Vascular changes of the choroid and their correlations with visual acuity in diabetic retinopathy.

Objective: To investigate changes in the choroidal vasculature and their correlations with visual acuity in diabetic retinopathy (DR). Methods: The cohort was composed of 225 eyes from 225 subjects, including 60 eyes from 60 subjects with healthy control, 55 eyes from 55 subjects without DR, 46 eyes from 46 subjects with nonproliferative diabetic retinopathy (NPDR), 21 eyes from 21 subjects with proliferative diabetic retinopathy (PDR), and 43 eyes from 43 subjects with clinically significant macular edema (CSME). Swept-source optical coherence tomography (SS-OCT) was used to image the eyes with a 12-mm radial line scan protocol. The parameters for 6-mm diameters of region centered on the macular fovea were analyzed. Initially, a custom deep learning algorithm based on a modified residual U-Net architecture was utilized for choroidal boundary segmentation. Subsequently, the SS-OCT image was binarized and the Niblack-based automatic local threshold algorithm was employed to calibrate subfoveal choroidal thickness (SFCT), luminal area (LA), and stromal area (SA) by determining the distance between the two boundaries. Finally, the ratio of LA and total choroidal area (SA + LA) was defined as the choroidal vascularity index (CVI). The choroidal parameters in five groups were compared, and correlations of the choroidal parameters with age, gender, duration of diabetes mellitus (DM), glycated hemoglobin (HbA1c), fasting blood sugar, SFCT and best-corrected visual acuity (BCVA) were analyzed. Results: The CVI, SFCT, LA, and SA values of patients with DR were found to be significantly lower compared to both healthy patients and patients without DR (P < 0.05). The SFCT was significantly higher in NPDR group compared to the No DR group (P < 0.001). Additionally, the SFCT was lower in the PDR group compared to the NPDR group (P = 0.014). Furthermore, there was a gradual decrease in CVI with progression of diabetic retinopathy, reaching its lowest value in the PDR group. However, the CVI of the CSME group exhibited a marginally closer proximity to that of the NPDR group. The multivariate regression analysis revealed a positive correlation between CVI and the duration of DM as well as LA (P < 0.05). The results of both univariate and multivariate regression analyses demonstrated a significant positive correlation between CVI and BCVA (P = 0.003). Conclusion: Choroidal vascular alterations, especially decreased CVI, occurred in patients with DR. The CVI decreased with duration of DM and was correlated with visual impairment, indicating that the CVI might be a reliable imaging biomarker to monitor the progression of DR.

Efficacy of TIPS plus extrahepatic collateral embolisation in real-world data: a validation study.

OBJECTIVES: The efficacy of transjugular intrahepatic portosystemic shunt (TIPS) plus extrahepatic collateral embolisation (TIPS+E) in reducing rebleeding and hepatic encephalopathy (HE) post-TIPS was recently reported in a meta-analysis, but further validation is essential. This study aims to confirm the effectiveness of TIPS+E using real-world data. METHODS: The multicentre retrospective cohort included 2077 patients with cirrhosis who underwent TIPS±E (TIPS: 631, TIPS+E: 1446) between January 2010 and December 2022. Regression and propensity score matching (PSM) were used to adjust for baseline characteristic differences. After PSM, clinical outcomes, including rebleeding, HE, survival and further decompensation (FDC), were analysed. Baseline data from all patients contributed to the construction of prognostic models. RESULTS: After PSM, 1136 matched patients (TIPS+E: TIPS=568:568) were included. TIPS+E demonstrated a significant reduction in rebleeding (HR 0.77; 95% CI 0.59 to 0.99; p=0.04), HE (HR 0.82; 95% CI 0.68 to 0.99; p=0.04) and FDC (HR 0.85; 95% CI 0.73 to 0.99; p=0.04), comparing to TIPS. Significantly, TIPS+E also reduced rebleeding, HE and FDC in subgroup of using 8 mm diameter stents and embolising of gastric varices+spontaneous portosystemic shunts (GV+SPSS). However, there were no differences in overall or subgroup survival analysis. Additionally, the random forest models showed higher accuracy and AUROC comparing to other models. Controlling post-TIPS portal pressure gradient (pPPG) within 7 mm Hg

Radiologic grading scores enhance clinical model's prognostic ability for Guillain-Barré syndrome.

OBJECTIVE: To assess the value of magnetic resonance imaging (MRI) grading scores based on lumbosacral muscle denervation edema in predicting the course of Guillain-Barré syndrome (GBS). METHODS: We collected data from 354 GBS patients and developed MRI grading criteria (5-point scale) based on the transverse area and longitudinal length of lumbosacral edema. Univariate and multivariate logistic regression analyses were conducted to identify factors associated with GBS prognosis among 12 demographic and radiological features. Clinical models and clinical-MRI models were separately trained and validated by data from Institution 1. External test was performed using data from Institution 2. Differences between the models were assessed using the z-test. RESULTS: Four clinical factors (sex, albumin cytological dissociation in cerebrospinal fluid, medical research council [MRC] sum score at admission, and MRC sum score at discharge [odds ratio, 0.24-5.15; all p < 0.001]) and MRI grading scores (odds ratio, 2.44; p < 0.001) are independent prognostic factors for GBS patients. The shallow neural network achieved the best prognostic performance both clinical model (accuracy of external test cohort, 83.96%) and clinical-MRI model (accuracy of external test cohort, 90.56%). A significant difference between clinical and clinical-MRI model was also found (clinical model vs. clinical-MRI model, area under the receiver operating curve, 0.84 (95% CI: [0.71, 0.91]) vs. 0.97 (95% CI: [0.86, 0.99]), p < 0.001). INTERPRETATION: The MRI grading scores for muscle denervation edema may serve as a potential prognostic risk factor for GBS. Furthermore, they significantly improve the prognostic performance of standalone clinical model in predicting GBS prognosis.

Circulating lncRNAs NONHSAT054669.2 and ENST00000525337 can be used as early biomarkers of gestational diabetes mellitus.

Early diagnosis can help prevent and reduce the adverse effects of gestational diabetes mellitus (GDM). This study intended to investigate key circulating long non-coding RNAs (lncRNAs) as novel biomarkers for diagnosis of GDM at the early stages. First, lncRNA microarray analysis was conducted for plasma samples of GDM women before delivery and 48 h after delivery. The expression of differentially expressed lncRNAs in clinical samples at different trimesters was randomly validated by quantitative polymerase chain reaction (PCR). Moreover, the correlation between lncRNA expression and oral glucose tolerance test (OGTT) level in GDM women during the second trimester was analyzed, followed by evaluating the diagnostic value of key lncRNAs during different trimesters using receiver operating characteristic (ROC) curve. Higher NONHSAT054669.2 expression and lower ENST00000525337 expression were revealed in GDM women before delivery relative to 48 h after delivery (P < 0.05). The expression of NONHSAT054669.2 and ENST00000525337 in GDM women during the first and second trimesters was dramatically higher than pregnant women (P < 0.05) with normal glucose tolerance (NGT). During the second trimester, NONHSAT054669.2 expression was positively related to OGTT level at 1 h (r = 0.41455, P < 0.001). Furthermore, ROC curve analysis revealed that ENST00000525337 alone, NONHSAT054669.2 alone, and their combination had high diagnostic value for GDM during the first (area under the ROC curve (AUC) = 0.979, 0.956, and 0.984, respectively) and second (AUC = 0.829, 0.809, and 0.838, respectively) trimesters (all P < 0.001). The plasma level of NONHSAT054669.2 and ENST00000525337 may be applied as novel diagnostic biomarkers for early diagnosis of GDM.

Quality of clinical practice guidelines relevant to rehabilitation of knee osteoarthritis: A systematic review.

OBJECTIVE: This systematic review summarized the rehabilitation recommendations for treating and managing knee osteoarthritis (OA) in practice guidelines and evaluated their applicability and quality using the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument. DATA SOURCES: PubMed, the Cochrane Library, EMBASE, CINAHL, PEDro, Guideline central, Guideline International Network and Agency for Healthcare Research and Quality (AHRQ) were used to search for relevant studies published between 1 January 2008 and 31 May 2022. METHODS: AGREE II was used to evaluate the included guidelines quality, SPSS 25.0 statistical software was used for data analysis, and the intra-group correlation coefficient value was calculated to verify the consistency between the raters. The two-way random effects model was used to calculate concordance scores, and each domain's total scores were calculated. Additionally, the median and interquartile range for domain and total scores were calculated. RESULTS: Twenty-four guidelines recommending knee OA rehabilitation were included. Inter-rater consistency evaluation ranged from 0.62 to 0.90. The domains where the guideline's overall and rehabilitation parts scored highest and lowest were scope and purpose (domain 1) and applicability (domain 5), respectively. The highly recommended rehabilitation opinions included aerobic exercise programs (21/24), weight control (16/24), self-education and management (16/24), gait/walking aids (7/24), and tai chi (6/24). However, the orthopedic insole and hot/cold therapy roles remain controversial. CONCLUSION: The clinical practice guidelines' overall quality for knee OA rehabilitation is good; however, the applicability is slightly poor. Therefore, we should improve the promoting factors and hindering factors, guideline application recommendations, tools, and resources when developing relevant guidelines.

Predicting the grade of meningiomas by clinical-radiological features: A comparison of precontrast and postcontrast MRI.

Objectives: Postcontrast magnetic resonance imaging (MRI) is important for the differentiation between low-grade (WHO I) and high-grade (WHO II/III) meningiomas. However, nephrogenic systemic fibrosis and cerebral gadolinium deposition are major concerns for postcontrast MRI. This study aimed to develop and validate an accessible risk-scoring model for this differential diagnosis using the clinical characteristics and radiological features of precontrast MRI. Methods: From January 2019 to October 2021, a total of 231 meningioma patients (development cohort n = 137, low grade/high grade, 85/52; external validation cohort n = 94, low-grade/high-grade, 60/34) were retrospectively included. Fourteen types of demographic and radiological characteristics were evaluated by logistic regression analyses in the development cohort. The selected characteristics were applied to develop two distinguishing models using nomograms, based on full MRI and precontrast MRI. Their distinguishing performances were validated and compared using the external validation cohort. Results: One demographic characteristic (male), three precontrast MRI features (intratumoral cystic changes, lobulated and irregular shape, and peritumoral edema), and one postcontrast MRI feature (absence of a dural tail sign) were independent predictive factors for high-grade meningiomas. The area under the receiver operating characteristic (ROC) curve (AUC) values of the two distinguishing models (precontrast-postcontrast nomogram vs. precontrast nomogram) in the development cohort were 0.919 and 0.898 and in the validation cohort were 0.922 and 0.878. DeLong's test showed no statistical difference between the AUC values of the two distinguishing models (p = 0.101). Conclusions: An accessible risk-scoring model based on the demographic characteristics and radiological features of precontrast MRI is sufficient to distinguish between low-grade and high-grade meningiomas, with a performance equal to that of a full MRI, based on radiological features.

Multi-trajectories of systolic and diastolic hypertension and coronary heart disease in middle-aged and older adults.

Objective: This study aimed to investigate multi-trajectories of systolic and diastolic hypertension and assess their association with the risk of coronary heart disease (CHD) in middle-aged and older Chinese adults. Methods: The study cohort comprised 4,102 individuals aged 40-75 years with records of at least four systolic blood pressure (SBP) and diastolic blood pressure (DBP). A group-based multi-trajectory model was adopted to identify multi-trajectories of systolic and diastolic hypertension, followed by a logistic model to assess the independent associations between these trajectories and CHD risk. The multinomial logistic model was used to evaluate the impact of baseline covariates on trajectory groups. Results: Six distinct trajectories for systolic and diastolic hypertension were identified which represent distinct stages of hypertension and were characterized as low-stable, low-increasing, medium-decreasing, medium-increasing-decreasing, isolated systolic hypertension phase, and high-decreasing. Compared with the low-stable group, the adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were 2.23 (1.34-3.70) for the medium-increasing-decreasing group and 1.87 (1.12-3.11) for the high-decreasing group after adjustment for baseline covariates. Compared with the low-increasing group, the ORs and 95% CIs were 1.88 (1.06-3.31) for the medium-increasing-decreasing group. Age, gender, drinking, body mass index (BMI), triglyceride (TG), and fasting plasma glucose (FPG) were independent predictors for trajectory groups 4 and 6. Conclusion: Novel, clinically defined multi-trajectories of systolic and diastolic hypertension were identified. Middle-aged and older adults with medium-increasing-decreasing or high-decreasing blood pressure trajectories are potentially critical periods for the development of CHD. Preventing adverse changes in hypertension status and reducing the high risk of CHD is necessary for people in distinct trajectory groups.

Circulating exosomal hsa_circRNA_0039480 is highly expressed in gestational diabetes mellitus and may be served as a biomarker for early diagnosis of GDM.

BACKGROUND: Gestational diabetes mellitus (GDM) seriously affects the health of mothers and babies, and there are still no effective early diagnostic markers. Therefore, it is necessary to find diagnostic biomarkers for screening GDM in early pregnancy. Circular RNA (circRNA) is more stable than linear RNA, and can be encapsulated in exosomes and participate in the pathological process of various diseases, which makes it a better candidate biomarker for various diseases. In this study, we attempted to identify the exosomal circRNA biomarkers for detecting early GDM. METHODS: We performed microarray analysis to compare the plasma exosomal circRNA expression profiles of three GDM patients 48 h before and 48 h after delivery. The repeatability of the expression of circRNAs were randomly validated by RT-PCR analysis. Pearson correlation analysis was applied to evaluate the correlation between circRNAs and OGTT level. ROC curve was established to assess the diagnostic value of circRNAs for GDM at different stages. RESULTS: Plasma exosomal hsa_circRNA_0039480 and hsa_circRNA_0026497 were highly expressed in GDM patients before delivery (P < 0.05). The hsa_circRNA_0039480 expression was higher for GDM group than NGT group at different stages, and was also positively correlated with OGTT during the second trimester (P < 0.05). The expression of hsa_circRNA_0026497 was higher for GDM group during the third, and second trimesters. And there was a strong correlation between two circRNAs in GDM patients during the first-trimester (r = 0.496, P = 0.014). Hsa_circRNA_0039480 showed significant diagnostic value in the first, second, and third trimesters of pregnancy (AUC = 0.704, P = 0.005; AUC = 0.898, P < 0.001 and AUC = 0.698, P = 0.001, respectively). Notably, the combination of hsa_circRNA_0039480 and hsa_circRNA_0026497 exhibited promising discriminative effect on GDM in the first trimesters (AUC = 0.754, P < 0.001). CONCLUSION: Plasma exosomal hsa_cirRNA_0039480 is highly expressed in GDM patients at different stages and may be served as a candidate biomarker for early detection of GDM.

Whole blood viscosity is an independent early predictor for metabolic syndrome and its components in men: A prospective cohort study in Northern Chinese population.

The association between whole blood viscosity (WBV) and metabolic syndrome (MetS) is still scarcely investigated in the population-based prospective cohort. We aim to explore the longitudinal effect of WBV on MetS, and to verify whether WBV measures can be used as early predictors for MetS. The longitudinal cohort consisted of 3,508 adults (2,350 males and 1,158 females) who visited the health check-up system twice. WBV were measured at four shear rate (200, 50, 10 and 1 s-1), and their values were classified into quartiles. Multivariate Cox models were used to estimate the adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) in men and women, respectively. A total of 444 (12.66%) incident MetS were observed at follow-up period. The incidences of MetS significantly increased with increasing quartiles of WBVs at all of the shear rate in men. After adjusting for baseline age, smoking, obesity, hypertension, hyperglycemia, and hyperlipidemia status, all of the WBV measures were significantly associated with incident MetS in men, and the HRs showed clear increasing trend across the quartiles of baseline WBVs. There were no significant association between WBVs and incident MetS in women. These findings suggest that MetS has a hemodynamic basis, and WBVs could be used as independent early predictor for MetS in men.

Development and validation of a nomogram prognostic model for esophageal cancer patients with oligometastases.

Platinum-based chemotherapy is recommended as the standard treatment for metastatic esophageal cancer (EC) patients; however, the outcome is poor. Oligometastasis is less aggressive and has limited growth potential. However, the prognostic factors for EC patients with oligometastases was largely unknown. Thus, we intend to determine the prognostic factors, and develop and validate nomograms for prediction of survival for EC patients with oligometastases. In this study, characteristics of 273 oligometastatic EC patients were analyzed using univariate and multivariate Cox models to determine the independent prognostic factors for progression-free survival (PFS) and overall survival (OS). The result showed that history of alcohol consumption, longer tumor, no local radiotherapy for EC, and no local treatment for metastases were independent factors for PFS. Sex, esophageal fistula, number of metastatic organs, and local radiotherapy for EC were independent prognostic factors for OS. On the basis of Cox models, the respective nomogram for prediction of PFS and OS was established with the corrected concordance index of 0.739 and 0.696 after internal cross-validation. In conclusion, local treatment for metastases and local radiotherapy for EC were demonstrated to be beneficial for oligometastatic EC patients, and the validated nomograms are valuable in prognosis prediction and could guide individualized management for these patients.

Development and Validation of a Deep Learning Radiomics Model Predicting Lymph Node Status in Operable Cervical Cancer.

Aim: To develop and validate a deep learning radiomics model, which could predict the lymph node metastases preoperatively in cervical cancer patients. Patients and methods: We included a cohort of 226 pathological proven operable cervical cancer patients in two academic medical institutions from December 2014 to November 2017. Then this dataset was split into training set (n = 176) and independent testing set (n = 50) randomly. Five radiomic features were selected and a radiomic signature was established. We then combined these five radiomic features with the preoperative tumor histology and grade of these patients together. Baseline logistic regression model (LRM) and support vector machine model (SVM) were established for the comparison. We then explored the performance of a deep neural network (DNN), which is a popular deep learning model nowadays. Finally, performance of this DNN was validated in another independent test set including 50 cases of operable cervical cancer patients. Results: One thousand forty-five radiomic features were extracted for each patient. Twenty-eight features were found to be significantly correlated with the lymph node status in these patients (P < 0.05). Five radiomic features were further selected for further study due to their higher predictive powers. Baseline LRM incorporating these five radiomic and two clinicopathological features was established, which had an area under receiver operating characteristic curve (ROC) of 0.7372 and an accuracy of 89.20%. The established DNN model had four neural layers, in which layer there were 10 neurons. Adagrad optimizer and 1,500 iterations were used in training. The trained DNN had an area under curve (AUC) of 0.99 and an accuracy of 97.16% in the internal validation. To exclude the overfitting, independent external validation was also performed. AUC and accuracy in test set could still retain 0.90 and 92.00% respectively. Conclusion: This study used deep learning method to provide a comprehensive predictive model using preoperative CT images, tumor histology, and grade in cervical cancer patients. This model showed an acceptable accuracy in the prediction of lymph node status in cervical cancer. Our model may help identifying those patients who could benefit a lot from radiation therapy rather than primary hysterectomy surgery if this model could resist strict testing of future randomized controlled trials (RCTs).

Analysis of Short-Term Effects of Air Pollution on Cardiovascular Disease Using Bayesian Spatio-temporal Models.

There has been an increasing number of clinical and epidemiologic research projects providing supporting evidence that short-term exposure to ambient air pollution contributes to the exacerbation of cardiovascular disease. However, few studies consider measurement error and spatial effects in the estimate of underlying air pollution levels, and less is known about the influence of baseline air pollution levels on cardiovascular disease. We used hospital admissions data for cardiovascular diseases (CVD) collected from an inland, heavily polluted city and a coastal city in Shandong Province, China. Bayesian spatio-temporal models were applied to obtain the underlying pollution level in each city, then generalized additive models were adopted to assess the health effects. The total cardiovascular disease hospitalizations were significantly increased in the inland city by 0.401% (0.029, 0.775), 0.316% (0.086, 0.547), 0.903% (0.252, 1.559), and 2.647% (1.607, 3.697) per 10 µg/m3 increase in PM2.5, PM10, SO2, and NO2, respectively. The total cardiovascular diseases hospitalizations were increased by 6.568% (3.636, 9.584) per 10µg/m3 increase in the level of NO2. Although the air pollution overall had a more significant adverse impact on cardiovascular disease hospital admissions in the heavily polluted inland city, the short-term increases in air pollution levels in the less polluted coastal areas led to excessive exacerbations of cardiovascular disease.

Body Shape and Alzheimer's Disease: A Mendelian Randomization Analysis.

Obesity has been reported to be related to memory impairment and decline in cognitive function, possibly further leading to the development of Alzheimer's disease (AD). However, observational studies revealed both negative and positive associations between body shape (BS) and AD, thereby making it difficult to confirm causality due to residual confounds and reverse causation. Thus, using genome-wide association study summary data, two-sample Mendelian randomization (MR) analyses were applied to identify whether there exists a causal association between BS and AD. BS was measured using anthropometric traits (ATs) in this study, including body mass index (BMI), waist-to-hip ratio (WHR), waist-to-hip ratio adjusted by body mass index (WHRadjBMI), and waist circumference (WC). The associations of single nucleotide polymorphisms (SNP) with each AT and AD were obtained separately from aggregated data from the Genetic Investigation of Anthropometric Traits (GIANT) consortium and International Genomics of Alzheimer's Project (IGAP) summary data (17,008 cases with AD and 37,154 controls). An inverse-variance weighted method was applied to obtain the overall causal estimate for multiple instrumental SNPs. The odds ratio (OR) [95% confidence interval (CI)] for AD risk per 1-SD difference in BMI was 1.04 (0.88, 1.23), in WHR was 1.01 (0.77, 1.33), in WHRadjBMI was 1.12 (0.89, 1.41), and in WC was 1.02 (0.82, 1.27). Furthermore, simulation analyses of survivor bias indicated the overall causal effect of BMI on risk of AD was not biased. In conclusion, the evidence from MR analyses showed no casual effect of BS on AD risk, which is inconsistent with the results from previous observational studies. The biological mechanism underlying the findings warrants further study.

Egg intake in extremely undernourished Chinese women during reproductive age and subsequent nonfatal perimenopausal coronary events.

BACKGROUND AND OBJECTIVES: Chinese women in rural areas who are currently >=55 years old have experienced extreme undernutrition during their childbearing age. Their specific experiences provided us with a natural quasiexperimental field for assessing the effects of consuming eggs to obtain nutrients during the childbearing period on preventing nonfatal coronary events (NCE) during the postmenopausal period in the framework of life course epidemiology. METHODS AND STUDY DESIGN: A population-based matched case-control design for NCE was conducted in Yiyuan County, Shandong Province, China. In this study, 462 women with NCE (cases; onset age >=55 years) were included from the Active Surveillance System for Chronic Diseases, and 462 age-matched women without NCE and stroke (controls) from the same village were included. Conditional logistic model analysis was used to determine the association between egg intake and NCE during the postmenopausal period in 3 specific life-periods, namely age 18 to 49 years (childbearing period), age 50 years to NCE onset (perimenopausal and postmenopausal period), and age 18 years to NCE onset (total period). RESULTS: We found that >=12 eggs vs. 0 egg intake per month under extreme undernutrition status during childbearing period exhibited a strong preventive effect against NCE during the postmenopausal period (OR=0.588, 95% CI=0.358-0.964). The window of protective effect was in the age 28 to 49 years, suggesting a critical period model of life course epidemiology. CONCLUSIONS: Egg intake under extreme undernutrition status during the childbearing period plays a critical role in preventing NCE during the postmenopausal period.

Differential response to neoadjuvant hormonal therapy in prostate cancer: Predictive morphological parameters and molecular markers.

OBJECTIVES: The predictive value of the histological parameters and molecular markers for neoadjuvant hormonal therapy (NHT) in prostate cancer (PCa) has not been well established. The aim of this study is to determine pathological variables that can predict differences in response to NHT in PCa. METHODS: A total of 85 locally high risk PCa patients with matched preoperative needle biopsies and radical prostatectomy (RP) specimens were included. All patients were treated with NHT for at least 3 months. We quantified the response to NHT using a new proposed pathological grading system. The system classified tumors into five groups (grades 0-4) according to the severity of histological response. We then categorized the PCa patients into drug-sensitive (DS) group (Grades 2-4) and drug-resistant (DR) group (Grades 0-1). Two pathologists assessed each pretreated tumors for presence or absence of nine morphological features. The expression of androgen receptor (AR), ERG, and PTEN were evaluated by immunohistochemistry (IHC) as well. Statistical analysis was performed to identify significant associations between differentially histological response to NHT and morphological features as well as molecular aberrations. We evaluated different prediction models using receiver operating characteristic (ROC) curves and area under the ROC curve (AUC) analysis. RESULTS: 73% (n = 62/85) of tumors in our cohort belonged to DS group, whereas 27% (n = 23/85) of tumors were DR. Univariate logistic analysis suggested four pathological variables, cribriform growth pattern, macronucleoli, ductal adenocarcinoma differentiation, and PTEN loss in needle biopsies were significantly associated with DR effect, all with P-value < 0.05. Multivariate logistic regression analysis revealed that the three parameters as significant predictive factors for predicting DR effect. These were macronucleoli (RR = 4.008, P = 0.002), ductal adenocarcinoma differentiation (RR = 11.659, P = 0.009) and PTEN loss expression (RR = 7.275, P = 0.015). The AUC of three integrated indicators model was 0.781. CONCLUSIONS: Our study suggested that the presence of tumor cribriform growth pattern, macronucleoli, ductal adenocarcinoma differentiation, and PTEN loss in needle biopsies are of value in predicting tumor response to NHT regimen. Multivariate logistic regression analysis revealed the performance of combined pathological indicators in predicting DR response was better than that of model based on individual factor alone.

Surgery of primary tumor improves the survival of newly diagnosed metastatic melanoma: a population-based, propensity-matched study.

BACKGROUND: For the melanoma patients who are with the primary tumor and metastatic disease concurrently (the newly diagnosed metastatic patients), the effect of primary tumor surgery on survival has never been discussed. OBJECTIVE: We sought to estimate this effect based on data from the Surveillance, Epidemiology, and End Results database. PATIENTS AND METHODS: We identified patients with newly diagnosed metastatic melanoma from 2004 to 2015. The effect of primary tumor surgery was assessed by using Cox proportional hazard regression modeling and propensity score matching. RESULTS: Eight thousand three hundred and forty-one patients who had been diagnosed with primary melanoma and metastatic disease at the same time were included in this analysis, of whom 2,554 (30.6%) received primary tumor surgery. In multivariable analysis of the unmatched cohort, primary tumor surgery was an independent protective factor of overall survival (HR =0.617, 95% CI 0.565-0.674; P<0.001) and melanoma-specific survival (HR =0.599, 95% CI 0.537-0.668; P<0.001). In the matched cohort, primary tumor surgery was still associated with better overall survival (13 vs 6 months, P<0.001) and melanoma-specific survival (18 vs 6 months, P<0.001). CONCLUSION: Our results reveal the benefit of primary tumor surgery on the survival of patients with newly diagnosed metastatic melanoma and may fill in the gaps of guidelines for this population. IRB: IRB approval is not required because the SEER data are freely accessible.

A Multicity Analysis of the Short-Term Effects of Air Pollution on the Chronic Obstructive Pulmonary Disease Hospital Admissions in Shandong, China.

Although there is growing evidence linking chronic obstructive pulmonary disease (COPD) hospital admissions to the exposure to ambient air pollution, the effect can vary depending on the local geography, pollution type, and pollution level. The number of large-scale multicity studies remains limited in China. This study aims to assess the short-term effects of ambient air pollution (PM2.5, PM10, SO2, NO2) on chronic obstructive pulmonary disease hospital admissions from 2015 to 2016, with a total of 216,159 records collected from 207 hospitals in 17 cities all over the Shandong province, east China. Generalized additive models and penalized splines were applied to study the data whilst controlling for confounding meteorological factors and long-term trends. The air pollution was analyzed with 0–6 day lag effects and the percentage change of hospital admissions was assessed for a 10-μg/m³ increase in the air pollution levels. We also examined the percentage changes for different age groups and gender, respectively. The results showed that air pollution was significantly associated with adverse health outcomes and stronger effects were observed for females. The air pollution health effects were also impacted by geographical factors such that the air pollution had weaker health effects in coastal cities.

Trajectories of Long-Term Normal Fasting Plasma Glucose and Risk of Coronary Heart Disease: A Prospective Cohort Study.

BACKGROUND: Fasting plasma glucose (FPG) levels can vary over time and its longitudinal changing patterns may predict cardiometabolic risk. We aim to identify different trajectories of FPG in those who remained normoglycemic and investigate the association between trajectory groups and coronary heart disease risk in a large prospective cohort study. METHODS AND RESULTS: A total of 20 514 subjects between ages 20 and 80 years were included at baseline. All participants had maintained normal FPG throughout an average follow-up period of 5.8 years. We identified 3 distinct trajectories using a group-based trajectory model, labeled by initial value and changing pattern: low-increasing (n=12 694), high-increasing-decreasing (n=5330), and high-decreasing-increasing (n=2490). The coronary heart disease incidence density among these 3 groups (3.00, 4.05, and 3.26 per 1000 person-years, respectively) was significantly different (P=0.038). The high-increasing-decreasing group was characterized by a starting FPG of 4.80 mmol/L, and increased up to 5.42 mmol/L at age 55, then decreased thereafter. Treating the low-increasing group as the reference, the age- and sex-adjusted hazard ratio was 1.58 (95% confidence interval, 1.23-2.02) for the high-increasing-decreasing group by Cox proportional hazard regression. After adjustment for other potential confounding factors, the hazard ratio is 1.40 (95% confidence interval, 1.08-1.81). The association persisted after adjustment for baseline FPG, mean, or SD of FPG. CONCLUSIONS: Distinct trajectories of long-term normal FPG are associated with the development of coronary heart disease, which is independent of other metabolic factors including FPG levels. These findings have implications for intervention and prevention of coronary heart disease among individuals who are normoglycemic.

The long-term spatial-temporal trends and burden of esophageal cancer in one high-risk area: A population-registered study in Feicheng, China.

BACKGROUND: Feicheng County is a high-risk area for esophageal cancer in Shandong province, China. It is important to determine the long-term spatio-temporal trends in epidemiological characteristics and the burden of esophageal cancer, especially since the implementation of the national esophageal cancer screening program for early detection and treatment in 2005. METHODS: The data collected in Feicheng County from 2001 to 2012 was extracted from the whole-population cancer registry system. The incidence, mortality, disability-adjusted life years (DALY) and changing trends in esophageal cancer according to age and sex were calculated and described. RESULTS: The incidence rate of esophageal cancer in Feicheng was consistently high, and increased significantly for male, but not for female from 2001 to 2012, according to the joinpoint regression analysis. The highest and lowest yearly crude incidence rates were 160.78 and 95.97 per 100000 for males, and 81.36 and 52.17 per 100000 for females. The highest and lowest crude yearly mortality rates were 122.26 and 94.40 per 100000 for males, and 60.75 and 49.35 per 100000for females. Esophageal squamous cell carcinoma was the main pathology type and the tumor location changed significantly from 2001 to 2012. Overall, the DALY remained roughly stable and was estimated as 11.50 for males and 4.90 for females per 1000 people. The burden was mainly caused by premature death. There is an obvious spatial pattern in the distribution of incidence density and burden. CONCLUSION: Esophageal cancer remains a public health issue in Feicheng County with a high incidence, mortality and disease burden. The incidence and burden have obvious spatial heterogeneity, and further studies should be conducted to identify geographical risk factors for precise local prevention and control measures.