Estimated Costs of Drug-Related Problems Prevented by Pharmacist Prescription Reviews Among Hospitalized Internal Medicine Patients.

BACKGROUND AND OBJECTIVES: Data are lacking on the estimated costs of pharmacist prescription reviews (PPRs) for hospitalized internal medicine patients. This study investigates the estimated costs of drug-related problems (DRPs) prevented by PPRs among hospitalized internal medicine patients. METHODS: We reviewed all medication orders for patients at an academic teaching hospital in China for 2 years. DRPs were categorized using the Pharmaceutical Care Network Europe classification. The severity of the potential harm of DRPs was assessed by the Harm Associated with Medication Error Classification (HAMEC) tool. The estimated cost of PPRs was calculated. RESULTS: A total of 162426 medication orders for 4314 patients were reviewed, and 1338 DRPs were identified by pharmacists who spent 2230 hours performing PPRs. Among the 1080 DRPs that were prospectively intervened upon, 703 were resolved. The HAMEC tool showed that 47.1% of DRPs were assessed as level 2, 30.4% as level 3, 20.6% as level 1, and 0.6% carried a life-threatening risk. Pharmacist interventions contributed to the prevention of DRP errors and a reduction of $339 139.44. This resulted in a mean cost saving of $482.42 per patient at an input cost of $21 495.06 over the 2 years. The benefit-cost ratio was 15.8. CONCLUSION: PPRs are beneficial for detecting potential DRPs and creating potential cost savings among hospitalized internal medicine patients.

Development and validation of a nomogram for predicting all-cause mortality in American adult hypertensive populations.

Backgrounds: Hypertension stands as the predominant global cause of mortality. A notable deficiency exists in terms of predictive models for mortality among individuals with hypertension. We aim to devise an effective nomogram model that possesses the capability to forecast all-cause mortality within hypertensive populations. Methods: The data for this study were drawn from nine successive cycles of the National Health and Nutrition Examination Survey (NHANES) spanning the years from 1999 to 2016. The dataset was partitioned into training and validation sets at a 7:3 ratio. We opted for clinical practice-relevant indicators, applied the least absolute shrinkage and selection operator (LASSO) regression to identify the most pertinent variables, and subsequently built a nomogram model. We also employed concordance index, receiver operating characteristic (ROC) curves, calibration curves and decision curve analysis (DCA) to assess the model's validity. Results: A total of 17,125 hypertensive participants were included in this study with a division into a training set (11,993 individuals) and a validation set (5,132 individuals). LASSO regression was applied for the training set to obtain nine variables including age, monocytes, neutrophils, serum albumin, serum potassium, cardiovascular disease, diabetes, serum creatinine and glycated hemoglobin (HbA1C), and constructed a nomogram prediction model. To validate this model, data from the training and validation sets were used for validation separately. The concordance index of the nomogram model was 0.800 (95% CI, 0.792-0.808, p < 0.001) based on the training set and 0.793 (95% CI, 0.781-0.805, p < 0.001) based on the validation set. The ROC curves, calibration curves, and DCA curves all showed good predictive performance. Conclusion: We have developed a nomogram that effectively forecasts the risk of all-cause mortality among American adults in hypertensive populations. Clinicians may use this nomogram to assess patient's prognosis and choose a proper intervention in a timely manner.

Predictive value of serum creatinine and total bilirubin for long-term death in patients with ischemic heart disease: A cohort study.

BACKGROUND: Ischemic heart disease (IHD) has a high mortality in the population. Although serum creatinine (Cr) and serum total bilirubin (TBil) are rapid and readily available biomarkers in routine blood tests, there is a lack of literature on the prognostic value of combined Cr and TBil tests for IHD. This study aimed to evaluate a combined equation based on Cr and TBil to predict the long-term risk of death in IHD and to find indicators sensitive to the prognosis of IHD patients. METHOD: In this study, 2625 patients with IHD were included, and the combined value and combined equations of Cr and TBil were obtained by logistic regression analysis based on Cr and TBil collected at the time of admission. Patients were divided into four groups according to the quartiles of the combined value. COX proportional hazard regression model was used to analyze the risk factors for long-term death in IHD patients. Receiver operating characteristic (ROC) curves were used to evaluate the prognostic effect of Cr, TBil and combined value on long-term death events. RESULTS: Logistic regression analysis was performed for long-term death events with Cr and TBil as independent variables, and the logit regression model was Logit(P) = 0.0129×TBil+0.007×Cr-0.417. Multifactorial Cox regression analysis showed that high values of the equation were independent risk factors for long-term death events (all-cause death: HR 1.457, 95% CI 1.256-1.689, P<0.001; cardiovascular death: HR 1.452, 95% CI 1.244-1.695, P<0.001). Combined Cr and TBil value are more valuable in predicting long-term death (AUC: 0.609, 95% CI 0.587-0.630, P<0.001). CONCLUSION: Combined Cr and TBil assay is superior to single biomarkers for predicting long-term death in patients with IHD. High values of the equation are independent predictors of long-term death and can be used to identify patients at high risk for IHD.

The role and mechanisms of microvascular damage in the ischemic myocardium.

Following myocardial ischemic injury, the most effective clinical intervention is timely restoration of blood perfusion to ischemic but viable myocardium to reduce irreversible myocardial necrosis, limit infarct size, and prevent cardiac insufficiency. However, reperfusion itself may exacerbate cell death and myocardial injury, a process commonly referred to as ischemia/reperfusion (I/R) injury, which primarily involves cardiomyocytes and cardiac microvascular endothelial cells (CMECs) and is characterized by myocardial stunning, microvascular damage (MVD), reperfusion arrhythmia, and lethal reperfusion injury. MVD caused by I/R has been a neglected problem compared to myocardial injury. Clinically, the incidence of microvascular angina and/or no-reflow due to ineffective coronary perfusion accounts for 5-50% in patients after acute revascularization. MVD limiting drug diffusion into injured myocardium, is strongly associated with the development of heart failure. CMECs account for > 60% of the cardiac cellular components, and their role in myocardial I/R injury cannot be ignored. There are many studies on microvascular obstruction, but few studies on microvascular leakage, which may be mainly due to the lack of corresponding detection methods. In this review, we summarize the clinical manifestations, related mechanisms of MVD during myocardial I/R, laboratory and clinical examination means, as well as the research progress on potential therapies for MVD in recent years. Better understanding the characteristics and risk factors of MVD in patients after hemodynamic reconstruction is of great significance for managing MVD, preventing heart failure and improving patient prognosis.

Nomograms for predicting overall survival in colorectal cancer patients with metastasis to the liver, lung, bone, and brain.

BACKGROUND: The aim of this study was to identify the heterogeneous and homogeneous prognostic factors associated with distant metastasis to the liver, lung, bone, and brain in colorectal cancer (CRC) patients and then construct nomograms to predict the prognosis. METHODS: CRC patients registered in the surveillance, epidemiology, and end results database between 2010 and 2017 were included. A Cox regression model was used to analyse homogeneous and heterogeneous prognostic factors, and Kaplan‒Meier analysis was performed to estimate overall survival (OS). Predictive nomograms were constructed, and their performance was evaluated with C-indexes, calibration curves and the area under the receiver operating characteristic (ROC) curve (AUC). RESULTS: A total of 37,641 patients with distant metastasis to the liver, lung, bone, and brain were included. The median survival times of patients with liver metastasis, lung metastasis, bone metastasis, and brain metastasis were 12.00 months (95% CI 11.73-12.27 months), 10.00 months (95% CI 9.60-10.41 months), 5.00 months (95% CI 4.52-5.48 months), and 3.00 months (95% CI 2.28-3.72 months), respectively. An older age, higher N stage, elevated carcinoembryonic antigen level, no surgery at the primary site and no/unknown treatment with chemotherapy were identified as homogeneous prognostic factors for the four types of metastases. The calibration curves, C-indexes and AUCs exhibited good performance for predicting the OS of patients with distant metastases to the liver, lung, bone, and brain. CONCLUSIONS: CRC patients with distant metastasis to the liver, lung, bone, and brain exhibited homogeneous and heterogeneous prognostic factors, all of which were associated with shorter survival. The nomograms showed good accuracy and may be used as tools for clinicians to predict the prognosis of CRC patients with distant metastasis.

Predictive Effect of Triglyceride-Glucose Index on Adverse Prognostic Events in Patients with Type 2 Diabetes Mellitus and Ischemic Cardiomyopathy.

Background: The triglyceride-glucose (TyG) index is regarded as an independent predictor of cardiovascular (CV) consequences and a reliable surrogate measure of insulin resistance (IR). However, the predictive significance of the TyG index in patients with type 2 diabetes mellitus (T2DM) and ischemic cardiomyopathy (ICM) remains unknown. Methods: This study included 1514 consecutive subjects with ICM and T2DM. The tertile of the TyG index values was used to categorize these patients into three groups. Major adverse cardiac and cerebral events (MACCEs) were also noted. The TyG index was calculated using the [fasting triglycerides (mg/dL) × fasting plasma glucose (mg/dL)/2] equation. Results: After adjusting for age, BMI, and other potential confounders, the scores of multivariate Cox proportional hazards regression models for chest pain [9.056 (4.370 to 18.767), p<0.001], acute myocardial infarction [4.437 (1.420 to 13.869), p=0.010], heart failure [7.334 (3.424 to 15.708), p<0.001], cardiogenic shock [3.707 (1.207 to 11.384), p=0.022], malignant arrhythmia [5.309 (2.367 to 11.908), p<0.001], cerebral infarction [3.127 (1.596 to 6.128), p<0.001], gastrointestinal bleeding [4.326 (1.612 to 11.613), p=0.004], all-cause death [4.502 (3.478 to 5.827), p<0.001] and cumulative incidence of MACCEs [4.856 (3.842 to 6.136), p<0.001] increased significantly with an increase in TyG index levels (all p<0.05). Time-dependent ROC analysis revealed that the area under the TyG index curve (AUC) reached 0.653 in the 3rd year, 0.688 in the 5th year, and 0.764 in the 10th year. The predictive efficiency of this model on MACCEs improved [net reclassification improvement (NRI): 0.361 (0.253 to 0.454); C-index: 0.678 (0.658 to 0.698); integrated discrimination improvement (IDI): 0.138 (0.098 to 0.175), all p<0.05] following the incorporation of the TyG index into the base risk model. Conclusion: TyG index could be useful in predicting MACCEs and initiating preventive measures in subjects with ICM and T2DM.

Circular RNAs in the chemoresistance of triple-negative breast cancer: A systematic review.

This study aims to assess studies on circular RNAs (circRNAs) in the chemoresistance of triple-negative breast cancer (TNBC) and provide relevant references for the development of new TNBC chemotherapy sensitivity biomarkers and therapeutic targets. The PubMed, Embase, Web of Knowledge, Cochrane Library, and four Chinese databases were searched up to January 27, 2023, and studies related to TNBC chemoresistance were included. The basic characteristics of the studies and the mechanisms of circRNAs in regulating TNBC chemoresistance were analyzed. A total of 28 studies published between 2018 and 2023 were included, and the chemotherapeutics included adriamycin, paclitaxel, docetaxel, 5-fluorouracil, lapatinib, and so forth. A total of 30 circRNAs were identified, 86.67% (n = 26) of these circRNAs were reported to act as microRNA (miRNA) sponges to regulate chemotherapy sensitivity, while only two circRNAs (circRNA-MTO1 and circRNA-CREIT) interacted with proteins. A total of 14, 12, and 2 circRNAs were reported to be associated with chemoresistance to adriamycin, taxanes, and 5-fluorouracil, respectively. Six circRNAs were found to act as miRNA sponges that promote chemotherapy resistance by regulating the PI3K/Akt signalling pathway. CircRNAs participate in the regulation of TNBC chemoresistance and can be used as biomarkers and therapeutic targets for improving chemotherapy sensitivity. However, further studies are needed to confirm the role of circRNAs in TNBC chemoresistance.

Prevalence of nonalcoholic fatty liver disease and the related risk factors among healthy adults: A cross-sectional study in Chongqing, China.

Background: Epidemiological characteristics of nonalcoholic fatty liver disease (NAFLD) in Chongqing, a west-central city of China, remain unclear. The objective of this study was to investigate the prevalence of NAFLD and the related risk factors among healthy adults for physical examination in Chongqing. Methods: A total of 110,626 subjects were enrolled in the present study. Each of the participants underwent physical examination, laboratory measurements, and abdominal ultrasonography. The chi-square test was employed to compare differences in the NAFLD prevalence, and logistic regression analysis was used to estimate the odds ratio for risk factors of NAFLD. Results: The prevalence of NAFLD in individuals in the population of Chongqing was 28.5%, and the prevalence in men (38.1%) was significantly higher than that in women (13.6%) (OR = 2.44; 95% CI: 2.31-2.58). NAFLD was more common in men aged 51-60 years and women over 60 years. Approximately 79.1% of the people with obesity and 52.1% of the people with central obesity had NAFLD. The prevalence of NAFLD in people with hypertension and cholelithiasis was 48.9 and 38.4%, respectively. Logistic regression showed that gender, age, body max index (BMI), central obesity, hypertension, impaired fasting glucose/diabetes mellitus (DM), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), hyperuricemia (HUA), alanine transaminase (ALT), and cholelithiasis were independently associated with the presence of NAFLD. Conclusion: The prevalence of NAFLD among healthy adults in Chongqing was high. To improve the prevention and management of NAFLD, special attention should be paid to the factors associated with the presence of NAFLD, including higher BMI, higher waist circumference, higher blood glucose, hypertension, hypertriglyceridemia, hyperuricemia, cholelithiasis, and elevated ALT.

Development and validation of a nomogram to predict mortality risk in patients with ischemic heart disease.

Background: Ischemic Heart Disease (IHD) is the leading cause of death from cardiovascular disease. Currently, most studies have focused on factors influencing IDH or mortality risk, while few predictive models have been used for mortality risk in IHD patients. In this study, we constructed an effective nomogram prediction model to predict the risk of death in IHD patients by machine learning. Methods: We conducted a retrospective study of 1,663 patients with IHD. The data were divided into training and validation sets in a 3:1 ratio. The least absolute shrinkage and selection operator (LASSO) regression method was used to screen the variables to test the accuracy of the risk prediction model. Data from the training and validation sets were used to calculate receiver operating characteristic (ROC) curves, C-index, calibration plots, and dynamic component analysis (DCA), respectively. Results: Using LASSO regression, we selected six representative features, age, uric acid, serum total bilirubin, albumin, alkaline phosphatase, and left ventricular ejection fraction, from 31 variables to predict the risk of death at 1, 3, and 5 years in patients with IHD, and constructed the nomogram model. In the reliability of the validated model, the C-index at 1, 3, and 5 years was 0.705 (0.658-0.751), 0.705 (0.671-0.739), and 0.694 (0.656-0.733) for the training set, respectively; the C-index at 1, 3, and 5 years based on the validation set was 0.720 (0.654-0.786), 0.708 (0.650-0.765), and 0.683 (0.613-0.754), respectively. Both the calibration plot and the DCA curve are well-behaved. Conclusion: Age, uric acid, total serum bilirubin, serum albumin, alkaline phosphatase, and left ventricular ejection fraction were significantly associated with the risk of death in patients with IHD. We constructed a simple nomogram model to predict the risk of death at 1, 3, and 5 years for patients with IHD. Clinicians can use this simple model to assess the prognosis of patients at the time of admission to make better clinical decisions in tertiary prevention of the disease.

SLC27A5 promotes sorafenib-induced ferroptosis in hepatocellular carcinoma by downregulating glutathione reductase.

Sorafenib, a first-line drug for advanced hepatocellular carcinoma (HCC), shows a favorable anti-tumor effect while resistance is a barrier impeding patients from benefiting from it. Thus, more efforts are needed to lift this restriction. Herein, we first find that solute carrier family 27 member 5 (SLC27A5/FATP5), an enzyme involved in the metabolism of fatty acid and bile acid, is downregulated in sorafenib-resistant HCC. SLC27A5 deficiency facilitates the resistance towards sorafenib in HCC cells, which is mediated by suppressing ferroptosis. Further mechanism studies reveal that the loss of SLC27A5 enhances the glutathione reductase (GSR) expression in a nuclear factor erythroid 2-related factor 2 (NRF2)-dependent manner, which maintains glutathione (GSH) homeostasis and renders insensitive to sorafenib-induced ferroptosis. Notably, SLC27A5 negatively correlates with GSR, and genetic or pharmacological inhibition of GSR strengthens the efficacy of sorafenib through GSH depletion and the accumulation of lipid peroxide products in SLC27A5-knockout and sorafenib-resistant HCC cells. Based on our results, the combination of sorafenib and carmustine (BCNU), a selective inhibitor of GSR, remarkably hamper tumor growth by enhancing ferroptotic cell death in vivo. In conclusion, we describe that SLC27A5 serves as a suppressor in sorafenib resistance and promotes sorafenib-triggered ferroptosis via restraining the NRF2/GSR pathway in HCC, providing a potential therapeutic strategy for overcoming sorafenib resistance.

Addictive behavior and incident gallstone disease: A dose-response meta-analysis and Mendelian randomization study.

Background: Previous studies have suggested associations between addictive behavior and gallstone disease (GSD) risk, yet conflicting results exist. It also remains unclear whether this association is causal or due to confounding or reverse associations. The present study aims to systematically analyze the epidemiological evidence for these associations, as well as estimate the potential causal relationships using Mendelian randomization (MR). Methods: We analyzed four common addictive behaviors, including cigarette smoking, alcohol intake, coffee, and tea consumption (N = 126,906-4,584,729 participants) in this meta-analysis based on longitudinal studies. The two-sample MR was conducted using summary data from genome-wide associations with European ancestry (up to 1.2 million individuals). Results: An observational association of GSD risk was identified for smoking [RR: 1.17 (95% CI: 1.06-1.29)], drinking alcohol [0.84 (0.78-0.91)], consuming coffee [0.86 (0.79-0.93)], and tea [1.08 (1.04-1.12)]. Also, there was a linear relationship between smoking (pack-years), alcohol drinking (days per week), coffee consumption (cups per day), and GSD risk. Our MRs supported a causality of GSD incidence with lifetime smoking [1.008 (1.003-1.013), P = 0.001], current smoking [1.007 (1.002-1.011), P = 0.004], problematic alcohol use (PAU) [1.014 (1.001-1.026), P = 0.029], decaffeinated coffee intake (1.127 [1.043-1.217], P = 0.002), as well as caffeine-metabolism [0.997 (0.995-0.999), P = 0.013], and tea consumption [0.990 (0.982-0.997), P = 0.008], respectively. Conclusion: Our study suggests cigarette smoking, alcohol abuse, and decaffeinated coffee are causal risk factors for GSD, whereas tea consumption can decrease the risk of gallstones due to the effect of caffeine metabolism or polyphenol intake.

Homogeneous and heterogeneous risk and prognostic factors for lung metastasis in colorectal cancer patients.

BACKGROUND: The lung is one of the most frequent distant metastasis sites in colorectal cancer (CRC) patients; however, lung metastasis risk and prognostic factors have not been comprehensively elucidated. This study aimed to identify the homogeneous and heterogeneous lung metastasis risk and prognostic factors in CRC patients using the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: CRC patients registered in the SEER database between 2010 and 2016 were included to analyse risk factors for developing lung metastasis by using univariable and multivariable logistic regression. Patients diagnosed between 2010 and 2015 were selected to investigate prognostic factors for lung metastasis by conducting Cox regression. Kaplan-Meier analysis was used to estimate overall survival outcomes. RESULTS: A total of 10,598 (5.2%) patients with synchronous lung metastasis were diagnosed among 203,138 patients with CRC. The median survival time of patients with lung metastasis was 10.0 months (95% CI 9.6-10.5 months). Older age, unmarried status, uninsured status, poor histological differentiation, more lymphatic metastasis, CEA positivity, liver metastasis, bone metastasis and brain metastasis were lung metastasis risk and prognostic factors. Black patients and those with left colon, rectum, and stage T4 disease were more likely to develop lung metastasis, while patients with right colon cancer and no surgical treatment of the primary tumour had poor survival outcomes. CONCLUSION: The incidence of lung metastasis in CRC patients was 5.2%. CRC patients with lung metastasis exhibited homogeneous and heterogeneous risk and prognostic factors. These results are helpful for clinical evaluation and individual treatment decision making.

Peripheral Neuropathy During Concomitant Administration of Proteasome Inhibitors and Factor Xa Inhibitors: Identifying the Likelihood of Drug-Drug Interactions.

Backgrounds: Proteasome inhibitors (PI) cause toxic peripheral neuropathy (PN), which is one of the dose-limiting adverse events of these treatments. Recent preclinical studies find that factor Xa inhibitor (FXaI), rivaroxaban, promotes PN in animals receiving oxaliplatin. Cancer patients can receive combined therapy of PI and FXaI. This study aimed to identify and characterize the interaction signals for the concomitant use of PI and FXaI resulting in PN. Methods: Reports from the United States FDA Adverse Event Reporting System (FAERS) were extracted from the first quarter of 2004 to the first quarter of 2020 for analysis. The Standardized Medical Dictionary for Regulatory Activities (MedDRA) query was used to identify PN cases. We conducted an initial disproportionality investigation to detect PN adverse event signals associated with the combined use of PI and FXaI by estimating a reporting odds ratio (ROR) with a 95% confidence interval (CI). The adjusted RORs were then analyzed by logistic regression analysis (adjusting for age, gender, and reporting year), and additive/multiplicative models were performed to further confirm the findings. Additionally, subset data analysis was performed on the basis of a single drug of PI and FXaI. Results: A total of 159,317 adverse event reports (including 2,822 PN reports) were included. The combined use of PI and FXaI was associated with a higher reporting of PN (RORadj = 7.890, 95%CI, 5.321-11.698). The result remained significant based on additive/multiplicative methods. The observed association was consistent in the analysis restricted to all specific PI agents (bortezomib and ixazomib) and FXaI (rivaroxaban), except apixaban. Conclusion: Analysis of FAERS data identified reporting associations of PN in the combined use of PI and FXaI, suggesting the need for more robust preclinical and clinical studies to elucidate the relationship.

Blood lipid metabolism and the risk of gallstone disease: a multi-center study and meta-analysis.

BACKGROUND: Gallstone disease (GSD) is a common and costly biliary disorder. Multiple studies have investigated the associations between blood lipid metabolism and GSD risk; however, the results are inconsistent. This research aimed to comprehensively evaluate the relationships among serum total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and GSD risk. METHODS: Firstly, a multi-center cross-sectional study was carried out. Subjects who participated in the health examination in three hospitals between January 2015 and May 2020 were recruited. Multivariable logistic regression was used to investigate blood lipid metabolism associated with GSD risk. Then, a meta-analysis was performed to verify the associations further. Medline and Embase databases were systematically searched before June 10, 2021. The DerSimonian and Laird random-effect model was utilized when the heterogeneity was high; otherwise, fixed-effect model was adopted. RESULTS: There were 548,934 eligible participants included in the multi-center study, and 45,392 of them were diagnosed with GSD. The results demonstrated that total cholesterol and HDL cholesterol were negatively associated with GSD risk in both high vs. low model and per mmol/L increase model, while triglyceride was positively associated with GSD risk in the per unit increase model. In the meta-analysis, 104 studies with approximately 3 million participants were finally included. The results verified that HDL cholesterol [odds ratio (OR) = 0.636, P = 5.97 × 10- 16 in high vs low model; OR = 0.974, P = 6.07 × 10- 05 in per unit model] and triglyceride (OR = 1.192, P = 3.47 × 10- 05 in high vs. low model; OR = 1.011, P = 5.12 × 10- 05 in per unit model) were related to GSD risk in the two models. CONCLUSIONS: The findings indicated that low HDL cholesterol levels and high triglyceride levels were risk factors for GSD. This study provides a basis for identifying the population at high risk for GSD and implementing tertiary prevention strategies for GSD, thus contributing to GSD prevention as well as disease burden relief.

Cost-effectiveness analysis of nasojejunal tube feeding for the prevention of pneumonia in adults who are critically ill.

BACKGROUND: Nasojejunal tube (NJT) feeding has demonstrated value in reducing pneumonia in adults who are critically ill who require enteral nutrition (EN) support. This study discusses whether EN support via NJT feeding is more cost-effective than nasogastric tube (NGT) feeding in reducing pneumonia. METHODS: A decision-tree model was created. The analysis was based on data from a health care provider in China. Model inputs were derived from published data. The end points included incremental cost per pneumonia infection avoided, incremental cost-effectiveness ratio (ICER), net monetary benefit (NMB), and incremental NMB (INMB) associated with prevention of pneumonia. The uncertainty was assessed through one-way and probabilistic sensitivity analysis. RESULTS: The base case analysis showed that EN support via NJT feeding resulted in 0.7453 quality-adjusted life years (QALYs) at a cost of $3018.83 compared with NGT feeding, which resulted in 0.7354 QALYs at a cost of $4788.76. NJT feeding was better than NGT feeding, providing an INMB of $2075.09 and an ICER of -$178,813.96 per QALY gained, and the cost per pneumonia infection prevented was $16,808.51. The probabilistic sensitivity analysis indicated that NJT feeding was more cost-effective in 83.4% of the cases, with a cost below the WTP threshold. The NMB and INMB estimation for different WTP thresholds also indicated that NJT feeding is the optimal strategy. CONCLUSIONS: EN support via NJT feeding was a more cost-effective strategy than NGT feeding in preventing pneumonia in adults who are critically ill.

The role of CD74 in cardiovascular disease.

Leukocyte differentiation antigen 74 (CD74), also known as invariant chain, is a molecular chaperone of major histocompatibility complex class II (MHC II) molecules involved in antigen presentation. CD74 has recently been shown to be a receptor for the macrophage migration inhibitory factor family proteins (MIF/MIF2). Many studies have revealed that CD74 plays an important role in cardiovascular disease. In this review, we summarize the structure and main functions of CD74 and then focus on the recent research progress on the role of CD74 in cardiovascular diseases. In addition, we also discuss potential treatment strategies that target CD74. Our systematic review of the role of CD74 in cardiovascular disease will fill some knowledge gaps in the field.

Prevalence and associated metabolic factors for thyroid nodules: a cross-sectional study in Southwest of China with more than 120 thousand populations.

OBJECTIVE: To explore the prevalence and its associated metabolic factors of thyroid nodules (TNs) among subjects who participated in the physical examinations in Chongqing, China. METHODS: The participants from the Health Management Center of JinShan Hospital of Chongqing Medical University, between September 2015 and May 2020, were included in this study. All of the participants underwent thyroid ultrasonography, anthropometric measurements, and serum examinations. Differences in the TNs prevalence were compared with the chi-square test or Wilcoxon rang-sum test. Multivariable logistic regression analyses were used to estimate the metabolic factors associated with TNs and multiple thyroid nodules (MTNs). RESULTS: Of the included 121,702 participants, 41,547 had TNs, and 20,899 had MTNs, with the prevalence of 34.1 and 17.0 %, respectively. Women had a significantly higher prevalence of TNs than men (40.6 % vs. 29.8 %; χ2 = 1517.33, P < 0.001), and TNs prevalence was gradually increased with age (P for trend < 0.001). Female gender, advanced age, and metabolic factors including central obesity, hypertension, diabetes and fatty liver were positively associated with TNs; BMI, hyperlipoidemia and hyperuricemia were not independent risk factors of TNs. While female gender, advanced age, central obesity, hypertension and diabetes were independent risk factors of MTNs. CONCLUSIONS: The prevalence of thyroid nodules was relatively high. The associated factors identified in this study could help the clinicians to detect the high-risk patients and make targeted screening strategies for the preventing of the occurrence of TNs.

Perfluoropentane-filled chitosan poly-acrylic acid nanobubbles with high stability for long-term ultrasound imaging in vivo.

Reducing the size of ultrasound contrast agents (UCAs) will decrease the intensity of the ultrasound echogenic signals and reduce the stability of the bubbles. Therefore, it is a challenge to design nanobubbles that are less than 200 nm in size and that have both good imaging abilities and high stability for long-term imaging in vivo. In this work, we successfully prepared perfluoropentane-filled chitosan poly-acrylic acid (PFP-CS-PAA) nanobubbles with a size of about 100 nm via a direct simple core-template-free strategy. In vitro tests demonstrated that the nanobubbles showed satisfactory imaging capabilities in non-linear harmonic imaging mode and had significantly better stability than commercial Sonovue® lipid microbubbles. It was valuable to discover that the prepared PFP-CS-PAA nanobubbles could exhibit good imaging quality in rat livers for 10 min after intravenous injection. Also, the PFP-CS-PAA nanobubbles could maintain imaging capabilities in nude mouse tumors for 7 days after intratumoral injection, which indicated that these nanobubbles could keep their stability for a long time in vivo. To the best of our knowledge, the ultrasound imaging persistence time in vivo was the longest of currently reported polymer nanobubbles that are smaller than 200 nm. This new nanosized UCA with high stability has great potential for long-term ultrasound imaging in vivo. Tumor cellular uptake and histological analysis revealed that PFP-CS-PAA nanobubbles could be taken up into tumor cells, but no intracellular uptake was observed in the case of Sonovue®. Animal fluorescence imaging in vivo demonstrated that PFP-CS-PAA nanobubbles could be effectively cleared after intravenous injection within 168 h. MTT assays indicated that PFP-CS-PAA nanobubbles had appropriate biocompatibility. Abnormal levels of blood urea nitrogen were detected after the intravenous administration of PFP-CS-PAA nanobubbles to rats, and body-weight gain was inhibited for up to 6 d, but, after that, body weights recovered their tendency to increase.

Nomogram based on homogeneous and heterogeneous associated factors for predicting distant metastases in patients with colorectal cancer.

BACKGROUND: The identification of the homogeneous and heterogeneous risk factors for different types of metastases in colorectal cancer (CRC) may shed light on the aetiology and help individualize prophylactic treatment. The present study characterized the incidence differences and identified the homogeneous and heterogeneous risk factors associated with distant metastases in CRC. METHODS: CRC patients registered in the SEER database between 2010 and 2016 were included in this study. Logistic regression was used to analyse homogeneous and heterogeneous risk factors for the occurrence of different types of metastases. Nomograms were constructed to predict the risk for developing metastases, and the performance was quantitatively assessed using the receiver operating characteristics (ROC) curve and calibration curve. RESULTS: A total of 204,595 eligible CRC patients were included in our study, and 17.07% of them had distant metastases. The overall incidences of liver metastases, lung metastases, bone metastases, and brain metastases were 15.34%, 5.22%, 1.26%, and 0.29%, respectively. The incidence of distant metastases differed by age, gender, and the original CRC sites. Poorly differentiated grade, more lymphatic metastasis, higher carcinoembryonic antigen (CEA), and different metastatic organs were all positively associated with four patterns of metastases. In contrast, age, sex, race, insurance status, position, and T stage were heterogeneously associated with metastases. The calibration and ROC curves exhibited good performance for predicting distant metastases. CONCLUSIONS: The incidence of distant metastases in CRC exhibited distinct differences, and the patients had homogeneous and heterogeneous associated risk factors. Although limited risk factors were included in the present study, the established nomogram showed good prediction performance.