Impact of preoperative antiviral therapy on the prognosis of hepatitis B virus-related hepatocellular carcinoma.

BACKGROUND: For chronic hepatitis B virus (HBV) infection patients, increasing evidence has demonstrated the effectiveness of expanding the indications and applicable population for antiviral therapy. However, the expanded indication of antiviral therapy for hepatocellular carcinoma (HCC) remains to be further explored. METHODS: 196 HBV-related HCC patients who received radical hepatectomy and nucleos(t)ide analogues (NAs) therapy at Sichuan Provincial People's Hospital were enrolled in this study. HCC recurrence, overall survival (OS), early virological (VR) and biochemical responses (BR) of patients were compared between different NAs therapy and the use of anti-programmed cell death protein 1 (PD-1) therapy. RESULTS: NAs therapy at different timing of surgery was a strong independent risk factor for postoperative recurrence and overall mortality of HBV-related HCC patients. Furthermore, in HCC patients who received postoperative anti-PD-1 therapy, patients with HBV DNA < 1000 copy/mL had significantly better recurrence-free survival (RFS) and OS than those with HBV DNA ≥ 1000 copy/mL (HR: 7.783; P = 0.002; HR: 6.699; P < 0.001). However, the differences of RFS and OS rates between entecavir group and tenofovir disoproxil fumarate group were not statistically significant. Similar results were also observed in the rates of early VR, BR and combined VR and BR. CONCLUSION: Timely and reasonable preoperative NAs therapy showed clinical benefit in improving the prognosis of patients with HBV-related HCC, even in the case of normal alanine aminotransferase (ALT) level and negative hepatitis e antigen (HBeAg). Furthermore, a possible synergistic effect between antiviral therapy and anti-PD-1 therapy was founded and need further verification.

Single-Cell RNA Sequencing Revealed That the Enrichment of TPI1+ Malignant Hepatocytes Was Linked to HCC Metastasis and Immunosuppressive Microenvironment.

Background: Tumor metastasis is the leading cause of high mortality in hepatocellular carcinoma (HCC). The metastasis-related HCC microenvironment is characterized by high heterogeneity. Single-cell RNA sequencing (scRNA-seq) may aid in determining specific cell clusters involved in regulating the immune microenvironment of HCC. Methods: The scRNA-seq data of 10 HCC samples were collected from the Gene Expression Omnibus (GEO) database GSE124395. Correlations between key gene expression and clinicopathological data were determined using public databases. HCC tissues and matched tumor-adjacent and normal tissue samples were obtained by surgical resection at Sichuan Cancer Hospital. Immune cell infiltration analysis was performed and verified by immunohistochemistry and immunofluorescent staining. Results: Nine malignant hepatocyte clusters with different marker genes and biological functions were identified. C3_Hepatocyte-SERF2 and C6_Hepatocyte-IL13RA2 were mainly involved in the regulation of the immune microenvironment, which was also a significant pathway in regulating HCC metastasis. Key genes in malignant hepatocyte clusters that associated with HCC metastasis were further screened by LASSO regression analysis. TPI1, a key gene in C6_Hepatocyte-IL13RA2 and HCC metastasis, could participate in regulating the HCC immune microenvironment in The Cancer Genome Atlas (TCGA) and Tumor Immune Estimation Resource (TIMER) databases. Moreover, immunohistochemistry analysis demonstrated that TPI1 expression was positively correlated with HCC metastasis and poor prognosis, while negatively correlated with CD8+ T cell infiltration. The negative correlation between TPI1 expression and CD8+ T cell infiltration was further confirmed by immunofluorescence staining. Conclusion: In summary, a cluster of TPI1+ malignant hepatocytes was associated with the suppression of CD8+ T cell infiltration and HCC metastasis, providing novel insights into potential biomarkers for immunotherapy in HCC.

Elevated blood malondialdehyde level contributed to a high stroke risk in a Chinese elderly population from rural areas: a cross-sectional study.

Individuals living in rural areas have a higher incidence rate of stroke than their urban counterparts in China. However, few studies have investigated the association between blood malondialdehyde (MDA), an end product of lipid oxidation caused by reactive oxygen species (ROS), and stroke risk in rural populations. We aimed to investigate whether blood MDA levels contribute to a higher stroke risk in a Chinese elderly population from rural areas. Data from 2011 to 2012 from the Chinese Longitudinal Healthy Longevity Survey (CLHLS), a national cohort of older adults in China, were analyzed. Smooth curve and multivariable correction analyses were used to evaluate the association between blood MDA levels and stroke risk in elderly populations from rural and urban areas, respectively. The median age of all included participants (N = 1598) was 84.04 years. The results of the smooth curve model revealed a gradual upward trend in the association of blood MDA levels with stroke risk in rural participants but not in urban participants. Similarly, the conditional logistic regression analysis suggested a significant association between MDA levels and stroke risk in rural participants but not in urban participants after adjustments for related confounding factors (age, sex, current smoker, current drinker, regular exercise, BMI and cardiovascular diseases (hypertension, heart disease, atrial fibrillation and diabetes)) were made. In brief, among the elderly population in China, elevated blood MDA levels were associated with increased stroke risk in rural participants but not in urban participants.

Deep convolutional neural network with fusion strategy for skin cancer recognition: model development and validation.

We aimed to develop an accurate and efficient skin cancer classification system using deep-learning technology with a relatively small dataset of clinical images. We proposed a novel skin cancer classification method, SkinFLNet, which utilizes model fusion and lifelong learning technologies. The SkinFLNet's deep convolutional neural networks were trained using a dataset of 1215 clinical images of skin tumors diagnosed at Taichung and Taipei Veterans General Hospital between 2015 and 2020. The dataset comprised five categories: benign nevus, seborrheic keratosis, basal cell carcinoma, squamous cell carcinoma, and malignant melanoma. The SkinFLNet's performance was evaluated using 463 clinical images between January and December 2021. SkinFLNet achieved an overall classification accuracy of 85%, precision of 85%, recall of 82%, F-score of 82%, sensitivity of 82%, and specificity of 93%, outperforming other deep convolutional neural network models. We also compared SkinFLNet's performance with that of three board-certified dermatologists, and the average overall performance of SkinFLNet was comparable to, or even better than, the dermatologists. Our study presents an efficient skin cancer classification system utilizing model fusion and lifelong learning technologies that can be trained on a relatively small dataset. This system can potentially improve skin cancer screening accuracy in clinical practice.

Lung immune prognostic index­based nomogram for recurrence of hepatocellular carcinoma after postoperative adjuvant TACE.

BACKGROUND: Transarterial chemoembolization (TACE), one of the most commonly used postoperative adjuvant therapy for HCC, has achieved satisfactory outcomes. This study aimed to explore the prognostic value of lung immune prognostic index (LIPI) and develop a novel nomogram for recurrence-free survival (RFS) of HCC patients received postoperative adjuvant TACE (PA-TACE). METHODS: The prognostic value of LIPI was evaluated by C-index, receiver operating characteristic (ROC) analysis, and Kaplan-Meier survival curve. An effective nomogram based on preoperative prognostic factors was established from multivariate analysis and validated in the validation cohort. RESULTS: The ROC and survival analysis demonstrated that the LIPI exhibited better prediction performance of HCC recurrence than other inflammatory biomarkers. According to univariate and multivariate analysis, LIPI, followed by AFP, MVI and age, were significant independent predictors for HCC recurrence and were utilized to construct the nomogram. The C-indexes of the nomogram were 0.746 (95% CI 0.721-0.770) and 0.738 (95% CI 0.701-0.775) in the training and validation cohort, respectively. The AUCs for the 1-, 2-, and 3-year RFS were 0.799, 0.867 and 0.884 in the training cohort and 0.798, 0.779 and 0.770 in the validation cohort, respectively. The calibration curves presented good consistencies. Moreover, compared with the LIPI and other clinical staging system, the established nomogram presented better prognostic performance. CONCLUSION: Preoperative LIPI might be a powerful predictor for RFS in HCC patients received PA-TACE. The LIPI-based nomogram could further effectively predict the risk of recurrence and help clinicians formulate personalized follow-up strategies and adjuvant therapy to improve patient outcomes.

A comparison of the effects of NOAC and VKA therapy on the incidence of dementia in patients with atrial fibrillation: A systematic review and meta-analysis.

Atrial fibrillation (AF) patients are more susceptible to dementia, but the results about the effect of oral anticoagulants (OACs) on the risk of dementia are not consistent. We hypothesize that OAC is associated with a reduced risk of dementia with AF and that nonvitamin K antagonist oral anticoagulants (NOAC) are superior to vitamin K antagonists (VKA). Four databases were systematically searched until July 1, 2022. Two reviewers independently selected literature, evaluated quality, and extracted data. Data were examined using pooled hazard ratios (HRs) and 95% confidence intervals (CIs). Fourteen research studies involving 910 patients were enrolled. The findings indicated that OACs were associated with a decreased risk of dementia (pooled HR: 0.68, 95% CI: 0.55-0.82, I2 = 87.7%), and NOACs had a stronger effect than VKAs (pooled HR: 0.87, 95% CI: 0.79-0.95, I2 = 72%), especially in participants with a CHA2DS2VASc score ≥ 2 (pooled HR: 0.85, 95% CI: 0.72-0.99). Subgroup analysis demonstrated no statistical significance among patients aged <65 years old (pooled HR: 0.83, 95% CI: 0.64-1.07), patients in "based on treatment" studies (pooled HR: 0.89, 95% CI: 0.75-1.06), or people with no stroke background (pooled HR: 0.90, 95% CI: 0.71-1.15). This analysis revealed that OACs were related to the reduction of dementia incidence in AF individuals, and NOACs were better than VKAs, remarkably in people with a CHA2DS2VASc score ≥ 2. The results should be confirmed by further prospective studies, particularly in patients in "based on treatment" studies aged <65 years old with a CHA2DS2VASc score < 2 or without a stroke background.

Glycemic variability and in-hospital death of critically ill patients and the role of ventricular arrhythmias.

BACKGROUND: Abnormal glycemic variability is common in the intensive care unit (ICU) and is associated with increased in-hospital mortality and major adverse cardiovascular events, but little is known about whether adverse outcomes are partly mediated by ventricular arrhythmias (VA). We aimed to explore the association between glycemic variability and VA in the ICU and whether VA related to glycemic variability mediate the increased risk of in-hospital death. METHODS: We extracted all measurements of blood glucose during the ICU stay from The Medical Information Mart for Intensive Care IV (MIMIC-IV) database version 2.0. Glycemic variability was expressed by the coefficient of variation (CV), which was calculated by the ratio of standard deviation (SD) and average blood glucose values. The outcomes included the incidence of VA and in-hospital death. The KHB (Karlson, KB & Holm, A) is a method to analyze the mediation effect for nonlinear models, which was used to decompose the total effect of glycemic variability on in-hospital death into a direct and VA-mediated indirect effect. RESULTS: Finally, 17,756 ICU patients with a median age of 64 years were enrolled; 47.2% of them were male, 64.0% were white, and 17.8% were admitted to the cardiac ICU. The total incidence of VA and in-hospital death were 10.6% and 12.8%, respectively. In the adjusted logistic model, each unit increase in log-transformed CV was associated with a 21% increased risk of VA (OR 1.21, 95% CI: 1.11-1.31) and a 30% increased risk (OR 1.30, 95% CI: 1.20-1.41) of in-hospital death. A total of 3.85% of the effect of glycemic variability on in-hospital death was related to the increased risk of VA. CONCLUSION: High glycemic variability was an independent risk factor for in-hospital death in ICU patients, and the effect was caused in part by an increased risk of VA.

Ubiquitin like protein FAT10 repressed cardiac fibrosis after myocardial ischemic via mediating degradation of Smad3 dependent on FAT10-proteasome system.

Cardiac fibrosis after myocardial ischemic (MI) injury is a key factor in heart function deterioration. We recently showed that ubiquitin-like protein human HLA-F adjacent transcript (FAT10) plays a novel role in ischemic cardiovascular diseases, but its function in cardiac fibrosis remains unknown. The present study aims to detail the pathophysiological function of FAT10 in MI injury-induced cardiac fibrosis and its underlying mechanism. In vivo, a systemic FAT10 deficiency mouse (Fat10 -/-) model was established which exhibited excessive cardiac fibrosis and deleterious cardiac function after MI when compared to wild-type mice. Cardiac fibrotic-related proteins (α-SMA, collagen I and collagen III) content were increased in MI-Fat10 -/- mice. Similarly, cardiac FAT10 restoration in Fat10-/- mice suppressed fibrosis and improved cardiac function. In vitro, FAT10 overexpression exert a protective effect against the transforming growth ß1 (TGF-ß1)-induced proliferation, migration and differentiation in cardiac fibroblast (CFs), primary CFs from Fat10-/- mice and human induced pluripotent stem cell-derived CFs (hiPSC-CFs). Furthermore, immunoprecipitation-mass spectrometry (IP-MS) data demonstrated that FAT10 might mediate Smad3, a critical factor in cardiac fibrosis. Combined with rescue assays both in vivo and vitro, the protective effects of FAT10 against cardiac fibrosis was detected to be dependent on Smad3. In depth, Smad3 as a FAT10 specific substrate, FAT10 specifically bind to the K378 site of Smad3 directly via its C-terminal glycine residues and mediated the degradation of Smad3 through the FAT10-proteasome system instead of ubiquitin. In conclusion, we here show that FAT10 is a novel regulator against cardiac fibrosis after MI by mediating Smad3 degradation through FAT10-mediated proteasome system. Our study confirms the cardioprotective role of FAT10 in the heart, and providing a new prospective insight into the regulation of cardiac fibrosis after MI.

Exosomes derived from human adipose mesenchymal stem cells ameliorate hepatic fibrosis by inhibiting PI3K/Akt/mTOR pathway and remodeling choline metabolism.

Liver fibrosis is a chronic liver disease with the presence of progressive wound healing response caused by liver injury. Currently, there are no approved therapies for liver fibrosis. Exosomes derived from human adipose mesenchymal stem cells (hADMSCs-Exo) have displayed a prominent therapeutic effect on liver diseases. However, few studies have evaluated therapeutic effect of hADMSCs-Exo in liver fibrosis and cirrhosis, and its precise mechanisms of action remain unclear. Herein, we investigated anti-fibrotic efficacy of hADMSCs-Exo in vitro and in vivo, and identified important metabolic changes and the detailed mechanism through transcriptomic and metabolomic profiling. We found hADMSCs-Exo could inhibit the proliferation of activated hepatic stellate cells through aggravating apoptosis and arresting G1 phase, effectively inhibiting the expression of profibrogenic proteins and epithelial-to-mesenchymal transition (EMT) in vitro. Moreover, it could significantly block collagen deposition and EMT process, improve liver function and reduce liver inflammation in liver cirrhosis mice model. The omics analysis revealed that the key mechanism of hADMSCs-Exo anti-hepatic fibrosis was the inhibition of PI3K/AKT/mTOR signaling pathway and affecting the changes of metabolites in lipid metabolism, and mainly regulating choline metabolism. CHPT1 activated by hADMSCs-Exo facilitated formation and maintenance of vesicular membranes. Thus, our study indicates that hADMSCs-Exo can attenuate hepatic stellate cell activation and suppress the progression of liver fibrosis, which holds the significant potential of hADMSCs-Exo for use as extracellular nanovesicles-based therapeutics in the treatment of liver fibrosis and possibly other intractable chronic liver diseases.

Adherence with cardiovascular medications and the outcomes in patients with coronary arterial disease: "Real-world" evidence.

BACKGROUND: Cardiovascular medications are vital for the secondary prevention of coronary arterial disease (CAD). However, the effect of cardiovascular medication may depend on the optimal adherence of the patients. This meta-analysis aims to determine the magnitude of adherence to vascular medications that influences the absolute and relative risks (RRs) of mortality in patients with CAD in real-world settings. METHODS: The Cochrane Library, PubMed, and EMBASE databases were searched through March 1, 2022. Prospective studies reporting association as RR and 95% confidence interval between cardiovascular medication adherence and any cardiovascular events and/or all-cause mortality in patients with CAD were included. A one-stage robust error meta-regression method was used to summarize the dose-specific relationships. RESULTS: A total of 18 studies were included. There is a significant inverse linear association between cardiovascular medication adherence and cardiovascular events (pnonlinearity = .68) or mortality (pnonlinearity = .82). The exposure-effect analysis showed that an improvement of 20% cardiovascular medication adherence was associated with 8% or 12% lower risk of any cardiovascular events or mortality, respectively. In subgroup analysis, the benefit was observed in adherence of stain (RR: 0.90, for cardiovascular events, RR: 0.85, for mortality), angiotensin-converting enzyme inhibitors (ACEI)/angiotensin II receptor blockers (ARB)(RR: 0.90, for mortality), and antiplatelet agent (RR: 0.89 for mortality) but not in beta-blocker (RR: 0.90, p = .14, for cardiovascular events, RR: 0.97, p = .32 for mortality). Estimated absolute differences per 1 million individuals per year for mortality associated with 20% improvement were 175 cases for statin, 129 cases for antiplatelet, and 117 cases for ACEI/ARB. CONCLUSION: Evidence from the real word showed poor adherence to vascular medications contributes to a considerable proportion of all cardiovascular disease events and mortality in patients with CAD.

Intranasal Immunization With a c-di-GMP-Adjuvanted Acellular Pertussis Vaccine Provides Superior Immunity Against Bordetella pertussis in a Mouse Model.

Pertussis, caused by the gram-negative bacterium Bordetella pertussis, is a highly contagious respiratory disease. Intranasal vaccination is an ideal strategy to prevent pertussis, as the nasal mucosa represents the first-line barrier to B. pertussis infection. The current intramuscular acellular pertussis (aP) vaccines elicit strong antibody and Th2-biased responses but not necessary cellular and mucosal immunity. Here, we formulated two cyclic dinucleotide (CDN)-adjuvanted aP subunit vaccines, a mammalian 2',3'-cGAMP-adjuvanted aP vaccine and a bacterial-derived c-di-GMP-adjuvanted aP vaccine, and evaluated their immunogenicity in a mouse model. We found that the aP vaccine alone delivered intranasally (IN) induced moderate systemic and mucosal humoral immunity but weak cellular immunity, whereas the alum-adjuvanted aP vaccine administered intraperitoneally elicited higher Th2 and systemic humoral immune responses but weaker Th1 and Th17 and mucosal immune responses. In contrast, both CDN-adjuvanted aP vaccines administered via the IN route induced robust humoral and cellular immunity systemically and mucosally. Furthermore, the c-di-GMP-adjuvanted aP vaccine generated better antibody production and stronger Th1 and Th17 responses than the 2',3'-cGAMP-adjuvanted aP vaccine. In addition, following B. pertussis challenge, the group of mice that received IN immunization with the c-di-GMP-adjuvanted aP vaccine showed better protection than all other groups of vaccinated mice, with decreased inflammatory cell infiltration in the lung and reduced bacterial burden in both the upper and lower respiratory tracts. In summary, the c-di-GMP-adjuvanted aP vaccine can elicit a multifaceted potent immune response resulting in robust bacterial clearance in the respiratory tract, which indicates that c-di-GMP can serve as a potential mucosal adjuvant for the pertussis vaccine.

Sex Differences in Dilated Cardiomyopathy Prognosis.

Dilated cardiomyopathy (DCM) is the most common type of cardiomyopathy, and it often has a poor outcome. Sex differences in the prognosis of patients with DCM remain controversial. The present meta-analysis aimed to investigate whether sex plays a role in the outcome of patients with DCM and to provide real-world information on these potential sex differences for physicians and patients.We searched the PubMed, Cochrane, and EMBASE databases for published cohort studies up to February 16, 2020 that reported sex-specific prognostic outcomes (e.g., all-cause mortality; sudden cardiac death (SCD) ) in patients with DCM.Finally, 5 clinical cohort studies with a total of 5,709 patients were included. The results showed that males with DCM had a higher risk of all-cause mortality than females (HR: 1.61, 95% CI: 1.36~1.90; P < 0.00001). Next, the included studies were divided into short-term (< 5 years) and long-term (≥ 5 years) outcome groups by follow-up duration. Males showed a higher risk of all-cause mortality in both subgroups (< 5 years, HR: 1.59, 95% CI: 1.13~2.23; P = 0.008; ≥ 5 years, HR: 1.65, 95% CI: 1.33~2.05; P < 0.00001). In addition, the risks of SCD (HR: 1.80, 95% CI: 1.63~2.61; P = 0.002) and cardiovascular mortality in males (HR: 1.67, 95% CI: 1.25~2.23; P = 0.0005) were higher than those in females.The evidence from the published studies suggested that compared with females, males with DCM had an increased risk of all-cause mortality, cardiovascular mortality, and SCD.

Increased blood alpha-carotene, all-trans-Beta-carotene and lycopene levels are associated with beneficial changes in heart rate variability: a CVD-stratified analysis in an adult population-based study.

BACKGROUND: Although the associations of antioxidant micronutrients, such as carotenoids and vitamins, with cardiovascular diseases (CVDs) have been studied extensively, blood concentrations of antioxidant micronutrients and heart rate variability (HRV), which has been proven to be an indicator of cardiac autonomic control, has not been reported. We aimed to explore whether blood concentrations of antioxidant micronutrients, including carotenoids and vitamins, are associated with elevated heart rate variability (HRV (beneficial change) in a cross-sectional analysis. METHODS: Data were obtained from the Midlife in the United States (MIDUS) study that includes a general adult population. A total of 1074 (aged 34-84) individuals were included. Multivariable analyses were performed to investigate the association between main blood carotenoids (total lutein, zeaxanthin, beta-cryptoxanthin, 13-cis-beta-carotene, alpha-carotene, all-trans-beta-carotene and total lycopene) and vitamins A (retinol) and E (gamma-tocopherol and alpha-tocopherol) and HRV after adjustments were made for lifestyle factors and age-related confounders. RESULTS: Pearson correlation analyses showed that the increased levels of carotenoids and vitamins were positively correlated with higher HRV (all P < 0.05). After adjustments were made for age, gender, race, body mass index(BMI), ever-smoker, number of drinking years and exercise, blood alpha-carotene, all-trans-beta-carotene and total lycopene levels were independently associated with higher HRV in the linear regression model (all P < 0.05). Sensitivity analysis by adding "ever chronic respiratory diseases" as a covariate suggested that blood concentrations of these three carotenoids were still associated with higher low-frequency (LF)-HRV and high-frequency (HF)-HRV (all P < 0.05). Furthermore, stratified analyses suggested that the associations were affected by adding "heart disease" and "hypertension" as covariates. CONCLUSIONS: We provide the first evidence that elevated blood concentrations of alpha-carotene, trans-beta-carotene and lycopene are associated with beneficial changes in HRV in the general population. Daily intake of fruit and vegetables may be beneficial to increase blood carotenoid status and further prevent autonomic dysfunction.

Prevalence and impact of cardiac injury on COVID-19: A systematic review and meta-analysis.

BACKGROUND: The exact prevalence and impact of cardiac injury in hospitalized patients with coronavirus disease 2019 (COVID-19) is still controversial. Hence, we aim to investigate prevalence of cardiac injury and its impact on the outcomes in patients with COVID-19. HYPOTHESIS: Cardiac injury is common and associated with higher risk of death. METHODS: We searched the Cochrane Library, PubMed, MedRxiv, and EMBASE databases from December 2019 to July 15, 2020 for studies that evaluated the prevalence and impact of cardiac injury on COVID-19. This study has been registered with PROSPERO (International prospective register of systematic reviews)-registration number-CRD-42020186120. RESULTS: Twenty-one studies including 6297 participants were identified. The proportions of cardiac injury were 22%, 28% among hospitalized patients with COVID-19 or severe COVID-19 patients, respectively. The incidences of cardiac injury in advance age (>60 years) (30%) was about two-fold than young patients (<60 years) (15%) with COVID-19. Severe cases (42%) have seven-fold prevalence cardiac injury than in their non- severe counterparts (6%). Furthermore, cardiac injury is associated with an increased risk of all-cause mortality in patients with COVID-19 (OR 10.11, 95% CI 4.49-22.77). In patients with severe COVID-19, cardiac injury is associated with an increased risk of all-cause mortality (OR: 16.79, 95% CI: 5.52-51.02). CONCLUSIONS: This was the first meta-analysis exploring the prevalence and impact of cardiac injury on COVID-19. Cardiac injury is common in hospitalized patients and advanced age and severe COVID-19 patients prone to experience more risk of cardiac injury. Furthermore, cardiac injury is associated with increased risk of all-cause mortality.

Serum Levels of CRP are Associated with Depression in a Middle-aged and Elderly Population with Diabetes Mellitus: A Diabetes Mellitus-Stratified Analysis in a Population-Based Study.

BACKGROUND: The direct relationship between inflammation and depression in patients with diabetes is still unclear. We examined the association between serum C-reactive protein (CRP) levels and the high prevalence of depression in populations (aged ≥49 years) with and without type 2 diabetes. METHODS: Cross-sectional and longitudinal data from 3895 participants obtained from The Irish Longitudinal Study on Ageing (TILDA) were analyzed to determine the association between serum CRP levels and depression, accounting for relevant confounding factors. RESULTS: Multivariable analyses showed a positive association between serum CRP and depression score, independent of age and gender, BMI, marital status, education, smoking status, alcohol drinking status, systolic BP, diastolic BP, physical activity, self-reported CVDs and laboratory measurements in subjects with diabetes mellitus (coefficient = 0.179, P<0.001) but not in subjects without diabetes mellitus (coefficient = 0.011, P = 0.495). Higher serum CRP levels were associated with an increased risk of depressive symptoms in subjects with diabetes mellitus (OR = 1.301, 95% CI 1.012-1.799, P = 0.011) but not in subjects without diabetes mellitus (OR = 1.004, 95% CI 0.992-1.013, P = 0.344) after adjusting for these same confounding factors. After a follow-up of 4 years, higher serum CRP levels were significantly associated with a higher possibility of depression events in subjects with diabetes mellitus. LIMITATIONS: Time-varying confounding factors may interfere with our results. CONCLUSION: We observed a significant positive association between serum CRP levels and the prevalence of depressive symptoms in a middle-aged and elderly population with diabetes after adjustment for a range of lifestyle factors.

Association of angiotensin converting enzyme inhibitors and angiotensin II receptor blockers with risk of COVID-19, inflammation level, severity, and death in patients with COVID-19: A rapid systematic review and meta-analysis.

An association among the use of angiotensin converting enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) with the clinical outcomes of coronavirus disease 2019 (COVID-19) is unclear. PubMed, EMBASE, MedRxiv, and BioRxiv were searched for relevant studies that assessed the association between application of ACEI/ARB and risk of COVID-19, inflammation level, severity COVID-19 infection, and death in patients with COVID-19. Eleven studies were included with 33 483 patients. ACEI/ARB therapy might be associated with the reduced inflammatory factor (interleukin-6) and elevated immune cells counts (CD3, CD8). Meta-analysis showed no significant increase in the risk of COVID-19 infection (odds ratio [OR]: 0.95, 95%CI: 0.89-1.05) in patients receiving ACEI/ARB therapy, and ACEI/ARB therapy was associated with a decreased risk of severe COVID-19 (OR: 0.75, 95%CI: 0.59-0.96) and mortality (OR: 0.52, 95%CI: 0.35-0.79). Subgroup analyses showed among the general population, ACEI/ARB therapy was associated with reduced severe COVID-19 infection (OR: 0.79, 95%CI: 0.60-1.05) and all-cause mortality (OR: 0.31, 95%CI: 0.13-0.75), and COVID-19 infection (OR: 0.85, 95% CI: 0.66-1.08) were not increased. Among patients with hypertension, the use of an ACEI/ARB was associated with a lower severity of COVID-19 (OR: 0.73, 95%CI: 0.51-1.03) and lower mortality (OR: 0.57, 95%CI: 0.37-0.87), without evidence of an increased risk of COVID-19 infection (OR: 1.00). On the basis of the available evidence, ACEI/ARB therapy should be continued in patients who are at risk for, or have COVID-19, either in general population or hypertension patients. Our results need to be interpreted with caution considering the potential for residual confounders, and more well-designed studies that control the clinical confounders are necessary to confirm our findings.

Sex differences in the associations between blood pressure and anxiety and depression scores in a middle-aged and elderly population: The Irish Longitudinal Study on Ageing (TILDA).

BACKGROUND: Anxiety and depression are considered risk factors for cardiovascular diseases (CVDs), but their relationship to blood pressure (BP) is still uncertain. Lifestyle factors and age-related comorbidities may confound these relationships. Our study aimed to evaluate the associations between BP and anxiety and depression scores in a population aged ≥49 years. METHODS: Data on 8504 participants from The Irish Longitudinal Study on Ageing (TILDA) were analyzed for associations between BP and anxiety and depression questionnaire scores, accounting for relevant confounding factors. RESULTS: Multivariable analyses showed negative associations between systolic BP and anxiety and depression scores, independent of age, body mass index (BMI), marital status, education level, smoking status, alcohol consumption, level of physical activity, self-reported CVDs (≥2) and antihypertensive medication use in men (coefficient=-0.112, P=0.013; coefficient=-0.051, P=0.026) but not in women (coefficient=-0.001, P=0.855; coefficient=-0.005, P=0.556). Diastolic BP was not associated with anxiety or depression scores in either men (coefficient=-0.018, P=0.223; coefficient=-0.001, P=0.924) or women (coefficient=-0.007, P=0.338; coefficient=-0.015, P=0.293) after adjusting for these same confounding factors. After a follow-up of 4 years, lower BP in subjects not using antihypertensive medications was significantly associated with more anxiety and depression events. LIMITATION: Time-varying confounding factors may have interfered with our results. CONCLUSION: Our results show that systolic BP in a middle-aged and elderly population is negatively associated with anxiety and depression scores in men but not women after adjustment for a range of lifestyle factors. These results contrast with the predisposition of anxious or depressed participants to CVDs in later life when decades of unhealthy lifestyles have persisted.

The Association between Serum Retinol-Binding Protein 4 Levels and Cardiovascular Events in Patients with Chronic Kidney Disease.

OBJECTIVE: The study aimed to assess whether serum retinol-binding protein 4 (RBP4) is associated with a risk of cardiovascular (CV) events in chronic kidney disease (CKD) patients. METHODS: One hundred sixty-nine patients with CKD were followed for a mean of 36 months (range, 5-39 months). Serum RBP4 and other laboratory indicators were measured at baseline. The relationship between RBP4 and the risk of CV events was evaluated by using Cox regression analysis. RESULTS: Patients with higher serum RBP4 levels had a higher rate of CV events and a higher mortality in a univariate analysis (P < 0.001). The multivariate Cox proportional hazard analysis revealed that RBP4 (hazard ratio, 2.259; 95% confidence interval, 2.067-5.489; P = 0.002) is an independent prognostic factor for CV events in patients with CKD. Kaplan-Meier analysis demonstrated that patients with RBP4 above the median value (>33.86 mg/L) had a higher rate of CV events than did patients with RBP4 at or below the median value (≤33.86 mg/L; P < 0.001). CONCLUSION: RBP4 levels are associated with CV events in patients with CKD. Elevated serum RBP4 levels may indicate an increased risk of CV complications in CKD patients.