Development and validation of a prognostic nomogram for 3-year all-cause mortality risk among elderly patients undergoing surgery for osteoporotic fractures.

Introduction: To develop and validate a comprehensive prognostic model for the mid-to-long term mortality risk among ≥50-year-old osteoporotic fracture (OPF) surgical patients. Methods: Our retrospective investigation included data from the Osteoporotic Fracture Registration System established by the Affiliated Kunshan Hospital of Jiangsu University, and involved 1,656 patients in the development set and 675 patients in the validation set. Subsequently, we employed a multivariable Cox regression model to establish a 3-year mortality predicting nomogram, and the model performance was further evaluated using C-index and calibration plots. Decision curve analysis (DCA) was employed to assess feasibility of the clinical application of this model. Results: Using six prognostic indexes, namely, patient age, gender, the American Society of Anesthesiologists (ASA) score, the Charlson comorbidity index (CCI), fracture site, and fracture liaison service (FLS), we generated a simple nomogram. The nomogram demonstrated satisfactory discrimination within the development (C-index = 0.8416) and validation (C-index = 0.8084) sets. Using calibration plots, we also revealed good calibration. The model successfully classified patients into different risk categories and the results were comparable in both the development and validation sets. Finally, a 1-70% probability threshold, according to DCA, suggested that the model has promise in clinical settings. Conclusion: Herein, we offer a robust tool to estimating the 3-year all-cause mortality risk among elderly OPF surgical patients. However, we recommend further assessments of the proposed model prior to widespread clinical implementation.

A novel fracture liaison service using digital health: impact on mortality in hospitalized elderly osteoporotic fracture patients.

We examined the performance of an intelligent fracture liaison service (FLS) assisted by digital health (DH) to reduce all-cause mortality (ACM) risk. According to our findings, the new FLS reduced ACM by 36%. INTRODUCTION: A well-designed secondary prevention program known as FLS enhances the bone densitometry-based assessment rate as well as osteoporosis (OP) medication usage following a fracture. However, there are only a few reports on FLS incorporating DH, and it remains unclear whether this integration has influenced patient ACM, which refers to the overall death rate from any cause during the study period. METHODS: This retrospective observational study was conducted on data from the Fragility Fracture Registration System database linked to the Regional Health Registration Platform of Kunshan City and the Population Death Registration System of Jiangsu Province for one tertiary-level A hospital in China. Patients aged ≥ 50 years, who experienced an OP fracture between January 1, 2017, and July 27, 2022, requiring hospitalization, were selected for analysis. We compared the outcomes of patients who received routine fragility fracture management (the no-FLS group) or FLS (the FLS group). We employed multivariable Cox regression with inverse probability weighting based on the propensity score (PS). RESULTS: Of 2317 patients, 756 (32.6%) received FLS and 1561 (67.4%) did not. Using PS matching, we minimized the baseline characteristic differences between the two groups in the propensity score-matched samples, relative to the unmatched samples. Based on our analysis, the new FLS reduced ACM by 36% (hazard ratio [HR], 0.64; 95% confidence interval [CI], 0.47 to 0.87; P-value = 0.004). Moreover, FLS patients experienced further reductions in fall-related mortality, refracture rate, and total refracture-related hospital costs, and had increased dual-energy X-ray absorptiometry (DXA) testing and treatment initiation rates, relative to the no-FLS patients. CONCLUSIONS: A new FLS model implementation assisted by DH can effectively reduce ACM among elderly patients with OP fractures requiring surgery. In future investigations, we recommend examining the scalability of this model.

Association between perioperative blood transfusion and length of hospital stay in patients with osteoporotic fractures.

BACKGROUND: Few studies have examined the relationship between perioperative blood transfusion (PBT) and length of hospital stay (LOS) in patients with osteoporotic fractures. This research aims to study the association between PBT and LOS. METHODS: This is a retrospective cross-sectional study from the Affiliated Kunshan Hospital of Jiangsu University, Suzhou, China, involving 2357 osteoporotic fractures (OPF) patients who received surgical treatment during hospitalization from January 2017 and March 2022. Multiple linear regression was used to analyze the relationship between PBT and LOS. In the analysis, PBT volume was the dependent variable, whereas LOS was the independent variable. Simultaneously, age, gender, body mass index, hemoglobin, primary diagnosis, American Society of Anesthesiologists, creatinine (Cr), anesthesia, surgical method, and Charlson comorbidity index were included as covariates. The generalized additive model was then used to study nonlinear associations. Two piecewise linear regression exemplary evaluated the inception results for smoothing the curve. RESULTS: Our results proved that PBT was positively correlated with LOS in the fully adjusted model (ß, 0.21; 95% CI, 0.04 to 0.37; P < 0.0001). Furthermore, a "U-shape" nonlinear relationship existed between PBT and LOS. When the concentration of PBT was between 0 and 1.5 units, it was manifested as a negative correlation between PBT and LOS. However, there was a positive association between PBT and LOS when PBT levels exceeded 1.5 units. CONCLUSIONS: This study demonstrated that PBT and LOS in the OPF population were independent with a nonlinear relationship. These results suggest that PBT may be protective for patients with long LOS. If these findings are confirmed, the LOS in OPF patients can be regulated through appropriate perioperative blood transfusion.

Association between serum 25-hydroxyvitamin D and fasting blood glucose in osteoporosis patients.

Osteoporosis (OP) is often associated with other complications, such as impaired glucose homeostasis. Vitamin D deficiency is common and has been linked to bone metabolism and the regulation of blood sugar levels. The aim of this study was to evaluate the independent relationship between serum 25-hydroxyvitamin D (25[OH]D) and fasting blood glucose levels (FBG) in a group of patients diagnosed with OP. This is a retrospective cross-sectional study from a prospectively collected database at our tertiary referral center. Consecutive 2084 OP patients who were hospitalization were finally analyzed in this study. FBG is the dependent variable, serum 25(OH)D level of OP patients is exposure variable of this study. There was a linear significantly negative association between serum 25(OH)D and FBG (ß, - 0.02; 95% CI - 0.03 to - 0.01; P = 0.0011) in the fully adjusted models. Specifically, when serum 25(OH)D level was less than 23.39 ng/mL, FBG decreased by 0.04 mmol/L for every 1 ng/mL increase of serum 25(OH)D level. When serum 25(OH)D was greater than 23.39 ng/ mL, the negative association was insignificant (P = 0.9616). If the association is confirmed, the clinical management of blood glucose in OP patients with serum 25(OH)D deficiency has instructive implications.

Association between lumbar endplate damage and bone mineral density in patients with degenerative disc disease.

BACKGROUND: To explore the independent association between lumbar endplate damage and bone mineral density (BMD) in patients with degenerative disc disease (DDD). METHODS: This retrospective investigation was based out of a prospectively collected database from the Affiliated Kunshan Hospital of Jiangsu University. Data from 192 DDD patients, collected between December 2018 and January 2022, were chosen for the final analysis. The average total endplate score (TEPS) of lumbar(L) 1-L4 was assessed by magnetic resonance imaging (MRI), and represents the extent of endplate damage. Osteoporosis severity was assessed via the L1-L4 BMD evidenced by dual-energy x-ray absorptiometry (DXA). Other analyzed information included gender, age, body mass index (BMI), and osteophyte score (OSTS). Uni- and multivariate linear regression analyses were employed to evaluate the association between average TEPS and BMD of L1-L4. Moreover, the generalized additive model (GAM) was employed for non-linear association analysis. RESULTS: Upon gender, age, BMI, and OSTS adjustments, a strong independent inverse relationship was observed between average TEPS and BMD (ß, -0.021; 95% CI, -0.035 to -0.007, P-value = 0.00449). In addition, the gender stratification analysis revealed a linear relationship in males, and a non-linear relationship in females. Specifically, there was a significantly stronger negative relationship between average TEPS and BMD in females, when the average TEPS was < 3.75 (ß, -0.063; 95% CI, -0.114 to -0.013; P-value = 0.0157). However, at an average TEPS > 3.75, the relationship did not reach significance (ß, 0.007; 95% CI, -0.012 to 0.027; P-value = 0.4592). CONCLUSIONS: This study demonstrated the independent negative association between average TEPS and BMD values of L1-L4. Upon gender stratification, a linear relationship was observed in males, and a non-linear association in females. The findings reveal that patients with osteoporosis or endplate damage require more detailed examinations and treatment regimen.

Association of 25-hydroxyvitamin D levels with lipid profiles in osteoporosis patients: a retrospective cross-sectional study.

BACKGROUND: In the literature, scarce data investigate the link between 25-hydroxyvitamin D (25[OH]D) and blood lipids in the osteoporosis (OP) population. 25(OH)D, as a calcium-regulating hormone, can inhibit the rise of parathyroid hormone, increase bone mineralization to prevent bone loss, enhance muscle strength, improve balance, and prevent falls in the elderly. This retrospective cross-sectional study aimed to investigate the association between serum 25(OH)D levels and lipid profiles in patients with osteoporosis, with the objective of providing insight for appropriate vitamin D supplementation in clinical settings to potentially reduce the incidence of cardiovascular disease, which is known to be a major health concern for individuals with osteoporosis. METHODS: This is a retrospective cross-sectional study from the Affiliated Kunshan Hospital of Jiangsu University, including 2063 OP patients who received biochemical blood analysis of lipids during hospitalization from January 2015 to March 2022. The associations between serum lipids and 25(OH)D levels were examined by multiple linear regression. The dependent variables in the analysis were the concentrations of serum lipoprotein, total cholesterol (TC), triglycerides (TGs), apolipoprotein-A, lipoprotein A, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol (LDL-C). The independent variable was the concentration of blood serum 25(OH)D. At the same time, age, body mass index, sex, time and year of serum analysis, primary diagnosis, hypertension, diabetes, statins usage, beta-C-terminal telopeptide of type I collagen, procollagen type I N-terminal propeptide were covariates. Blood samples were collected in the early morning after the overnight fasting and were analyzed using an automated electrochemiluminescence immunoassay on the LABOSPECT 008AS platform (Hitachi Hi-Tech Co., Ltd., Tokyo, Japan). The generalized additive model was further applied for nonlinear associations. The inception result for smoothing the curve was evaluated by two-piecewise linear regression exemplary. RESULTS: Our results proved that in the OP patients, the serum 25(OH)D levels were inversely connected with blood TGs concentration, whereas they were positively associated with the HDL, apolipoprotein-A, and lipoprotein A levels. In the meantime, this research also found a nonlinear relationship and threshold effect between serum 25(OH)D and TC, LDL-C. Furthermore, there were positive correlations between the blood serum 25(OH)D levels and the levels of TC and LDL-C when 25(OH)D concentrations ranged from 0 to 10.04 ng/mL. However, this relationship was not present when 25(OH)D levels were higher than 10.04 ng/mL. CONCLUSIONS: Our results demonstrated an independent relationship between blood lipids and vitamin D levels in osteoporosis patients. While we cannot establish a causal relationship between the two, our findings suggest that vitamin D may have beneficial effects on both bone health and blood lipid levels, providing a reference for improved protection against cardiovascular disease in this population. Further research, particularly interventional studies, is needed to confirm these associations and investigate their underlying mechanisms.

Association between serum uric acid levels and bone mineral density in patients with osteoporosis: a cross-sectional study.

BACKGROUND: The results of studies exploring the association between serum uric acid (SUA) and bone mineral density (BMD) have been controversial and inconsistent. We thus sought to explore whether SUA levels were independently associated with BMD in patients with osteoporosis (OP). METHODS: This cross-sectional analysis was conducted using prospectively obtained data from the Affiliated Kunshan Hospital of Jiangsu University database pertaining to 1,249 OP patients that were hospitalized from January 2015 - March 2022. BMD was the outcome variable for this study, while baseline SUA levels were the exposure variable. Analyses were adjusted for a range of covariates including age, gender, body mass index (BMI) and a range of other baseline laboratory and clinical findings. RESULTS: SUA levels and BMD were independently positively associated with one another in OP patients. Following adjustment for age, gender, BMI, blood urae nitrogen (BUN), and 25(OH)D levels, a 0.0286 g/cm2 (ß, 0.0286; 95% confidence interval [CI], 0.0193-0.0378, P < 0.000001) increase in BMD was observed per 100 µmol/L rise in SUA levels. A non-linear association between SUA and BMD was also observed for patients with a BMI < 24 kg/m2, with a SUA level inflection point at 296 µmol/L in the adjusted smoothed curve. CONCLUSIONS: These analyses revealed SUA levels to be independently positively associated with BMD in OP patients, with an additional non-linear relationship between these two variables being evident for individuals of normal or low body weight. This suggests that SUA levels may exert a protective effect on BMD at concentrations below 296 µmol/L in normal- and low-weight OP patients, whereas SUA levels above this concentration were unrelated to BMD.

Correlation between meteorological factors and vitamin D status under different season.

Pregnant women with low vitamin D levels tend to have poor clinical outcomes. Meteorological factors were associated with vitamin D. Here, we aimed to study the current status of 25-Hydroxy vitamin D (25(OH)D) concentrations in pregnant women in Kunshan city and investigate the meteorological factors associated with 25(OH)D levels under different seasons. The correlation between meteorological factors and 25(OH)D levels was estimated by cross-correlation analysis and multivariate logistic regression. A restrictive cubic spline method was used to estimate the non-linear relationship. From 2015 to 2020, a total of 22,090 pregnant women were enrolled in this study. Pregnant women with 25(OH)D concentrations below 50 nmol/l represent 65.85% of the total study population. There is a positive correlation between temperature and 25(OH)D. And there is a protective effect of the higher temperature on vitamin D deficiency. However, in the subgroup analysis, we found that in autumn, high temperatures above 30 °C may lead to a decrease in 25(OH)D levels. This study shows that vitamin D deficiency in pregnant women may widespread in eastern China. There is a potential inverted U-shaped relationship between temperature and 25(OH)D levels, which has implications for understanding of vitamin D changes under different seasons.

Predicting monthly hospital outpatient visits based on meteorological environmental factors using the ARIMA model.

Accurate forecasting of hospital outpatient visits is beneficial to the rational planning and allocation of medical resources to meet medical needs. Several studies have suggested that outpatient visits are related to meteorological environmental factors. We aimed to use the autoregressive integrated moving average (ARIMA) model to analyze the relationship between meteorological environmental factors and outpatient visits. Also, outpatient visits can be forecast for the future period. Monthly outpatient visits and meteorological environmental factors were collected from January 2015 to July 2021. An ARIMAX model was constructed by incorporating meteorological environmental factors as covariates to the ARIMA model, by evaluating the stationary [Formula: see text], coefficient of determination [Formula: see text], mean absolute percentage error (MAPE), and normalized Bayesian information criterion (BIC). The ARIMA [Formula: see text] model with the covariates of [Formula: see text], [Formula: see text], and [Formula: see text] was the optimal model. Monthly outpatient visits in 2019 can be predicted using average data from past years. The relative error between the predicted and actual values for 2019 was 2.77%. Our study suggests that [Formula: see text], [Formula: see text], and [Formula: see text] concentration have a significant impact on outpatient visits. The model built has excellent predictive performance and can provide some references for the scientific management of hospitals to allocate staff and resources.

Particulate matter may have a limited influence on maternal vitamin D levels.

Evidence for an association between the amount of particulate matter (PM) in the atmosphere and vitamin D status of pregnant women is limited. We aimed to examine the independent association between PM and maternal levels of serum 25-hydroxyvitamin D (25OHD) during the second trimester and to explore possible modifications to the association by meteorological factors. 27,768 pregnant women presenting for prenatal examination who were tested for serum 25OHD concentration during the second trimester between January 1, 2016, and December 31, 2020, were included in this retrospective analysis. Exposure to PM was evaluated based on daily average PM with an aerodynamic diameter of ≤ 2.5 µm (PM2.5) and PM with an aerodynamic diameter of ≤ 10 µm (PM10). Corresponding meteorological data for daily average atmospheric temperature, atmospheric pressure, relative humidity, sunshine duration, and wind speed were collected. The maximum cumulative effects of PM2.5 occurred at lag 45 days, and the maximum cumulative effects of PM10 occurred at lag 60 days. In crude models, 45-day moving daily average PM2.5 concentrations were negatively associated with 25OHD levels (ß, - 0.20; 95% CI - 0.21 to - 0.19), as were 60-day moving daily average PM10 concentrations (ß, - 0.14; 95% CI - 0.15 to - 0.14). After adjusting for temporal and meteorological factors, the effect values were drastically reduced (adjusted ß of PM2.5, - 0.032; 95% CI - 0.046 to - 0.018; adjusted ß of PM10, - 0.039; 95% CI - 0.049 to - 0.028). Our study showed there was a small, independent, negative association between PM in the atmosphere and maternal serum 25OHD levels during the second trimester of pregnancy after adjusting for temporal and/or meteorological factors, which indicates that PM may have a limited influence on maternal serum 25OHD levels. Besides taking vitamin D supplements, pregnant women should keep participating in outdoor activities while taking PM protection measures to improve their vitamin D levels when PM levels are high in winter and spring.

Association between vitamin D and zoledronate-induced acute-phase response fever risk in osteoporotic patients.

Objectives: To elucidate the independent correlation between vitamin D content and zoledronate (ZOL)-triggered acute-phase response (APR) fever risk in osteoporotic (OP) patients, and to examine the potential threshold for optimal vitamin D concentrations that prevent the occurrence of ZOL-induced fever. Methods: This retrospective investigation was based on a prospectively documented database compiled at the Affiliated Kunshan Hospital of Jiangsu University between January 2015 and March 2022. In total, 2095 OP patients, who received ZOL during hospitalization, were selected for analysis. The primary endpoint was the presence (>37.3°C) or absence (≤37.3°C) of fever, quantified by the maximum body temperature, measured within 3 days of ZOL infusion. The exposure variable was the baseline serum 25-hydroxyvitamin D (25[OH]D) levels. Results: The OP patients with fever exhibited markedly reduced 25(OH)D content than those without fever. Upon adjusting for age, gender, order of infusion of ZOL, main diagnosis, season of blood collection, year of blood collection, calcitonin usage, and beta-C-terminal telopeptide of type I collagen (ß-CTX) levels, a 10 ng/mL rise in serum 25(OH)D content was correlated with a 14% (OR, 0.86; 95% CI, 0.76 to 0.98, P-value = 0.0188) decrease in the odds of ZOL-induced fever. In addition, a non-linear relationship was also observed between 25(OH)D levels and fever risk, and the turning point of the adjusted smoothed curve was 35 ng/mL of serum 25(OH)D content. Conclusions: Herein, we demonstrated the independent negative relationship between serum 25(OH)D content and ZOL-induced fever risk. According to our analysis, 25(OH)D above 35 ng/mL may be more effective in preventing ZOL-induced APR. If this is confirmed, a "vitamin D supplemental period" is warranted prior to ZOL infusion, particularly the first ZOL infusion, to ensure appropriate 25(OH)D levels that protect against ZOL-induced fever.

Consequences of Preoperative Oral Carbohydrate Consumption in Septal Deviation Patients Undergoing Endoscopic Septoplasty: A Retrospective Cohort Study.

PURPOSE: Multiple reports have demonstrated the benefits of preoperative oral carbohydrates (CHO) in patients receiving open abdominal, thoracic, and orthopedic surgeries. However, thus far, no reports have investigated the benefits of CHO in patients undergoing nasal endoscopic surgery. Our goal was to evaluate the outcome of preoperative oral of administration of CHO in septal deviation patients, undergoing endoscopic septoplasty, under general anesthesia. DESIGN: A retrospective cohort study from a prospectively collected database. METHODS: Consecutive 400 septal deviation patients, undergoing endoscopic septoplasty, were randomly assigned to receive CHO or plain water (80 CHO cohort vs. 320 control cohort) before general anesthesia. The primary outcome was the risk of acute postoperative hypertension (APH). The secondary outcomes included length of hospital stay (LOS), hospitalization cost, sleep time the day before surgery, fluid infusion volume on surgical day, as well the incidence of postoperative nausea and vomiting (PONV) and aspiration. FINDINGS: Patients in the CHO cohort experienced a lower risk of both diastolic blood pressure (DBP)-based APH (OR, 0.49; 95% CI, 0.25 to 0.96; P = 0.0375) and total APH (OR, 0.49; 95% CI, 0.26 to 0.92; P = 0.0258), lower LOS, lower hospitalization cost, longer sleep time and less fluid infusion volume after adjusting for gender, age, BMI, preoperative blood pressure and pulse. Besides, data showed no significant differences in the incidence of (P = 0.4173) and aspiration (P > 0.99). CONCLUSIONS: Preoperative CHO administration can reduce APH risk in patients undergoing endoscopic septoplasty under general anesthesia. Besides, preoperative CHO administration can improve other clinical outcomes, such as, LOS, hospitalization cost, sleep time, and fluid infusion volume. Moreover, CHO safety was confirmed in our study. In the future, additional investigation is necessary to confirm our results.

Impact of Visit-to-Visit Triglyceride-Glucose Index Variability on the Risk of Cardiovascular Disease in the Elderly.

Background: The aging population is increasingly susceptible to cardiovascular disease (CVD). Visit-to-visit variability in glucose and lipid levels both contributed to CVD risk independent of their mean values. However, whether variability in the triglyceride-glucose (TyG) index is a risk factor for CVD remains unknown. Research Design and Methods. In this retrospective study of electronic health records, 27,520 participants aged over 60 years were enrolled. The visit-to-visit variability of TyG index was calculated from annual health examination data and defined as average real variability (ARV), standard deviation (SD), or the coefficient of variability (CV). CVD events were identified from the chronic disease registry or follow-up database and included myocardial infarction, angina, coronary, and stroke. Multivariate Cox regression was used to examine the correlation between TyG variability and incident CVD. Results: Over a median follow-up of 6.2 years, there were 2,178 CVD events. When participants were divided into four quartiles according to their TyG variability, after adjusting for established CVD risk factors, subjects in the top quartile had (HR = 1.18, 95% CI 1.05-1.34, P=0.005) significantly higher CVD risk than those in the bottom quartile. The association remained significant in overweight individuals or those without diabetes (P < 0.005 and P < 0.01, respectively). Conclusions: High variability in TyG was significantly associated with elevated CVD risk in the elderly, independent of average TyG and other risk factors. Close monitoring variability in TyG might be informative to identify old individuals at high risk of CVD.

Predicting the individualized risk of nonadherence to zoledronic acid among osteoporosis patients receiving the first infusion of zoledronic acid: development and validation of new predictive nomograms.

Introduction: Achieving optimal adherence to zoledronic acid (ZOL) among osteoporosis (OP) patients is a challenging task. Here, we aimed to develop and validate a precise and efficient prediction tool for ZOL nonadherence risk in OP patients. Methods: We prospectively collected and analyzed survey data from a clinical registry. A total of 1010 OP patients treated for the first time with ZOL in two separate hospitals were selected for nonadherence analysis. The evaluation included a 16-item ZOL Nonadherence Questionnaire and potential risk factors for ZOL nonadherence were assessed via univariate and multivariate analyses. We next developed and validated two distinct-stage nomograms. Discrimination, calibration, and clinical usefulness of the predicting models were assessed using the area under the curve (AUC), calibration curves, and decision curve analysis (DCA). Results: The total nonadherence rate was 20.30% after the first ZOL infusion. To generate a model predicting ZOL nonadherence risk, six predictors of 16 items were retained. Model 2 (AUC, 0.8486; 95% confidence interval [CI], 0.8171-0.8801) exhibited considerably more discrimination in desirable functional outcomes, relative to Model 1 (AUC, 0.7644; 95% CI, 0.7265-0.8024). The calibration curves displayed good calibration. DCA revealed that a cutoff probability of 5-54% (Model 1) and 1-85% (Model 2) indicated that the models were clinically useful. External validation also exhibited good discrimination and calibration. Conclusions: This study developed and validated two novel, distinct-stage prediction nomograms that precisely estimate nonadherence risk among OP patients receiving the first infusion of ZOL. However, additional evaluation and external validation are necessary prior to widespread implementation.

Predicting the acute-phase response fever risk in bisphosphonate-naive osteoporotic patients receiving their first dose of zoledronate.

INTRODUCTION: To devise a precise and efficient tool for predicting the individualized risk of acute-phase response (APR) in bisphosphonate (BP)-naive osteoporotic (OP) patients, receiving their first intravenous dose of zoledronate (ZOL). METHODS: The baseline clinical and laboratory data of 475 consecutive BP-naive OP patients, who received their first intravenous dose of ZOL between March 2016 and March 2021 in the Affiliated Kunshan Hospital of Jiangsu University, were chosen for analysis. Univariate and multivariable logistic regression models were generated to establish candidate predictors of APR fever risk, using three distinct fever thresholds, namely, 37.3 °C (model A), 38.0 °C (model B), and 38.5 °C (model C). Next, using predictor regression coefficients, three fever-threshold nomograms were developed. Discrimination, calibration, and clinical usefulness of each predicting models were then assessed using the area under the curve (AUC), calibration curve (CC), and decision curve analysis (DCA). The internal and external model validations were then performed. RESULTS: The stable predictors were age, serum 25-hydroxy vitamin D, serum total calcium, and peripheral blood erythrocytes count. These were negatively associated with the APR fever risk. The AUCs of models A, B, and C were 0.828 (95% confidence intervals [CI], 0.782 to 0.874), 0.825 (95% CI, 0.767 to 0.883), and 0.879 (95% CI, 0.824 to 0.934), respectively. Good agreement was observed between the predictions and observations in the CCs of all three nomograms. CONCLUSIONS: This study developed and validated nomogram prediction models that can predict APR fever risk in BP-naive OP patients receiving their first infusion of ZOL.

Exercise training in patients with corrected tetralogy of Fallot: A protocol for systematic review and meta-analysis.

BACKGROUND: The arrival of transcatheter mitral valve therapies has provided feasible and safe alternatives to medical and surgical treatments for mitral regurgitation. The aim of this study is to estimate the relative efficacy and safety of exercise training in patients with corrected tetralogy of Fallot through meta-analysis. METHODS: : A systematic search will be performed using PubMed, EMBASE, the Cochrane Library, Web of Science, CBM, CNKI, WanFang Data, and VIP to include random controlled trials or nonrandom controlled trials comparing the efficacy and safety of exercise training in corrected tetralogy of Fallot patients. The risk of bias for the included nonrandom controlled studies will be evaluated according to Risk of Bias in Nonrandomized Studies of Interventions. We will use the Cochrane Collaboration's tool (version 2 of the Cochrane risk of bias tool for randomized trials) to assess risk of bias of included random controlled trials. Revman 5.4 and STATA 15.0 will be used to complete the meta-analysis and generate forest plots. Grading of recommendations assessment, development, and evaluation will be used to assess the quality of evidence. RESULTS: : The results of this systematic review and meta-analysis will be submitted to a peer-reviewed journal for publication. CONCLUSION: : This study will provide broad evidence of efficacy and safety of exercise training in patients with corrected tetralogy of Fallot and provide suggestions for clinical practice and future research. PROTOCOL REGISTRATION NUMBER: INPLASY202150006.

Intelligent Diagnosis of Heart Murmurs in Children with Congenital Heart Disease.

Heart auscultation is a convenient tool for early diagnosis of heart diseases and is being developed to be an intelligent tool used in online medicine. Currently, there are few studies on intelligent diagnosis of pediatric murmurs due to congenital heart disease (CHD). The purpose of the study was to develop a method of intelligent diagnosis of pediatric CHD murmurs. Phonocardiogram (PCG) signals of 86 children were recorded with 24 children having normal heart sounds and 62 children having CHD murmurs. A segmentation method based on the discrete wavelet transform combined with Hadamard product was implemented to locate the first and the second heart sounds from the PCG signal. Ten features specific to CHD murmurs were extracted as the input of classifier after segmentation. Eighty-six artificial neural network classifiers were composed into a classification system to identify CHD murmurs. The accuracy, sensitivity, and specificity of diagnosis for heart murmurs were 93%, 93.5%, and 91.7%, respectively. In conclusion, a method of intelligent diagnosis of pediatric CHD murmurs is developed successfully and can be used for online screening of CHD in children.

Hsa-miR-140-5p down-regulates LDL receptor and attenuates LDL-C uptake in human hepatocytes.

BACKGROUND AND AIMS: MicroRNAs (miRs) exert important regulatory effects in cholesterol metabolism. Hepatic low density lipoprotein receptor (LDLR) pathway, as the major mechanism for clearing circulating low density lipoprotein cholesterol (LDL-C) in bloodstream, is a pivotal therapeutic target to treat hypercholesterolemia and atherosclerosis. This study aimed to identify novel miRs that regulate LDLR expression. METHODS AND RESULTS: Hsa-miR-140-5p was predicted by bioinformatics analyses to interact with human LDLR mRNA. To evaluate its functional effects in regulating LDLR, hsa-miR-140-5p and anti-miR-140-5p were transfected into human and mouse liver cells, followed by qRT-PCR, western blot, immunofluorescence, flow cytometry, and LDL-C uptake assays. It was observed that hsa-miR-140-5p over-expression dramatically down-regulated LDLR expression and reduced LDL-C uptake, whereas inhibition of hsa-miR-140-5p significantly up-regulated LDLR expression and enhanced LDL-C uptake in human HepG2 and LO2 cells, but not in mouse Hepa1-6 cells. Luciferase reporter assay and site-directed mutagenesis identified that hsa-miR-140-5p interacts with the predicted seed sequence "AAACCACU" in the 3'-UTR of human LDLR mRNA. Hsa-miR-140-5p over-expression attenuated LDL-C uptake and decreased intracellular cholesterol levels in the presence of 50 µg/ml ox-LDL in HepG2 cells. Additionally, palmitic acid and simvastatin suppressed, whereas LDL-C up-regulated the expression of miR-140-5p in HepG2 cells. CONCLUSIONS: Hsa-miR-140-5p is a negative regulator of LDLR expression in human hepatocytes, but not in mouse hepatocytes. Simvastatin inhibits hsa-miR-140-5p expression in human hepatocytes, which is likely to be a novel mechanism for treating hypercholesterolemia with statins in clinic. Antagonism of hsa-miR-140-5p could be a new therapeutic strategy for the treatment of hypercholesterolemia and atherosclerosis.

Lunasin Improves the LDL-C Lowering Efficacy of Simvastatin via Inhibiting PCSK9 Expression in Hepatocytes and ApoE-/- Mice.

Statins are the most popular therapeutic drugs to lower plasma low density lipoprotein cholesterol (LDL-C) synthesis by competitively inhibiting hydroxyl-3-methyl-glutaryl-CoA (HMG-CoA) reductase and up-regulating the hepatic low density lipoprotein receptor (LDLR). However, the concomitant up-regulation of proprotein convertase subtilisin/kexin type 9 (PCSK9) by statin attenuates its cholesterol lowering efficacy. Lunasin, a soybean derived 43-amino acid polypeptide, has been previously shown to functionally enhance LDL uptake via down-regulating PCSK9 and up-regulating LDLR in hepatocytes and mice. Herein, we investigated the LDL-C lowering efficacy of simvastatin combined with lunasin. In HepG2 cells, after co-treatment with 1 µM simvastatin and 5 µM lunasin for 24 h, the up-regulation of PCSK9 by simvastatin was effectively counteracted by lunasin via down-regulating hepatocyte nuclear factor 1α (HNF-1α), and the functional LDL uptake was additively enhanced. Additionally, after combined therapy with simvastatin and lunasin for four weeks, ApoE-/- mice had significantly lower PCSK9 and higher LDLR levels in hepatic tissues and remarkably reduced plasma concentrations of total cholesterol (TC) and LDL-C, as compared to each monotherapy. Conclusively, lunasin significantly improved the LDL-C lowering efficacy of simvastatin by counteracting simvastatin induced elevation of PCSK9 in hepatocytes and ApoE-/- mice. Simvastatin combined with lunasin could be a novel regimen for hypercholesterolemia treatment.