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Background: The overall survival (OS) for patients with recurrent glioma is meager. Also, the effect of radionecrosis and prognostic factors for recurrent glioma remains controversial. In this regard, developing effective predictive models and guiding clinical care is crucial for these patients. Methods: We screened patients with recurrent glioma after radiotherapy and those who received surgery between August 1, 2013, and December 31, 2020. Univariate and multivariate Cox regression analyses determined the independent prognostic factors affecting the prognosis of recurrent glioma. Moreover, nomograms were constructed to predict recurrent glioma risk and prognosis. Statistical methods were used to determine the prediction accuracy and discriminability of the nomogram prediction model based on the area under the curve (AUC), the C-index, the decision curve analysis (DCA), and the calibration curve. In order to distinguish high-risk and low-risk groups for OS, the X-Tile and Kaplan-Meier (K-M) survival curves were employed, and the nomogram prediction model was further validated by the X-Tile and K-M survival curves. Results: According to a Cox regression analysis, independent prognostic factors of recurrent glioma after radiotherapy with radionecrosis were World Health Organization (WHO) grade and gliosis percentage. We utilized a nomogram prediction model to analyze results visually. The C-index was 0.682 (95% CI: 0.616–0.748). According to receiver operating characteristic (ROC) analysis, calibration plots, and DCA, the nomogram prediction model was found to have a high-performance ability, and all patients were divided into low-risk and high-risk groups based on OS (P <.001). Conclusion: WHO grade and gliosis percentage are prognostic factors for recurrent glioma with radionecrosis, and a nomogram prediction model was established based on these two variables. Patients could be divided into high- and low-risk groups with different OS by this model, and it will provide individualized clinical decisions for future treatment. [ABSTRACT FROM AUTHOR]

Background: Glioblastoma (GBM) is the most malignant primary tumor in the brain, with poor prognosis and limited effective therapies. Although Bevacizumab (BEV) has shown promise in extending progression-free survival (PFS) treating GBM, there is no evidence for its ability to prolong overall survival (OS). Given the uncertainty surrounding BEV treatment strategies, we aimed to provide an evidence map associated with BEV therapy for recurrent GBM (rGBM). Methods: PubMed, Embase, and the Cochrane Library were searched for the period from January 1, 1970, to March 1, 2022, for studies reporting the prognoses of patients with rGBM receiving BEV. The primary endpoints were overall survival (OS) and quality of life (QoL). The secondary endpoints were PFS, steroid use reduction, and risk of adverse effects. A scoping review and an evidence map were conducted to explore the optimal BEV treatment (including combination regimen, dosage, and window of opportunity). Results: Patients with rGBM could gain benefits in PFS, palliative, and cognitive advantages from BEV treatment, although the OS benefits could not be verified with high-quality evidence. Furthermore, BEV combined therapy (especially with lomustine and radiotherapy) showed higher efficacy than BEV monotherapy in the survival of patients with rGBM. Specific molecular alterations (IDH mutation status) and clinical features (large tumor burden and double-positive sign) could predict better responses to BEV administration. A low dosage of BEV showed equal efficacy to the recommended dose, but the optimal opportunity window for BEV administration remains unclear. Conclusions: Although OS benefits from BEV-containing regimens could not be verified in this scoping review, the PFS benefits and side effects control supported BEV application in rGBM. Combining BEV with novel treatments like tumor-treating field (TTF) and administration at first recurrence may optimize the therapeutic efficacy. rGBM with a low apparent diffusion coefficient (ADCL), large tumor burden, or IDH mutation is more likely to benefit from BEV treatment. High-quality studies are warranted to explore the combination modality and identify BEV-response subpopulations to maximize benefits. [ABSTRACT FROM AUTHOR]

Purpose. Gliosarcoma is a histopathological variant of glioblastoma, which is characterized by a biphasic growth pattern consisting of glial and sarcoma components. Owing to its scarcity, data regarding the impact of available treatments on the clinical outcomes of gliosarcoma are inadequate. The purpose of this retrospective cohort study was to analyze the prognostic factors of gliosarcoma. Methods. By screening the clinical database of neurosurgical cases at a single center, patients with gliosarcoma diagnosed histologically from 2013 to 2021 were identified. Clinical, pathological, and molecular data were gathered founded on medical records and follow-up interviews. Prognostic factors were derived using the Cox proportional hazards model with backward stepwise regression analysis. Results. Forty-five GSM patients were included. Median overall survival was 25.6 months (95% CI 8.0–43.1), and median relapse-free survival was 15.2 months (95% CI 9.7–20.8). In multivariable analysis, total resection (p = 0.023 , HR = 0.192 , 95% CI 0.046–0.797) indicated an improved prognosis. And low expression of Ki-67 (p = 0.059 , HR = 2.803 , 95% CI 0.963–8.162) would be likely to show statistical significance. However, there might be no statistically significant survival benefit from radiotherapy with concurrent temozolomide (n = 33 , 73.3%, log-rank p = 0.99) or adjuvant temozolomide (n = 32 , 71.1%, log-rank p = 0.74). Conclusion. This single-center retrospective study with a limited cohort size has demonstrated the treatment of gross total resection and low expression of Ki-67 which are beneficial for patients with GSM, while radiotherapy or temozolomide is not. [ABSTRACT FROM AUTHOR]

Background: Ferroptosis is a recently discovered type of regulated necrosis and glutathione peroxidase 4 (GPX4) has been recognized as a key enzyme that protects against ferroptosis. However, the role of platelet GPX4 in systemic lupus erythematosus (SLE) has not been explored. In this study, GPX4 levels in platelets were measured and the correlation with clinical features were analyzed. Methods: Platelet GPX4 protein expression was detected by Western blot and immunofluorescence in 37 SLE patients and 23 healthy controls. Clinical data were recorded at time points of blood sampling. Platelet activation was analyzed by flow cytometry, LDH release by LDH release assay and plasma oxidized DNA levels by a general 8-OHdG ELISA kit. Results: Patients with SLE had significantly decreased expression of platelet GPX4 and increased percentage of platelet activation as compared with healthy controls. Furthermore, levels of platelet GPX4 were negatively correlated with SLEDAI-2K score, 24-hour urine protein and oxidized DNA. Low GPX4 expression were associated with skin and joint involvements of SLE patients. Interestingly, deferoxamine (DFO), a ferroptosis inhibitor, could protect SLE platelets from death. Conclusions: These findings confirmed that downregulated GPX4 protein in platelets of SLE patients negatively correlated with plasma oxidized DNA, SLE disease activity and 24-hour urine protein, suggesting the potential role of platelet ferroptosis in oxidized DNA release and the pathogenesis of SLE. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to investigate the predictive models based on O-[2-(18F)fluoroethyl]-l-tyrosine positron emission tomography/computed tomography (18F-FET PET/CT) radiomics features for the isocitrate dehydrogenase (IDH) genotype identification in adult gliomas. Methods: Fifty-eight consecutive pathologically confirmed adult glioma patients with pretreatment 18F-FET PET/CT were retrospectively enrolled. One hundred and five radiomics features were extracted for analysis in each modality. Three independent radiomics models (PET-Rad Model, CT-Rad Model and PET/CT-Rad Model) predicting IDH mutation status were generated using the least absolute shrinkage and selection operator (LASSO) regression analysis based on machine learning algorithms. All-subsets regression and cross validation were applied for the filter and calibration of the predictive radiomics models. Besides, semi-quantitative parameters including maximum, peak and mean tumor to background ratio (TBRmax, TBRpeak, TBRmean), standard deviation of glioma lesion standardized uptake value (SUVSD), metabolic tumor volume (MTV) and total lesion tracer uptake (TLU) were obtained and filtered for the simple model construction with clinical feature of brain midline involvement status. The area under the receiver operating characteristic curve (AUC) was applied for the evaluation of the predictive models. Results: The AUC of the simple predictive model consists of semi-quantitative parameter SUVSD and dichotomized brain midline involvement status was 0.786 (95% CI 0.659-0.883). The AUC of PET-Rad Model building with three 18F-FET PET radiomics parameters was 0.812 (95% CI 0.688-0.902). The AUC of CT-Rad Model building with three co-registered CT radiomics parameters was 0.883 (95% CI 0.771-0.952). While the AUC of the combined 18F-FET PET/CT-Rad Model building with three CT and one PET radiomics features was 0.912 (95% CI 0.808-0.970). DeLong test results indicated the PET/CT-Rad Model outperformed the PET-Rad Model (p = 0.048) and simple predictive model (p = 0.034). Further combination of the PET/CT-Rad Model with the clinical feature of dichotomized tumor location status could slightly enhance the AUC to 0.917 (95% CI 0.814-0.973). Conclusion: The predictive model combining 18F-FET PET and integrated CT radiomics features could significantly enhance and well balance the non-invasive IDH genotype prediction in untreated gliomas, which is important in clinical decision making for personalized treatment. [ABSTRACT FROM AUTHOR]

Aim: To investigate the impact of biological subtypes in locoregional recurrence in Chinese breast cancer patients receiving postmastectomy radiotherapy (PMRT). Methods and Materials: About 583 patients who received postmastectomy radiation between 2010 and 2012 were retrospectively analyzed. According to immunohistochemical staining profile, patients were classified into: Luminal A‐like, Luminal B‐like, HER2‐positive, and triple‐negative breast cancer (TNBC). Local and regional recurrence (LRR) cumulative incidences were calculated by competing risks methodology and the power of prognostic factors was examined by Gray's test and the test of Fine and Gray. Results: The median follow‐up was 70.9 months. About 34 LRR events occurred. For Luminal A, Luminal B, HER2‐positive, and TNBC patients, the 5‐year LRR cumulative incidence rates were 1.57%, 4.09%, 10.74%, and 10.28%. Compared with Luminal A, HER2‐positive subtype and TNBC had a significant increased risk of LRR (HR was 5.034 and 5.188, respectively). In univariate analysis, predictive factors for higher LRR were HER2‐positive subtype (HR = 4.43, P <.05), TNBC (HR = 4.70, P <.05), and pN3 (HR = 5.83, P <.05). In the multivariate model, HER2‐positive subtype (HR = 5.034, P <.05), TNBC (HR = 5.188, P <.05), and pN3 (HR = 9.607, P <.01) were independent predictors of LRR. LRR without trastuzumab was similar to that of TNBC (without vs TNBC, 17.88% vs 10.28%, P >.05) in HER2‐positive subtype patients, while LRR with trastuzumab was approximate to Luminal A (with vs Luminal A, P >.05). Additionally, endocrine therapy also significantly reduced LRR incidence in the luminal subtype cohort (without vs with therapy, 6.25% vs 2.89%, HR = 0.365, P <.1). Conclusions: Biological subtype was a prognostic factor of LRR in the PMRT setting among Chinese breast cancer patients. [ABSTRACT FROM AUTHOR]

Background: High prevalence of erectile dysfunction (ED) has been observed in patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). However, whether or not CP/CPPS is a risk factor of ED remains unknown and controversial. Therefore, we conducted this systematic review and meta-analysis to evaluate the relationship between CP/CPPS and ED. Methods: PubMed, Embase, Web of Science, and The Cochrane Library were searched up to November 11, 2014 to identify studies reporting the association between CP/CPPS and ED. Case–control, cohort and cross-sectional studies were included. Quality of the included studies was assessed. The odds ratio of ED and the mean difference of five-item International Index of Erectile Function (IIEF-5) score were pooled using a random effects model. Subgroup analysis and sensitivity analyses were performed. Results: Three cross-sectional studies, two case–control studies, and four retrospective studies with 31,956 participants were included to calculate the pooled odds ratio of ED, and two studies with 1499 participants were included to calculate the pooled mean difference of IIEF-5 scores. A strong correlation was found between CP/CPPS and ED (pooled odds ratio: 3.02, 95% CI: 2.18–4.17, P < 0.01), with heterogeneity across studies (I2 = 65%; P < 0.01). A significant decrease in the IIFE-5 score was observed in the CP/CPPS group (pooled mean difference: −4.54, 95% CI: −5.11–−3.98; P < 0.01). Conclusion: Our study indicates that patients with CP/CPPS have an increased risk of suffering from ED. Assessment of erectile function is necessary for the therapy of patients with CP/CPPS. Further evidence is necessary to confirm the relationship between CP/CPPS and ED. [ABSTRACT FROM AUTHOR]

Background Differentiating between malignant and benign biliary lesions is critical in clinical practice but is difficult. Objective To systematically evaluate the diagnostic performance of single-operator peroral cholangioscopy on indeterminate biliary lesions. Design A systematic review and meta-analysis. Patients Patients with indeterminate biliary lesions or equivocal ERCP findings. Main Outcome Measurements The diagnostic performance of single-operator peroral cholangioscopy on indeterminate biliary lesions. The area under the summary receiver-operating characteristic curve was used as the main indicator for the overall diagnostic performance of single-operator peroral cholangioscopy visual impression (VI) and SpyBite biopsy (SB). The sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio were also synthesized. Results A total of 8 studies met the inclusion criteria, involving 335 patients who had data on VI and 337 who had data on SB. The area under the curve values on the summary receiver-operating characteristic curve of single-operator peroral cholangioscopy VI and SB were 0.94 (95% confidence interval [CI], 0.92-0.96) and 0.93 (95% CI, 0.90-0.95) respectively. The combined sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio were 90% (95% CI, 73%-97%), 87% (95% CI, 76%-94%), 7.1 (95% CI, 3.8-13.3), 0.12 (95% CI, 0.04-0.33) for VI and 69% (95% CI, 57%-79%), 98% (95% CI, 92%-99%), 30.1 (95% CI, 8.5-106.9), and 0.32 (95% CI, 0.23-0.44) for SB, respectively. Limitations Small number of included studies; comparison with ERCP could not be made. Conclusion Single-operator peroral cholangioscopy is a good tool for differentiating malignant and benign biliary lesions. VI is useful for detecting malignant lesion, whereas SB is better at confirming a malignant diagnosis, but VI is not perfect in excluding biliary cancer, nor is SB, and their negative results should be interpreted with caution. [ABSTRACT FROM AUTHOR]

This updated meta-analysis investigated whether operative treatment is superior to nonoperative treatment in complex proximal humeral fractures. The authors searched the Cochrane Central Register of Controlled Trials, PubMed, and EMBASE. Randomized controlled trials that evaluated operative vs nonoperative treatment for exclusively 3- or 4-part proximal humeral fractures were considered. Six studies with a total of 287 patients who had proximal humeral fractures were included. According to the meta-analysis, no statistically significant differences were found between operative and nonoperative treatment in Constant-Murley shoulder scores (Constant scores); Disabilities of the Arm, Shoulder, and Hand scores; total complication events; mortality; infection; nonunion; avascular necrosis; osteoarthritis; redisplacement of fractures; or dislocation or resorption of tuberosity. For health-related quality of life, EuroQol-5D (EQ-5D) favored operative treatment, but 15D scores showed no significant difference. Compared with nonoperative treatment, open reduction and internal fixation required significantly more additional surgeries (risk ratio, 6.50; 95% confidence interval, 1.54-27.50; P=.01), and more penetrations into joint space occurred (risk ratio, 9.56; 95% confidence interval, 2.27-40.13; P=.002). The limited evidence suggests that no convincing findings support the use of either open reduction and internal fixation or hemiarthroplasty for the treatment of complex proximal humeral fractures. The findings of the current study should be interpreted cautiously because of the modest sample size and the short follow-up period. [ABSTRACT FROM AUTHOR]

Background: Acute coronary syndrome and atrial fibrillation are common cardiovascular diseases in elderly individuals. Patients with comorbidities face increased risks of bleeding and ischemia; however, there is a lack of prognostic models for quantifying these risks in this special population., Methods and Results: In this retrospective cohort study, 1851 patients (≥65 years old) with acute coronary syndrome and atrial fibrillation from 2 hospitals in China were included in the development cohort (1252 individuals) and 2 external validation cohorts (284 and 315 individuals). During 1-year follow-up, 96 Bleeding Academic Research Consortium type 3 or 5 bleeding events and 245 thromboembolic events were observed. In the development cohort, the concordance indexes for bleeding at 3, 6, and 12 mo ranged from 0.737 to 0.845 and for ischemia ranged from 0.723 to 0.777. The calibration curve and decision curve analysis indicated adequate calibration and clinical practicability. The concordance indexes varied from 0.679 to 0.809 in the validation cohorts. Subgroup analyses focusing on anticoagulant drugs and antithrombotic therapy were conducted, revealing similar discrimination and calibration. Kaplan-Meier curves demonstrated significant differences (log-rank P <0.001). Additionally, the models outperformed conventional models in concordance indexes, integrated discrimination improvement, and net reclassification improvement., Conclusions: Our study provides 2 robust prognostic models with easily available clinical factors for predicting bleeding and ischemia in elderly patients with acute coronary syndrome and atrial fibrillation. Furthermore, we provide online calculators to facilitate individualized risk evaluation and clinical decision-making., Registration: URL: www.chictr.org.cn/. Unique Identifier: ChiCTR2200067185.

Objectives: The objective was to utilize a smartwatch sphygmomanometer to predict new-onset hypertension within a short-term follow-up among individuals with high-normal blood pressure (HNBP)., Methods: This study consisted of 3180 participants in the training set and 1000 participants in the validation set. Participants underwent both ambulatory blood pressure monitoring (ABPM) and home blood pressure monitoring (HBPM) using a smartwatch sphygmomanometer. Multivariable Cox regressions were used to analyze cumulative events. A nomogram was constructed to predict new-onset hypertension. Discrimination and calibration were assessed using the C-index and calibration curve, respectively., Results: Among the 3180 individuals with HNBP in the training set, 693 (21.8%) developed new-onset hypertension within a 6-month period. The nomogram for predicting new-onset hypertension had a C-index of 0.854 (95% CI, 0.843-0.867). The calibration curve demonstrated good agreement between the nomogram's predicted probabilities and actual observations for short-term new-onset hypertension. In the validate dataset, during the 6-month follow-up, the nomogram had a good C-index of 0.917 (95% CI, 0.904-0.930) and a good calibration curve. As the score increased, the risk of new-onset hypertension significantly increased, with an HR of 8.415 (95% CI: 5.153-13.744, p = .000) for the middle-score vs. low-score groups and 86.824 (95% CI: 55.071-136.885, p  = .000) for the high-score vs. low-score group., Conclusions: This study provides evidence for the use of smartwatch sphygmomanometer to monitor blood pressure in individuals at high risk of developing new-onset hypertension in the near future., Trial Registration: ChiCTR2200057354.

Introduction: Patients with myasthenia gravis (MG) are prone to the development of pneumonia due to the long-term immunotherapies they receive and a tendency for aspiration. Pneumonia remains a risk factor for MG worsening and is the most prevalent cause of mortality in MG patients. Classification of the pathogens involved and exploration of the risk factors for mechanical ventilation (MV) could aid in improving clinical outcomes., Methods: Between January 2013 and October 2022, we performed an inpatient database review for MG patients with pneumonia concurrence in a tertiary research center specializing in neuromuscular disorders. The clinical and microbiological characteristics of 116 MG patients with pneumonia were retrospectively analyzed., Results: In our cohort, 90.32% (112/124) of organisms were bacteria and 42.86% (48/112) of pathogenic bacteria were carbapenem-resistant. A high abundance of Epstein-Barr virus (EBV) was detected using next-generation sequencing (NGS) in 12 patients, while cytomegalovirus (CMV) was detected in 8 patients. Non-fermentative Gram-negative bacilli were the most prevalent microorganisms, in which ampicillin, sulfamethoxazole-trimethoprim (SMZ-TMP), piperacillin, cefoperazone, ceftazidime, and cefepime may have an anti-infectious effect. Moreover, peripheral lymphocyte percentage [odds ratio (OR) 0.88, 95% CI 0.75-0.96, p = 0.02] and serum globulin (OR 1.16, 95% CI 1.02-1.35, p = 0.03) were significantly associated with the risk of MV demand., Discussion: Our identification of the microbial etiology of pneumonia in MG patients may provide future perspectives on accurate antibiotic options and enable early interventions when risk factors are present., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Su, Jin, Jiao, Yan, Song, Xi, Zhao, Zhou, Zheng and Luo.)

Background: Neurosurgery is the standard of care for resectable solitary brain metastasis (BM) from non-small cell lung cancer (NSCLC), but still with a poor outcome. Postoperative whole-brain radiotherapy (WBRT) was reported to reduce local recurrence, whether it could prolong survival was uncertain. In this study, we attempted to evaluate WBRT and other prognostic for overall survival (OS) in these patients., Methods: In this retrospective study, NSCLC patients with a solitary BM and controlled primary tumor who underwent neurosurgical resection were selected from the medical records database between January 2014 and December 2018. Clinical data, disease control/progression results and survival outcomes were obtained from the medical records, regular outpatient follow-up and telephone interviews. Univariable and multivariable Cox analyses of potential prognostic factors including patients' characteristics, BM features, tissue-based parameters and postoperative treatments were conducted. OS was illustrated using Kaplan-Meier curves, and group differences were assessed using the log-rank test. The subgroup analysis compared each variable between the WBRT group and the untreated control by the hazard ratio and its 95% confidence interval (CI)., Results: A total of 94 patients were included, with a median OS of 812 days. Univariable analysis showed that postoperative WBRT and targeted therapy were associated with OS. Multivariable analysis demonstrated that postoperative WBRT [P<0.001, hazard ratio (HR) 0.357], chemotherapy (P=0.008, HR 0.512), targeted therapy (P<0.001, HR 0.265), and smaller tumor size (P=0.018, HR 0.553) were independent prognostic factors for prolonged OS. However, tissue-based parameters (Ki67 tumor cell proliferation index, epidermal growth factor receptor, and checkpoint levels) were identified as statistically insignificant factors. In the subgroup analysis, the beneficial effect of WBRT was only observed in patients that did not receive systematic treatments., Conclusions: Postoperative WBRT and systematic treatments after solitary BM resection improve the prognosis of NSCLC patients with a controlled primary tumor. Postoperative WBRT could be considered, especially for those who not receive systematic chemotherapy or targeted therapy treatments, as they might be more likely to benefit from it., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-22-1279/coif). The authors have no conflicts of interest to declare., (2022 Journal of Thoracic Disease. All rights reserved.)

Background and Objectives: Myasthenia gravis (MG) is a T cell-driven, autoantibody-mediated disorder affecting transmission in neuromuscular junctions. The associations between the peripheral T cells and MG have been extensively studied. However, they are mainly of observational nature, thus limiting our understanding of the effect of inflammatory biomarkers on MG risk. With large data sets now available, we used Mendelian randomization (MR) analysis to investigate whether the biomarkers on T cells are causally associated with MG and further validate the relationships., Methods: We performed a two-sample MR analysis using genetic data from one genome-wide association study (GWAS) for 210 extensive T-cell traits in 3,757 general population individuals and the largest GWAS for MG currently available (1,873 patients versus 36,370 age/gender-matched controls) from US and Italy. Then the biomarkers of interest were validated separately in two GWASs for MG in FIN biobank (232 patients versus 217,056 controls) and UK biobank (152 patients versus 386,631 controls)., Results: In the first analysis, three T-cell traits were identified to be causally protective for MG risk: 1) CD8 on terminally differentiated CD8 + T cells (OR [95% CI] = 0.71 [0.59, 0.86], P = 5.62e-04, adjusted P =2.81e-02); 2) CD4 + regulatory T proportion in T cells (OR [95% CI] = 0.44 [0.26, 0.72], P = 1.30e-03, adjusted P =2.81e-02); 3) HVEM expression on total T cells (OR [95% CI] = 0.67 [0.52, 0.86], P = 1.61e-03, adjusted P =2.81e-02) and other eight T-cell subtypes (e.g., naïve CD4+ T cells). In particular, HVEM is a novel immune checkpoint on T cells that has never been linked to MG before. The SNPs on the TNFRSF14 per se further support a more direct link between the HVEM and MG. The validation analysis replicated these results in both FIN and UK biobanks. Both datasets showed a concordant protective trend supporting the findings, albeit not significant., Conclusion: This study highlighted the role of HVEM on T cells as a novel molecular-modified factor for MG risk and validated the causality between T cells and MG. These findings may advance our understanding of MG's immunopathology and facilitate the future development of predictive disease-relevant biomarkers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhong, Jiao, Huan, Zhao, Su, Goh, Zheng, Zhou, Luo and Zhao.)

Purpose: We aimed to investigate the predictive models based on O-[2-( 18 F)fluoroethyl]-l-tyrosine positron emission tomography/computed tomography ( 18 F-FET PET/CT) radiomics features for the isocitrate dehydrogenase (IDH) genotype identification in adult gliomas., Methods: Fifty-eight consecutive pathologically confirmed adult glioma patients with pretreatment 18 F-FET PET/CT were retrospectively enrolled. One hundred and five radiomics features were extracted for analysis in each modality. Three independent radiomics models (PET-Rad Model, CT-Rad Model and PET/CT-Rad Model) predicting IDH mutation status were generated using the least absolute shrinkage and selection operator (LASSO) regression analysis based on machine learning algorithms. All-subsets regression and cross validation were applied for the filter and calibration of the predictive radiomics models. Besides, semi-quantitative parameters including maximum, peak and mean tumor to background ratio (TBRmax, TBRpeak, TBRmean), standard deviation of glioma lesion standardized uptake value (SUV SD ), metabolic tumor volume (MTV) and total lesion tracer uptake (TLU) were obtained and filtered for the simple model construction with clinical feature of brain midline involvement status. The area under the receiver operating characteristic curve (AUC) was applied for the evaluation of the predictive models., Results: The AUC of the simple predictive model consists of semi-quantitative parameter SUV SD and dichotomized brain midline involvement status was 0.786 (95% CI 0.659-0.883). The AUC of PET-Rad Model building with three 18 F-FET PET radiomics parameters was 0.812 (95% CI 0.688-0.902). The AUC of CT-Rad Model building with three co-registered CT radiomics parameters was 0.883 (95% CI 0.771-0.952). While the AUC of the combined 18 F-FET PET/CT-Rad Model building with three CT and one PET radiomics features was 0.912 (95% CI 0.808-0.970). DeLong test results indicated the PET/CT-Rad Model outperformed the PET-Rad Model ( p = 0.048) and simple predictive model ( p = 0.034). Further combination of the PET/CT-Rad Model with the clinical feature of dichotomized tumor location status could slightly enhance the AUC to 0.917 (95% CI 0.814-0.973)., Conclusion: The predictive model combining 18 F-FET PET and integrated CT radiomics features could significantly enhance and well balance the non-invasive IDH genotype prediction in untreated gliomas, which is important in clinical decision making for personalized treatment., Competing Interests: Authors YL and YD were employed by Jinan Guoke Medical Engineering Technology Development Co., LTD. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhou, Huang, Wen, Li, Zhu, Liu, Dai, Guan, Zhou and Hua.)

Osteoporosis is one of the most common diseases affecting bone metabolism. Nitric oxide (NO), an endogenous gas molecule involved in osteogenesis, can effectively promote the proliferation and differentiation of osteoblasts. Although exogenous NO can reverse osteoporosis to a certain extent, the transitory half-life and short diffusion radius of NO severely limit its application. In this work, a gas generation nanoplatform of NO with bone targeting property (UCPA) is developed based on the upconversion nanoparticles (UCNPs) that can convert 808 nm near-infrared (NIR) light into UV/blue light, and further stimulate the NO donor (BNN) to release NO. With an adjustment of the output power of the 808 nm NIR, the amount of released NO can be precisely controlled. Both in vitro and in vivo experiments demonstrate the favorable affinity of UCPA to bone due to the modification of alendronate; thus, it can directly release NO in bone and reverse osteoporosis. In addition, the cellular uptake of nanocomposites and intracellular NO release can be observed in preosteoblasts, thereby promoting their differentiation efficiently.

Background: To investigate the differences in treatment effect sizes between progression-free survival (PFS) and overall survival (OS) in advanced non-small cell lung cancer (NSCLC) treated with programmed cell death 1 (PD-1) and its ligand (PD-L1) blockade-based treatments., Methods: The differences in treatment effect sizes between PFS and OS were assessed by using a ratio of hazard ratio (rHR): the HR for PFS to that for OS. A random effects meta-analysis across trials was conducted to generate the combined rHR. We also evaluated the feasibility of adopting PFS as the surrogate of OS by using Spearman correlation coefficient ( R ) between logHR PFS and logHR OS ., Results: A total of 27 randomized controlled trials (RCTs) with 15,590 patients were included. Treatment effect sizes were comparable, on average, for OS than for PFS (pooled rHR, 0.98; 95% CI, 0.91 to 1.08). Subgroup analysis revealed that treatment effect sizes were greater for OS than for PFS for trials with immunotherapy as second or above line treatment (rHR, 1.17; 95% CI, 1.06 to 1.29), while the differences were greater for PFS than for OS for trials with immunotherapy as first-line setting (rHR, 0.91; 95% CI, 0.84 to 0.99; P interaction <0.01). The coefficient of determination was 40% and R was 0.63 between logHR PFS and logHR OS . Subgroup analysis showed that coefficient of determination and R were 62% and 0.79 in trials with immunotherapy as first-line setting, 22% and 0.47 in trials with immunotherapy as second or above line treatment, respectively., Discussion: Treatment effect sizes between PFS and OS were roughly consistent in trials with different anti-PD-(L)1 inhibitor-based therapies. PFS could be a potential alternative endpoint for OS in trials with immunotherapy as first-line setting, but PFS should be cautiously interpreted without OS data for trials with immunotherapy as second or above line treatment., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tlcr-21-199). CZ serves as an Editor-in-Chief of Translational Lung Cancer Research from Aug 2020 to Jul 2022. TJ serves as an unpaid editorial board member of Translational Lung Cancer Research from Feb 2018 to Jan 2021. The other authors have no conflicts of interest to declare., (2021 Translational Lung Cancer Research. All rights reserved.)

Background: The present study aimed to explore the efficacy of easily obtained intratumoral heterogeneous parameters, other than regular semi-quantitative parameters, based on static O-(2-[18F]fluoroethyl)-l-tyrosine ( 18 F-FET) positron emission tomography (PET) imaging in glioma grade and isocitrate dehydrogenase ( IDH ) gene 1 mutation prediction., Methods: Fifty-eight adult patients with untreated glioma (grades II-IV) who underwent preoperative 18 F-FET PET/computed tomography (CT) imaging were enrolled in the present study. Eight semi-automatically obtained static PET imaging parameters after lesion delineation were chosen for analysis. These were: maximal tumor-to-background ratio (TBRmax), peak tumor-to-background ratio (TBRpeak), mean tumor-to-background ratio (TBRmean), coefficient of variation (COV), heterogeneity index (HI), the standard deviation of lesion standardized uptake value (SUVsd), metabolic tumor volume (MTV), and total lesion tracer standardized uptake (TLU). Pathological and immunohistochemical results were used as a reference. The receiver-operating characteristic analysis was used to investigate the predictive efficacy of these parameters in glioma grade and IDH1 mutation status., Results: TLU [area under the curve (AUC): 0.841, P<0.0001], TBRpeak (AUC: 0.832, P<0.0001), and HI (AUC: 0.826, P<0.0001) had the top 3 single-parameter predictive performance between grade II or III and grade IV glioma patients. Combinations of TBRmax, SUVsd, and TBRmean (AUC: 0.850, P<0.0001); HI, SUVsd, and MTV (AUC: 0.848, P<0.0001); and HI, SUVsd, and TLU (AUC: 0.848, P<0.0001) had the top 3 multiple-parameter predictive performance. SUVsd (AUC: 0.710, P=0.0028), TLU (AUC: 0.698, P=0.0074), and HI (AUC: 0.676, P=0.0159) had the top 3 single-parameter predictive performance in the IDH1 genotype. Combinations of TBRmax, SUVsd, and TBRmean (AUC: 0.821, P<0.0001); SUVsd and TBRmean (AUC: 0.804, P<0.0001); and SUVsd, HI, and TBRmean (AUC: 0.799, P<0.0001) had the top 3 multiple-parameter predictive performance., Conclusions: These easily obtained and highly repetitive heterogeneous parameters based on static 18 F-FET PET/CT imaging can non-invasively predict glioma grade and IDH1 mutation, crucial in treatment planning, and prognostic evaluation., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/qims-20-723). The authors have no conflicts of interest to declare., (2021 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Purpose: We developed a 11 C-Methionine positron emission tomography/computed tomography ( 11 C-MET PET/CT)-based nomogram model that uses easy-accessible imaging and clinical features to achieve reliable non-invasive isocitrate dehydrogenase (IDH)-mutant prediction with strong clinical translational capability. Methods: One hundred and ten patients with pathologically proven glioma who underwent pretreatment 11 C-MET PET/CT were retrospectively reviewed. IDH genotype was determined by IDH1 R132H immunohistochemistry staining. Maximum, mean and peak tumor-to-normal brain tissue (TNRmax, TNRmean, TNRpeak), metabolic tumor volume (MTV), total lesion methionine uptake (TLMU), and standard deviation of SUV (SUV SD ) of the lesions on MET PET images were obtained via a dedicated workstation (Siemens. syngo.via). Univariate and multivariate logistic regression models were used to identify the predictive factors for IDH mutation. Nomogram and calibration plots were further performed. Results: In the entire population, TNRmean, TNRmax, TNRpeak, and SUV SD of IDH-mutant glioma patients were significantly lower than these values of IDH wildtype. Receiver operating characteristic (ROC) analysis suggested SUV SD had the best performance for IDH-mutant discrimination (AUC = 0.731, cut-off ≤ 0.29, p < 0.001). All pairs of the 11 C-MET PET metrics showed linear associations by Pearson correlation coefficients between 0.228 and 0.986. Multivariate analyses demonstrated that SUV SD (>0.29 vs. ≤ 0.29 OR: 0.053, p = 0.010), dichotomized brain midline structure involvement (no vs. yes OR: 26.52, p = 0.000) and age (≤ 45 vs. >45 years OR: 3.23, p = 0.023), were associated with a higher incidence of IDH mutation. The nomogram modeling showed good discrimination, with a C-statistics of 0.866 (95% CI: 0.796-0.937) and was well-calibrated. Conclusions: 11 C-Methionine PET/CT imaging features (SUV SD and the involvement of brain midline structure) can be conveniently used to facilitate the pre-operative prediction of IDH genotype. The nomogram model based on 11 C-Methionine PET/CT and clinical age features might be clinically useful in non-invasive IDH mutation status prediction for untreated glioma patients., (Copyright © 2020 Zhou, Zhou, Wen, Xie, Zhu, Zhang, Xiao, Chen, Li, Guan and Hua.)

Non-small cell lung cancer (NSCLC) is the most common cancer and the leading cause of cancer-related deaths worldwide. Age at diagnosis of advanced NSCLC is much older, but studies describing the practice patterns for octogenarians with distant metastasis NSCLC are limited. A retrospective, population-based study using national representative data from the Surveillance, Epidemiology, and End Results (SEER) program was conducted to evaluate 34 882 NSCLC patients with extrathoracic metastases from 2010 to 2013. Patients were classified into three groups (older group: ≥80 yrs, middle-aged group: 60-79 yrs, and younger group: ≤59 yrs). The role of different age at diagnosis of NSCLC in metastasis patterns was investigated, and survival of different age groups of metastatic NSCLC was assessed. The analysis revealed that older patients were more likely to only have bone or liver metastasis (p< 0.001), but less likely to have brain only metastasis (p<0.001) and multiple metastatic sites (p< 0.001) than other two groups. Age at diagnosis was an independent risk factor for different metastasis types. Older group had the worst overall survival (p<0.001) and cancer-specific survival (p<0.001). Furthermore, older age patients with only bone metastasis had the best cancer specific survival (p<0.05) while younger patients with only brain metastasis had the best prognosis (p<0.001). Over 60% octogenarians with metastatic NSCLC did not receive anti-cancer therapy and had the highest rate of cancer deaths among all patients. Our results may help clinicians make positive decisions regarding personalized treatment of metastatic NSCLC in the elderly., Competing Interests: Conflict of interest The authors declare that they have no conflict of interest., (Copyright: © 2019 Gu et al.)

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. During the recent years, external-beam radiation therapy (EBRT) has been safely and effectively employed for the management of HCC. We overviewed the current evidence regarding the efficacy and safety of EBRT for HCC according to the different target population. PubMed database was searched for identifying English-language full-text articles regarding EBRT for the treatment of HCC. Search items were "hepatocellular carcinoma AND radiation therapy". Until now, preliminary evidence has suggested the following role of EBRT for HCC. 1) EBRT, especially stereotactic body radiation therapy, is an emerging choice of therapy for small HCC. 2) EBRT combined with non-surgical treatment can achieve an excellent intrahepatic tumor control and a potential survival benefit for huge HCC. 3)Adjunctive EBRT may improve the efficacy of transarterial chemoembolization for HCC with portal vein tumor thrombosis. 4) EBRT can relieve the pain and improve the quality of life for patients with extrahepatic metastases. 5) EBRT may be a bridge to liver transplantation by minimizing the tumor progression. 6) Adjunctive EBRT may reduce the tumor recurrence and improve the survival after resection. In summary, EBRT is a promising choice of treatment of HCC. However, more high-quality evidence is needed to further establish the status of EBRT for the management of HCC.

BACKGROUND This study aimed to evaluate differences in the radiosensitivities of triple-negative breast cancer (TNBC) and luminal-type breast cancer cells and to investigate the effects of estrogen receptor (ER) expression on the biological behaviors of the cells. MATERIAL AND METHODS Colony-forming assays were performed to detect differences in radiosensitivities in breast cancer cell lines. Gene transfection technology was used to introduce the expression of ERα in TNBC cells to compare the difference in radiosensitivity between the TNBC cells and ERα transfected cells. CCK-8 assays were used to observe changes in the proliferation of TNBC cells after ERα transfection. Immunofluorescence was used to detect the number of γH2AX foci in nuclei. Flow cytometry was used to detect changes in cell cycle distribution and apoptosis. Western blotting was used to detect changes in autophagy-associated proteins. RESULTS The radioresistance of the TNBC cell line MDA-MB-231 (231 cells) was greater than that of ERα-positive luminal-type breast cancer cell line MCF-7. Moreover, 231 cell proliferation and radioresistance decreased after ERα transfection. Interestingly, ERα-transfected 231 cells showed increased double-stranded breaks and delayed repair compared with 231 cells, and ERα-transfected 231 cells showed increased G2/M phase arrest and apoptosis after irradiation compared with those in 231 cells. ERα transfection in 231 cells reduced autophagy-related protein expression, suggesting that autophagy activity decreased in 231 ER-positive cells after irradiation. CONCLUSIONS TNBC cells were more resistant to radiation than luminal-type breast cancer cells. ERα expression may have major roles in modulating breast cancer cell radiosensitivity.

Growing evidence has demonstrated that human epidermal growth factor receptor 2 (HER2) is involved in the radiation response to breast cancer. However, the underlying mechanism remains elusive. Therefore, we investigated if HER2 overexpression is associated with radiosensitivity of breast cancer. We constructed breast cancer cell lines differing in HER2 expression by transducing HER2 cDNA or short hairpin RNA against HER2. We then assessed the radiosensitivity and investigated the potential mechanism by using cell proliferation assay, cell adhesion assays, anoikis assays, colony formation assays, and western blotting analyses. We found that HER2 introduction in breast cancer cell lines MCF-7 (low HER2 expression) and MDA-MB-231 (HER2 is not expressed) promoted cell proliferation and invasion and enhanced cell adhesion and resistance to anoikis. Moreover, HER2 reduced radiosensitivity in these two cells compared with the corresponding control. The opposite results were observed when HER2 was silenced in breast cancer cell lines ZR-7530 and SK-BR-3 (both cells with high expression of HER2) using HER2 shRNA. In addition, animal experiment results showed HER2 could enhance the radioresistance of xenograft tumors. Further studies showed HER2 promoted the phosphorylation of focal adhesion kinase (Fak) and thereby up-regulated the expression of proteins associated with the epithelial-to-mesenchymal transition such as Claudin-1, ZO-1, and ZEB-1. The inhibition of Fak activity using the Fak inhibitor (PF-562281) restored the radiosensitivity in HER2-overexpressing cells. In conclusion, HER2 reduces the radiosensitivity of breast cancer by activating Fak in vitro and in vivo. Fak might be a potential target for the radiosensitization of HER2-overexpressed breast cancer., Competing Interests: The authors declare no conflicts of interest.

We conducted a study to evaluate the quality of guidelines for squamous cell carcinoma of the head and neck (SCCHN) with the exception of nasopharyngeal cancer. Electronic searches were conducted of the U.S. National Guideline Clearinghouse, the Canadian Medical Association Infobase, the Guidelines International Network, the Scottish Intercollegiate Guidelines Network, the China Biology Medicine disc, PubMed, and Embase. Two independent reviewers assessed the eligible guidelines using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument. The degree of agreement among these sources was evaluated by using the intraclass correlation coefficient (ICC). A total of 514 articles were found to be clinical-guideline-related, and 49 guidelines were included in our analysis. Scores were assigned for each of the AGREE II domains: scope and purpose (mean: 71.63% ± 2.80; median: 75%; ICC: 0.76), stakeholder involvement (mean: 43.37% ± 2.96; median: 50%; ICC: 0.93), rigor of development (mean: 45.63% ± 3.84; median: 42%; ICC: 0.83), clarity of presentation (mean: 68.08% ± 2.53; median: 72%; ICC: 0.85), applicability (mean: 32.41% ± 3.03; median: 29%; ICC: 0.92), and editorial independence (mean: 42.55% ± 4.57; median: 42%; ICC: 0.95). We considered a domain score of greater than 60% to represent an acceptable level of quality. We conclude that, overall, the quality of SCCHN guidelines is moderate in relation to international averages. Greater efforts are needed to provide high-quality guidelines that serve as a useful and reliable tool for clinical decision making in this field.

Background: There is ongoing debate about the efficacy of placebos in the treatment of mental disorders. In randomized control trials (RCTs) about the treatment of generalized anxiety disorder, the administration of a psychological placebo or placement on a waiting list are the two most common control conditions. But there has never been a systematic comparison of the clinical effect of these different strategies., Aim: Compare the change in symptom severity among individuals treated with cognitive behavioral therapy, provided a psychological placebo, or placed on a waiting list using data from RCTs on generalized anxiety disorder., Methods: The following databases were searched for RCTs on generalized anxiety disorder: PubMed, PsycInfo, EMBASE, The Cochrane Library, CNKI, Chongqing VIP, Wanfang, Chinese Biological Medical Literature Database, and Taiwan Electronic Periodical Services. Studies were selected based on pre-defined inclusion and exclusion criteria and the quality of each included study - based on the risk of bias and the level of evidence - was formally assessed. Meta-analysis was conducted using RevMan5.3 and network meta-analyses comparing the three groups were conducted using R., Results: Twelve studies with a combined sample size of 531 were included in the analysis. Compared to either control method (placebo or waiting list), cognitive behavioral therapy was more effective for generalized anxiety disorder. Provision of a psychological placebo was associated with a significantly greater reduction of symptoms than placement on a waiting list. Eight of the studies were classified as 'high risk of bias', and the overall level of evidence was classified as 'moderate', indicating that further research could change the overall results of the meta-analysis., Conclusions: RCTs about the treatment of generalized anxiety disorders are generally of moderate quality; they indicate the superiority of CBT but the results cannot, as yet, be considered robust. There is evidence of a non-negligible treatment effect of psychological placebos used as control conditions in research studies. This effect should be considered when designing and interpreting the results of randomized controlled trials about the effectiveness of psychotherapeutic interventions.