Prognostic and diagnostic significance of mid-regional pro-atrial natriuretic peptide in acute exacerbation of chronic obstructive pulmonary disease and acute heart failure: data from the ACE 2 Study

Abstract

Purpose: To compare the diagnostic and prognostic value of mid-regional pro-ANP (MR-proANP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients with acute dyspnea.

Methods: MR-proANP and NT-proBNP were measured with commercial immunoassays at hospital admission (n?=?313), on day 2 (n?=?234), and before discharge (n?=?91) and compared for diagnosing acute heart failure (HF; n?=?143) and to predict mortality among patients with acute HF and acute exacerbation of chronic obstructive pulmonary disease (AECOPD; n?=?84) separately.

Results: The correlation coefficient between MR-proANP and NT-proBNP was 0.89 (p?<?0.001) and the receiver-operating area under the curve (AUC) was 0.85 (95% CI 0.81–0.89) for MR-proANP and 0.86 (0.82–0.90) for NT-proBNP to diagnose acute HF. During a median follow-up of 816?days, mortality rates were 46% in acute HF patients and 42% in AECOPD patients. After adjustment for other risk variables by multivariate Cox regression analysis, MR-proANP and NT-proBNP concentrations were associated with mortality in patients with acute HF, but only MR-proANP were associated with mortality among patients with AECOPD: hazard ratio (_lnMR-proANP) 1.98 (95% CI 1.17–3.34).

Conclusion: MR-proANP and NT-proBNP concentrations provide similar diagnostic and prognostic information in patients with acute HF. In contrast to NT-proBNP, MR-proANP measurements also provided independent prognostic information in AECOPD patients.     

YKL-40 in patients with end-stage renal disease receiving haemodialysis

Purpose: This study aimed to determine serum YKL-40 in patients with end-stage renal disease (ESRD) on haemodialysis (HD) and to evaluate the prognostic value of serum YKL-40.

Methods: Patients >18?years on maintenance HD were included. Serum YKL-40 was measured using ELISA before and after a single HD treatment.

Results: A total of 306 patients were included. Median serum YKL-40 concentration was 238?µgL^?1 (IQR: 193–291?µgL^?1) before HD treatment and 198?µgL^?1 (IQR: 147–258?µgL^?1) after HD treatment, which corresponded to age-corrected 93th percentile in healthy subjects. All-cause mortality after 2.8?years was 35.9%. Patients with serum YKL-40 in the highest quartile compared with the lowest quartile had a univariate HR of 4.0 (95% CI: 2.2–7.3, p?p?=?0.01) in multivariate analysis. Time-dependent receiver operating characteristic curves showed that serum YKL-40 after HD treatment had significant higher area under the curves from 90?d (p?=?0.004) and throughout the rest of the follow-up period when compared to serum YKL-40 before HD treatment.

Conclusion: YKL-40 was highly elevated in patients with ESRD on HD, and dialysis reduced serum YKL-40 concentrations approximately one-sixth. YKL-40 measured after dialysis was independently associated with mortality in HD patients.     

Growth hormone for risk stratification and effects of therapy in acute myocardial infarction

Abstract

Context: Excess growth hormone (GH) is associated with early mortality.

Objectives: We assessed the association of GH with prognosis after acute myocardial infarction (AMI), and the effects of secondary prevention therapies.

Methods: GH was measured using a high-sensitivity assay in 953 AMI patients (687 males, mean age 66.1?±?12.8 years).

Results: During 2 years follow-up, there were 281 major adverse cardiac events (MACE). Patients with MACE had higher GH levels (median [range], 0.91 [0.04–26.28] μg/L) compared to event-free survivors (0.59 [0.02–21.6], p?<?0.0005). In multivariate Cox survival analysis, GH was a significant predictor of MACE (hazard ratios 1.43, p?=?0.026 and 1.49, p?=?0.01, respectively) with significant interactions with beta blocker therapy (p?=?0.047) and angiotensin converting enzyme inhibitor or angiotensin receptor blocker (ACE/ARB) therapy (p?=?0.016).

Conclusions: GH levels post-AMI are prognostic for MACE and may indicate those patients who benefit from beta blocker and ACE/ARB therapy.     

Serum Procalcitonin Levels are Associated with Clinical Outcome in Intracerebral Hemorrhage

Procalcitonin (PCT) has emerged as a new prognostic inflammatory marker in a variety of diseases. This study aimed to evaluate whether PCT is associated with increased risk of unfavorable outcome in intracerebral hemorrhage (ICH) patients. During January 2015–December 2016, we conducted a prospective cohort investigation involved 251 primary ICH patients who were admitted within 24 h after the onset of symptoms. We assessed serum PCT levels for all patients at admission. The functional outcome after 3 months was evaluated by modified Rankin Scale (mRS) and dichotomized as favorable (mRS 0–2) and unfavorable (mRS 3–6). The independent risk factors for unfavorable outcome and mortality after 3 months were examined by binary logistic regression. Of 251 ICH patients, the median PCT concentration was 0.053 µg/L (interquartile range 0.035–0.078 µg/L). Unfavorable outcome and mortality at 3 months were observed in 161 (64.1%) and 51 (20.3%) patients, respectively. After adjusting for potential confounders, patients with PCT levels in the top quartile (>0.078 ug/L), compared with the lowest quartile (<0.035 μg/L) were more likely to have a higher risk of poor functional outcome [odds ratio (OR) 7.341; 95% confidence interval (CI) 2.770–21.114; P = 0.001] and mortality (OR 7.483; 95% CI 1.871–24.458, P = 0.006). Furthermore, the area under the receiver operating characteristic curve of PCT showed 0.701 (95% CI 0.635–0.767) for worse functional prognosis, and 0.652 (95% CI 0.569–0.735) for mortality. This study demonstrated that elevated PCT levels at admission were independently associated with unfavorable clinical outcome in ICH patients.     

Change in plasma copeptin level after acute spontaneous basal ganglia hemorrhage

High plasma copeptin levels are associated with mortality after intracerebral hemorrhage (ICH). However, there is a paucity of data available on whether copeptin is an independent prognostic marker of mortality. Thus, we sought to furthermore evaluate this relation. Thirty healthy controls and 86 patients with acute ICH were included. Plasma samples were obtained on admission and at days 1, 2, 3, 5, and 7 after ICH. Its concentration was measured by enzyme-linked immunosorbent assay. After ICH, plasma copeptin level in patients increased during the 6-h period immediately, peaked in 24 h, decreased gradually thereafter, and was substantially higher than that in healthy controls during the 7-day period. A multivariate analysis showed plasma copeptin level was an independent predictor for 1-week mortality (odds ratio, 1.013; 95% confidence interval (CI), 1.003-1.023; P = 0.009) and positively associated with hematoma volume (t = 6.616, P < 0.001). A receiver operating characteristic curve identified that a baseline plasma copeptin level >577.5 pg/mL predicted 1-week mortality with 87.5% sensitivity and 72.2% specificity (area under curve (AUC), 0.873; 95% CI, 0.784-0.935). The AUC of the copeptin concentration was similar to those of Glasgow Coma Scale (GCS) scores and hematoma volumes (P = 0.136 and 0.280). However, copeptin did not statistically significantly improve the AUCs of GCS scores and hematoma volumes (P = 0.206 and 0.333). Hence, increased plasma copeptin level is associated with hematoma volume and an independent prognostic marker of mortality after ICH.     

A systematic review and meta-analysis of higher expression of folate receptor alpha (FOLR1) predicts poor cancer prognosis

Abstract

Folate receptor alpha (FOLR1), a glycosylphosphatidylinositol-linked protein, is a well characterized folate transporter. However, the prognostic power of FOLR1 in cancer remains controversial. We conducted a meta-analysis to assess the prognostic roles of FOLR1 on different cancers. Twelve studies involving 4471 patients were included in this meta-analysis. The pooled analysis indicated that high FOLR1 significantly predicted poor overall survival (OS) (pooled hazard ratio (HR)?=?0.78, 95% confidence interval (CI)?=?0.64–0.94, p?=?0.009) and the disease-free survival (DFS) (HR?=?1.25, 95% CI?=?1.07–1.47, p?=?0.005). Subgroup analyses based on tumour type found that high FOLR1 level was associated with poor OS in breast cancer (HR?=?2.66, 95% CI?=?1.54–4.59, p?=?0.0005) and endometrial carcinoma (HR?=?1.30, 95% CI?=?1.05–1.61, p?=?0.02). However, FOLR1 has relatively weakly correlation with gender, tumour size and chemotherapy. Additionally, overexpression of FOLR1 was correlated with grade, FIGO stage, vital status and nodule status. The present meta-analysis indicated that the high expression of FOLR1 is associated with the poor survival of cancer patients, which is helpful for the clinical decision-making process.     

Tumour necrosis factor-α gene polymorphisms in asbestos-induced diseases

Background: Tumour necrosis factor (TNF)-α influences the pathogenesis of lung fibrosis and carcinogenesis in normal cells. Polymorphisms of this gene have been suggested to be associated with susceptibility to lung diseases.

Methods: Association studies were performed in German subjects, using control subjects (n?=?177), pulmonary fibrosis patients (n?=?612) and bronchial carcinoma patients (n?=?374).

Results: Compared with a healthy (control) group, a significant result could be obtained for the asbestosis (patient) group (crude odds ratio (OR_crude)?=?1.57; 95% confidence interval (CI) 1.05–2.36; p?=?0.03), especially with severe lung asbestosis (OR_crude?=?4.15; 95% CI 1.06–16.16; p?=?0.04). A significant association was revealed when comparing asbestosis patients (OR_crude?=?4.08; 95% CI 1.53–10.54; p?=?0.004 and OR_adjusted?=?3.89; 95% CI 1.49–10.17; p?=?0.006) with asbestos-induced lung cancer patients.

Conclusion: The results confirm the hypothesis that TNF-α polymorphisms are associated with asbestos-induced fibrotic or malignant lung diseases in Germans.     

NTproBNP and ST2 as predictors for all-cause and cardiovascular mortality in elderly patients with symptoms suggestive for heart failure

Background: A new biomarker, suppression of tumorigenicity 2 (ST2) has been introduced as a marker for fibrosis and hypertrophy. Its clinical value in comparison with N-terminal pro-hormone of brain natriuretic peptide /Amino-terminal pro-B-type natriuretic peptide (NTproBNP) in predicting mortality in elderly patients with symptoms of heart failure (HF) is still unclear.

Aim: To evaluate the prognostic value for all-cause- and cardiovascular mortality of ST2 or NTproBNP and the combination of these biomarkers.

Patients and methods: One hundred seventy patients patients with clinical symptoms of HF (77 (45%) were with verified HF) were recruited from one selected primary health care center (PHC) in Sweden and echocardiography was performed in all patients. Blood samples were obtained from 159 patients and stored frozen at –70?°C. NTproBNP was analyzed at a central core laboratory using a clinically available immunoassay.ST2 was analyzed with Critical Diagnostics Presage ST2 ELISA immunoassay.

Results: We studied 159 patients (mean age 77?±?8.3?years, 70% women). During ten years of follow up 78 patients had died, out of which 50 deaths were for cardiovascular reasons. Continuous NTproBNP and ST2 were both significantly associated with all-cause mortality (1.0001; 1.00001–1.0002, p?=?0.04 and 1.03; 1.003–1.06, p?=?0.03), NTproBNP but not ST2 remained significant for cardiovascular mortality after adjustments (1.0001; 1.00001–1.0002, p?=?0.03 and 1.01; 0.77–1.06, p?=?0.53), respectively. NTproBNP above median (>328?ng/L) compared to below median was significantly associated with all-cause mortality(HR: 4.0; CI :2.46–6.61; p?p?Conclusion: In elderly patients with symptoms of heart failure ST2 was not superior to NTproBNP to predict all cause or cardiovascular mortality. Furthermore, it is unclear if the combination of ST2 and NTproBNP will improve long-term prognostication beyond what is achieved by NTproBNP alone.     

Diagnostic utility of MR-proANP and NT-proBNP in elderly outpatients with a high risk of heart failure: the Copenhagen heart failure risk study

Abstract

Background: Amino-terminal-pro-B-type-natriuretic-peptide (NT-proBNP) is a diagnostic biomarker for heart failure (HF), but plasma concentrations are influenced by numerous factors. Mid-regional-pro-atrial-natriuretic-peptide (MR-proANP) have comparable diagnostic value in acute HF. However, data are lacking in the non-acute setting. This study sought to assess the diagnostic utility of MR-proANP in outpatients with a high risk of HF.

Methods: This prospective study included 399 outpatients. Inclusion criteria were: age?≥?60?years, ≥1 risk factor for HF (diabetes, chronic kidney disease, vascular disease, atrial fibrillation, hypertension), without known or suspected HF. Unrecognized HF was diagnosed based on clinical signs, patient-reported symptoms and echocardiography. Plasma concentrations of MR-proANP and NT-proBNP were analysed.

Results: In total, 65 patients were diagnosed with HF or asymptomatic left ventricular systolic dysfunction (N?=?12 LVEF?≤?40%, N?=?7 LVEF?>?40% to ≤50%, N?=?46 LVEF?>?50%). Both MR-proANP (odds-ratio: 1.77; 95% CI:1.16–2.72; p?=?0.009) and NT-proBNP (odds-ratio: 1.49; 95% CI:1.22–1.82; p?<?0.001) were associated with HF. Area under receiver-operator characteristics curve (AUC) for the diagnosis of HF or asymptomatic left ventricular systolic dysfunction was higher for MR-proANP (AUC?=?0.886; p?<?0.001) and NT-proBNP (AUC?=?0.910; p?<?0.001) compared to patient-reported symptoms of HF (AUC?=?0.830), but NT-proBNP added more diagnostic information compared to MR-proANP (p?=?0.022).

Conclusions: Both NT-proBNP and MR-proANP are useful biomarkers in the diagnosis of HF or asymptomatic left ventricular systolic dysfunction in a non-acute setting. However, NT-proBNP added more diagnostic information compared to MR-proANP.     

“MOONSTROKE”: Lunar patterns of stroke occurrence combined with circadian and seasonal rhythmicity—A hospital based study

Both time of the day and season have been shown to have a significant effect on stroke incidence. In contrast, the role played by the moon has been little studied. We aimed to investigate the potential association of the lunar phase with the incidence of stroke subtypes [intracerebral hemorrhage (ICH), transient ischemic attack (TIA) and ischemic stroke (IS)], adjusted by circadian and seasonal variations. Consecutive stroke admissions to the Royal Melbourne Hospital (RMH) were analyzed from 2004–2011. Of 6252 patients, 4085 (65.3%) had confirmed dates and hour of the day. Of these, 632 (15.5%) had ICH, 658 (16.1%) presented with TIA and 2202 (53.9%) had IS. There were also 593 (14.5%) stroke mimics. We measured the association of stroke incidence with a particular lunar phase using an incidence rate ratio (IRR) with 95% confidence intervals (CI) using Poisson regression model (new moon set as reference). Compared with new moon phase, ICHs occurred significantly more during the first quarter (IRR, 1.55; 95%CI, 1.04 to 2.30; p?=?0.03). More TIAs were observed during the first quarter and full moon than in new moon (IRR, 1.69; 95%CI, 1.16 to 2.46; p?=?0.01; IRR, 1.52; 95%CI, 0.00 to 2.31; p?=?0.05; respectively). Both ICH and TIA occurrence slightly decreased as lunar illumination increased (IRR, 0.99; 95%CI, 0.99 to 1.00; p?=?0.01; IRR, 0.99; 95%CI, 0.99 to 1.00; p?=?0.04; respectively). No association was found between lunar phase or illumination and IS. All stroke subtypes were less likely to happen between 12AM and 6AM than the remaining 18 h of the day. IS occurrence was significantly higher during the spring than summer (IRR, 1.14; 95%CI, 1.02 to 1.28; p?=?0.03). For the patients older than 65 years, incidence of both ICH and IS was higher in spring than in summer (IRR, 1.33; 95%CI, 1.01 to 1.74; p?=?0.04; IRR, 1.22; 95%CI, 1.06 to 1.39; p?=?0.005; respectively). The lunar phase and illumination are associated with both ICH and TIA incidence. These findings should be tested on other stroke databases.     

Plasma copeptin concentration and outcome after pediatric traumatic brain injury

Higher plasma copeptin level has been associated with poor outcomes of critical illness. The present study was undertaken to investigate the plasma copeptin concentrations in children with traumatic brain injury (TBI) and to analyze the correlation of copeptin with disease outcome. Plasma copeptin concentrations of 126 healthy children and 126 children with acute severe TBI were measured by enzyme-linked immunosorbent assay. Twenty-one patients (16.7%) died and 38 patients (30.2%) had an unfavorable outcome (Glasgow Outcome Scale score of 1–3) at 6 months. Plasma copeptin level was obviously higher in patients than in healthy children (46.2 ± 20.8 pmol/L vs. 9.6 ± 3.0 pmol/L, P < 0.001). Plasma copeptin level was identified as an independent predictor for 6-month mortality [odds ratio (OR) 1.261, 95% confidence interval (CI) 1.112–1.538, P = 0.005] and unfavorable outcome (OR 1.313, 95% CI 1.146–1.659, P = 0.003). The predictive value of copeptin was similar to that of Glasgow Coma Scale (GCS) score for 6-month mortality [area under curve (AUC) 0.832, 95% CI 0.755–0.892 vs. AUC 0.873, 95% CI 0.802–0.926, P = 0.412] and unfavorable outcome (AUC 0.863, 95% CI 0.790–0.918 vs. AUC 0.885, 95% CI 0.816–0.935, P = 0.596). Copeptin improved the AUC of GCS score for 6-month unfavorable outcome (AUC 0.929, 95% CI 0.869–0.967, P = 0.013), but not for 6-month mortality (AUC 0.887, 95% CI 0.818–0.936, P = 0.600). Thus, plasma copeptin level represents a novel biomarker for predicting 6-month clinical outcome in children with TBI.     

Validation of the Chinese version of the FOUR score in the assessment of neurosurgical patients with different level of consciousness

Background

The Glasgow Coma Scale (GCS) is currently the most widely used scoring system for comatose patients. A decade ago, the Full Outline of Unresponsiveness (FOUR) score was devised to better capture four functional aspects of consciousness (eye, motor responses, brainstem reflexes, and respiration). This study aimed to validate the Chinese version of the FOUR score in patients with different levels of consciousness.

Methods

The study had two phases: (1) translation of the FOUR score, and (2) assessment of its reliability and validity. The Chinese version of the FOUR score was developed according to a standardized protocol. One hundred-twenty consecutive patients with acute brain damage, admitted to Nanfang Hospital (Southern Medical University, Guangdong, China) from November 2014 to February 2015, were enrolled. The inter-rater agreement for the FOUR score and GCS was evaluated using intraclass correlation coefficient (ICC). Receiver operating characteristic (ROC) curves were established to determine the scales’ abilities to predict outcome.

Results

The rater agreement was excellent both for FOUR (ICC?=?0.970; p?<?0.001) and GCS (ICC?=?0.958; p?<?0.001). The FOUR score yielded an excellent test-retest reliability (ICC?=?0.930; p?<?0.001). Spearman’s correlation coefficients between GCS and the FOUR score were high: r?=?0.932, first rating; r?=?0.887, second rating (all p?<?0.001). Areas under the curve (AUC) for mortality were 0.834 (95 % CI, 0.740–0.928) and 0.815 (95 % CI, 0.723–0.908) for the FOUR score and GCS, respectively.

Conclusions

The Chinese version of the FOUR score is a reliable scale for evaluating the level of consciousness in patients with acute brain injury.

     

Thrombin activity throughout the acute phase of acute ST-elevation myocardial infarction and the relation to outcome

Background: Thrombin and plasmin play a central role in ongoing thrombosis and platelet activation in patients with acute ST-elevation myocardial infarction (STEMI). Data of thrombin and plasmin activity in the early course of STEMI and the relation to outcome are scarce.

Methods: We included 68 consecutive patients (53 male, 59?±?11.4 years) with STEMI who underwent acute catheter-based reperfusion therapy within the first 12?h after onset of symptoms. Blood samples were taken at admission and after 4, 8, 12 and 24?h. Thrombin activity and generation was measured by changes in the thrombin/antithrombin-III complex (TAT) and prothrombin fragment (F1.2); plasmin was measured by changes in the plasmin-α₂/antiplasmin complex (PAP). A follow-up with respect to the combined primary endpoint consisting of death, acute myocardial infarction or urgent need for revascularization up to 6 weeks post-discharge was carried out.

Results: TAT values showed no significant change over time in patients with and without the primary endpoint but there was a borderline difference between these groups at 4?h after admission (event group 9.0 vs no event group 4.7?μg l^?1, p?=?0.057). F1.2 values were different between groups only after 24?h (event group 1.5 vs no event group 0.9?nmol l^?1, p?=?0.028) and did not differ in serial sampling of 24?h. PAP values were higher in patients with events after 4 and 8?h and declined over time in the group without events (p?<0.001). Odds ratios (OR) with respect to the primary endpoint were highest for TAT?>4.8?μg l^?1 at 0?h and TAT?>8.4?μg?l^?1 at 4?h (OR 7.1, 95% confidence interval (CI) 1.5–34, p?=?0.015 and OR 5.5, 95% CI 1.5–20.0, p?=?0.01, respectively). The predictive value of plasmin concentrations were equally high after 4?h (PAP?>962?μg l^?1; OR 6.8, 95% CI 1.8–26.2, p?=?0.005) and 8?h (PAP?>495?μg l^?1, OR 6.7, 95% CI 1.4–32.9, p?=?0.024). Values for F1.2 were only predictive after 24?h (F1.2?>0.85?nmol l^?1, OR 13, 95% CI 1.4–117.8, p?=?0.023).

Conclusions: Markers of thrombin and plasmin activity in acute STEMI are related to outcome. The marker for thrombin generation F1.2 becomes a significant predictor of outcome at 24?h after admission, reflecting the potentially adverse effects of ongoing thrombin generation. This underlines the potential for direct thrombin inhibition and individualization of treatment by thrombin markers in STEMI.     

The GALA study: relationship between galectin-3 serum levels and short- and long-term outcomes of patients with acute heart failure

Objective: We tested the hypothesis that early measurement of galectin-3 at the emergency department (ED) during an episode of acute heart failure (AHF) allows predicting short- and long-term outcomes.

Methods: We performed an exploratory study including 115 patients consecutively diagnosed with AHF in a single ED. Clinical and analytical variables were recorded. The primary endpoint was 30-day all-cause mortality, and secondary endpoints were 30-day composite outcome (death, rehospitalization or ED reconsultation, whichever first) and 1-year mortality.

Results: Seven patients (6.1%) died within 30?days and 43 (37.4%) within 1?year. The 30-day composite endpoint was observed in 21.1% of patients. Galectin-3 was correlated with NT-proBNP and the glomerular filtration rate but not with age and s-cTnI. Measured at time of ED arrival, galectin-3 showed good discriminatory capacity for 30-day mortality (AUC ROC: 0.732; 95% CI 0.512–0.953; p?=?0.041) but not for 1-year mortality (0.521; 0.408–0.633; p?=?0.722). Patients with galectin-3 concentrations?>42?μg/L had an OR?=?7.67(95%CI?=?1.57-37.53; p?=?0.012) for 30-day mortality. Conversely, NT-proBNP only showed predictive capacity for 1-year mortality (0.642; 0.537–0.748; p?=?0.014). Patients with NT-proBNP concentrations?>5400?ng/L had an OR?=?4.34 (95%CI?=?1.93-9.77; p?<?0.001) for 1-year mortality. These increased short- (galectin-3) and long-term (NT-proBNP) risks remained significant after adjustment for age or renal function. s-cTnI failed in both short- and long term death prediction. No biomarker predicted the short-term composite endpoint.

Conclusion: These results suggest that galectin-3 could help to monitor the risk of short-term mortality in unselected patients with AHF attended in the ED.     

New scoring system combining the FIB-4 index and cytokeratin-18 fragments for predicting steatohepatitis and liver fibrosis in patients with nonalcoholic fatty liver disease

Purpose: To establish a new scoring system as a noninvasive tool for predicting steatohepatitis and liver fibrosis in patients with nonalcoholic fatty liver disease (NAFLD).

Methods: A total of 170 patients histologically diagnosed with nonalcoholic steatohepatitis (NASH) (n?=?130) or nonalcoholic fatty liver (NAFL) (n?=?40) were enrolled. We analyzed receiver operating characteristic (ROC) curves and performed multivariate analysis to predict steatohepatitis and liver fibrosis.

Results: Multivariate analysis showed that cytokeratin-18 fragment (CK18-F) levels (≥278?U/L) (odds ratio [OR], 4.46; 95% confidence interval [CI], 1.42–14.00; p?=?0.010) and the FIB-4 index (≥1.46) (OR, 4.54; 95% CI, 1.93–29.50; p?=?0.004) were independently associated with prediction of NASH. We then established a new scoring system (named the FIC-22 score) for predicting NASH using CK18-F levels and FIB-4 index. The areas under the ROC curve (AUROCs) of the FIC-22 score and NAFIC score were 0.82 (95% CI, 0.75–0.89) and 0.71 (95% CI, 0.62–0.78) (p?=?0.044). Additionally, the AUROC of the FIC-22 score for predicting the presence of fibrosis (F?≥?1) was 0.78 (95% CI, 0.70–0.85).

Conclusions: In patients with NAFLD, the FIC-22 score had high predictive accuracy not only for steatohepatitis but also for the presence of liver fibrosis.     

Circadian variation in clinical features and outcome of intracerebral hemorrhage: The INTERACT studies

Previous studies consistently reported a diurnal variation in the occurrence of intracerebral hemorrhage (ICH), with a morning peak. However, limited knowledge exists on the circadian pattern of ICH severity and outcome. This study aimed to determine possible associations between ICH onset time and admission severity and 90-day outcomes using the combined data set of the pilot and main-phase Intensive blood pressure (BP) reduction in an acute cerebral hemorrhage trial (INTERACT). The ICH onset time was categorized into three groups (1: 00:00–07:59; 2: 08:00–15:59; and 3: 16:00–23:59). We found an association between onset time and low Glasgow Coma Scale score: aOR (time 1: 1.72, 95% CI 1.12–2.66; time 3: 1.95, 95% CI 1.31–2.89, p = 0.003; in comparison to time 2). There was no association between onset time and volume of ICH (adjusted p = 0.354) or 90-day outcomes of death or major disability, and death and major disability separately (all adjusted p > 0.4). The results showed that more severe cases of ICH patients, defined by a reduced level of consciousness, had late afternoon to early morning stroke onset, but this was unrelated to baseline hematoma volume or location. There was no circadian influence on ICH clinical outcome.     

A systematic review and meta-analysis of the association of transforming growth factor β receptor I 6A/9A gene polymorphism with ovarian cancer risk

Abstract

Ovarian cancer is the leading cause of cancer-related death in women. This meta-analysis was conducted to evaluate the association of transforming growth factor β receptor I (TβR-I) 6A/9A gene polymorphism with ovarian cancer risk. The association literatures were identified from PubMed and Cochrane Library on 1 October 2013, and eligible reports were recruited and synthesized. Four reports were recruited into this meta-analysis for the association of TβR-I 6A/9A gene polymorphism with ovarian cancer risk. 6A allele and 6A/6A genotype of TβR-I were associated with the ovarian cancer risk (6A: OR?=?1.24, 95% CI: 1.02–1.51, p?=?0.03; 6A/6A: OR?=?2.30, 95% CI: 1.01–5.22, p?=?0.05). However, TβR-I 9A/9A genotype was not associated with the risk of ovarian cancer (OR?=?0.82, 95% CI: 0.66–1.02, p?=?0.08). In conclusion, TβR-I 6A allele and 6A/6A genotype are associated with the ovarian cancer risk. However, more studies should be performed to confirm this relationship in the future.     

Prognostic value of rising mean platelet volume during hospitalization in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention

Background

The prognostic significance of changes in mean platelet volume (MPV) during hospitalization in ST segment elevation myocardial infarction (STEMI) patients underwent primary percutaneous coronary intervention (pPCI) has not been previously evaluated. The aim of this study was to determine the association of in-hospital changes in MPV and mortality in these patients.

Methods

Four hundred eighty consecutive STEMI patients were enrolled in this retrospective study. The patients were grouped as survivors (n?=?370) or non-survivors (n?=?110). MPV at admission, and at 48–72?h was evaluated. Change in MPV (MPV at 48–72?h minus MPV on admission) was defined as ΔMPV.

Results

At follow-up, long-term mortality was 23%. The non-survivors had a high ΔMPV than survivors (0.37 (??0.1–0.89) vs 0.79 (0.30–1.40) fL, p?<? 0.001). A high ΔMPV was an independent predictor of all cause mortality ((HR: 1.301 [1.070–1.582], p?=?0.008). Morever, for long-term mortality, the AUC of a multivariable model that included age, LVEF, Killip class, and history of stroke/TIA was 0.781 (95% CI:0.731–0.832, p?<? 0.001). When ΔMPV was added to a multivariable model, the AUC was 0.800 (95% CI: 0.750–0.848, z?=?2.256, difference p?=?0.0241, Fig. 1). Also, the addition of ΔMPV to a multivariable model was associated with a significant net reclassification improvement estimated at 24.5% (p?=?0.027) and an integrated discrimination improvement of 0.014 (p?=?0.0198).

Conclusions

Rising MPV during hospitalization in STEMI patients treated with pPCI was associated with long-term mortality.

     

Association between red blood cell distribution width and long-term mortality among patients undergoing percutaneous coronary intervention with previous history of cancer

Abstract

Background: The number of patients suffering from coronary heart disease with cancer is rising. There is scarce evidence concerning the biomarkers related to prognosis among patients undergoing percutaneous coronary intervention (PCI) with cancer. Thus, the aim of this study was to investigate the association between red blood cell distribution width (RDW) and prognosis in this population.

Methods: A total of 172 patients undergoing PCI with previous history of cancer were enrolled in this retrospective study. The endpoint was long-term all-cause mortality. According to tertiles of RDW, the patients were classified into three groups: Tertile 1 (RDW <12.8%), Tertile 2 (RDW ≥12.8% and <13.5%) and Tertile 3 (RDW ≥13.5%).

Results: During an average follow-up period of 33.3 months, 29 deaths occurred. Compared with Tertile 3, mortality of Tertile 1 and Tertile 2 was significantly lower in the Kaplan–Meier analysis. In multivariate Cox regression analysis, RDW remained an independent risk factor of mortality (HR: 1.938, 95% CI: 1.295–2.655, p?<?0.001). The all-cause mortality in Tertile 3 was significantly higher than that in Tertile 1 (HR: 5.766; 95% CI: 1.426–23.310, p?=?0.014).

Conclusions: An elevated RDW level (≥13.5%) was associated with long-term all-cause mortality among patients undergoing PCI with previous history of cancer.