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Objective The study aimed to evaluate site‐specific recurrent patterns via competing risks analysis and hazard function to provide evidence for adjuvant treatment and follow‐up for early staged endometrial cancer (EC). Methods A total of 858 patients with International Federation of Gynecology and Obstetrics stage I–II EC who received adjuvant radiotherapy at our institution (2000–2017) were included. The radiotherapy modality comprised external beam radiotherapy (EBRT) with or without vaginal brachytherapy (VBT) or VBT alone. Competing risks analysis and hazard rate function were employed to evaluate the recurrence rate according to the ESMO–ESGO–ESTRO risk classification. Results The 5‐year overall survival rates of the low‐risk (LR), intermediate‐risk (IR), high–intermediate risk (HIR), and high‐risk (HR) groups were 96.1%, 95%, 93%, and 89.7%, respectively (p = 0.018). Sixty‐eight patients developed recurrence. The 5‐year incidence of distant recurrence was the highest in the HR group (14.87%), followed by the HIR (7.71%), IR (5.27%), and LR (1.26%) groups (Gray's test, p, The recurrence pattern of endometrial cancer is affected by risk groups and adjuvant treatment. The time‐varying competing risk analysis and hazard function modeling were established. The site‐specific recurrence patterns differed across the risk classification and adjuvant radiotherapy modality. More intense and targeted follow‐up schedules should be administrated to the high‐risk group.

Yuncan Zhou, Weiping Wang, Ke Hu, Fuquan Zhang Department of Radiation Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of ChinaCorrespondence: Ke Hu; Fuquan Zhang Email huk@pumch.cn; zhangfuquan3@sina.comPurpose: No consensus has been reached regarding the survival difference between cervical adenocarcinoma (ADC) and adenosquamous carcinoma (ASC) patients. The purpose of this study was to compare survival outcomes and prognostic factors between early-stage ADC and ASC patients.Patients and Methods: We retrospectively reviewed stage IB-IIA patients with ADC and ASC who underwent radical hysterectomy and postoperative radiotherapy between June 2012 and December 2017.Results: A total of 125 patients were enrolled in our study (97 with ADC and 28 with ASC). The median follow-up period was 53.4 months. Compared with ASC patients, patients with ADC tended to have a higher proportion of positive pelvic lymph nodes (7.1% and 26.8%, respectively; p = 0.028). The most common site of distant metastasis was the lung, followed by the intestine and colon. The 5-year overall survival (OS), disease-free survival (DFS), pelvic control, and distant control rates for ADC and ASC patients were 83.6% and 92.0% (p = 0.349), 77.5% and 87.7% (p = 0.279), 81.8% and 96.2% (p = 0.121), and 88.3% and 87.7% (p = 0.948), respectively. Parametrial invasion was a prognostic factor for OS. Lymphovascular space involvement was a prognostic factor for DFS.Conclusion: ADC patients were more likely to have positive pelvic lymph nodes than those with ASC. There was no significant difference in survival outcomes between patients with ADC and ASC.Keywords: cervical adenocarcinoma, adenosquamous carcinoma, survival outcomes, parametrial invasion, lymphovascular space involvement

To systematically investigate the effect of imaging features at different DCE-MRI phases to optimise a radiomics model based on DCE-MRI for the prediction of tumour-infiltrating lymphocyte (TIL) levels in breast cancer. This study retrospectively collected 133 patients with pathologically proven breast cancer, including 73 patients with low TIL levels and 60 patients with high TIL levels. The volumes of breast cancer lesions were manually delineated on T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), and each phase of DCE-MRI, followed by 6250 quantitative feature extractions. The least absolute shrinkage and selection operator (LASSO) method was used to select predictive feature sets for the classifiers. Four models were developed for predicting TILs: (1) single enhanced phase radiomics models; (2) fusion enhanced multi-phase radiomics models; (3) fusion multi-sequence radiomics models; and (4) a combined radiomics-based clinical model. Image features extracted from the delayed phase MRI, especially DCE_Phase 6 (DCE_P6), demonstrated dominant predictive performances over features from other phases. The fusion multi-sequence radiomics model and combined radiomics-based clinical model achieved the highest predictive performances with areas under the curve (AUCs) of 0.934 and 0.950, respectively; however, the differences were not statistically significant. The DCE-MRI radiomics model, especially image features extracted from the delayed phases, can help improve the performance in predicting TILs. The radiomics nomogram is effective in predicting TILs in breast cancer. • Radiomics features extracted from DCE-MRI, especially delayed phase images, help predict TIL levels in breast cancer. • We developed a nomogram based on MRI to predict TILs in breast cancer that achieved the highest AUC of 0.950.

Objective To explore the effect of age at diagnosis as a continuous variable on survival and treatment choice of patients with early-stage endometrial carcinoma (EC). Materials and methods We retrospectively analyzed data from patients with early-stage EC from January 1999 to December 2015 in multiple institutions in China. All patients received primary hysterectomy/bilateral salpingo-oophorectomy and adjuvant radiotherapy for EC confirmed pathology of stage I and II disease (FIGO 2009 staging). All patients were divided into low-risk, intermediate-risk, high-intermediate-risk and high-risk groups according to ESMO-ESGO-ESTRO risk classification. Results The median follow-up time was 57months, and the 5-year cancer-specific survival (CSS) was 95.7%. Age as a continuous variable was an independent prognostic factor for CSS. With an increase in age, the hazard ratio (HR) for CSS increases gradually. Other independent prognostic factors included myometrial invasion (MI), grade, and chemotherapy. In the stratified analysis of age, the HRs of age on CSS in patients >70y were 5.516, 5.015, 4.469, 4.618, 5.334, and 5.821 after adjusting for cancer characteristics, local treatment, chemotherapy and treatment-related late toxicity. In patients 66-70-year-old, the HRs were 2.509, 2.074, 2.101, 2.091, 2.157 and 1.621 after adjusting for the above covariates. In patients ≤65y, there was no significant difference in the HR of age on CSS after adjustment. Conclusion Age as a continuous variable is an independent prognostic factor and 65 year-old may be the best cut-off point for CSS in patients with early-stage EC in the Asian population. Quality of life should be given greater weight in the choice of therapeutic schedule for those patients >70 y.

Obstructive sleep apnea–hypopnea syndrome (OSAHS) is an independent risk factor for cardiovascular diseases, including hypertension. In our previous study, it was demonstrated that oral microbiota alteration in patients with OSAHS, particularly in the genera Aggregatibacter and Porphyromonas, may influence the development of hypertension. Continuous positive airway pressure (CPAP) is the main therapy for OSAHS and OSAHS-associated hypertension. However, the role of oral microbiota post CPAP treatment remains unknown. We conducted 16S rDNA pyrosequencing and bioinformatic analyses to compare the bacterial composition of oral specimens from patients with OSAHS before and after overnight CPAP treatment. This approach enabled a relatively comprehensive description of oral microbiota, with decreases in Gemella and increases in Staphylococcus, f_Lachnospiraceae, Parabacteroides, and f_Ruminococcaceae after CPAP treatment. Alteration of oral microbiota may shed new insight on the underlying pathogenesis of OSAHS-associated hypertension.

Background Immune checkpoint inhibitor (ICI) therapy elicits durable antitumor responses in patients with many types of cancer. Genomic mutations may be used to predict the clinical benefits of ICI therapy. NOTCH homolog-4 (NOTCH4) is frequently mutated in several cancer types, but its role in immunotherapy is still unclear. Our study is the first to study the association between NOTCH4 mutation and the response to ICI therapy. Methods We tested the predictive value of NOTCH4 mutation in the discovery cohort, which included non-small cell lung cancer, melanoma, head and neck squamous cell carcinoma, esophagogastric cancer, and bladder cancer patients, and validated it in the validation cohort, which included non-small cell lung cancer, melanoma, renal cell carcinoma, colorectal cancer, esophagogastric cancer, glioma, bladder cancer, head and neck cancer, cancer of unknown primary, and breast cancer patients. Then, the relationships between NOTCH4 mutation and intrinsic and extrinsic immune response mechanisms were studied with multiomics data. Results We collected an ICI-treated cohort (n = 662) and found that patients with NOTCH4 mutation had better clinical benefits in terms of objective response rate (ORR: 42.9% vs 25.9%, P = 0.007), durable clinical benefit (DCB: 54.0% vs 38.1%, P = 0.021), progression-free survival (PFS, hazard ratio [HR] = 0.558, P Conclusions Our findings indicated that NOTCH4 mutation serves as a novel biomarker correlated with a better response to ICI therapy.

BACKGROUND: Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly spread throughout the world. In this study, we aimed to identify the risk factors for severe COVID-19 to improve treatment guidelines. METHODS: A multicenter, cross-sectional study was conducted on 313 patients hospitalized with COVID-19. Patients were classified into two groups based on disease severity (nonsevere and severe) according to initial clinical presentation. Laboratory test results and epidemiological and clinical characteristics were analyzed using descriptive statistics. Univariate and multivariate logistic regression models were used to detect potential risk factors associated with severe COVID-19. RESULTS: A total of 289 patients (197 nonsevere and 92 severe cases) with a median age of 45.0 (33.0, 61.0) years were included in this study, and 53.3% (154/289) were male. Fever (192/286, 67.1%) and cough (170/289, 58.8%) were commonly observed, followed by sore throat (49/289, 17.0%). Multivariate logistic regression analysis suggested that patients who were aged ≥ 65 years (OR: 2.725, 95% confidence interval [CI]: 1.317-5.636; P = 0.007), were male (OR: 1.878, 95% CI: 1.002-3.520, P = 0.049), had comorbid diabetes (OR: 3.314, 95% CI: 1.126-9.758, P = 0.030), cough (OR: 3.427, 95% CI: 1.752-6.706, P 

BACKGROUND: Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) continues to make a deadly impact on human life all over the world. Therefore, we aimed to analyze the changes in clinical characteristics of coronavirus disease 2019 (COVID-19) patients over time. METHODS: We recruited 896 patients who were admitted to the Renmin Hospital of Wuhan University between 30th January 2020 and 16st March 2020. We conducted a retrospective study collecting clinical characteristics, radiologic and laboratory findings, treatments administered, and clinical outcomes in the patients. The data collected were compared between patients with onset of illness in January 2020 and patients with onset of illness in February 2020, in Wuhan, China. Categorical data and non-normally distributed continuous data were examined by the χ2 test and the Mann-Whitney-Wilcoxon test respectively, and the Kaplan-Meier plot was used to analyze survival data. Univariate and multivariate logistic regression methods were used to explore the risk factors associated with in-hospital death. RESULTS: A total of 896 patients were enrolled; the median age was 60 (range, 47-69) years, 685 (76.5%) were categorized into group A (patients with onset of illness in January 2020), and 211 (23.5%) were categorized into group B (patients with onset of illness in February 2020). Compared with group B, group A had a higher incidence of fever (P

Objective:The aim of this study is to evaluate the clinical characteristics and outcomes in 2019 coronavirus disease (COVID-19) patients and to help clinicians perform correct treatment and evaluate prognosis and guide the treatment.Methods:Patients totaling 239 were diagnosed with COVID-19 and were included in this study. Patients were divided into the improvement group and the death group according to their outcome (improvement or death). Clinical characteristics and laboratory parameters were collected from medical records. Continuous variables were tested by an independent sample T test, and categorical variables were analyzed by the chi-square test or Fisher’s exact test. The Cox proportional hazard regression model was used for survival analysis in death patients. The time-dependent area under curves (AUC) based on white blood cell count, lymphocyte count, neutrophil count by age, blood urea nitrogen, and C-reactive protein were plotted.Results:Efficacy evaluation indicated that 99 (41.4%) patients had deteriorated, and 140 (58.6%) patients had improved. Oxygen saturation, hemoglobin levels, infection-related indicators, lymphocyte and platelet counts, C-reactive protein, serum albumin, liver and kidney function, and lactate dehydrogenase in improvement group were statistically significant between the improvement and death groups. A survival analysis revealed that comorbidities, lymphocyte counts, platelet count, serum albumin, C-reactive protein level, and renal dysfunction may be risk factors in patients with COVID-19.Conclusion:Patients with comorbidities, lower lymphocyte counts in hemogram, platelet count and serum albumin, high C-reactive protein level, and renal dysfunction may have higher risk for death. More attention should be given to risk management in the progression of COVID-19.

Background: The genomic spectrum of biliary tract carcinoma (BTC) has been characterized and is associated with distinct anatomic and etiologic subtypes, yet limited studies have linked genomic alterations with personalized therapies in BTC patients. Methods: This study analyzed 803 patients with BTC:164 with gallbladder cancer, 475 with intrahepatic cholangiocarcinoma (ICC) and 164 with extrahepatic cholangiocarcinoma. We determined genomic alterations, mutational signatures related to etiology and histopathology and prognostic biomarkers. Personalized targeted therapies for patients harboring potentially actionable targets (PATs) were investigated. Results: The median tumor mutation burden (TMB) was 1.23 Mut/Mb, with 4.1% of patients having hypermutated BTCs. Unlike the results obtained from the Western population, the most frequently altered cancer-related genes in our cohort included TP53 (53%), KRAS (26%), ARID1A (18%), LRP1B (14%) and CDKN2A (14%). Germline mutations occurred mostly in DNA damage repair genes. Notably, 35.8% of the ICCs harbored aristolochic acid related signatures and an elevated TMB. TP53 and KRAS mutations and amplified 7q31.2 were demonstrated to negatively affect patient prognosis. Moreover, 19 genes were proposed to be PATs in BTCs, with 25.4% of patients harboring these PATs. Forty-six patients received PAT-matched targeted therapies, achieving a 26.1% objective response rate; the median progression-free survival (PFS) was 5.0 months, with 56.8% of patients obtaining PFS benefits. Conclusions: Extensive genomic diversity and heterogeneity were observed among BTC patients, with contributions according to potential etiology exposures, anatomical subtypes and clinicopathological characteristics. We also demonstrated that patients with refractory BTCs who have PATs can derive considerable benefit from receiving a matched therapy, initiating further prospective clinical trials guided by molecular profiling among this aggressive cancer.

The coronavirus disease 2019 (COVID-19) has caused a global pandemic, resulting in considerable morbidity and mortality. Tocilizumab, an inhibitor of IL-6, has been widely repurposed as a treatment of severely ill patients without robust evidence supporting its use. In this study, we aimed to systematically describe the effectiveness of treatment and prevention of the cytokine storms in COVID-19 patients with tocilizumab. In this multicentered retrospective and observational cohort study, 65 patients with COVID-19 receiving tocilizumab and 130 not receiving tocilizumab were propensity score matched at a ratio of 2:1 based on age, sex, and comorbidities from January 20, 2020 to March 18, 2020 in Wuhan, China. After adjusting for confounding, the detected risk for in-hospital death was lower in the tocilizumab group versus nontocilizumab group (hazard ratio = 0.47; 95% confidence interval = 0.25–0.90; p = 0.023). Moreover, use of tocilizumab was associated with a lower risk of acute respiratory distress syndrome (odds ratio = 0.23; 95% confidence interval = 0.11–0.45; p < 0.0001). Furthermore, patients had heightened inflammation and more dysregulated immune cells before treatment, which might aggravate disease progression. After tocilizumab administration, abnormally elevated IL-6, C-reactive protein, fibrinogen, and activated partial thromboplastin time decreased. Tocilizumab may be of value in prolonging survival in patients with severe COVID-19, which provided a novel strategy for COVID-19–induced cytokine release syndrome. Our findings could inform bedside decisions until data from randomized, controlled clinical trials become available.

Objective To evaluate the prognostic factors and optimal management of cervical cancer patients with brain metastasis (BM). Materials and methods We retrospectively reviewed the medical records of 7098 consecutive patients with cervical cancer from January 2000 to December 2019. Data for a total of 24 BM patients with cervical cancer were analyzed retrospectively in the present study. Results The incidence of BM from cervical cancer in our institution was 0.38%. The mean survival time was 7.2 months (median 6.2 months, 0.1-21.2 months). In the univariate analysis, the histopathology of neuroendocrine cancer, 2018 FIGO stage, Karnofsky performance status (KPS) at BM diagnosis, and treatment strategy were identified to be significant prognostic indicators for the survival of patients with BM from cervical cancer. In the multivariate analysis, KPS, chemotherapy, and radiotherapy were independent prognostic factors for survival. Recursive partition analysis (RPA) appeared to be a better prognostic tool than the other prognosis scoring classification systems. Conclusion When patients with BM from cervical cancer have good performance status and undergo comprehensive treatment, such as radiotherapy and chemotherapy, their survival time could be significantly prolonged. Patients with surgical indications may get better survival by postoperative radiotherapy and chemotherapy. Patients with BMs ≥3 may get better survival by whole-brain radiotherapy. But further studies are needed regarding the selection of surgical indications and radiotherapy modes. The prognosis scoring classification system for BM from cervical cancer needs to be improved.

Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) are associated with mild cognitive impairment (MCI). However, this association is unclear. This study aimed to assess the prevalence of MCI in patients with overlap syndrome, determine whether OSA increases the risk of MCI in patients with COPD, and investigate the potential mechanisms for this association.Participants with stable Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 2-4 COPD and complaints of snoring in 2016-2018 were enrolled in this cross-sectional observational study. All were free of asthma, acute left-sided congestive heart failure, unstable coronary heart disease, uncontrolled hypertension, diabetes, encephalitis, and epilepsy. They underwent pulmonary function tests and overnight polysomnography and completed the Montreal Cognitive Assessment (MoCA). MCI was defined by an MoCA score of23, while OSA was defined by an apnea-hypopnea index (AHI) of ≥15 per hour. The association between MCI, demographics, and comorbidities was tested by logistic regression analysis with adjustment for confounders. Sleep-disordered breathing measures were investigated as potential mechanisms underlying this relationship.MCI was significantly more common in patients with overlap syndrome than in those with COPD (40.6% [43/106] vs 24.6% [42/171]). After adjustment, severe OSA was an independent contributor to MCI (odds ratio, OR 2.27; 95% confidence interval, CI 1.12-4.62). Increased percent of night-time spent with oxygen saturation90% (TSatMCI is more prevalent in overlap syndrome than in COPD. OSA may contribute to MCI in COPD. The mechanism may involve TSat

Objective The aim of this study was to explain "obesity paradox" in chronic obstructive pulmonary disease (COPD) by evaluating the effect of body mass index (BMI) on lung function in Chinese patients with COPD. Methods A total of 1644 patients diagnosed with COPD were recruited from four Chinese tertiary hospitals and were divided into four groups including underweight, normal weight, overweight and obese according to BMI classification standard. The medical data of these patients were collected and used for the multiple linear regression analyses. Results After adjustment for age, sex, educational level, economic status, smoking status, alcohol consumption, duration of COPD history, events of acute exacerbation in previous year, hypertension, diabetes mellitus, cardiovascular disease, cerebrovascular disease and osteoporosis, BMI had a curvilinear correlation with the forced expiratory volume in the first second (FEV1) in patients with Global Initiative for Obstructive Lung Disease (GOLD) 1-2 grade (first-order coefficient β, 0.09; 95% CI, 0.03-0.16; second-order coefficient β, -0.002; 95% CI, -0.003--0.001; P

Whether there are increased rates of chronic diseases associated with the combination of chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) overlap syndrome (OVS) has not been determined. The purpose of this study was to assess the prevalence of five comorbidities in COPD and OVS patients. A total of 968 patients with confirmed COPD were included in this study. Participants were requested to fill out a questionnaire involving their basic information and medical history. All subjects underwent one overnight polysomnography and were then divided into an OVS group or a COPD only group according to their apnea-hypopnea index. The prevalence of hypertension, diabetes, cardiovascular disease, arrhythmia and cerebrovascular disease were compared and risk factors for comorbidities in COPD patients were identified. Compared with the COPD only group, the prevalence of hypertension was significantly higher in the OVS group, however, the prevalence rates of the other four kinds of diseases were not statistically different between the two groups. In COPD patients, the prevalence of hypertension increased with the severity of OSA and the prevalence of arrhythmia increased with airflow limitation severity. Risk factors for OSA in patients with COPD included BMI, FEV1%, Epworth Sleepiness Scale score and the Sleep Apnea Clinical Score. OSA was an independent risk factor for hypertension. The other risk factors for hypertension in COPD patients included age, BMI, CAT score and alcohol consumption. Age, lower FEV1% may be risk factors for arrhythmia. OVS patients were associated with a high prevalence rate of hypertension, while OSA was an independent risk factor for hypertension.

Purpose In this study, we investigated the acute exacerbation and outcomes of COPD patients during the outbreak of COVID-19 and evaluated the prevalence and mortality of COPD patients with confirmed COVID-19. Methods A prospectively recruited cohort of 489 COPD patients was retrospectively followed-up for their conditions during the COVID-19 pandemic from December 2019 to March 2020 in Hubei, China. In addition, the features of 821 discharged patients with confirmed COVID-19 were retrospectively analyzed. Results Of the 489 followed-up enrolled COPD patients, 2 cases were diagnosed as confirmed COVID-19, and 97 cases had exacerbations, 32 cases of which were hospitalized, and 14 cases died. Compared with the 6-month follow-up results collected 1 year ago, in 307 cases of this cohort, the rates of exacerbations and hospitalization of the 489 COPD patients during the last 4 months decreased, while the mortality rate increased significantly (2.86% vs 0.65%, p=0.023). Of the 821 patients with COVID-19, 37 cases (4.5%) had pre-existing COPD. Of 180 confirmed deaths, 19 cases (10.6%) were combined with COPD. Compared to COVID-19 deaths without COPD, COVID-19 deaths with COPD had higher rates of coronary artery disease and/or cerebrovascular diseases. Old age, low BMI and low parameters of lung function were risk factors of all-cause mortality for COVID-19 patients with pre-existing COPD. Conclusion Our findings imply that acute exacerbations and hospitalizations of COPD patients were infrequent during the COVID-19 pandemic. However, COVID-19 patients with pre-existing COPD had a higher risk of all-cause mortality.

Objective Maisonneuve fracture is a special type of injury which are rare in clinic. The manifestation of such fractures is variable. The aim of this study is to describe the pathoanatomical features of typical Maisonneuve fracture on the basis of radiographs, computed tomography (CT) scans, magnetic resonance imaging (MRI), and intraoperative exploration findings, and to investigate the injury mechanism of this variety. Methods The data of 41 patients with Maisonneuve fracture from April 2014 to September 2019 were retrospectively analyzed. There were 32 males and nine females, the average age was 37.9 years (range, 18 to 61 years), the fractures occurred on the left side in 20 patients and on the right side in 21 patients. The cause of injuries were traffic accident in five patients, sprain injury in 20 patients, and falling injury from height in 16 patients. All patients underwent posteroanterior and lateral X-ray examinations of the ankle and calf. CT scan of the ankle was performed in 38 patients, including three-dimensional reconstruction in 33 patients. MRI examination of the ankle and calf was performed in 28 and five patients, respectively. Forty patients were treated with open reduction and internal fixation. The features of proximal fibular fracture, injuries of the medial and posterior structures of the ankle, injuries of the anterior inferior tibiofibular ligament and the interosseous membrane were recorded and analyzed. Results Forty-one patients had proximal one-third fractures of the fibula including six patients with fracture involving the fibular neck, 30 with proximal one-third fractures of the fibular shaft, and five with proximal-medial one-third junction fracture of the fibular shaft. Thirty-five patients (35/41, 85.37%) with injury of posterior structures, 34 patients had posterior malleolar fracture (34/41, 82.93%), and one patient had posterior inferior tibiofibular ligament rupture (1/41, 2.44%). There were 20 patients with type I fracture, four patients with type II fracture, and 10 patients with type III fracture according to the Haraguchi classification of posterior malleolus fracture. The fracture of the medial malleolus was in 30 patients (30/41, 73.17%), rupture of the deltoid ligament was in 10 patients (10/41, 24.39%), and medial structures intact were in one patient (1/41, 2.44%). All 41 patients had injury of the anterior inferior tibiofibular ligament. Conclusions Maisonneuve fracture is characterized by fractures of the proximal fibula and the complete rupture of the anterior inferior tibiofibular ligament. Pronation-external rotation is the main injury mechanism. The manifestations of typical Maisonneuve fracture including that the fibular fracture located in proximal one-third diaphysis and the fracture line was from anterosuperior to posteroinferior.

Objective To determine the toxicity and efficacy of radiotherapy for cervical cancer in patients with systemic lupus erythematosus (SLE). Methods Medical records of patients with SLE who received radiation for cervical cancer from January 2011 to January 2019 were reviewed. For definitive radiotherapy, a dose of 50.4 Gy in 28 fractions was delivered by intensity-modulated radiation therapy (IMRT) combined with high-dose-rate brachytherapy of 28 to 30 Gy in 5 fractions. A dose of 45 to 50.4 Gy in 25-28 fractions was delivered for postoperative radiation. All patients were in remission with or without a low dosage of prednisone or immunosuppressive medication. Survival data were analyzed with the Kaplan-Meier method. The incidence of severe toxicities among patients was compared with the chi-square test or Fisher's exact test. Results Twelve patients with SLE were included in this study. Definitive radiotherapy was delivered in 7 patients with FIGO (2009) stage II-III disease. Five patients with FIGO I disease received postoperative radiation. The median follow-up time was 22.1 months. The 3-year overall survival (OS) and 3-year progression-free survival (PFS) were 77.8% and 83.3%, respectively. One patient of definitive radiotherapy and one patient of postoperative radiation died due to distant metastasis of cervical cancer. Grade 3 or higher acute and chronic reactions occurred in 58.3% and 8.3% patients, respectively. Acute grade 3 or higher toxicity correlated with the presence of chemotherapy (p = 0.045). Conclusion Modern radiotherapy for cervical cancer was well tolerated in SLE patients with remission and provided a favorable outcome.

Both chronic intermittent hypoxia (CIH) and chronic continuous hypoxia (CCH) are risk factors for cardiovascular disease, which are associated with cardiac systolic function and associated with dysfunction of endothelia and coagulation-fibrinolysis system in the vasculature. However, the different effects of these two hypoxic models are not fully understood. In our study, we systemically compared the effects of CIH and CCH on cardiac function and related factor levels in serum using rat model.Forty-five male Sprague-Dawley rats were randomly divided into the normoxia control (NC), CIH and CCH groups. The rat CIH and CCH models were established, then the blood and tissue samples were collected to analyze the function of endothelium and the coagulation-fibrinolysis system. Also, the ultrasound cardiogram was performed to directly assess myocardial contractility.Both CIH and CCH significantly decreased the NO, eNOS, P-eNOS and AT-III levels in the rat serum but significantly increased the levels of ET-1, vWF, COX-2, NF-κB, FIB, FVIII and PAI-1 in the rat serum (P 0.05). The expression of ET-1, VWF and ICAM-1 in CIH group were higher than CCH group (P 0.05), however, the expression of CD62p was increased in CCH group but not in CIH group. The expression of t-PA in CIH group were lower than CCH group (P 0.05), but there were no significant differences in CCH group and NC group (P 0.05). Using transmission electron microscope, we found that the mitochondrial ultrastructure of thoracic aorta endothelial cells in CIH and CCH group were damaged. Moreover, the myocardial contractility in CIH and CCH group were significantly decreased compared with NC group.Our results suggested that CIH and CCH could cause endothelial dysfunction, dysfunction of the coagulation-fibrinolysis system and decreasing of myocardial contractility. Compared with CCH, CIH has greater effect on vasoconstriction and adhesion of vascular endothelial cells, and stronger procoagulant effect.

Objective: Previous studies have shown that prophylactic extended-field irradiation can reduce para-aortic lymph node failure (PALNF) rates in patients with cervical cancer. As such, this type of irradiation may particularly benefit patients with a high risk of PALNF. In the present study, we analyzed the risk factors for PALNF in patients with cervical cancer treated with pelvic irradiation in order to identify potential indications of prophylactic extended-field irradiation. Methods: We evaluated patients with 2018 FIGO stage IB3-IIIC1 cervical cancer who were treated with definitive pelvic radiotherapy or concurrent chemoradiotherapy at our institution between 2011 and 2014. Univariate and multivariate analyses were performed to identify risk factors for PALNF. Results: We included 572 patients in the study. The median follow-up period was 37.9 months. Eighteen patients (3.1%) first site of tumor relapse was the para-aortic lymph nodes, and thus showed PALNF. Using multivariate Cox regression analysis, we identified two significant risk factors for PALNF: tumor extension to the pelvic wall (hazard ratio, HR 3.60, p=0.026) and ≥ 2 pelvic MLNs (HR 5.30, p=0.005). For patients with and without risk factors, the 3-year overall survival, disease-free survival, and PALNF rates were 77.3% and 90.1% (p

Coronavirus disease 2019 (COVID-19) is spreading worldwide, and has been declared as an international public health concern. Patients with lung cancer are highly susceptible to infection compared to healthy individuals because of systemic immunosuppression induced by malignancy and anticancer therapy. Furthermore, patients with cancer demonstrate poorer outcomes following infection. Hence, patients with lung cancer should be considered a priority group for COVID-19 prevention. Furthermore, the routine treatment of patients with cancer has been affected during the COVID-19 pandemic, and patients may not have been able to undergo timely and effective antitumor treatment, thereby indicating a poor prognosis. Here, we provide some suggestions for early identification of COVID-19 and differential diagnosis in patients with lung cancer who have fever and respiratory symptoms. Our medical team also provide clinical recommendations on lung cancer management during the COVID-19 pandemic, for carrying out meticulous and individualized clinical management of lung cancer patients and maximum protection to effectively prevent COVID-19. KEY POINTS: Significant findings of the study This article provides suggestions for early identification of COVID-19 and differential diagnosis in patients with lung cancer with fever and respiratory symptoms. What this study adds This article makes clinical recommendations on lung cancer management during the COVID-19 pandemic.

Background Determination of plasma adrenocotrophic hormone (ACTH) concentration (endogenous or thyrotropin-releasing hormone [TRH] stimulation test) is the most commonly used diagnostic test for pituitary pars intermedia dysfunction (PPID) in horses. Because ACTH is unstable, samples often are frozen to be shipped to laboratories or to allow for batch analysis of research samples. However, the effect of multiple freeze-thaw cycles on equine ACTH is unknown. Objective To determine the effects of multiple freeze-thaw cycles on immunoreactive ACTH concentration. Animals Twenty-eight horses ranging from 10 to 27 years of age were used. Methods Prospective study. Horses were divided into 4 groups: group 1, PPID-negative, without TRH stimulation; group 2, PPID-negative, with TRH stimulation; group 3, PPID-positive, without TRH stimulation; and group 4, PPID-positive, with TRH stimulation. Whole blood was collected from each horse at baseline or 30 minutes after TRH stimulation. Immunoreactive plasma ACTH concentration was determined using a chemiluminescence assay. Plasma samples then were frozen at -80°C >24 hours, thawed at 4°C and reanalyzed for 5 freeze-thaw cycles. Changes in plasma ACTH concentration were analyzed using a linear mixed-effect model. Results Significant effects of freeze-thaw cycles (P = .001) and PPID status (P = .04) on plasma ACTH concentration were observed, but no significant effect of TRH stimulation was identified. Conclusions and clinical importance The plasma ACTH concentration is altered by freeze-thaw cycles, and the effect is observed sooner in horses with PPID. To diagnose PPID, multiple freeze-thaw cycles should be avoided when measuring plasma ACTH concentration.

Background: To evaluate the efficacy and treatment related morbidity of neoadjuvant chemoradiotherapy or radiotherapy in elderly patients (aged 75 years or older) with locally advanced rectal cancer (LARC). Methods: We reviewed clinical records of elderly patients with LARC treated with neoadjuvant chemoradiotherapy or radiotherapy between January 2008 and June 2017 at our institute. A dose of 45-50Gy in 25 fractions was delivered to pelvis. The primary tumor received a dose of 55Gy concomitantly for patients receiving intensity modulated radiotherapy (IMRT). The concurrent chemotherapy included capecitabine alone and capecitabine plus oxaliplatin (Xelox). Surgery was performed for suitable patients at least 6 weeks after neoadjuvant treatment. Overall survival (OS), disease specific survival (DSS), disease free survival (DFS) and local control (LC) were calculated with Kaplan-Meier method. Results: A total of 85 patients were enrolled in this study, the median age was 80 years old (range: 75-90 years). After neoadjuvant treatment, surgery was performed in 56 patients (65.9%). Downstaging rate was 85.7% (48/56) with T downstaging in 35 patients (62.5%) and N downstaging in 36 patients (64.3%). Twelve patients (21.4%) obtained pathological complete response (pCR). The incidence of grade 3 or greater acute hematological, gastrointestinal and genitourinary toxicities were 10.7%, 5.2% and 1.8%, respectively. Seven patients (12.5%) experienced postoperative complications. The median follow-up duration was 35.7 months (range: 4.3-100.3 months), The 3-year and 5-year OS, DSS, DFS, LC were 68.9% and 47.2%, 75.8% and 60.4%, 68.2% and 56.1%, 83.9% and 78.3%, respectively. Conclusion: In patients aged 75 years or older with LARC, neoadjuvant chemoradiotherapy followed by surgery was well tolerated with promising survival outcomes, which should be strongly suggested if medically suitable.

Healing of the chronic diabetic ulceration and large burns remains a clinical challenge. Therapeutic fasting has been shown to improve health. Our study tested whether fasting facilitates diabetic and burn wound healing and explored the underlying mechanism. Methods: The effects of fasting on diabetic and burn wound healing were evaluated by analyzing the rates of wound closure, re-epithelialization, scar formation, collagen deposition, skin cell proliferation and neovascularization using histological analyses and immunostaining. In vitro functional assays were conducted to assess fasting and refeeding on the angiogenic activities of endothelial cells. Transcriptome sequencing was employed to identify the differentially expressed genes in endothelial cells after fasting treatment and the role of the candidate genes in the fasting-induced promotion of angiogenesis was demonstrated. Results: Two times of 24-h fasting in a week after but especially before wound injury efficiently induced faster wound closure, better epidermal and dermal regeneration, less scar formation and higher level of angiogenesis in mice with diabetic or burn wounds. In vitro, fasting alone by serum deprivation did not increase, but rather reduced the abilities of endothelial cell to proliferate, migrate and form vessel-like tubes. However, subsequent refeeding did not merely rescue, but further augmented the angiogenic activities of endothelial cells. Transcriptome sequencing revealed that fasting itself, but not the following refeeding, induced a prominent upregulation of a variety of pro-angiogenic genes, including SMOC1 (SPARC related modular calcium binding 1) and SCG2 (secretogranin II). Immunofluorescent staining confirmed the increase of SMOC1 and SCG2 expression in both diabetic and burn wounds after fasting treatment. When the expression of SMOC1 or SCG2 was down-regulated, the fasting/refeeding-induced pro-angiogenic effects were markedly attenuated. Conclusion: This study suggests that fasting combined with refeeding, but not fasting solely, enhance endothelial angiogenesis through the activation of SMOC1 and SCG2, thus facilitating neovascularization and rapid wound healing.

Purpose To validate the 2018 revised FIGO cervical cancer staging system for stage III patients with a cohort from China. Patients and Methods Patients with stage III cervical cancer (FIGO 2018) treated with definitive radiotherapy at our institute were reviewed. Each patient was evaluated with both the 2014 and 2018 staging systems. Disease-free survival (DFS) was calculated with the Kaplan-Meier method. Receiver operative characteristic (ROC) curves for the predictive accuracy of DFS in patients with cervical cancer according to different FIGO staging systems were created. Results Between January 2008 and December 2014, a total of 586 patients with FIGO stage IIIC cervical cancer (2018) were treated with definitive radiotherapy at our institute. The 3-year DFS for patients according to FIGO stage (2014) were as follows: IB2 73.2%, IIA 63.7%, IIB 66.7%, IIIA 64.7%, and IIIB 59.6% (P=0.580). The 3-year DFS according to FIGO stage (2018) were IIIA 79.9%, IIIB 70.4%, IIIC1 66.3% and IIIC2 29.8% (P

Background: Coronavirus disease 2019 (COVID-19) is now a global pandemic. It is unclear to radiotherapy practitioners how to carry out radiotherapy during the epidemic. Patients and Methods: After the outbreak of COVID-19, our Institute established measures for the prevention and control of COVID-19, and continues to treat patients according to these measures. The Radiotherapy Department has been divided into a clean zone and a semi-contaminated zone, and corresponding personal protective equipment is used in these zones. The temperature of patients and their escorts, and history of fever are assessed daily. Special procedures are performed during radiotherapy setup and intracavitary brachytherapy. Results: Over a period of 2 months, 655 patients were treated in the Department. Sixteen patients with fever were identified and no patient undergoing radiotherapy or medical staff have been infected with COVID-19. Conclusion: Our protective measures were found to be effective and can be used as a reference in places where COVID-19 situations are not markedly serious.

Background The new staging system of cervical cancer issued in 2018 by the International Federation of Gynecology and Obstetrics (FIGO), calls for a new evaluation of the efficacy of prophylactic extended field irradiation (EFI) in the concomitant chemoradiotherapy/brachytherapy treatment of locally advanced cervical cancer patients (stage IIIB). Methods We performed a retrospective study consisting of 133 FIGO IIIB cervical cancer patients treated in the Peking Union Medical College Hospital from 2002 to 2010. The patients were distributed in two groups depending whether they were treated with EFI or pelvic only irradiation. The therapeutic efficacy, toxicity and prognostic factors of EFI were evaluated in the frame of the new FIGO staging system. Results When compared to patients who received pelvic only irradiation, patients who received prophylactic EFI showed significantly less distant metastasis and a significant improvement in their 5 years overall survival (OS), disease free survival (DFS), out of field recurrence free survival (OFRFS) and para-aortic lymph node metastasis free survival (PALNMFS). Multivariate analysis revealed that EFI is an independent prognosis factor for DFS, OFRFS and PALNMFS. Finally, although more acute complications were observed in the EFI group, there is no significantly worst acute toxicity in the EFI group. Conclusion Our retrospective analysis supports the prophylactic effect of EFI in the concomitant chemoradiotherapy treatment of IIIB patients and suggests that this prophylactic effect is associated with a clear improvement in 5-years OS, DFS, OFRFS and PALNMFS. Consequently, EFI appears to be a very valid treatment option for FIGO IIIB cervical cancer patients.

Purpose To analyze the characteristics and survival of patients with mesorectum metastatic lymph nodes (MLNs) from cervical cancer. Patients and methods We retrospectively reviewed 1194 consecutive patients with FIGO stage IA-IVA cervical cancer who were treated with definitive radiotherapy between January 2011 and December 2015 in our institute. Patients were treated with intensity-modulated radiation therapy (IMRT) and brachytherapy, combined with concurrent chemotherapy. Mesorectum, pelvic and para-aortic MLNs were boosted 59-61Gy with IMRT. We calculated the clinical characteristics and survival of the patients with and without mesorectum MLNs and made comparisons between them. Results The incidence rate of mesorectum MLNs was 0.8% (10/1194). The incidence rates for patients with FIGO stages I, II, III, and IVA disease were 0%, 0.4%, 2.0%, and 33.3%, respectively. Mesorectum MLNs were associated with more advanced stage (p

A differentiation switch of bone marrow mesenchymal stem/stromal cells (BMSCs) from osteoblasts to adipocytes contributes to age‐ and menopause‐associated bone loss and marrow adiposity. Here it is found that osteocytes, the most abundant bone cells, promote adipogenesis and inhibit osteogenesis of BMSCs by secreting neuropeptide Y (NPY), whose expression increases with aging and osteoporosis. Deletion of NPY in osteocytes generates a high bone mass phenotype, and attenuates aging‐ and ovariectomy (OVX)‐induced bone‐fat imbalance in mice. Osteocyte NPY production is under the control of autonomic nervous system (ANS) and osteocyte NPY deletion blocks the ANS‐induced regulation of BMSC fate and bone‐fat balance. γ‐Oryzanol, a clinically used ANS regulator, significantly increases bone formation and reverses aging‐ and OVX‐induced osteocyte NPY overproduction and marrow adiposity in control mice, but not in mice lacking osteocyte NPY. The study suggests a new mode of neuronal control of bone metabolism through the ANS‐induced regulation of osteocyte NPY., Normally, norepinephrine (NE) and acetylcholine (ACh) production is maintained at a balanced level in bone, so that osteocytes cannot generate excessive neuropeptide Y (NPY) to favor bone marrow mesenchymal stem/stromal cell adipogenesis rather than osteogenesis. With aging/estrogen deficiency, sympathetic overactivity, and decreased parasympathetic activity cause NE overproduction and ACh reduction, resulting in excess osteocyte NPY generation and subsequent bone‐fat imbalance.

Background: Coronavirus disease 2019 (COVID-19) has outbroken in China and subsequently spread worldwide since the end of 2019. Chest computed tomography (CT) plays an important role in the diagnosis of lung diseases, but its value in the diagnosis of cardiac injury remains unknown.Methods: We enrolled 241 consecutive hospitalized patients (aged 61 ± 16 years, 115 males) with laboratory-confirmed COVID-19 at Renmin Hospital of Wuhan University from January 11 to March 2, 2020. They were divided into two groups according to whether major adverse cardiovascular events (MACEs) occurred during the follow-up. The anteroposterior diameter of the left atrium (LAD), the length of the left ventricle (LV), and cardiothoracic ratio (CTR) were measured. The values of myocardial CT were also recorded.Results: Of 241 patients, 115 patients (47.7%) had adverse cardiovascular events. Compared with no MACEs, patients with MACEs were more likely to have bilateral lesions (95.7% vs. 86.5%, p = 0.01). In multivariable analysis, bronchial wall thickening would increase the odds of MACEs by 13.42 (p = 0.01). LAD + LV and CTR was the best predictor for MACEs (area under the curve = 0.88, p < 0.001) with a sensitivity of 82.6% and a specificity of 80.2%. Plasma high-sensitivity troponin I levels in patients with cardiac injury showed a moderate negative correlation with minimum CT value (R2 = −0.636, p < 0.001).Conclusions: Non-contrast chest CT can be a useful modality for detection cardiac injury and provide additional value to predict MACEs in COVID-19 patients.

ObjectiveThis work aims to analyze the 100 most cited papers in radiotherapy or chemoradiotherapy for cervical cancer.MethodsThe 100 most cited papers in radiotherapy or chemoradiotherapy between 1990 and 2020 were identified with Thompson Reuters Web of Science citation indexing on August 24, 2020. The publication years, source titles, countries/regions, total citations, and average citations per year were extracted from the Web of Science. The research type and research domain were classified by the authors.ResultsThese 100 papers were cited a total of 28,714 times, and the median number of citations was 169.5 (ranging from 116 to 1,700 times). The most cited paper was “Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer” by Rose et al., with a total citation of 1,700 times. The International Journal of Radiation Oncology Biology Physics (40 papers), Radiotherapy and Oncology (14 papers), and the Journal of Clinical Oncology (12 papers) published the largest number of papers. USA (47 papers), Austria (18 papers), Canada (13 papers), and England (13 papers) contributed the largest number of papers. Image-guided adaptive brachytherapy (IGABT) had the largest number of papers (25 papers). Concurrent chemotherapy was the most cited research domain, with 10,663 total citations and 592.4 citations per paper.ConclusionIn the present study, we conducted a bibliometric analysis of the 100 most cited papers in radiotherapy or concurrent chemoradiotherapy for cervical cancer in the past 30 years. IGABT and concurrent chemotherapy were the most cited research domains.

ObjectiveThe role of salvage radiotherapy (RT) in the treatment for vaginal recurrence of cervical cancer in patients after prior surgery remains controversial. The aim of this study was to evaluate the efficacy and toxicity of salvage RT and explore prognostic factors associated with the survival after recurrence.MethodsPatients with cervical cancer, treated for vaginal recurrences at Peking Union Medical College Hospital between July 2011 and November 2019, were identified. All the patients underwent prior surgery for primary tumor and received salvage RT including external beam radiotherapy (EBRT), brachytherapy (BT), or both. The irradiation field and dose depended on the conditions of patients. Recurrence patterns were classified into four categories according to the site of recurrence. Prognostic factors on the overall survival (OS), progression-free survival (PFS), and local control (LC) were analyzed, and late toxicity was evaluated.ResultsA total of 141 patients were included in the analysis, with a median follow-up time of 40.8 months. The estimated 5-year OS, PFS, and LC rates were 81%, 75%, and 87%, respectively. In multivariate analysis, endovaginal recurrence and no irradiation history were favorable prognostic factors associated with OS (all p < 0.05), PFS (all p < 0.05), and LC (all p < 0.05). The area under the receiver operating characteristic (ROC) curve (AUC) of the recurrence pattern is larger than the stage of primary tumor (0.734 vs. 0.670).ConclusionsRT was an effective treatment with tolerable toxicity for vaginal recurrences of cervical cancer in patients with prior surgery. Recurrence pattern and irradiation history were important prognostic factors.

Background The effect of preoperative sarcopenia on postoperative complications and prognosis in patients undergoing gastrectomy for gastric cancer has been controversial. The purpose of this study was to explore the effect of preoperative sarcopenia on postoperative complications and prognosis of patients with gastric cancer through meta-analysis method, providing new ideas for the prognosis study of patients undergoing gastrectomy for gastric cancer. Methods From databases establishment to April 2021, we systematically searched PubMed, Embase, Web of Science, the Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP, WanFang Data, and Chinese Biomedical Literature Database (CBM) to collect cohort studies on the effect of sarcopenia on postoperative complications or prognosis of gastric cancer. Based on the inclusion and exclusion criteria, two researchers independently screened the literature and extracted the data. The Newcastle-Ottawa Scale was used to evaluate the quality of the included studies and Revman 5.3 software was used for the meta-analysis. Result A total of 20 studies (11 prospective cohort studies and 9 retrospective cohort studies) involving 7615 patients were finally included. Meta-analysis showed that: 1) preoperative sarcopenia significantly increased the risk of overall complications (risk ratio[RR] =2.89, 95% confidence interval[CI]: 1.86, 4.49; P 0.000 01), serious complications (Clavien-Dindo grade ≥ III, RR = 3.01, 95% CI: 1.73, 5.23; P 0.000 01), pneumonia (RR =2.64, 95% CI: 1.71, 4.09; P 0.0001), and obstruction (RR = 3.96, 95% CI: 2.27, 6.90; P 0.000 01), but did not increase the risk of postoperative delayed gastric emptying (RR = 1.44, 95% CI: 0.63, 3.25; P = 0.38), intra-abdominal infection (RR =2.09, 95% CI: 0.88, 5.00; P = 0.10), and anastomotic leakage (RR = 1.26, 95% CI: 0.69, 2.32; P = 0.45); 2) preoperative sarcopenia reduced the overall survival rate (HR = 1.71, 95% CI: 1.53, 1.91; P 0.00001). Conclusion Preoperative sarcopenia increased the risk of postoperative complications and reduced the overall survival rate of patients undergoing gastrectomy for gastric cancer. Therefore, for patients with gastric cancer, preoperative risk assessment and active intervention for sarcopenia are necessary to reduce the risk of postoperative complications and improve poor prognosis. Future studies should focus on the effect of preoperative sarcopenia on the quality of life after gastrectomy for gastric cancer.

PurposeTo evaluate the role of the pre-treatment cervical and lymph node (LN) metabolic parameters of 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT) for locally advanced cervical cancer (LACC) patients receiving concurrent chemoradiotherapy or radiotherapy.Methodswe reviewed 125 consecutive patients with LACC who underwent pre-treatment 18F-FDG PET/CT examination and concurrent chemoradiotherapy or radiotherapy from February 2010 to December 2015 at our institute. The mean standardized uptake value (SUVmean), maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of cervical lesion and lymph node (LN) were recorded. Receiver operator characteristic curve, C-index, Kaplan-Meier method, and Cox proportional hazards models were performed.ResultsThe median follow-up was 62 months (range, 4-114 months). For 125 included patients with cervical cancer, the 5-year overall survival (OS), disease-free survival (DFS), local control (LC) and distant metastasis-free survival (DMFS) rates were 83.6%, 75.1%, 92.3% and 79.9%, respectively. Cervical MTV (c-index 0.59-0.61) and cervical TLG (c-index 0.60-0.62) values calculated with a threshold of 40% SUVmax presented stronger prediction capability than cervical SUVmean (c-index 0.51-0.58) and cervical SUVmax (c-index 0.53-0.57) for OS, DFS, LC, and DMFS. In univariate analysis, cervical TLG ≥ 113.4 had worse DFS and DMFS. Cervical MTV ≥ 18.3 cm3 had worse OS and DMFS. In multivariate analysis, cervical TLG ≥ 113.4 implied worse OS, DFS, and DMFS. In either univariate or multivariate analyses, cervical SUVmean and cervical SUVmax had no statistically significant correlation with OS, DFS, LC and DMFS. For 55 cervical cancer patients with positive LN, LN SUVmax presented strongest prediction capability for OS (c-index = 0.79), DFS (c-index = 0.72), LC (c-index = 0.62), and DMFS (c-index = 0.79). In multivariate analysis, LN SUVmax remained significant biomarker linked to OS, DFS, and DMFS.ConclusionPre-treatment cervical and LN metabolic parameters were associated with survival outcomes in patients with LACC. In our study, we found that pre-treatment cervical TLG and LN SUVmax may be important prognostic biomarkers for OS, DFS, and DMFS. However, further prospective studies with a large number of patients are required to evaluate the value of the metabolic parameters in survival outcomes prediction.

BackgroundObstructive sleep apnea (OSA) is prevalent in chronic obstructive pulmonary disease (COPD). Underweight and overweight have paradoxical effect on COPD prognosis, while obesity is a risk factor for OSA. We aimed to examine the association between BMIs and OSA risk in COPD patients. MethodsThis cross-section study included 1637 COPD subjects in the final analysis. BMI was classified into different groups. OSA was defined as varying severity by AHI. The associations between BMIs and risks of diverse severity of OSA were examined. ResultsFor varying severity of OSA, obesity associated with higher risk, while normal weight group associated with lower risk; overweight had no differences and underweight group had lower risk of moderate-to-severe OSA. Compared with normal weight, for OSA, the overweight group showed a trend of high risk whereas the underweight group indicated a higher risk (OR 1.424, 95% CI 1.015-1.988) (multivariable adjusted). BMI exhibited a J-shaped association with OSA; the risk for OSA was relatively flat at BMIs of 20-24 kg/m2 and above or below the risk increased (P for non-linearity 0.0057); for severe OSA, the plot depicted a S-shaped relation, the risk reached the lowest around 24 kg/m2 and then increased thereafter (P for non-linearity 0.0200). ConclusionsIn COPD population, for various severity of OSA, obesity is a firmly risk factor, overweight not influence the risk, while normal weight associate with lower risk; compared with normal weight, underweight increased the risk for OSA; BMI had a J-shaped association with OSA and a S-shaped with severe OSA.

Obstructive sleep apnea (OSA) has been increasingly recognized as a risk factor for idiopathic pulmonary fibrosis (IPF). The intermittent hypoxia (IH) and re-oxygenation of OSA contribute to poor outcomes of IPF, however, the potential mechanism remains unknown. Here, C57BL/6J mice were administered intratracheal injection of Bleomycin (BLM) or saline and then exposed to IH (alternating cycles of FiO2 21% for 60S and FiO2 10% for 30 s, 40 cycles/hour, 8 h/day) to mimic OSA or intermittent air (IA) for 4 days, 8 days or 21 days. This study found that pulmonary fibrosis in BLM + IH treated mice was more severe than that in BLM + IA group at day 8 and 21, but not observed at day 4. Besides, the expression of reactive oxygen species (ROS) and hypoxia inducible factor-1α (HIF-1α),which are related to hypoxia reduced oxidative stress and inflammation, were higher in BLM + IH treated mice than BLM + IA mice, and IH increased these indexes in BLM treated mice from day 4 to day 21. Interestingly, a positive linear correlation between the HIF-1α expression and hydroxyproline (HYP) content was observed. We further found some inflammatory cells in bronchoalveolar lavage fluid were increased significantly from day 4 to 21, and there was a positive correlation between inflammation and ROS expression. Our results demonstrated that IH aggravated BLM-induced pulmonary fibrosis, and ROS/HIF-1α related oxidative stress and inflammation involved. The increase of ROS/HIF-1α related oxidative stress and inflammation may be a potential mechanism of moderate-to-severe OSA in potentiating pulmonary fibrosis of IPF, which warrants further study.

Patients with chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) are referred to as having overlap syndrome (OVS). However, the relationship of lung function with the apnea-hypopnea index (AHI) in patients with OVS has not been evaluated. This multicenter study aimed to evaluate the relationship. COPD patients diagnosed by spirometry were recruited from four Chinese tertiary hospitals. Those patients were requested to attend an overnight polysomnography (PSG). The relationships between parameters of lung function and sleep respiration in patients with OVS were assessed using multiple regression analyses. A total of 520 OVS patients and 246 patients with COPD only finally met inclusion criteria for study. After adjustment for age, sex, body mass index, neck circumference, economic status, smoking status, alcohol consumption, and hypertension, the forced expiratory volume in the first second (FEV1) had a positive correlation with the AHI in patients with OVS (β, 0.17; 95% CI, 0.06–0.28; P 0.05). Additionally, The FEV1 was positively correlated with the nadir oxygen saturation (SaO2) (β, 0.18; 95% CI, 0.08–0.27; P < 0.01) and was negatively correlated with the percentage of time spent with an SaO2 below 90% (TS90%) (β,− 0.41; 95% CI,− 0.61–0.21; P < 0.01) in patients with OVS using multiple regression analyses. Lung function was associated with the AHI in patients with OVS. The lower FEV1 may play some protective role in the severity of AHI in OVS patients. Trial registry ClinicalTrials.gov , No.: NCT 03182309, URL: www.clinicaltrials.gov .

Objective To compare the performance of Epworth sleepiness scale (ESS), sleep apnea clinical score (SACS), Berlin questionnaire (BQ), and STOP-BANG questionnaire (SBQ) in screening for obstructive sleep apnea (OSA) in patients with chronic obstructive pulmonary disease (COPD). Methods A total of 431 patients were analyzed. All subjects completed lung function test, ESS, SACS, BQ, and SBQ survey and overnight polysomnography (PSG). According to lung function and PSG results, participants were divided into COPD with OSA group (OVS, AHI ≥5) and without OSA group (AHI Results Of the 431 subjects, there were 96 cases in COPD without OSA group, and 335 cases in OVS group including 183, 96, and 56 cases of COPD combined with mild, moderate or severe OSA. In predicting different degrees of severity of OSA in patients with COPD, the value of ESS was poor with all the values of area under the curve (AUC) 2 was considered high risk of OSA; the sensitivity, specificity, and AUC were 92.8%, 40.6%, and 0.723 respectively, the odds ratio (OR) was 2.161. When AHI ≥15, AUC for SBQ was 0.737. In predicting severe OSA (AHI ≥30), the ROC curve showed cut-off point, sensitivity, specificity, and AUC for SBQ was >4, 66.1%, 82.1%, and 0.824 respectively; the positive and negative likelihood ratio was 3.70, 0.41 separately, the OR was 2.977. Conclusion SBQ performed better than ESS, SACS, and BQ in predicting OSA in patients with COPD.

Background:. There are only very few reports on clinical outcomes using multi-channel applicators (MCA) for patients with endometrial cancer (EC) in China. We aimed to evaluate the clinical experience of treating intermediate-risk (IR) to high-risk (HR) stage I EC using in-house made multi-channel applicators (IH-MCA) in a single institution. Methods:. Three hundred and ninety patients with stage I IR to HR EC were treated with hysterectomy and adjuvant radiotherapy from 2003 to 2015. All patients received post-operative vaginal cuff brachytherapy (VBT) alone or as a boost after external beam radiotherapy (EBRT). The prescriptions were 500 cGy per fraction for a total of 5 to 6 fractions with brachytherapy alone or 400 to 600 cGy per fraction for 2 to 3 fractions if it was combined with EBRT. Two types of applicators including a traditional rigid IH-MCA and a recent model custom-made with 3 dimension printing technology were used for treatment. The Kaplan-Meier method was used to calculate survival rate. Results:. Follow-up rate was 92.8% and the median follow-up time was 48 months (range 4–172 months). The 5-year overall survival (OS), progression-free survival, local recurrence, and distant metastasis rates for all patients were 96.3%, 92.1%, 2.9%, and 4.8% respectively. Two patients had isolated relapse in vagina outside the irradiated volume. The univariate and multivariate analysis showed that age and grade were the prognostic factors correlated with OS (hazard ratio: 0.368, 95% confidence interval [CI]: 0.131–1.035, P = 0.048; hazard ratio: 0.576, 95% CI: 0.347–0.958, P = 0.026,). Conclusions:. For patients with IR to HR stage I EC, adjuvant VBT alone or in combination with EBRT using IH-MCA led to excellent survival and recurrence rates. Age and grade were the prognostic factors correlated with OS.

BACKGROUND Acute respiratory distress syndrome (ARDS) is a common acute and severe disease in clinic. Recent studies indicated that Cxc chemokine ligand 5 (CXCL5), an inflammatory chemokine, was associated with tumorigenesis. The present study investigated the role of the CXCL5/Cxc chemokine receptor 2 (CXCR2) bio-axis in ARDS, and explored the underlying molecular mechanism. MATERIAL AND METHODS The pathological morphology of lung tissue and degree of pulmonary edema were assessed by hematoxylin-eosin staining and pulmonary edema score, respectively. Real-time PCR and Western blot analysis were performed to detect the expression levels of CXCL5, CXCR2, Matrix metalloproteinases 2 (MMP2), and Matrix metalloproteinases 9 (MMP9) in lung tissues. Enzyme-linked immunosorbent assay (ELISA) was performed to determine the expression levels of CXCL5 and inflammatory factors (IL-1s, IL-6, TNF-alpha, and IL-10) in serum. RESULTS The results demonstrated that diffuse alveolar damage and pulmonary edema appeared in lipopolysaccharide (LPS)-induced ARDS and were positively correlated with the severity of ARDS. In addition, CXCL5 and its receptor CXCR2 were overexpressed by upregulation of MMP2 and MMP9 in lung tissues of ARDS. In addition, CXCL5 neutralizing antibody effectively alleviated inflammatory response, diffuse alveolar damage, and pulmonary edema, and decreased the expression levels of MMP2 and MMP9 compared to LPS-induced ARDS. CONCLUSIONS We found that CXCL5/CXCR2 accelerated the progression of ARDS, partly by upregulation of MMP2 and MMP9 in lung tissues with the release of inflammatory factors.

Objective: To identify the predictors of distant metastasis in patients with cervical cancer treated with definitive radiotherapy and develop a model for predicting distant metastasis. Methods: We reviewed the clinical records of patients with cervical cancer treated with definitive radiotherapy (IMRT) at Peking Union Medical College Hospital between January 2011 and December 2015. Eligible patients were randomly assigned into model development cohort and validation cohort in a 2:1 ratio. Distant metastasis rate (DMR) was calculated with Kaplan-Meier method. Univariate and multivariate analyses using cox proportional hazard model was performed to identify the risk factors of distant relapse. Based on the identified risk factors for distant metastasis, a model for predicting distant metastasis was developed and validated. A two-side P

Objective To reveal the correlation between APACHE III score and sleep quality in patients in the intensive care unit (ICU). Methods This prospective, observational study included patients aged ≥18 years, who had been admitted to an integrated ICU for ≥48 h. Age, sex, Pittsburgh Sleep Quality Index (PSQI) prior to ICU, Numeric Rating Scales (NRS), noise, illumination, number of nursing interventions, Richards Campbell Sleep Questionnaire (RCSQ), and APACHE III score during sleep were evaluated. Results A total of 124 ICU patients were included, all with APACHE III scores Conclusion In ICU patients with APACHE III scores below 60 points, APACHE III score was not associated with sleep quality. PSQI score prior to ICU and noise were significantly inversely associated with sleep quality in this ICU patient population.

Objective To evaluate the efficacy and toxicity of stereotactic body radiation therapy (SBRT) for oligometastatic pulmonary tumors from cervical cancer. Methods A total of 29 oligometastatic pulmonary lesions from cervical cancer in 19 patients were treated with SBRT in our institute from 2011 to 2016. Thirteen patients (68.4%) suffered with solitary lung metastasis, three patients (15.8%) with multiple unilateral lesions and three patients (15.8%) with bilateral lesions. The median size of lung lesions was 2 cm (0.7–5.6 cm). Patients underwent cone‐beam CT before the delivery of SBRT. The most common dose fractionation schemes were 64 Gy in eight fractions (eight lesions) and 56 Gy in seven fractions (seven lesions). Nine patients (47.4%) received systemic chemotherapy. Results The median follow‐up was 9.5 months (3.0–62.4 months). The one‐year overall survival (OS), progression‐free survival (PFS) and local control (LC) rates were 76.8%, 55.8% and 75.6%, respectively. The median PFS was 12.7 months. Six patients (31.6%) gained more than 20 months disease‐free survival. Eleven patients (57.9%) experienced tumor relapse, including seven patients with pulmonary relapse and four patients with extra‐pulmonary disease. Only one patient (5.3%) experienced symptomatic radiation pneumonitis (grade 2). Conclusion SBRT was an efficacy and safe approach for patients with oligometastatic pulmonary tumor from cervical cancer. SBRT should be considered as a potential alternative to resection for these patients.

Gut microbiota alterations manifest as intermittent hypoxia and fragmented sleep, thereby mimicking obstructive sleep apnea–hypopnea syndrome (OSAHS). Here, we sought to perform the first direct survey of gut microbial dysbiosis over a range of apnea–hypopnea indices (AHI) among patients with OSAHS. We obtained fecal samples from 93 patients with OSAHS [5 < AHI ≤ 15 (n=40), 15 < AHI ≤ 30 (n=23), and AHI ≥ 30 (n=30)] and 20 controls (AHI ≤ 5) and determined the microbiome composition via 16S rRNA pyrosequencing and bioinformatics analysis of variable regions 3–4. We measured fasting levels of homocysteine (HCY), interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α). Results revealed gut microbial dysbiosis in several patients with varying severities of OSAHS, reliably separating them from controls with a receiver operating characteristic-area under the curve (ROC-AUC) of 0.789. Functional analysis in the microbiomes of patients revealed alterations; additionally, decreased in short-chain fatty acid (SCFA)-producing bacteria and increased pathogens, accompanied by elevated levels of IL-6. Lactobacillus levels correlated with HCY levels. Stratification analysis revealed that the Ruminococcus enterotype posed the highest risk for patients with OSAHS. Our results show that the presence of an altered microbiome is associated with HCY among OSAHS patients. These changes in the levels of SCFA affect the levels of pathogens that play a pathophysiological role in OSAHS and related metabolic comorbidities.

The aim of this study was to evaluate and compare the intestinal function recovery time and other short-term outcomes between robotic-assisted total mesorectal excision (R-TME) and laparoscopic total mesorectal excision (L-TME) for rectal cancer. This is a retrospective study using a prospectively collected database. Patients’ records were obtained from Gansu Provincial Hospital between July 2015 and October 2017. Eighty patients underwent R-TME, and 116 with the same histopathological stage of the tumor underwent an L-TME. Both operations were performed by the same surgeon, comparing intra- and postoperative outcomes intergroups. The time to the first passage of flatus ( P < 0.001), the time to the first postoperative oral fluid intake ( P < 0.001), and the length of hospital stay ( P < 0.01) of the R-TME group were about three days faster than those in the L-TME group. The rate of conversion to open laparotomy ( P = 0.038) and postoperative urinary retention ( P = 0.016) were significantly lower in the R-TME group than in the L-TME group. Intraoperative blood loss of the R-TME group was more than that of the L-TME group ( P < 0.01).The operation time, number of lymph nodes harvested, and rate of positive circumferential resection margin were similar intergroup. The total cost of the R-TME group was higher than that of the L-TME group, but with a lack of statistical significance (85,623.91 ± 13,310.50 vs 67,356.79 ± 17,107.68 CNY, P = 0.084). The R-TME is safe and effective and has better postoperative short-term outcomes and faster intestinal function recovery time, contrasting with the L-TME. The large, multicenter, prospective studies were needed to validate the advantages of robotic surgery system used in rectal cancer.

Purpose The purpose of this study was to evaluate the efficacy and toxicity of concomitant dose-escalated Tomotherapy in locally advanced mid-low rectal cancer. Patients and methods Patients with locally advanced (T3/T4 or N+), low-mid (≤10 cm from anal verge) rectal carcinoma treated with neoadjuvant chemoradiotherapy followed by surgery between May 2012 and October 2017 in Peking Union Medical College Hospital were included in this study. A dose of 45/50 Gy in 25 fractions was delivered to the pelvis with Tomotherapy, and 55 Gy was prescribed for the primary tumor with a simultaneous, integrated boost. Megavolt computed tomography was performed before every delivery. The concurrent chemotherapy regimen included capecitabine alone and XELOX. Results A total of 141 patients were enrolled; 129 patients (91.5%) had stage cT3 or cT4, and 121 patients (85.8%) had positive lymph nodes. The location of the tumors was in the lower rectum in 88 patients (62.4%). After neoadjuvant chemoradiotherapy, 113 patients (80.1%) underwent sphincter-preserving resection. Downstaging was observed in 121 patients (85.8%), including 80 patients (56.7%) with T downstaging and 101 patients (83.5%) with N downstaging. Thirty-two patients (22.7%) obtained pathological complete response (pCR). The median follow-up was 38.5 months (range, 9.3-73.6 months). Only 36 patients (25.5%) experienced treatment failure, including distant metastasis in 29 patients (20.6%) and pelvic recurrent in 7 patients (5.0%). The estimated 5-year overall survival (OS), disease-free survival (DFS), and local control (LC) rates of patients were 75.1%, 70.9%, and 95.5%, respectively. pCR was an independent prognostic factor for DFS (HR 0.13, 95% CI: 0.02-0.93, P = 0.043), but it did not improve OS or LC. Grade 3 or greater acute leukopenia and diarrhea rates were 5.7% and 7.8%, respectively, and 15 patients (10.6%) developed postoperative complications. Conclusion This study indicates that neoadjuvant, image-guided Tomotherapy with 55 Gy boosted to the primary tumor was well tolerated and resulted in high rates of sphincter-preserving surgery, pCR, LC, and DFS for locally advanced rectal cancer.

The arachidonic acid pathway metabolite 20-hydroxyeicosatetraenoic acid (20-HETE) contributes to ischemia/reperfusion brain injury. Inhibition of 20-HETE formation can protect the developing brain from global ischemia. Here, we examined whether treatment with the 20-HETE synthesis inhibitor N-hydroxy-N-4-butyl-2-methylphenylformamidine (HET0016) can protect the immature brain from traumatic brain injury (TBI). Male rats at postnatal day 9–10 underwent controlled cortical impact followed by intraperitoneal injection with vehicle or HET0016 (1 mg/kg, 5 min and 3 h post-injury). HET0016 decreased the lesion volume by over 50% at 3 days of recovery, and this effect persisted at 30 days as the brain matured. HET0016 decreased peri-lesion gene expression of proinflammatory cytokines (tumor necrosis factor-α [TNF-α], interleukin-1β [IL-1β]) at 1 day and increased reparative cytokine (IL-4, IL-10) expression at 3 days. It also partially preserved microglial ramified processes, consistent with less activation. HET0016 decreased contralateral hindlimb foot faults and improved outcome on the novel object recognition memory task 30 days after TBI. In cultured BV2 microglia, HET0016 attenuated the lipopolysaccharide-evoked increase in release of TNF-α. Our data show that HET0016 improves acute and long-term histologic and functional outcomes, in association with an attenuated neuroinflammatory response after contusion of an immature rat brain.

Objective This study was conducted to evaluate the efficacy and toxicity of extended-field intensity-modulated radiation therapy combined with concurrent chemotherapy in patients with cervical cancer with positive para-aortic lymph nodes (PALN). Methods From September 2007 to December 2014, a total of 59 patients who had cervical cancer with para-aortic lymph node metastasis were treated with concurrent chemoradiotherapy at our institution. A dose of 45–50.4 Gy in 25–28 fractions with extended-field intensity-modulated radiation therapy was prescribed to planning target volume, and a dose of 30–36 Gy in 5–6 fractions was prescribed to Point A with high-dose-rate brachytherapy. A concurrent first-line cisplatin-based chemotherapy regimen was used. Results The median duration of follow-up was 32.1 months (range, 3.2–103.7 months). The 2- and 3-year overall survival, disease-free survival and local control rates were 69.0 and 52.8%, 45.0 and 41.3% and 83.4 and 81.0%, respectively. Distant metastasis was the major pattern of treatment failure, which occurred in 26 patients (44.1%). The incidence of Grade 3 or greater acute hematologic, gastrointestinal and genitourinary toxicity was 50.9, 1.7 and 3.4%, respectively. Only one patient had both Grade 3 late gastrointestinal and genitourinary toxicity. Conclusions The study found that extended-field intensity-modulated radiation therapy combined with concurrent chemotherapy was safe and effective in patients who had cervical cancer with positive PALN.

Objective Image guidance should be used for patients with cervical cancer treated with definitive intensity-modulated radiation therapy (IMRT). In this study, we provided a pattern of image guidance and verified it in a large population. Methods We retrospectively analyzed patients with stages IB1–IVA cervical cancer treated with IMRT combined with high-dose brachytherapy and concurrent chemotherapy in our institute from January 2005 to December 2015. A dose of 50.4 Gy in 28 fractions was prescribed to the planning target volume with fixed-field IMRT, volumetric modulated arc therapy, or helical tomotherapy. Daily megavoltage computed tomography (CT) or weekly cone-beam CT (CBCT)/CT-on-rail were used for image guidance. Considering tumor regression during treatment, a second CT simulation and IMRT planning after 20 fractions of IMRT was performed. Results A total of 1433 patients were included in this study. Four hundred thirteen patients (28.8%) had regional lymph node metastases. A total of 1261 patients (88.0%) received concurrent chemotherapy. The median follow-up was 32.2 months (range, 1.9–124.9 months). The 3-year overall survival (OS), disease-free survival (DFS), and local control (LC) rates were 83.0%, 75.0%, and 87.4%, respectively. The 3-year DFS rates for patients with stages IB1, IB2, IIA, IIB, IIIA, IIIB, and IVA disease were 90.2%, 87.6%, 84.0%, 76.7%, 61.6%, 59.8%, and 25.9%. The incidence rates of grade 3 or greater chronic gastrointestinal and genitourinary toxicities were 2.3% and 1.3%. Conclusion This pattern of image guidance was rational for patients with cervical cancer treated with IMRT. The survival rates were high, and the toxicities were acceptable.