the coefficients of the model was developed. The C‐index of the predictive model and the validation was 0.662 and 0.690, respectively. The goodness‐of‐fit test indicated good calibration for model development and validation (p = 0.272, 0.572). Conclusions: The proposed nomogram achieved significant potential for clinical utility in the prediction of DRE among PTE patients. The risk of DRE for individual PTE patients can be estimated by using this nomogram, and identified high‐risk patients might benefit from non‐pharmacological therapies at an early stage. [ABSTRACT FROM AUTHOR]

Objective: Fear aura has traditionally been considered relevant to epileptic discharges from mesial temporal areas, and few studies have investigated its effect on surgical outcome in drug‐resistant epilepsy. We aim to assess the localizing and lateralizing value as well as prognostic significance of fear aura in patients with focal epilepsy. Methods: The occurrence of fear aura in relation to epileptogenic origin and its association with postoperative outcome were analyzed in 146 consecutive patients undergoing resective surgery for intractable epilepsy. Results: Ninety‐four (64.4%) patients reported auras, and 31 (21.2%) reported fear aura in their seizures. One hundred ten (75.3%) patients had an Engel class I outcome until last follow‐up, of whom 24 experienced fear aura preoperatively. Fear aura appeared more frequently during temporal and frontal lobe seizures, but did not lateralize the seizure onset zone. There were no significant baseline differences between patients with and without fear aura. No correlation was found between postoperative outcome and the presence of auras. Occurrence of fear aura failed to show predictive value in surgical outcome whether in pooled or subgroup analysis. Interpretation: This study advances our understanding of the origin of fear aura, and is helpful for presurgical evaluation and outcome prediction. Without lateralizing value, fear aura is more commonly seen with temporal or frontal origin. When taken as a whole, auras do not have a significant impact on seizure outcome in focal epilepsy. Patients with fear aura are no more likely to become seizure‐free than those without fear aura. [ABSTRACT FROM AUTHOR]

Background: The role of cancer stem cells in esophageal squamous cell carcinoma (ESCC) remains unclear. Methods: The mRNA stemness index (mRNAsi) of 179 ESCC patients (GSE53625) was calculated using a machine learning algorithm based on their mRNA expression. Stemness-related genes were identified by weighted correlation network analysis (WGCNA) and LASSO regression, whose associations with mutation status, immune cell infiltrations, and potential compounds were also analyzed. The role of these genes in proliferation and their expressions was assessed in ESCC cell lines and 112 samples from our center. Results: The ESCC samples had significantly higher mRNAsi than the normal tissues. Patients with high mRNAsi exhibited higher worse OS. Seven stemness-related genes were identified by WGCNA and LASSO regression, based on which a risk-predicted score model was constructed. Among them, CST1, CILP, PITX2, F2RL2, and RIOX1 were favorable for OS, which were adverse for DPP4 and ZFHX4 in the GSE53625 dataset. However, RIOX1 was unfavorable for OS in patients from our center. In vitro assays showed that CST1, CILP, PITX2, F2RL2, and RIOX1 were pro-proliferated, which were opposite for DDP4 and ZFHX4. In addition, SMARCA4, NOTCH3, DNAH5, and KALRN were more mutated in the low-score group. The low-score group had significantly more memory B cells, monocytes, activated NK cells, and Tregs and less macrophages M2, resting mast cells, and resting dendritic cells. Conclusions: Seven stemness-related genes are significantly related to the prognosis, gene mutations, and immune cell infiltration of ESCC. Some potential anticancer compounds may be favorable for OS. [ABSTRACT FROM AUTHOR]

Objectives: Early‐onset anti‐N‐methyl‐D‐aspartate receptor encephalitis (anti‐NMDARE) differs from late‐onset anti‐NMDARE regarding clinical characteristics. Until recently, research focusing on prognosis of elder adults has been scarce and showed inconsistent results. This study aims to evaluate the prognosis of late‐onset anti‐NMDARE in China. Materials & Methods: One hundred and twelve adults diagnosed as anti‐NMDARE in four hospitals in China were reviewed retrospectively. Outcome data were assessed using modified Rankin Scale (mRS) score in short term (3 months after discharge) and long term (≥12 months after discharge). The relapse rate was also computed. Multivariable logistic regression was used to evaluate whether there are substantial differences in functional outcomes and recurrence rate across two groups. Results: Of the 112 patients with anti‐NMDARE, 81 (72.3%) were early‐onset disease and 31 (27.7%) were late‐onset disease. Of these, all had short‐term follow‐up and 70 completed long‐term follow‐up. Late‐onset anti‐NMDARE group showed better short‐term (OR 2.70, 95% CI 1.09–6.71) and long‐term prognoses (OR 10.25, 95% CI 1.90–55.15). Recurrence rates were statistically different between the groups (OR 4.25, 95% CI 1.22–14.75). Conclusion: The prognosis for anti‐NMDARE in China was poorer for older adults relative to younger adults. The relapse rates were higher in late‐onset group compared to early‐onset group. [ABSTRACT FROM AUTHOR]

Abstract Background The optimal treatment for pulmonary mucoepidermoid carcinoma (MEC), a rare type of tumor, has not been established yet. This study analyzed the survival of pulmonary MEC patients and attempted to find clues for optimal treatment. Methods A total of 21 patients with pulmonary MEC from November 2004 to January 2011 were included in the investigation. Immunohistochemistry, epidermal growth factor receptor (EGFR) mutation, and survival were retrospectively studied. Results Among the 21 pulmonary MEC patients, 17 were diagnosed with low-grade malignancy and 4 with high-grade malignancy through pathological examination. The prognosis was found to be poor in the presence of lymph nodes. The expression rates of EGFR and HER2 were 28.6% and 0%, respectively, which correlated with neither grade nor prognosis. The mutation rate of EGFR was 0. Log-rank test results indicated that age, grade, lymph node metastasis, and tumor-node-metastasis stage were prognostic factors. Conclusion Age, grade, lymph node metastasis and tumor-node-metastasis stage correlate with the survival of pulmonary MEC patients. Trial registration This study was approved and registered by the Ethics Committee of Zhongshan Hospital. Written informed consent was obtained from all participants prior to treatment.

Background: This study aimed to analyze the clinical characteristics of anti-leucine-rich glioma-inactivated protein 1 (LGI1) encephalitis patients and investigate prognostic factors by using a large-sample and long-term follow-up cohort. Methods: The clinical data of 45 patients (29 males; mean age, 57.0 years) from May 2014 to August 2019 were collected. All patients were followed up by face-to-face interviews in the third month after discharge and then by telephone and/or face-to-face interviews every 6 months until November 2020. We evaluated each patient's response to the initial treatments at the first interview and divided them into "responders" and "nonresponders." Relapses were recorded. At the end of follow-up, each patient was evaluated and reclassified into "complete recovery" or "unhealed" groups. Intergroup differences were assessed. Results: All patients presented with seizures at the initial consultation. Other common manifestations included cognitive dysfunction (82.2%), psychiatric disturbance (66.7%), sleep disorder (54.5%), and hyponatremia (66.7%). During the follow-up period (32.8 ± 13.5 months), six patients experienced relapse within 6–37 months. We observed that the patients who did not respond to the initial treatments and those who relapsed all had a poor long-term prognosis. The patients in the "unhealed" group were older (p = 0.009), had a lower incidence of generalized tonic–clonic seizures (p = 0.041), and had a higher probability of cerebrospinal fluid (CSF) abnormalities (p = 0.024) than those in the "complete recovery" group. Conclusion: Anti-LGI1 encephalitis was characterized by seizures, cognitive impairment, psychiatric disturbance, and sleep disorders and was often accompanied by hyponatremia. Patients who responded poorly to the initial treatments and those patients who relapsed had dismal long-term prognoses. Advanced age and CSF abnormalities may be risk factors for poor prognosis, but these still need to be verified. [ABSTRACT FROM AUTHOR]

The aim of this retrospective study was to derive and validate a reliable nomogram for predicting prognosis of autoimmune encephalitis (AE). A multi-center retrospective study was conducted in four hospitals in China, using a random split-sample method to allocate 173 patients into either a training (n = 126) or validation (n = 47) dataset. Demographic, radiographic and therapeutic presentation, combined with clinical features were collected. A modified Rankin Scale (mRS) at discharge was the principal outcome variable. A backward-stepwise approach based on the Akaike information criterion was used to test predictors and construct the final, parsimonious model. Multivariable analysis was conducted using logistic regression to develop a prognosis model and validate a nomogram using an independent dataset. The performance of the model was assessed using receiver operating characteristic curves and a Hosmer-Lemeshow test. The final nomogram model considered age, viral prodrome, consciousness impairment, memory dysfunction and autonomic dysfunction as predictors. Model validations displayed a good level of discrimination in the validation set: area under the Receiver operator characteristic curve = 0.72 (95% Confidence Interval: 0.56–0.88), Hosmer–Lemeshow analysis suggesting good calibration (chi-square: 10.33; p = 0.41). The proposed nomogram demonstrated considerable potential for clinical utility in prediction of prognosis in autoimmune encephalitis. [ABSTRACT FROM AUTHOR]

Background: Lung adenocarcinoma (LUAD) is one of the most common malignancies worldwide. However, the molecular mechanism of LUAD tumorigenesis and development remains unclear. The purpose of this study was to comprehensively illustrate the role of GTF2E2 in the growth and progression of LUAD. Methods and materials: We obtained the mRNA expression data from The Cancer Genome Atlas, Gene Expression Omnibus database, and our institution. Systematic bioinformatical analyses were performed to investigate the expression and prognostic value of GTF2E2 in LUAD. The results were validated by immunohistochemistry and qPCR. The effect of knocking down GTF2E2 using two short hairpin RNAs was investigated by in vitro and in vivo assays. Subsequently, shotgun liquid chromatography coupled with tandem mass spectrometry (LC–MS/MS) analyses were applied to identified potential GTF2E2 interacting proteins, and the downstream molecular mechanisms of GTF2E2-signaling were further explored by a series of cellular functional assays. Results: We found that GTF2E2 expression was significantly increased in LUAD tissue compared with adjacent normal tissue and was negatively associated with patients' overall survival. Besides, we demonstrated that GTF2E2 knockdown inhibited LUAD cell proliferation, migration, invasion, and promote apoptosis in vitro, as well as attenuated tumor growth in vivo. Results from LC–MS/MS suggested that RPS4X might physically interact with GTF2E2 and mediated GTF2E2's regulatory effect on LUAD development through the mTOR pathway. Conclusion: Our findings indicate that GTF2E2 promotes LUAD development by activating RPS4X. Therefore, GTF2E2 might serve as a promising biomarker for the diagnosis and prognosis of LUAD patients, thus shedding light on the precise and personalized therapy for LUAD in the future. [ABSTRACT FROM AUTHOR]

This study aims to evaluate the association between age and prognosis in patients with anti-N-methyl-D-aspartate receptor encephalitis (anti-NMDARE) under the age of 45 years. A retrospective study was conducted in patients younger than 45 years diagnosed as anti-NMDARE in four hospitals in China. Age at admission was divided into four categories: <15, 15–24, 25–34, 35–45 years. Neurological prognosis was evaluated using modified Rankin Scale. Adjusted multivariable logistic regression was used to analyze the association. The multivariable-adjusted odds ratios (95% confidence interval) of prognosis in anti-NMDARE across the categories of age were as follows: in males, 1.00 (reference), 4.76 (0.39–58.76), 13.50 (0.79–230.40), and 8.81 (0.36–218.39) (P for trend = 0.171); in females, 1.00 (reference), 7.27 (0.36–146.19), 20.08 (1.09–370.39), and 54.41 (1.60–1,849.10) (P for trend = 0.01). We concluded that the increasing age was associated with a poorer prognosis of anti-NMDARE in females but not males. [ABSTRACT FROM AUTHOR]

Background: Most non-small cell lung cancer patients with enlarged mediastinal lymph nodes (LN) in preoperative computer tomography (CT) images are diagnosed with N0 in the pathological examination after surgery. However, these patients seem to have worse survival than those without enlarged mediastinal LN in our clinical practice. This study aimed to investigate whether the size of mediastinal LN is correlated with the prognosis in pathological N0 patients, which could help us to predict the prognoses further. Methods: The retrospective cohort study involved 758 N0 patients with a thin layer CT scan. We have measured the size of mediastinal LN, including long diameter, short diameter, and volume on CT image, and classified patients by X-tile. Next, we explored the risk factors of enlarged LN by univariate and multivariate logistic analysis. Then, we have compared the 5-year cancer-specific survival by Kaplan–Meier and log-rank method. Multivariate Cox analysis was utilized to further survival analysis. Finally, we have constructed the prediction model by nomogram. Results: A total of 150 N0 patients (19.8%) had mediastinal LN enlargement in our study. After multivariate logistic analysis, we found the LN enlargement was significantly correlated with age (p=0.001), pathology (p < 0.001) and tumor recurrence (p < 0.001). The patients with LN enlargement had a worse 5-year cancer-specific survival (75.3% vs 92.8%, p < 0.001) after Kaplan–Meier analysis. Patients with a larger volume had increased risk of tumor-associated death when compared with the normal group (p < 0.001) by multivariate Cox analyses. Conclusion: N0 patients with larger mediastinal LN had a worse 5-year cancer-specific survival and a higher risk of recurrence. The volume of LN was the most valuable prognostic factor in N0 patients. [ABSTRACT FROM AUTHOR]

Objective: To investigate the value of pre-treatment kisspeptin (KISS-1) expression for diagnosis and prognosis prediction of pancreatic cancer. Methods: The clinical data of 90 patients with pancreatic cancer (pancreatic cancer group) in Cancer Hospital of Hubei Province from April 2015 to December 2018 were retrospectively analyzed; in addition, 40 patients with benign pancreatic lesions were selected as the benign pancreatic lesion group and 30 healthy people were chosen as control group. The serum levels of KISS-1 and CA19-9 in each group were detected by ELISA. The diagnostic efficacies of CA19-9 and KISS-1 in pancreatic cancer and their relationship with the prognosis of pancreatic cancer were analyzed. Results: The serum KISS-1 level in the pancreatic cancer group was significantly higher than that in the benign pancreatic lesion group and the control group (both P<0.01); the area under the curve (AUC) of serum KISS-1, CA19-9 and their combination for pancreatic cancer detection was 0.757 (95% CI: 0.684-0.831, P=0.000), 0.900 (95% CI: 0.854-0.946, P=0.000), and 0.906 (95% CI: 0.861-0.950, P=0.000), respectively. The AUC value of the combined detection was statistically different from that of KISS-1 (Z=3.124, P=0.024), and the AUC value of CA19-9 was also statistically differently from KISS-1 (Z=3.253, P=0.025). Correlation analysis showed that there was a significant negative correlation between KISS-1 and CA19-9 (r=-0.358, P=0.002). The results of survival curve analysis showed that the survival time of patients with serum KISS-1≥73.6 pg/ml was significantly better than that of patients with KISS-1<73.6 pg/ml (χ² =4.520, P=0.036); KISS-1<73.6 pg/ml was independently related to the patient's prognosis with an OR of 2.37 (1.08-4.75). Conclusion: Serum KISS-1 is helpful for the early diagnosis of pancreatic cancer, and the combined detection of KISS-1 and CAI9-9 can improve the sensitivity and specificity of pancreatic cancer diagnosis, and also is beneficial for prognosis evaluation. [ABSTRACT FROM AUTHOR]

Primary pulmonary mucosa‐associated lymphoid tissue‐derived (MALT) lymphoma is a rare disease with a favorable prognosis. However, its clinical characteristics, diagnosis, treatment, and prognoses remain unclear. We retrospectively analyzed 80 patients with pathologically confirmed MALT lymphoma from 2006 to 2018. The clinical characteristics, diagnosis, treatments, and prognoses of all the 80 patients were recorded. Patients were stratified into surgery and biopsy groups, respectively, to evaluate the role of surgery in the diagnosis and treatment of MALT lymphoma. The prognoses were compared between different clinical characteristics and treatments. Pathological diagnoses were confirmed by surgery, bronchoscopy, and percutaneous biopsy. Thirty patients were treated by surgery. While MALT lymphoma was only diagnosed by bronchofiberoscopy or bercutaneous biopsy in four of 18 patients in the surgery group who underwent the procedure. Six patients received adjuvant chemotherapy and one patient received involved‐field radiotherapy in surgery group. Thirty‐one patients were treated with chemotherapy alone, one patient was treated with radiotherapy, one patient received only symptomatic and supportive treatment, and waiting and watching without treatment were recommended in 17 patients in biopsy group. Eight patients died during follow‐up and the 5‐year survival rate was 87.1%. Tumor number, treatment, and age were prognostic factors for overall survival (OS), but age was the only independent prognostic factor according to multivariate analysis. While, tumor number was the only prognostic factor in the analysis about progression‐free survival (PFS). No significant difference was found in OS or PFS between patients treated with and without surgical resection. MALT lymphoma is an indolent disease with favorable treatment outcome. Tumor number is associated with PFS and age is the only significant prognostic factor for pulmonary MALT lymphoma patients because of its indolent nature, but surgery still plays an important role in the diagnosis and treatment of MALT lymphoma. [ABSTRACT FROM AUTHOR]

Purpose: Risk stratification of patients with non-small cell lung cancer (NSCLC) is crucial to select the appropriate treatments, but available models for patients with complete resection are unsatisfactory. The purpose of this study was to determine a prediction model based on clinical information, routine physical and blood tests, and molecular markers. Patients and Methods: This was a retrospective cohort study of patients who underwent surgical resection for lung cancer between 2009 to 2013. Potential prognostic factors were used to build a full prediction model based on a multivariable Cox regression analysis. A nomogram was constructed. The risk stratification cutoffs for clinical use were determined based on the model. Results: A total of 368 NSCLC patients with R0 resection were included. The final multivariable model indicated that low diffusing capacity of the lung for carbon monoxide (HR=1.66, 95% CI: 1.18–2.34), high platelet-to-lymphocyte ratio (HR=1.42, 95% CI: 1.04–1.95), histology type of squamous cell carcinoma and others (squamous cell carcinoma vs adenocarcinoma, HR=1.40, 95% CI: 1.01–1.96; others vs adenocarcinoma, HR=2.36, 95% CI: 1.15–4.84; P trend=0.001), N>0 status (HR=1.96, 95% CI: 1.42–2.70), high serum carcinoembryonic antigen levels (HR=1.61, 95% CI: 1.13–2.27), and postoperative chemotherapy (HR=0.53, 95% CI: 0.33–0.87) were independently associated with poor OS. The patients were classified into four risk groups according to the nomogram, and the OS was different among the four groups (P<0.05). Conclusion: A nomogram was successfully constructed based on a multivariable analysis, and the nomogram can discriminate the OS of patients with NSCLC based on risk categories, but external validation is still necessary. [ABSTRACT FROM AUTHOR]

Background: The effect of neoadjuvant radiotherapy (NRT) was controversial in non‐cervical esophageal cancer. The aim of this study was to identify which stage of non‐cervical esophageal cancer would get benefit from NRT using propensity score matching (PSM) and survival analysis based on the Surveillance Epidemiology, and End Results (SEER) database. Methods: A selection process was used for case screening from the SEER database. Seven baseline variables were included in PSM. The survival analysis were based on T stage (T2 and T3) and status of lymph node involvement (N0 and N+) using Kaplan‐Meier method and log‐rank test for comparing the overall survival of patient with NRT plus surgery versus those who with surgery alone (SA). Results: A total of 1631 cases were included in this study. After PSM, 225 cases of esophageal squamous cell carcinoma (ESCC) and 606 cases of esophageal adenocarcinoma (EAC) were enrolled in survival analysis. We found that only T3N+ stage of EAC would got survival benefit from NRT (P = 0.0052), while NRT showed no significant benefit in overall survival in other stages of EAC and ESCC. Conclusions: NRT followed by resection had a significant survival benefit in non‐cervical EAC patients with T3N+ stage. For patients with ESCC and other EAC stages, NRT versus SA did not demonstrate a statistical significant survival difference. [ABSTRACT FROM AUTHOR]

Background: Malignant pleural mesothelioma (MPM) is a rare malignancy with heterogeneous outcomes. This study was aimed to develop a nomogram to precisely and visually predict survival of MPM patients.Methods: Data from Surveillance, Epidemiology, and End Results database (1973-2014) on MPM were screened and retrieved. The prognostic effects of variables, including age, sex, race, year of diagnosis, laterality, histology, tumor stage, surgery, chemotherapy, and radiotherapy were analyzed using Kaplan-Meier method and Cox proportional hazard model. A nomogram was formulated to predict overall survival of MPM patients.Results: A total of 1092 cases who met inclusion criteria were included in this study. The overall 1-, 2-, and 3-year survival rate in the entire cohort was 45.1, 23.0, and 12.1%, with median survival of 11 months. Cox regression analysis showed that age (P < 0.001), race (P = 0.003), histology type (P < 0.001), T stage (P < 0.001), M stage (P < 0.001), TNM stage (P < 0.001), cancer-directed surgery (P < 0.001), and chemotherapy (P < 0.001) were all independent prognostic factors of MPM patients. A nomogram was established based on the results of multivariate analysis. The internal bootstrap resampling approach suggested the nomogram had sufficient discriminatory power with the C-index of 0.705 (95% CI 0.681-0.729). The calibration plots also demonstrated good consistence between the prediction and the observation.Conclusions: We developed a nomogram to accurately predict clinical outcomes of MPM patients based on individual characteristics. Risk stratification by the survival nomogram could optimize individual therapies and follow-up. [ABSTRACT FROM AUTHOR]

Abstract: Previous studies have identified potential risk factors for pulmonary carcinoid tumors and evaluated the effect of various treatments; however, the results were not entirely consistent. We conducted a population‐based study to further explore relevant prognostic issues. We extracted cases with pulmonary carcinoid tumors from the Surveillance Epidemiology and End Results database. Cox proportional hazard regression was utilized to identify potential significant risk factors, which helped establish a nomogram for predicting long‐term survival. Survival analysis and a competing risk study were conducted to evaluate the value of different surgical approaches. There were 7057 cases included in the study. Univariate and multivariate analyses showed that age, sex, tumor size, stage, histology, surgical type, chemotherapy, and radiation therapy were all significant prognostic factors. A nomogram with good accuracy for predicting 10‐year survival was formulated. Furthermore, patients who had undergone surgery had a significantly better survival than those who did not undergo surgery. There was no significant prognostic difference between lobectomy and sublobectomy stratified by tumor stage; however, lobectomy was associated with a significantly better survival in atypical tumors, especially those with regional disease. Our research identified possible risk factors in a large cohort and constructed a nomogram to visually predict 10‐year survival of pulmonary carcinoid tumors. We showed that lobectomy and sublobectomy should be considered as the mainstay of treatment, especially lobectomies for atypical tumor. [ABSTRACT FROM AUTHOR]

Background: Cisplatin-based adjuvant chemotherapy is the standard of care for patients with resected stage II-IIIA non-small-cell lung cancer (NSCLC). RADIANT and SELECT trial data suggest patients with EGFR-mutant stage IB-IIIA resected NSCLC could benefit from adjuvant EGFR tyrosine kinase inhibitor treatment. We aimed to compare the efficacy of adjuvant gefitinib versus vinorelbine plus cisplatin in patients with completely resected EGFR-mutant stage II-IIIA (N1-N2) NSCLC.Methods: We did a randomised, open-label, phase 3 trial at 27 centres in China. We enrolled patients aged 18-75 years with completely resected (R0), stage II-IIIA (N1-N2), EGFR-mutant (exon 19 deletion or exon 21 Leu858Arg) NSCLC. Patients were stratified by N stage and EGFR mutation status and randomised (1:1) by Pocock and Simon minimisation with a random element to either gefitinib (250 mg once daily) for 24 months or intravenous vinorelbine (25 mg/m2 on days 1 and 8) plus intravenous cisplatin (75 mg/m2 on day 1) every 3 weeks for four cycles. The primary endpoint was disease-free survival in the intention-to-treat population, which comprised all randomised patients; the safety population included all randomised patients who received at least one dose of study medication. Enrolment to the study is closed but survival follow-up is ongoing. The study is registered with ClinicalTrials.gov, number NCT01405079.Findings: Between Sept 19, 2011, and April 24, 2014, 483 patients were screened and 222 patients were randomised, 111 to gefitinib and 111 to vinorelbine plus cisplatin. Median follow-up was 36·5 months (IQR 23·8-44·8). Median disease-free survival was significantly longer with gefitinib (28·7 months [95% CI 24·9-32·5]) than with vinorelbine plus cisplatin (18·0 months [13·6-22·3]; hazard ratio [HR] 0·60, 95% CI 0·42-0·87; p=0·0054). In the safety population, the most commonly reported grade 3 or worse adverse events in the gefitinib group (n=106) were raised alanine aminotransferase and asparate aminotransferase (two [2%] patients with each event vs none with vinorelbine plus cisplatin). In the vinorelbine plus cisplatin group (n=87), the most frequently reported grade 3 or worse adverse events were neutropenia (30 [34%] patients vs none with gefitinib), leucopenia (14 [16%] vs none), and vomiting (eight [9%] vs none). Serious adverse events were reported for seven (7%) patients who received gefitinib and 20 (23%) patients who received vinorelbine plus cisplatin. No interstitial lung disease was noted with gefitinib. No deaths were treatment related.Interpretation: Adjuvant gefitinib led to significantly longer disease-free survival compared with that for vinorelbine plus cisplatin in patients with completely resected stage II-IIIA (N1-N2) EGFR-mutant NSCLC. Based on the superior disease-free survival, reduced toxicity, and improved quality of life, adjuvant gefitinib could be a potential treatment option compared with adjuvant chemotherapy in these patients. However, the duration of benefit with gefitinib after 24 months might be limited and overall survival data are not yet mature.Funding: Guangdong Provincial Key Laboratory of Lung Cancer Translational Medicine; National Health and Family Planning Commission of People's Republic of China; Guangzhou Science and Technology Bureau; AstraZeneca China. [ABSTRACT FROM AUTHOR]

Background: Several staging systems for MPM have been introduced. However, none of them provide perfect survival stratification among heterogeneous patients. The aim of this population-based cohort study was to propose adjustments to current staging system for malignant pleural mesothelioma (MPM).Methods: We retrieved MPM data from Surveillance, Epidemiology, and End Results database (1973-2014). Kaplan-Meier method was derived to examine the prognostic effects of tumor, lymph node, metastasis and histology features. Proportional hazards models guided adjustments to stage groupings. The accuracy of staging systems at predicting survival was evaluated by concordance index and bootstrap resampling.Results: A total of 1110 MPM cases were extracted from SEER. T stage failed to demonstrate survival difference between adjacent categories with the exception of T3 versus T4 (P < 0.001). Patients in M0 had better prognosis than those in M1 (P < 0.001). Exploratory analyses suggested important survival difference for single-versus multiple-site M1 cases (P < 0.001), but not for different metastatic sites (P = 0.286). Histology subtype was a significant prognostic indicator (P < 0.001). Regrouping of TNM and histology combinations resulted in the best concordance index (0.683), compared with UICC 2010 (0.578) and IASLC 2016 (0.585) staging systems. The revised staging system also improved patients distribution (IA:33.8%, IB:17.0%, II: 20.7%, IIIA:10.6%, IIIB: 6.8%, IV:11.1%). Log-rank analyses and calibration plots both demonstrated the new stage achieved optimal survival prediction and discrimination.Conclusion: The revised staging system improved patients distribution and survival stratification for MPM. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to identify risk factors affecting overall survival (OS) of elderly patients with early stage NSCLC, and develop a nomogram for prognostic prediction of these patients using data from the Surveillance, Epidemiology, and End Results (SEER) database.Methods: Data from the SEER database of patients aged ≥ 65 years with early (T1N0M0) NSCLC diagnosed between 2004 and 2013 were examined. The prognostic effect of each variable on survival was evaluated using the Kaplan-Meier method and the Cox proportional hazards regression model. A nomogram was formulated to predict the 3- and 5-year OS rates of elderly patients with early stage NSCLC.Results: Finally, a total of 20,782 patients were included in this research. Cox regression analysis showed that sex, age, pathological type, diameter, differentiation, and surgery type were independent risk factors. A nomogram was formulated based on the results of multivariate analysis (all p < 0.001) and validated using an internal bootstrap resampling approach, which showed that the nomogram exhibited a sufficient level of discrimination according to the C-index (0.638, 95% CI = 0.629-0.647).Conclusions: The nomogram developed in this study demonstrated its discrimination capability to predict the 3- and 5-year OS rates of elderly patients with early stage NSCLC based on individual characteristics. [ABSTRACT FROM AUTHOR]

Purpose: Video-assisted thoracoscopic surgery (VATS) is widely used in thoracic surgery and increasingly applied to pulmonary metastasectomy. The purpose of this study was to identify prognostic factors of patients undergoing VATS pulmonary metastasectomy from colorectal cancer (CRC). Methods: Between January 2005 and June 2015, a total of 154 patients underwent VATS pulmonary metastasectomy from CRC. Patient demographic data and characteristics of the primary tumor and pulmonary metastasis were analyzed to identify factors significantly correlated with prognosis. Results: The median follow-up period after pulmonary resection was 37 months. The cumulative 5-year overall survival rate after VATS pulmonary metastasectomy from CRC was 71.3%. History of metastasis to other sites ( p = 0.035), status of mediastinal lymph nodes ( p < 0.001), and preoperative carcinoembryonic antigen (CEA) level ( p = 0.013) were identified as independent prognostic factors. Subgroup analysis with a combination of these three independent prognostic factors revealed 5-year OS rates of 91.0, 70.0, 30.3, and 0.0% for patients with zero, one, two, and three risk factors, respectively. Other factors, such as sex, disease-free interval, T stage of primary tumor, and status of lymph node near the primary tumor, were not significantly associated with prognosis. Conclusion: VATS pulmonary metastasectomy is efficacious for patients with CRC pulmonary metastases. History of metastasis to other sites, status of mediastinal lymph nodes, and preoperative CEA level were identified as independent prognostic factors. The number of risk factors significantly influenced patient survival. [ABSTRACT FROM AUTHOR]

Objectives: Mediastinal lymph node dissection is an essential component of lung cancer surgery; however, choosing mediastinal lymph nodes stations to be dissected is subjective. We carried out this research to investigate the need for dissection of station 9 lymph nodes during lung cancer surgery.Methods: Patients with primary lung cancer who underwent radical surgery between 2010 and 2014 were retrospectively reviewed. Clinical, pathologic, and prognosis data were obtained and analyzed.Results: A total number of 1397 patients were included in this research. The metastasis rate of station 9 was 3.45%, which was significantly lower than other mediastinal stations. This metastasis rate was significantly correlated with pT stage, the lobe where the tumor was located, metastasis status of intrapulmonary lymph nodes, pTNM stage, and most of the other mediastinal lymph node stations. In males or ground glass opacity (GGO) patients, the metastasis of station 9 nodes was more unlikely to occur, even though there was no statistical significance. The staging results of most patients (99.63%) would not be impaired, even if station 9 nodes were not dissected, and the prognostic analysis showed that the metastasis status of station 9 had no significant influence on survival.Conclusion: The metastasis rate of station 9 lymph nodes was significantly lower than other mediastinal stations in lung cancer patients. The metastasis status of station 9 had no significant influence on tumor staging or prognosis. Routine dissection of station 9 lymph nodes may not be necessary, especially in patients with a low T stage, upper or middle lobe tumors, or without intrapulmonary lymph node metastasis. [ABSTRACT FROM AUTHOR]

Background: FoxC2 is an epithelial-mesenchymal transition (EMT) regulator which induces metastasis. The purpose of this study is to assess the prognostic value of FoxC2 expression in non-small cell lung cancer (NSCLC), alone or in combination with E-cadherin expression.Methods: A retrospective study was conducted using immunohistochemistry to investigate FoxC2 and E-cadherin expression in a cohort of 309 patients with surgically resected NSCLCs. The prognostic value of FoxC2 and E-cadherin on overall survival (OS) and recurrence-free survival (RFS) was determined by Kaplan-Meier analysis and Cox proportional hazard models.Results: High FoxC2 expression was detected in 26.5% of tumors, and significantly correlated with tobacco use (p = 0.047), adenocarcinoma (p = 0.008) and nodal involvement (p < 0.001). Univariate analysis revealed its association with OS (p = 0.036) and RFS (p = 0.011). By multivariate analysis, high FoxC2 expression lost its significance as an independent predictor of recurrence (p = 0.077), while TNM stage, nodal status and the presence of high FoxC2 and impaired E-cadherin expression retained independent prognostic significance in relation to both OS and RFS. Subset analyses indicated that high FoxC2 expression was significantly associated with disease outcome in node-positive, but not in node-negative patients.Conclusion: Evaluation of FoxC2 expression, alone or in combination with E-cadherin expression, may help to stratify NSCLC patients for risk of disease progression, pointing to this EMT regulator as a potential prognostic marker. [ABSTRACT FROM AUTHOR]

Abstract: Ras interaction/interference 1 (RIN1), originally identified as a Ras effector protein, has been implicated in tumorigenesis and development of human cancers. The aim of this study was to detect RIN1 expression in human non-small cell lung cancer (NSCLC) and to analyze its association with prognosis of NSCLC patients. Quantitative real-time RT-PCR was performed to examine the expression of RIN1 mRNA in 25 cases of NSCLC and corresponding non-tumor tissue samples. Immunohistochemistry was performed to detect the expression of RIN1 in 90 NSCLC tissues. We found that the expression levels of RIN1 mRNA in NSCLC tissues were significantly higher than those in corresponding non-tumor tissues. High-level RIN1 expression was observed in 53.3% (48 of 90 cases), and correlated with poor tumor differentiation (P =0.024), TNM stage (P =0.032), and lymph node metastasis (P =0.018). Patients with high expression levels of RIN1 showed lower overall survival rate than those with low expression levels (P =0.033). Multivariate analysis showed that high RIN1 protein expression was an independent prognostic factor for NSCLC patients (P =0.021). Our study suggests that over-expression of RIN1 may play an important role in the progression of NSCLC and RIN1 expression may offer a valuable marker for predicting the outcome of patients with NSCLC. [Copyright &y& Elsevier]

Objectives: Spontaneous intracerebral hemorrhage remains a major cause of death and disability throughout the world. We tried to establish accurate long‐term outcome prediction models for hypertensive intracerebral hemorrhage (HICH) using CT radiomics and machine learning. Methods: In a retrospective study of 270 patients with HICH between June 2013 and June 2018, CT images and patients' 6‐month outcome based on the modified Rankin Scale were collected. Hematomas on CT images were selected as volumes of interests (VOIs), and 1,029 radiomics features of the VOIs were extracted. Based on correlations with patients' outcome, radiomics features underwent dimensionality reduction analyses. Then, the support vector machine (SVM), k‐nearest neighbor (KNN), logistic regression (LR), decision tree (DT), random forest (RF), and XGBoost algorithms were applied with the screened features to establish prognostic prediction models of HICH. Accuracies of all models were compared. Results: Eighteen radiomics features were screened as prognosis‐associated radiomics signature of HICH based on the variance threshold, SelectKBest, and least absolute shrinkage and selection operator (LASSO) regression models. Patients were randomly allocated into training (n = 215) and validation (n = 55) sets. Accuracies of all 6 machine learning algorithms in the validation set exceeded 80%. The sensitivity, specificity, and accuracy in the validation set were 93.3%, 92.5%, and 92.7% for the RF model and 92.3%, 88.1%, and 89.1% for the XGBoost model, respectively, which were the best two among all models. Conclusions: Taking advantage of radiomics and machine learning, we established accurate prognostic prediction models of HICH. The RF model and XGBoost model returned the best accuracies. [ABSTRACT FROM AUTHOR]

Lung cancer is the main reason for cancer-associated death globally, and lung adenocarcinoma (LUAD) is the most prevalent subtype of lung cancer. Recently, AGRN is considered playing an vital role in the development of some cancers. However, the regulatory effects and mechanisms of AGRN in LUAD remain elusive. In this study, we clarified the significant upregulation of AGRN expression in LUAD by single-cell RNA sequencing combined with immunohistochemistry. Besides, we confirmed that LUAD patients with high AGRN expression are more susceptible to lymph node metastases and have a worse prognosis by a retrospective study of 120 LUAD patients. Next, we demonstrated that AGRN directly interact with NOTCH1, which results in the release of the intracellular structural domain of NOTCH1 and the subsequent activation of the NOTCH pathway. Moreover, we also found that AGRN promotes proliferation, migration, invasion, EMT and tumorigenesis of LUAD cells in vitro and in vivo, and that these effects are reversed by blocking the NOTCH pathway. Furthermore, we prepared several antibodies targeting AGRN, and clarify that Anti-AGRN antibody treatment could significantly inhibit proliferation and promote apoptosis of tumor cells. Our study highlights the important role and regulatory mechanism of AGRN in LUAD development and progression, and suggests that antibodies targeting AGRN have therapeutic potential for LUAD. We also provide theoretical and experimental evidence for further development of monoclonal antibodies targeting AGRN. [Display omitted] • AGRN is upregulated in LUAD, and high AGRN expression is associated with higher N stage and worse prognosis. • AGRN promotes proliferation, migration, invasion, EMT, and tumorigenic capacity of LUAD cells. • AGRN directly interacts with NOTCH1, which results in activation of the NOTCH pathway. • AGRN antibodies inhibit LUAD in vitro and in vivo. [ABSTRACT FROM AUTHOR]

This study aimed to investigate prognostic significance and brain metabolic mechanism of hyponatremia in anti-leucine-rich glioma-inactivated protein 1 (LGI1) encephalitis. After adjusting for confounders, patients with moderate and severe hyponatremia had significantly increased risk of poor functional outcome and sequelae of seizures. In addition, serum sodium was negatively correlated with normalized ratio of the standardized uptake value of medial temporal lobe (MTL), basal ganglia (BG), and hypothalamus on positron emission tomography (PET) and which was further validated using voxel-wise analysis, suggesting an extra-hypothalamus (BG and MTL) localization for hyponatremia. [Display omitted] • Hyponatremia is a common early finding in anti-LGI1 encephalitis. • Hyponatremia may be a potential predictor of outcome for anti-LGI1 encephalitis. • There exists extra-hypothalamus mechanism for hyponatremia in anti-LGI1 encephalitis. [ABSTRACT FROM AUTHOR]

Objective: To explore the expression of cyclophilin A (CypA) in esophageal tissues and its clinical significance. Method: Expression of CypA was detected in 236 esophageal cancer tissues and 236 normal tissues by using an immunohistochemical method, and the relationship between CypA expression and clinical outcomes was observed. Results: There were 166 patients with high expression of CypA (70.23%) and a higher expression in 69.3% of males and 73.3% in females. The CypA expression was irrelevant to age, tumor location, lymph node metastasis, and tumor differentiation degree. The Kaplan-Meier survival curve analysis showed that the expression of CypA was associated with the prognosis of patients with esophageal squamous cell carcinoma. Conclusion: The poor prognosis of esophageal cancer patients was associated with high expression of CypA. [ABSTRACT FROM AUTHOR]