Urinary 8-OxoGsn as a Potential Indicator of Mild Cognitive Impairment in Frail Patients With Cardiovascular Disease.

Oxidative RNA damage has been found to be associated with age-related diseases and 8-oxo-7,8-dihydroguanosine (8-oxoGsn) is a typical marker of oxidative modification of RNA. Urine tests are a feasible non-invasive diagnostic modality. The present study aimed to assess whether the measurement of urinary 8-oxoGsn could represent a potential early maker in mild cognitive impairment (MCI) of frail patients with cardiovascular disease (CVD). In this cross-sectional study performed in China from September 2018 to February 2019. Urinary 8-oxoGsn was measured in frail (Fried phenotype: 3-5) in patients with CVD and was adjusted by urinary creatinine (Cre) levels. Cognitive function was assessed by the Chinese version of the Mini-Mental State Examination (MMSE) and participants were classified into non-MCI (≥24) and MCI (<24) groups. Univariate and multivariate logistic regression models were used to determine the relationship between 8-oxoGsn/Cre and MCI. Receiver operating characteristic (ROC) curve analysis was used to assess the 8-oxoGsn/Cre ratio in relation to MCI in frail patients with CVD. A total of 106 elderly patients were enrolled in this study. The mean age of participants was 77.9 ± 6.8 years, the overall prevalence of MCI was 22.6% (24/106), and 57.5% (61/106) of participants were women. In the multivariate logistic regression analysis, urinary 8-oxoGsn/Cre was independently associated with MCI (odds ratio [OR] = 1.769, 95% confidence interval [CI] = 1.234-2.536, P = 0.002), after adjusting for age, sex, education level, marital status, and serum prealbumin levels. The area under the ROC curve was 0.786 (0.679-0.893) (P < 0.001), and the optimal cut-off value was 4.22 µmol/mol. The urinary 8-oxoGsn/Cre ratio showed a sensitivity of 87.5% and a specificity of 69.5%. The present study suggests the urinary 8-oxoGsn/Cre ratio may be a useful indicator for the early screening of MCI in frail patients with CVD. CLINICAL TRIAL REGISTRATION: ChiCTR1800017204; date of registration: 07/18/2018. URL: http://www.chictr.org.cn/showproj.aspx?proj=28931.

Prevalence and Prognostic Value of Heart Failure Stages: An Elderly Inpatient Based Cohort Study.

Background: The prevalence and prognostic value of heart failure (HF) stages among elderly hospitalized patients is unclear. Methods: We conducted a prospective, observational, multi-center, cohort study, including hospitalized patients with the sample size of 1,068; patients were age 65 years or more, able to cooperate with the assessment and to complete the echocardiogram. Two cardiologists classified all participants in various HF stages according to 2013 ACC/AHA HF staging guidelines. The outcome was rate of 1-year major adverse cardiovascular events (MACE). The Kaplan-Meier method and Cox proportional hazards models were used for survival analyses. Survival classification and regression tree analysis were used to determine the optimal cutoff of N-terminal pro-brain natriuretic peptide (NT-proBNP) to predict MACE. Results: Participants' mean age was 75.3 ± 6.88 years. Of them, 4.7% were healthy and without HF risk factors, 21.0% were stage A, 58.7% were stage B, and 15.6% were stage C/D. HF stages were associated with worsening 1-year survival without MACE (log-rank χ2 = 69.62, P < 0.001). Deterioration from stage B to C/D was related to significant increases in HR (3.636, 95% CI, 2.174-6.098, P < 0.001). Patients with NT-proBNP levels over 280.45 pg/mL in stage B (HR 2; 95% CI 1.112-3.597; P = 0.021) and 11,111.5 pg/ml in stage C/D (HR 2.603, 95% CI 1.014-6.682; P = 0.047) experienced a high incidence of MACE adjusted for age, sex, and glomerular filtration rate. Conclusions : HF stage B, rather than stage A, was most common in elderly inpatients. NT-proBNP may help predict MACE in stage B. Trial Registration: ChiCTR1800017204; 07/18/2018.

Frailty related all-cause mortality or hospital readmission among adults aged 65 and older with stage-B heart failure inpatients.

BACKGROUND: Frailty increases the adverse outcomes of clinical heart failure; however, the relationship between frailty and stage-B heart failure (SBHF) remains unknown. We aimed to explore the epidemiology and predictive value of frailty in older adults with SBHF. METHODS: A prospective cohort of SBHF inpatients aged 65 years or older who were hospitalized between September 2018 and February 2019 and were followed up for 6 months were included. SBHF was defined as systolic abnormality, structural abnormality (left ventricular enlargement, left ventricular hypertrophy, wall motion abnormalities, valvular heart disease), or prior myocardial infarction. Frailty was assessed by the Fried frailty phenotype. Multivariable Cox proportional hazards regression was used to explore the independent risk and prognostic factors. RESULTS: Data of 443 participants (age: 76.1 ± 6.79 years, LVEF: 62.8 ± 4.92%, men: 225 [50.8%], frailty: 109 [24.6%]) were analyzed. During the 6-month follow-up, 83 (18.7%) older SBHF inpatients experienced all-cause mortality or readmission, and 29 (6.5%) of them developed clinical HF. Frail individuals had a 1.78-fold (95%CI: 1.02-3.10, P = 0.041) higher risk of 6-month mortality or readmission and a 2.83-fold (95%CI 1.24-6.47, P = 0.014) higher risk of developing clinical HF, independent of age, sex, left ventricular ejection fraction, and N-terminal pro-B-type natriuretic peptide level. CONCLUSIONS: Frailty is common in older SBHF inpatients and should be considered to help identify individuals with an increased risk of mortality or readmission, and developing clinical HF. TRIAL REGISTRATION: ChiCTR1800017204 .

Adding high-sensitivity C-reactive protein to frailty assessment to predict mortality and cardiovascular events in elderly inpatients with cardiovascular disease.

OBJECTIVE: Chronic inflammation is associated with major adverse cardiovascular events (MACEs), mortality, and frailty. Our aim was to add high-sensitivity C-reactive protein (hsCRP) to the frailty assessment to predict its association with prognosis of older adults with cardiovascular disease (CVD). METHODS: A comprehensive geriatric assessment was conducted at baseline in 720 in-patients aged ≥65 years with CVD. We divided the population into frailty and non-frailty groups according to the Fried phenotype, and hsCRP was further combined with frailty to stratify all patients into c-frailty and non-c-frailty groups. Predictive validity was tested using Cox proportional hazards regression model analysis and the discriminative ability was evaluated by receiver operating characteristic (ROC) curves. RESULTS: Of all the subjects enrolled, 51.0% were male and the mean age was 75.32 ± 6.52 years. The all-cause death and MACE rate was 6.4% at the 1-year follow-up. Frailty and c-frailty were independent predictors of all-cause death and MACE (hazard ratio [HR]: 2.55, 95% confidence interval [CI]: 1.35-4.83, p = 0.004; HR: 3.67, 95% CI: 1.83-7.39, p < 0.001). Adding hsCRP to the frailty model resulted in a significant increase in the area under the ROC curve from 0.74 (95% CI: 0.70-0.77) to 0.77 (95% CI: 0.71-0.84) (p = 0.0132) and a net reclassification index of 7.9% (95% CI: 1.96%-12.56%, p = 0.012). CONCLUSION: Adding hsCRP to the frailty assessment is helpful to identify a subgroup of older CVD patients with a higher risk of death and MACE over a period of 1 year. TRIAL REGISTRATION: ChiCTR1800017204; date of registration: 07/18/2018. URL: http://www.chictr.org.cn/showproj.aspx?proj=28931.

Prevalence and Prognostic Significance of Frailty in Gerontal Inpatients With Pre-clinical Heart Failure: A Subgroup Analysis of a Prospective Observational Cohort Study in China.

Objective: To evaluate the prognostic value of frailty in gerontal pre-clinical heart failure (stage B heart failure, SBHF) inpatients. Background: The association between frailty and SBHF remains unknown. Methods: We conducted a subgroup analysis of a prospective observational cohort study on frailty. The previous study recruited 1,000 elderly inpatients who were consecutively admitted to a tertiary referral hospital in Beijing, China, from September 2018 to February 2019. The outcomes were all-cause death or readmission at 1-year follow-up. SBHF was diagnosed for asymptomatic cardiac structural or functional abnormalities. Frailty was assessed using the Comprehensive Geriatric Assessment-Frailty Index (CGA-FI). Results: Overall, 531 inpatients aged ≥65 years were deemed to have SBHF and followed up for 1 year. Of them, 34.5% exhibited frailty. During the follow-up period, all-cause death or readmission occurred in 157 (29.5%) participants. Of these participants, 36.6% (67/183) and 25.9% (90/348) belonged to the frail and non-frail groups, respectively (χ2 = 6.655, P = 0.010). Frailty, defined by the CGA-FI, rather than Fried frailty phenotype, could independently predict 1-year all-cause death or readmission (hazard ratio, 1.56; 95% confidence interval, 1.03-2.35; P = 0.034) and was more suitable for predicting all-cause death or readmission than N-terminal pro-B-type natriuretic peptide in female SBHF inpatients aged 80 years or over(AUCCGA-FI vs. AUCNT-proBNP 0.654 vs. 0.575, P = 0.017). Conclusions: Frailty is highly prevalent even among SBHF inpatients aged ≥65 years. The CGA-FI can independently predict 1-year all-cause death or readmission, rather than Fried frailty phenotype. Frailty in gerontal SBHF inpatients deserves more attention. Clinical Trial registration: ChiCTR1800017204; date of registration: 07/18/2018.

Trimethylamine N-Oxide, a Gut Microbiota-Dependent Metabolite, is Associated with Frailty in Older Adults with Cardiovascular Disease.

OBJECTIVE: Our study aimed to explore the association between trimethylamine N-oxide and frailty in older adults with cardiovascular disease. PATIENTS AND METHODS: This cross-sectional study analyzed a total of 451 people aged 65 years or older who underwent comprehensive geriatric assessments. Frailty status was determined using a frailty index constructed with 48 variables according to the cumulative deficits model. Physical frailty and cognitive frailty were also assessed in detail. Fasting plasma TMAO was measured by mass spectrometry. RESULTS: The proportion of frail subjects was 29.9% (135/451). Plasma TMAO levels were significantly higher in frail patients than in nonfrail individuals (4.04 [2.84-7.01] vs 3.21 [2.13-5.03] µM; p<0.001). Elevated plasma TMAO levels were independently associated with the likelihood of frailty (OR 2.12, 95% CI 1.01-4.38, p=0.046). Dose-response analysis revealed a linear association between the TMAO concentration and the OR for frailty. A 2-unit increase in TMAO was independently correlated with physical frailty (OR 1.23, 95% CI 1.08-1.41, p for trend 0.002) and cognitive frailty (OR 1.21, 95% CI 1.01-1.45, p for trend 0.04). CONCLUSION: Elevated circulating TMAO levels are independently associated with frailty among older adults with cardiovascular disease.

Predicting non-elective hospital readmission or death using a composite assessment of cognitive and physical frailty in elderly inpatients with cardiovascular disease.

BACKGROUND: We aimed to assess the utility of the combination of the mini-mental state examination (MMSE) + clock drawing test (CDT) and the Fried phenotype for predicting non-elective hospital readmission or death within 6 months in elderly inpatients with cardiovascular disease (CVD). METHODS: A single-center prospective cohort was conducted from September 2018 to February 2019. Inpatients ≥65 years old were recruited. Predictive validity was tested using a Cox proportional hazards regression model analysis, and the discriminative ability was evaluated by the receiver operating characteristic (ROC) curve. RESULTS: A total of 542 patients were included. Overall, 12% (64/542) screened positive for cognitive impairment, 16% (86/542) were physically frail and 8% (44/542) had cognitive impairment combined with physical frailty, showing an older age (P < 0.001) and a lower education level (P < 0.001) than physically frail patients. A total of 113 patients (20.9%) died or were readmitted at 6 months. Frail participants with a normal (hazard ratio [HR]: 1.73, 95% confidence interval [CI]: 1.06-2.82, P = 0.028) or impaired cognition (HR: 2.50, 95% CI: 1.27-4.91, P = 0.008) had a higher risk of non-elective hospital readmission or death than robust patients after adjusting for the age, sex, education level, marital status, the presence of diabetes mellitus, heart failure, and history of stroke. The area under the ROC curve (AUC) showed that the discriminative ability in relation to 6 months readmission and death for the MMSE + CDT + Fried phenotype was 0.65 (95% CI: 0.60-0.71), and the AUC for men was 0.71 (95% CI: 0.63-0.78), while that for women was 0.60 (95% CI: 0.51-0.69). CONCLUSIONS: Accounting for cognitive impairment in the frailty phenotype may allow for the better prediction of non-elective hospital readmission or death in elderly inpatients with CVD in the short term. TRIAL REGISTRATION: ChiCTR1800017204; date of registration: 07/18/2018.

Urinary 8-oxo-7,8-dihydroguanosine as a potential biomarker of frailty for elderly patients with cardiovascular disease.

The diagnosis of frailty is usually subjective, which calls for objective biomarkers in clinical medicine. 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGsn) and 8-oxo-7, 8-dihydroguanosine (8-oxoGsn) in urine are two aging biomarkers that have not been explored deeply in cases of frailty. A total of 508 elderly patients with cardiovascular disease (mean age 75.0 ± 6.5 years, 50.8% males) were enrolled consecutively. Frailty was assessed by the Fried phenotype (robust: 0 score; pre-frail: 1-2 scores; frail: 3-5 scores). The concentrations of 8-oxoGsn and 8-oxodGsn in urine were measured by improved ultra-high-performance liquid chromatography-mass spectrometry (UPLC-MS/MS). Urinary creatinine (Cre) was tested to correct the 8-oxoGsn and 8-oxodGsn levels. According to the Fried phenotype score, the proportions of robust, pre-frail, and frail subjects were 20.5% (104/508), 53.9% (274/508), and 25.6% (130/508), respectively. The urinary 8-oxoGsn/Cre (P < 0.001) differed significantly among these 3 groups, but the urinary 8-oxodGsn/Cre (P = 0.600) showed no marked difference. Univariate and multivariate logistic regression showed that the age (odds ratio [OR] = 1.090, P < 0.001), systolic blood pressure (OR = 0.981, P = 0.008), 8-oxoGsn/Cre (OR = 1.203, P = 0.007), hemoglobin (OR = 0.980, P = 0.007), and sodium (OR = 0.915, P = 0.044) were independently associated with frailty. The sensitivity and specificity to identify frailty were 53.08% and 71.96%, respectively, for 8-oxoGsn/Cre at the optimal cut-off value of 3.879 µmol/mol according to the maximal Youden index. Urinary 8-oxoGsn, as a recognized biomarker of RNA oxidation, is independently associated with frailty in elderly patients with cardiovascular disease. However, the urinary 8-oxodGsn shows no obvious correlation with frailty. To obtain a better diagnostic performance for frailty, more biomarkers from different pathophysiological pathways should be explored in the future.

Combined acoustic radiation force impulse, aminotransferase to platelet ratio index and Forns index assessment for hepatic fibrosis grading in hepatitis B.

AIM: To investigate the combined diagnostic accuracy of acoustic radiation force impulse (ARFI), aspartate aminotransferase to platelet ratio index (APRI) and Forns index for a non-invasive assessment of liver fibrosis in patients with chronic hepatitis B (CHB). METHODS: In this prospective study, 206 patients had CHB with liver fibrosis stages F0-F4 classified by METAVIR and 40 were healthy volunteers were measured by ARFI, APRI and Forns index separately or combined as indicated. RESULTS: ARFI, APRI or Forns index demonstrated a significant correlation with the histological stage (all P < 0.001). According to the AUROC of ARFI and APRI for evaluating fibrotic stages more than F2, ARFI showed an enhanced diagnostic accuracy than APRI (P < 0.05). The combined measurement of ARFI and APRI exhibited better accuracy than ARFI alone when evaluating ≥ F2 fibrotic stage (Z = 2.77, P = 0.006). Combination of ARFI, APRI and Forns index did not obviously improve the diagnostic accuracy compared to the combination of ARFI and APRI (Z = 0.958, P = 0.338). CONCLUSION: ARFI + APRI showed enhanced diagnostic accuracy than ARFI or APRI alone for significant liver fibrosis and ARFI + APRI + Forns index shows the same effect with ARFI + APRI.

[Efficacy of Peg-interferon alpha-2a combinated with entecavir on HBeAg positive chronic hepatitis B patients with high serum hepatitis B viral loads].

OBJECTIVE: This study aimed at evaluating the efficacy and safety of a combination treatment of entecavir and Peginterferon alpha-2a for HBeAg positive chronic hepatitis B patients with high serum hepatitis B viral loads. METHODS: 60 treatment-naive HBeAg-positive CHB patients with high serum hepatitis B viral loads were enrolled and randomly divided into three groups: group A received Peginterferon alpha-2a monotherapy for 48 weeks (n = 20); group B received entecavir monotherapy for more than 48 weeks (n = 20); group C received Peginterferona alpha-2a combined with entecavir for 12 weeks, then Peginterferon alpha-2a monotherapy for 36 weeks (n = 20). Virological response, ALT normalization, HBeAg and HBsAg seroclearance rate were analysed at the end of 4, 12 and 24 weeks after the treatment. RESULTS: The ratio of undetectable hepatitis B virus (HBV) DNA were 50% and 10%, 95% and 25% and 100% and 30% in group C and group A respectively, 50% and 20%, 95% and 75% and 100% and 90% in group C and group B respectively at the end of 4, 12 and 24 weeks of treatment. The differences were significant between group C and A (Z = -4.6, P < 0.001), group C and B (Z = -2.53, P = 0.0114). ALT normalization rate was significantly lower in group A than that of group C (Z = -2.63, P = 0.0086). HBeAg levels declined more in group C than the other two groups after 24 weeks of treatment. CONCLUSIONS: For HBeAg positive chronic hepatitis B patients with high serum hepatitis B viral loads, combination treament of Peginterferon alpha-2a with entecavir is more effective than Peginterferon alpha-2a monotherapy in virologic response and ALT normalization after 24 weeks of treatment.

[Soluble expression of A/H1N1 influenza virus HA with Drosophila S2 cell line and its bio-activity identification].

OBJECTIVE: To express soluble HA of A/H1N1 influenza virus in drosophila S2 cell line and identify its bio-activity. METHODS: HA gene was amplified from A/Shenzhen/71/09 virus strain using RT-PCR, then we constructed pAC5.1-HA expression vector, which was co-transfected into S2 cell with pCoblast vector. After transfection, stable S2 cell was selected through Blasticindin. HA in the supernatant was identified with Western Blot assay and purified with Ni-column. Recombinant HA was immunized into BALB/c mice 3 times, and the Abs titers were evaluated with ELISA. RESULTS: We successfully cloned HA gene with 1.7 x 10(3) bp of A/Shenzhen/71/09 virus strain and got recombinant pAC5. 1-HA expression vector. Stable S2 cell line was established after transfection and selection, which continuously expressed HA with molecular weight 75 x 10(3) D. After immunization with HA, the Abs titers were 1:1280 and 1: 5120 respectively on 10 d, 30 d. CONCLUSION: We expressed soluble HA with good bio-activity, which contributed to research on immune diagnosis, subunit vaccine, and monoclonal Abs for influenza.

[The association between HBV genotyping and clinical characteristics and expression of TH1/TH2 cytokines].

OBJECTIVE: To explore the association between HBV genotyping and clinical characteristics and expression of TH1/TH2 cytokines. METHODS: The expression of IL-4 and IFN-gamma was detected with flow cytometry for 102 HBV infections and 48 healthy controls. 50 CHB patients were randomly selected for HBV genotyping with real-time fluorescence PCR assay. RESULTS: Higher expression of IL-4 in peripheral blood was detected in patients with HBV infection than healthy controls (P < 0.001); No significant differences on expression of Th1/Th2 cytokines were observed in CHB patients with different HBV DNA levels or HBeAg status (P > 0.05). There were 34 (68%) patients with genotype B infection and 16 (32%) with genotype C infection. Compared to patients with genotype B infection, the patients with genotype C infection showed higher levels of IL-4 (P = 0.018), and Th1/Th2 ratio decreased,but the difference was not statistically significant (P = 0.2262). CONCLUSION: The different expression of TH1/TH2 cytokines may elucidate cellular immune response and clinical outcome difference between patients with genotype B infection and genotype C infection.

[Diagnosis and treatment of 11 patients with acquired immune deficiency syndrome complicated with tuberculosis of mesenteric lymph nodes.].

OBJECTIVE: To study the clinical features of acquired immune deficiency syndrome (AIDS) complicated with tuberculosis of mesenteric lymph nodes. METHODS: Cases (n = 153) with AIDS complicated with tuberculosis hospitalized in this hospital from September 1999 to December 2008 were retrospectively analyzed. Mesenteric lymph node tuberculosis was found in 11 cases, including 7 males and 4 females. One patient was 8 years old, and the other 10 were over 22 years (ranging from 8 to 55 years). RESULTS: In patients with AIDS complicated with tuberculosis, 7% (11/158) had tuberculosis of the mesenteric lymph nodes. The CD(4)(+) cell count was less than 50 x 10(6) cells/L in 8 cases, and (50 - 100) x 10(6) cells/L in 3 cases. The symptoms included fever (11/11), abdominal pain (11/11), abdominal distension (11/11), night sweat (7/11), weight loss (10/11), diarrhea (7/11), anemia (5/11), abdominal mass (3/11), and ascites (1/11). Abdominal ultrasound showed multiple enlarged mesenteric lymph nodes in all of the 11 cases, and abdominal CT scanning presented typical enhanced ring shadows. Biopsy of mesenteric lymph nodes was obtained from 2 cases, and both revealed tuberculoma, caseous necrosis. Longerhan cell infiltration, and positive stain for fast anti-acid bacilli. Enlarged mesenteric lymph nodes became smaller and disappeared after treatment with antituberculous drugs for 6 months and highly active antiretroviral therapy (HAART) for 5 months in all the 11 patients. CONCLUSIONS: There were no specific clinical manifestations in AIDS patients with tuberculosis of mesenteric lymph nodes. However, AIDS patients with CD(4)(+) cell count less than 50 x 10(6) cells/L might be more prone to developing tuberculosis of the mesenteric lymph nodes. Abdominal CT scanning with typical strengthened ring shadow is suggestive of the diagnosis. Anti-tuberculous therapy combined with HAART is recommended for the treatment of patients with suspected tuberculosis.