Astrocyte Elevated Gene-1 as a Novel Clinicopathological and Prognostic Biomarker for Gastrointestinal Cancers: A Meta-Analysis with 2999 Patients

Background

There have been numerous articles as to whether the staining index (SI) of astrocyte elevated gene-1 (AEG-1) adversely affects clinical progression and prognosis of gastrointestinal cancers. Nevertheless, controversy still exists in terms of correlations between AEG-1 SI and clinicopathological parameters including survival data. Consequently, we conducted a comprehensive meta-analysis to confirm the role of AEG-1 in clinical outcomes of gastrointestinal carcinoma patients.

Methods

We performed a comprehensive search in PubMed, ISI Web of Science, Cochrane Central Register of Controlled Trials, EMBASE, Science Direct, Wiley Online Library, China National Knowledge Infrastructure (CNKI), WanFang and Chinese VIP databases. STATA 12.0 (STATA Corp., College, TX) was used to analyze the data extracted from suitable studies and Newcastle-Ottawa Scale was applied to assess the quality of included articles.

Results

The current meta-analysis included 2999 patients and our results suggested that strong associations emerged between AEG-1 SI and histological differentiation (OR = 2.129, 95%CI: 1.377–3.290, P = 0.001), tumor (T) classification (OR = 2.272, 95%CI: 1.147–4.502, P = 0.019), lymph node (N) classification (OR = 2.696, 95%CI: 2.178–3.337, P<0.001) and metastasis (M) classification (OR = 3.731, 95%CI: 2.167–6.426, P<0.001). Furthermore, high AEG-1 SI was significantly associated with poor overall survival (OS) (HR = 2.369, 95%CI: 2.005–2.800, P<0.001) and deteriorated disease-free survival (DFS) (HR = 1.538, 95%CI: 1.171–2.020, P = 0.002). For disease-specific survival (DSS) and relapse-free survival (RFS), no statistically significant results were observed (HR = 1.573, 95%CI: 0.761–3.250, P = 0.222; HR = 1.432, 95%CI: 0.108–19.085, P = 0.786). Subgroup analysis demonstrated that high AEG-1 SI was significantly related to poor prognosis in esophageal squamous cell carcinoma (ESCC) (HR = 1.715, 95%CI: 1.211–2.410, P = 0.002), gastric carcinoma (GC) (HR = 2.255, 95%CI: 1.547–3.288, P<0.001), colorectal carcinoma (CRC) (HR = 2.922, 95%CI: 1.921–4.444, P<0.001), gallbladder carcinoma (GBC) (HR = 3.047, 95%CI: 1.685–5.509, P<0.001), hepatocellular carcinoma (HCC) (HR = 2.245, 95%CI: 1.620–3.113, P<0.001), pancreatic adenocarcinoma (PAC) (HR = 2.408, 95%CI: 1.625–3.568, P<0.001).

Conclusions

The current meta-analysis indicated that high AEG-1 SI might be associated with tumor progression and poor survival status in patients with gastrointestinal cancer. AEG-1 might play a vital role in promoting tumor aggression and could serve as a potential target for molecular treatments. Further clinical trials are needed to validate whether AEG-1 SI provides valuable insights into improving treatment decisions.     

Coenzyme Q10 Levels Are Decreased in the Cerebellum of Multiple-System Atrophy Patients

Background

The objective of this study was to evaluate whether the levels of coenzyme Q10 (CoQ10) in brain tissue of multiple system atrophy (MSA) patients differ from those in elderly controls and in patients with other neurodegenerative diseases.

Methods

Flash frozen brain tissue of a series of 20 pathologically confirmed MSA patients [9 olivopontocerebellar atrophy (OPCA) type, 6 striatonigral degeneration (SND) type, and 5 mixed type] was used for this study. Elderly controls (n = 37) as well as idiopathic Parkinson''s disease (n = 7), dementia with Lewy bodies (n = 20), corticobasal degeneration (n = 15) and cerebellar ataxia (n = 18) patients were used as comparison groups. CoQ10 was measured in cerebellar and frontal cortex tissue by high performance liquid chromatography.

Results

We detected a statistically significant decrease (by 3–5%) in the level of CoQ10 in the cerebellum of MSA cases (P = 0.001), specifically in OPCA (P = 0.001) and mixed cases (P = 0.005), when compared to controls as well as to other neurodegenerative diseases [dementia with Lewy bodies (P<0.001), idiopathic Parkinson''s disease (P<0.001), corticobasal degeneration (P<0.001), and cerebellar ataxia (P = 0.001)].

Conclusion

Our results suggest that a perturbation in the CoQ10 biosynthetic pathway is associated with the pathogenesis of MSA but the mechanism behind this finding remains to be elucidated.     

Prognostic Significance of Tumor Volume in Locally Recurrent Nasopharyngeal Carcinoma Treated with Salvage Intensity-Modulated Radiotherapy

Introduction

To evaluate the prognostic value of gross tumor volume (TV) in patients with locally recurrent, nonmetastatic nasopharyngeal carcinoma.

Methods

Between 2001 and 2012, 291 consecutive patients with locally recurrent, nonmetastatic nasopharyngeal carcinoma underwent salvage IMRT were retrospectively reviewed. The correlations between TV and recurrent T classification were analyzed. Survival analyses were performed. Receiver operating characteristic (ROC) curves were calculated to identify cut-off point of TV. The Akaike information criterion and Harrell’s concordance index (c-index) were utilized to test the prognostic value.

Results

The median TV significantly increased with advancing recurrent T classification (P<0.001). The 5-year overall survival rate was 33.2% for the entire cohort. On multivariate analysis, TV was an independent negative prognostic factor for distant metastasis-free survival (hazard ratio =1.013, P =0.003), overall survival (hazard ratio = 1.015, P<0.001) and toxicity-related death (hazard ratio = 1.014, P<0.001). The 5-year overall survival rates were 63.1% and 20.8% for patients with a TV < 22 cm³ and TV ≥22 cm³, respectively (P < 0.001). In patient with TV <22 cm³, locoregional failure is the leading cause of death. In patients with TV≥22 cm³, distant metastasis rate is higher and occurred within short term after local recurrence; meanwhile, radiation-induced injuries became more common and led to half of deaths in this group. The Akaike information criterion and c-index analyses indicated that the predictive ability of recurrent T classification improved when combined with TV.

Conclusions

Our data suggests TV is a significant prognostic factor for predicting the distant metastasis, overall survival and toxicity-related death of patients with locally recurrent, nonmetastatic nasopharyngeal carcinoma after salvage IMRT. TV should be considered when designing personalized salvage treatments for these patients. For patients with bulky local recurrent tumor, radiation may need to be de-emphasized in favor of systemic treatment or best supportive care.     

Association of Big Endothelin-1 with Coronary Artery Calcification

Background

The coronary artery calcification (CAC) is clinically considered as one of the important predictors of atherosclerosis. Several studies have confirmed that endothelin-1(ET-1) plays an important role in the process of atherosclerosis formation. The aim of this study was to investigate whether big ET-1 is associated with CAC.

Methods and Results

A total of 510 consecutively admitted patients from February 2011 to May 2012 in Fu Wai Hospital were analyzed. All patients had received coronary computed tomography angiography and then divided into two groups based on the results of coronary artery calcium score (CACS). The clinical characteristics including traditional and calcification-related risk factors were collected and plasma big ET-1 level was measured by ELISA. Patients with CAC had significantly elevated big ET-1 level compared with those without CAC (0.5±0.4 vs. 0.2±0.2, P<0.001). In the multivariate analysis, big ET-1 (Tertile 2, HR = 3.09, 95% CI 1.66–5.74, P <0.001, Tertile3 HR = 10.42, 95% CI 3.62–29.99, P<0.001) appeared as an independent predictive factor of the presence of CAC. There was a positive correlation of the big ET-1 level with CACS (r = 0.567, p<0.001). The 10-year Framingham risk (%) was higher in the group with CACS>0 and the highest tertile of big ET-1 (P<0.01). The area under the receiver operating characteristic curve for the big ET-1 level in predicting CAC was 0.83 (95% CI 0.79–0.87, p<0.001), with a sensitivity of 70.6% and specificity of 87.7%.

Conclusions

The data firstly demonstrated that the plasma big ET-1 level was a valuable independent predictor for CAC in our study.     

Incidence and Predictive Factors of Central Nervous System Dysfunction in Patients Consulting for Dengue Fever in Cayenne Hospital,French Guiana

Introduction

The frequency, the clinical characteristics, and the prognosis of dengue is highly variable. Dengue fever is associated with a range of neurological manifestations. The objective of the present study was to determine the incidence of neurological signs and their predictive factors using data from cases of dengue seen and followed in Cayenne Hospital during the Dengue 2 epidemic in 2013.

Methods

In 2013, a longitudinal study using data from all cases of dengue seen in Cayenne hospital was collected. Medical records used a standardized form to collect demographic information, clinical signs and biological results and the date at which they were present. The analysis used Cox proportional modeling to obtain adjusted Hazard ratios.

Results

A total of 1574 patients were included 221 of whom developed central nervous system signs. These signs were spontaneously resolutive. There were 9298person days of follow-up and the overall incidence rate for central nervous system signs was 2.37 per 100 person-days. The variables independently associated with central nervous system anomalies were headache, Adjusted Hazard ratio (AHR) = 1.9(95%CI = 1.4–2.6), bleeding AHR = 2 ((95%CI = 1.3–3.1), P = 0.001, abdominal pain AHR = 1.9 ((95%CI = 1.4–2.6), P<0.001, aches AHR = 2.1 ((95%CI = 1.5–2.9), P<0.001, and fatigue AHR = 1.5 ((95%CI = 1.3–1.7), P<0.001.

Discussion

Overall, the present study suggests that neurological signs of dengue are not exceptional even in patients without the most severe features of dengue. These manifestations were spontaneously resolutive. Here it was not possible to distinguish between encephalitis or encephalopathy. Further studies would require more in depth exploration of the patients.     

Rye-Based Evening Meals Favorably Affected Glucose Regulation and Appetite Variables at the Following Breakfast; A Randomized Controlled Study in Healthy Subjects

Background

Whole grain has shown potential to prevent obesity, cardiovascular disease and type 2 diabetes. Possible mechanism could be related to colonic fermentation of specific indigestible carbohydrates, i.e. dietary fiber (DF). The aim of this study was to investigate effects on cardiometabolic risk factors and appetite regulation the next day when ingesting rye kernel bread rich in DF as an evening meal.

Method

Whole grain rye kernel test bread (RKB) or a white wheat flour based bread (reference product, WWB) was provided as late evening meals to healthy young adults in a randomized cross-over design. The test products RKB and WWB were provided in two priming settings: as a single evening meal or as three consecutive evening meals prior to the experimental days. Test variables were measured in the morning, 10.5–13.5 hours after ingestion of RKB or WWB. The postprandial phase was analyzed for measures of glucose metabolism, inflammatory markers, appetite regulating hormones and short chain fatty acids (SCFA) in blood, hydrogen excretion in breath and subjective appetite ratings.

Results

With the exception of serum CRP, no significant differences in test variables were observed depending on length of priming (P>0.05). The RKB evening meal increased plasma concentrations of PYY (0–120 min, P<0.001), GLP-1 (0–90 min, P<0.05) and fasting SCFA (acetate and butyrate, P<0.05, propionate, P = 0.05), compared to WWB. Moreover, RKB decreased blood glucose (0–120 min, P = 0.001), serum insulin response (0–120 min, P<0.05) and fasting FFA concentrations (P<0.05). Additionally, RKB improved subjective appetite ratings during the whole experimental period (P<0.05), and increased breath hydrogen excretion (P<0.001), indicating increased colonic fermentation activity.

Conclusion

The results indicate that RKB evening meal has an anti-diabetic potential and that the increased release of satiety hormones and improvements of appetite sensation could be beneficial in preventing obesity. These effects could possibly be mediated through colonic fermentation.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT02093481","term_id":"NCT02093481"}}NCT02093481     

Set Configuration in Resistance Exercise: Muscle Fatigue and Cardiovascular Effects

Purpose

Cardiovascular responses of traditional resistance (TS) training have been extensively explored. However, the fatigue mechanisms associated with an intra-set rest configuration (ISR) have not been investigated. This study compares two modalities of set configurations for resistance exercise that equates work to rest ratios and measures the central and peripheral fatigue in combination with cortical, hemodynamic and cardiovascular measures.

Methods

11 subjects performed two isometric knee extension training sessions using TS and ISR configurations. Voluntary activation (VA), single twitch amplitude, low frequency fatigue (LFF), Mwave, motor evoked potential (MEP), short intracortical inhibition (SICI), intracortical facilitation (ICF) and heart rate variability were evaluated before and after each training session. During each session beat to beat heart rate, blood pressure and rate pressure product (RPP) were also evaluated.

Results

After exercise VA decreased significantly for TS but not for ISR (P < 0.001), single twitch amplitude and LFF values were lower for TS than ISR (P < 0.004), and SICI was reduced only for the TS configuration (P = 0.049). During exercise RPP values were significantly higher for the TS than for ISR (P = 0.001). RPP correlated with VA for TS (r = -.85 P < 0.001) suggesting a relationship between central fatigue and cardiovascular stress.

Conclusions

We conclude that ISR induced lower central and peripheral fatigue as well as lower cardiovascular stress in comparison with TS configuration. Our study suggests that set configuration is a key factor in the regulation of the neuromuscular and cardiovascular responses of resistance training.     

Outcome of Patients with Carbon Monoxide Poisoning at a Far-East Poison Center

Introduction

Many cases of carbon monoxide poisoning in Taiwan are due to burning charcoal. Nevertheless, few reports have analyzed the mortality rate of these patients who survive to reach a hospital and die despite intensive treatment. Therefore, this study examined the clinical features, physiological markers, and outcomes after carbon monoxide poisoning and the associations between these findings.

Methods

We analyzed the records of 261 patients who were referred for management of carbon monoxide intoxication between 2000 and 2010. Patients were grouped according to status at discharge as alive (survivor, n = 242) or dead (non-survivor, n = 19). Demographic, clinical, laboratory, and mortality data were obtained for analysis.

Results

Approximately half of the cases (49.4%) attempted suicide by burning charcoal. Most of the patients were middle-aged adults (33±19 years), and were referred to our hospital in a relatively short period of time (6±10 hours). Carbon monoxide produced many serious complications after exposure: fever (26.1%), hypothermia (9.6%), respiratory failure (34.1%), shock (8.4%), myocardial infarction (8.0%), gastrointestinal upset (34.9%), hepatitis (18.4%), renal failure (25.3%), coma (18.0%) and rhabdomyolysis (21.8%). Furthermore, the non-survivors suffered greater incidences of hypothermia (P<0.001), respiratory failure (P<0.001), shock (P<0.001), hepatitis ((P=0.016), renal failure (P=0.003), coma (P<0.001) than survivors. All patients were treated with high concentration of oxygen therapy using non-rebreather mask. However, hyperbaric oxygen therapy was only used in 18.8% of the patients. In a multivariate-Cox-regression model, it was revealed that shock status was a significant predictor for mortality after carbon monoxide poisoning (OR 8.696, 95% CI 2.053-37.370, P=0.003). Finally, Kaplan-Meier analysis confirmed that patients with shock suffered greater cumulative mortality than without shock (Log-rank test, Chi-square 147.404, P<0.001).

Conclusion

The mortality rate for medically treated carbon monoxide-poisoned patients at our center was 7.3%. Furthermore, the analysis indicates that shock was most strongly associated with higher risk of mortality.     

Sympathetic Activation Does Not Affect the Cardiac and Respiratory Contribution to the Relationship between Blood Pressure and Pial Artery Pulsation Oscillations in Healthy Subjects

Introduction

Using a novel method called near-infrared transillumination backscattering sounding (NIR-T/BSS) that allows for the non-invasive measurement of pial artery pulsation (cc-TQ) and subarachnoid width (sas-TQ) in humans, we assessed the influence of sympathetic activation on the cardiac and respiratory contribution to blood pressure (BP) cc-TQ oscillations in healthy subjects.

Methods

The pial artery and subarachnoid width response to handgrip (HGT) and cold test (CT) were studied in 20 healthy subjects. The cc-TQ and sas-TQ were measured using NIR-T/BSS; cerebral blood flow velocity (CBFV) was measured using Doppler ultrasound of the left internal carotid artery; heart rate (HR) and beat-to-beat mean BP were recorded using a continuous finger-pulse photoplethysmography; respiratory rate (RR), minute ventilation (MV), end-tidal CO₂ (EtCO2) and end-tidal O₂ (EtO2) were measured using a metabolic and spirometry module of the medical monitoring system. Wavelet transform analysis was used to assess the relationship between BP and cc-TQ oscillations.

Results

HGT evoked an increase in BP (+15.9%; P<0.001), HR (14.7; P<0.001), SaO₂ (+0.5; P<0.001) EtO₂ (+2.1; P<0.05) RR (+9.2%; P = 0.05) and MV (+15.5%; P<0.001), while sas-TQ was diminished (-8.12%; P<0.001), and a clear trend toward cc-TQ decline was observed (-11.0%; NS). CBFV (+2.9%; NS) and EtCO₂ (-0.7; NS) did not change during HGT. CT evoked an increase in BP (+7.4%; P<0.001), sas-TQ (+3.5%; P<0.05) and SaO₂(+0.3%; P<0.05). HR (+2.3%; NS), CBFV (+2.0%; NS), EtO₂ (-0.7%; NS) and EtCO₂ (+0.9%; NS) remained unchanged. A trend toward decreased cc-TQ was observed (-5.1%; NS). The sas-TQ response was biphasic with elevation during the first 40 seconds (+8.8% vs. baseline; P<0.001) and subsequent decline (+4.1% vs. baseline; P<0.05). No change with respect to wavelet coherence and wavelet phase coherence was found between the BP and cc-TQ oscillations.

Conclusions

Short sympathetic activation does not affect the cardiac and respiratory contribution to the relationship between BP—cc-TQ oscillations. HGT and CT display divergent effects on the width of the subarachnoid space, an indirect marker of changes in intracranial pressure.     

Fluctuations of Serum Neuron Specific Enolase and Protein S-100B Concentrations in Relation to the Use of Shunt during Carotid Endarterectomy

Objective

To evaluate the changes in serum neuron specific enolase and protein S-100B, after carotid endarterectomy performed using the conventional technique with routine shunting and patch closure, or eversion technique without the use of shunt.

Materials and Methods

Prospective non-randomized study included 43 patients with severe (>80%) carotid stenosis undergoing carotid endarterectomy in regional anesthesia. Patients were divided into two groups: conventional endarterectomy with routine use of shunt and Dacron patch (csCEA group) and eversion endarterectomy without the use of shunt (eCEA group). Protein S-100B and NSE concentrations were measured from peripheral blood before carotid clamping, after declamping and 24 hours after surgery.

Results

Neurologic examination and brain CT findings on the first postoperative day did not differ from preoperative controls in any patients. In csCEA group, NSE concentrations decreased after declamping (P<0.01), and 24 hours after surgery (P<0.01), while in the eCEA group NSE values slightly increased (P=ns), accounting for a significant difference between groups on the first postoperative day (P=0.006). In both groups S-100B concentrations significantly increased after declamping (P<0.05), returning to near pre-clamp values 24 hours after surgery (P=ns). Sub-group analysis revealed significant decline of serum NSE concentrations in asymptomatic patients shunted during surgery after declamping (P<0.05) and 24 hours after surgery (P<0.01), while no significant changes were noted in non-shunted patients (P=ns). Decrease of NSE serum levels was also found in symptomatic patients operated with the use of shunt on the first postoperative day (P<0.05). Significant increase in NSE serum levels was recorded in non-shunted symptomatic patients 24 hours after surgery (P<0.05).

Conclusion

Variations of NSE concentrations seemed to be influenced by cerebral perfusion alterations, while protein S-100B values were unaffected by shunting strategy. Routine shunting during surgery for symptomatic carotid stenosis may have the potential to prevent postoperative increase of serum NSE levels, a potential marker of brain injury.     

Plasma Concentrations of Hepcidin in Anemic Zimbabwean Infants

Objective

Anemia in infancy is a global public health problem. We evaluated the relative contributions of iron deficiency and inflammation to infant anemia.

Methods

We measured plasma hepcidin, ferritin, soluble transferrin receptor (sTfR), alpha-1-acid glycoprotein and C-reactive protein (CRP) by ELISA on archived plasma from 289 HIV-unexposed anemic or non-anemic Zimbabwean infants at ages 3mo, 6mo and 12mo. Among anemic infants, we determined the proportion with iron-deficiency anemia (IDA) and anemia of inflammation (AI). We undertook regression analyses of plasma hepcidin and anemia status, adjusting for sex, age and birthweight.

Results

Anemic infants at 3mo were more stunted and had higher CRP (median 0.45 vs 0.21mg/L; P = 0.037) and hepcidin (median 14.7 vs 9.7ng/mL; P = 0.022) than non-anemic infants, but similar levels of ferritin and sTfR; 11% infants had IDA and 15% had AI. Anemic infants at 6mo had higher hepcidin (median 7.9 vs 4.5ng/mL; P = 0.016) and CRP (median 2.33 vs 0.32mg/L; P<0.001), but lower ferritin (median 13.2 vs 25.1μg/L; P<0.001) than non-anemic infants; 56% infants had IDA and 12% had AI. Anemic infants at 12mo had lower ferritin (median 3.2 vs 22.2μg/L; P<0.001) and hepcidin (median 0.9 vs 1.9ng/mL; P = 0.019), but similar CRP levels; 48% infants had IDA and 8% had AI. Comparing anemic with non-anemic infants, plasma hepcidin was 568% higher, 405% higher and 64% lower at 3mo, 6mo and 12mo, respectively, after adjusting for sex and birthweight (all p<0.01). Plasma hepcidin declined significantly with age among anemic but not non-anemic infants. Girls had 61% higher hepcidin than boys, after adjusting for age, anemia and birthweight (p<0.001).

Conclusion

Anemia is driven partly by inflammation early in infancy, and by iron deficiency later in infancy, with plasma hepcidin concentrations reflecting the relative contribution of each. However, there is need to better characterize the drivers of hepcidin during infancy in developing countries.     

Factors Influencing Utilization of the Primary Prevention Implantable Defibrillator

Background

A growing literature suggests underutilization of the primary prevention implantable cardioverter-defibrillator (ICD); thus, factors influencing utilization need to be understood. We performed a comprehensive assessment of patient characteristics and health insurance status among subjects eligible for primary prevention ICD in a tertiary care center.

Methods

From among a group of patients who met criteria for primary prevention ICD based on left ventricular dysfunction (LVEF ≤ 35%), ICD recipients (n = 110) were compared to ICD non-recipients (n = 110) to identify determinants of ICD implantation. We evaluated demographics, clinical profile including Charlson Comorbidity Index [CCI, categorized as low (≤3) or high (>3)] and health insurance status.

Results

ICD recipients were younger (62.1±15.0 vs. 68.0±18.2; P = 0.01), with more males (80% vs. 65.5%; P = 0.01), higher NYHA class (II/III: 75.5% vs. 40.2%; P<0.001) and more likely to have supplemental private health insurance (61.8% vs. 46.4%; P = 0.02). CCI was not significantly different between the two groups (low CCI 61.8% vs. 62.7%; P = 0.89). In multivariable analysis, factors independently associated with ICD implantation were male sex (OR, 2.77, [1.31-5.85]; P = 0.01), age<75 (OR, 2.68, [1.30-5.50]; P = 0.01), private insurance (OR, 2.17, [1.08-4.36], P = 0.03) and NYHA Class II/III (OR, 5.91, [2.91-12.01]; P<0.001). Documentation of discussion about primary prevention ICD was absent in the majority (57.2%) of non-recipients.

Conclusion

In a contemporary urban tertiary care setting, age, sex and heart failure symptom class were associated with ICD utilization, with socioeconomic/insurance status also potentially playing a role. These findings have implications for optimizing appropriate utilization of the prophylactic ICD and warrant follow-up in larger, more diverse populations.     

Male Sex Is Independently Associated with Faster Disability Accumulation in Relapse-Onset MS but Not in Primary Progressive MS

Background

Multiple Sclerosis is more common in women than men and females have more relapses than men. In a large international cohort we have evaluated the effect of gender on disability accumulation and disease progression to determine if male MS patients have a worse clinical outcome than females.

Methods

Using the MSBase Registry, data from 15,826 MS patients from 25 countries was analysed. Changes in the severity of MS (EDSS) were compared between sexes using a repeated measures analysis in generalised linear mixed models. Kaplan-Meier analysis was used to test for sex difference in the time to reach EDSS milestones 3 and 6 and the secondary progressive MS.

Results

In relapse onset MS patients (n = 14,453), males progressed significantly faster in their EDSS than females (0.133 vs 0.112 per year, P<0.001,). Females had a reduced risk of secondary progressive MS (HR (95% CI) = 0.77 (0.67 to 0.90) P = 0.001). In primary progressive MS (n = 1,373), there was a significant increase in EDSS over time in males and females (P<0.001) but there was no significant sex effect on the annualized rate of EDSS change.

Conclusion

Among registrants of MSBase, male relapse-onset patients accumulate disability faster than female patients. In contrast, the rate of disability accumulation between male and female patients with primary progressive MS is similar.     

Health-Related Quality of Life in Chinese Patients with Mild and Moderately Active Ulcerative Colitis

Background

Ulcerative colitis (UC) impairs the health-related quality of life (HRQOL). The difference in HRQOL between patients with mild and moderately active UC is not well-defined. Few studies have been conducted to explore the factors that influence HRQOL in Chinese patients. Our study aims were to (1) compare HRQOL of mildly active UC patients with moderate patients; (2) explore the factors that influence HRQOL in Chinese patients with UC; and (3) analyze demographic and disease characteristics of UC in China.

Methods

A total of 110 mild and 114 moderate patients with UC were enrolled. The demographic and disease characteristics were recorded. HRQOL was measured by the Chinese version of the inflammatory bowel disease questionnaire (IBDQ) between mild and moderate patients, male and female patients, and different disease distributions. Stepwise regression analysis was used to assess factors influencing the IBDQ score.

Results

Patients with moderate UC had significantly lower IBDQ total scores compared to patients with mild UC (P=0.001). The IBDQ total score had a negative correlation with the Mayo score (r=–0.263, P<0.001). Stepwise regression analysis showed that the disease activity index and gender had an influence on the IBDQ total score (P<0.05). The female patients had a lower score than the male patients (P<0.05), especially in the emotional function domain (P=0.002). Different disease distributions were not statistically significant in the IBDQ total score (P=0.183).

Conclusions

UC has a negative influence on HRQOL. HRQOL in patients with moderate UC was lower than HRQOL in patients with mild UC, as measured by the IBDQ. UC disease activity has a negative correlation with HRQOL. Gender and the disease activity index are important factors involved in the impairment of HRQOL in Chinese patients with UC. Chinese females may benefit from increased psychological care as part of UC therapy.     

The Value of MRI in the Diagnosis of Primary Biliary Cirrhosis and Assessment of Liver Fibrosis

Objectives

To evaluate MRI findings in patients with primary biliary cirrhosis (PBC) and to determine the value of MRI in the diagnosis of PBC and assessment of liver fibrosis.

Materials and Methods

This study reviewed the prevalence of MRI abnormalities seen in 45 PBC patients in the past four years, including 33 patients who underwent liver biopsy. Correlation between the MRI findings and the pathological stage was determined.

Results

There were 33 patients who underwent liver biopsy. Twenty-five patients (75.8%) had non-homogeneous changes in the liver signal intensity, 25 (75.8%) had a periportal halo sign, and 29 (87.9%) had lymphadenopathy. The short axis of the enlarged lymph nodes was a mean of 1.2±0.3 cm. A strong positive correlation was observed between histological stage and the inhomogeneity of liver signal intensity (P<0.001). There were significant differences among the four histological stages based on the periportal halo sign (P=0.034), and the grading of the periportal halo sign was found to be significantly correlated with the histological stage (P<0.001). Grading of the periportal halo sign was significantly different at stage II versus III, and stage III versus IV; no significant difference was found between stages I and II. There were also no significant differences among the four histological states in the occurrence and size of enlarged lymph nodes (P=0.674 and P=0.394).

Conclusion

MRI is valuable in the diagnosis of PBC, and the periportal halo sign and liver signal intensity help to evaluate the degree of liver fibrosis.     

Prognostic Value of Cavernous Sinus Invasion in Patients with Nasopharyngeal Carcinoma Treated with Intensity-Modulated Radiotherapy

Purpose

To investigate the prognostic value of cavernoussinus invasion (CSI) in patients with nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT).

Patients and Methods

Retrospective review of data from 1,087 patients with biopsy-proven, non-metastatic NPC. All patients were diagnosed using magnetic resonance imaging (MRI) scans and received IMRT as the primary treatment.

Results

The incidence of cavernoussinus invasion in this cohort was 12.1%. In univariate analysis, 5-year overall survival (OS) (70.6% vs. 88.5%, P < 0.001) and distant metastasis-free survival (DMFS) (71.4% vs. 87.7%, P < 0.001), but not locoregional relapse-free survival (LRFS) (93.9% vs. 93.7%, P = 0.341), were significantly different between patients with and without cavernoussinus invasion. In the T4 subgroup, the 5-year OS, DMFS, and LRFS of patients with and without cavernoussinus extension were 70.6% vs. 81.9% (P = 0.011), 71.4% vs. 84.1% (P = 0.011), and 91.2% vs. 89.7% (P = 0.501), respectively. In multivariate analysis, cavernoussinus invasion was an independent prognostic factor for poorer OS (HR = 1.782; P = 0.013) and DMFS (HR = 1.771; P = 0.016), but not LRFS (HR = 0.632; P = 0.294). In patients with lymph node metastasis, the DMFS rates of patients with and without cavernoussinus invasion were significantly different (P < 0.001). Preliminaryanalysis indicated that neoadjuvant chemotherapy led to better DMFS and OS in patients with cavernoussinus invasion than concurrent chemotherapy or radiotherapy alone; however, the differences were not significant.

Conclusions

In the IMRT era, cavernoussinus invasion remains a prognostic factor for poor DMFS and OS in NPC, even in patients with T4 disease.     

STEMI Outcomes in Guangzhou and Hong Kong: Two-Centre Retrospective Interregional Study

Background and Objectives

Healthcare systems are organized very differently in Hong Kong (HK) and Guangzhou (GZ). This study compared managements of the emergency departments (ED) and one-year mortalities of ST-segment elevation myocardial infarction (STEMI) patients in two teaching hospitals in Guangzhou and Hong Kong.

Methods

Retrospective observational study of STEMI mortalities and treatments in the Prince of Wales Hospital (PWH) and the Second Affiliated Hospital of Guangzhou Medical University (AHGZMU), was conducted between January and December 2010. The primary outcome was one-year all cause mortality.

Results

Univariate analysis of 76 cases from PWH and 111 cases from AHGZMU showed similar clinical characteristics, except for lower proportions of males (74% vs 92%, P = 0.002), hyperlipidemia (5% vs 25%, P<0.001), and Killip class I (56% vs 91%; P<0.001) in AHGZMU. The onset-to-door time of STEMI patients in AHGZMU was longer than in PWH (median 205 min [(IQR: 95–432) vs 120 min (IQR: 55–225), P = 0.001]. In AHGZMU, 85 (77%) patients received primary percutaneous coronary intervention (PPCI) as the main reperfusion treatment, whereas 18 (24%) received PPCI and 51 (67%) patients received thrombolytic therapy in PWH. Overall the one-year mortality in AHGZMU was 20%, whilst in PWH it was 14% (P = 0.436). The standardized one-year all-cause mortality ratios for AHGZMU and PWH were comparable (18.7 vs. 18.2%, P = 0894). Independent predictors of one-year mortality included older age (>67 years) and hyperglycemia (>10 mmol/L). Aged over 65 years, presence of anterior wall infarct, body weight ≤65 kg, SBP <100 mmHg at ED and glucose level >10 mmol/L were the independent predictors of in-hospital MACE.

Conclusion

There was no statistically significant difference between the standardized one-year all-cause mortalities of STEMI patients in the setting mainly using thrombolysis with shorter door-to-treatment time and the setting mainly using PCI with longer door-to-treatment time. Aged over 67 years and glucose level over 10 mmol/L were the independent predictors of one-year mortality. Older age, presence of anterior wall infarct, lower body weight, lower SBP at ED and hyperglycemia were the independent predictors of in-hospital MACE.     

Effects of Unfermented and Fermented Whole Grain Rye Crisp Breads Served as Part of a Standardized Breakfast,on Appetite and Postprandial Glucose and Insulin Responses: A Randomized Cross-over Trial

Background

Whole grain rye products have been shown to increase satiety and elicit lower postprandial insulin response without a corresponding change in glucose response compared with soft refined wheat bread. The underlying mechanisms for these effects have not been fully determined The primary aim of the study was to investigate if whole grain rye crisp bread compared to refined wheat crisp bread, elected beneficial effects on appetite and postprandial insulin response, similarly as for other rye products.

Methods

In a randomized cross-over trial, 23 healthy volunteers, aged 27-70 years, BMI 18-31.4 kg/m², were served a standardized breakfast with unfermented whole grain rye crisp bread (uRCB), fermented whole grain rye crisp bread (RCB) or refined wheat crisp bread (WCB), Appetite was measured using a visual analogue scale (VAS) until 4 h after breakfast. Postprandial glucose and insulin were measured at 0-230 min. Breads were chemically characterized including macronutrients, energy, dietary fiber components, and amino acid composition, and microstructure was characterized with light microscopy.

Results

Reported fullness was 16% higher (P<0.001), and hunger 11% and 12% lower (P<0.05) after ingestion of uRCB and RCB, respectively, compared with WCB. Postprandial glucose response did not differ significantly between treatments. Postprandial insulin was 10% lower (P<0.007) between 0-120 min but not significantly lower between 0-230 min for RCB compared with WCB. uRCB induced 13% (P<0.002) and 17% (P<0.001) lower postprandial insulin response between 0-230 min compared with RCB and WCB respectively.

Conclusion

Whole grain rye crisp bread induces higher satiety and lower insulin response compared with refined wheat crisp bread. Microstructural characteristics, dietary fiber content and composition are probable contributors to the increased satiety after ingestion of rye crisp breads. Higher insulin secretion after ingestion of RCB and WCB compared with uRCB may be due to differences in fiber content and composition, and higher availability of insulinogenic branched chain amino acids.

Trial Registration

ClinicalTrials.gov NCT02011217     

Renal Function Interferes with Copeptin in Prediction of Major Adverse Cardiac Events in Patients Undergoing Vascular Surgery

Objective

Precise perioperative risk stratification is important in vascular surgery patients who are at high risk for major adverse cardiovascular events (MACE) peri- and postoperatively. In clinical practice, the patient’s perioperative risk is predicted by various indicators, e.g. revised cardiac index (RCRI) or modifications thereof. Patients suffering from chronic kidney disease (CKD) are stratified into a higher risk category. We hypothesized that Copeptin as a novel biomarker for hemodynamic stress could help to improve the prediction of perioperative cardiovascular events in patients undergoing vascular surgery including patients with chronic kidney disease.

Methods

477 consecutive patients undergoing abdominal aortic, peripheral arterial or carotid surgery from June 2007 to October 2012 were prospectively enrolled. Primary endpoint was 30-day postoperative major adverse cardiovascular events (MACE).

Results

41 patients reached the primary endpoint, including 63.4% aortic, 26.8% carotid, and 9.8% peripheral surgeries. Linear regression analysis showed that RCRI (P< .001), pre- (P< .001), postoperative Copeptin (P< .001) and Copeptin level change (P= .001) were associated with perioperative MACE, but CKD remained independently associated with MACE and Copeptin levels. Multivariate regression showed that increased Copeptin levels added risk predictive information to the RCRI (P= .003). Especially in the intermediate RCRI categories was Copeptin significantly associated with the occurrence of MACE. (P< .05 Kruskal Wallis test). Subdivision of the study cohort into CKD stages revealed that preoperative Copeptin was significantly associated with CKD stages (P< .0001) and preoperative Copeptin measurements could not predict MACE in patients with more severe CKD stages.

Conclusion

Preoperative Copeptin loses its risk predictive potential for perioperative MACE in patients with chronic kidney disease undergoing vascular surgery.     

Ethnic Variations in Central Corneal Thickness in a Rural Population in China: The Yunnan Minority Eye Studies

Purpose

To describe the ethnic differences in central corneal thickness (CCT) in population-based samples of ethnic Bai, Yi and Han people living in rural China.

Methods

6504 adults (2119 ethnic Bai, 2202 ethnic Yi and 2183 ethnic Han) aged 50 years or older participated in the study. Each subject underwent standardized ocular examinations and interviewer-administered questionnaires for risk factor assessment. CCT was measured for both eyes using an ultrasound pachymeter. Regression and principal component analysis were performed to examine the relationship of ethnicity and other factors with CCT.

Results

The mean CCT readings were 536.4 ± 34.2 μm in ethnic Bai, 532.1 ± 32.1 μm in ethnic Yi and 529.6 ± 32.7 μm in ethnic Han adults (P<0.001), respectively. There was a decreasing trend of mean CCT with increasing age across all ethnic groups. In multivariate linear regression models, increasing CCT was associated with younger age (P<0.001), male gender (P<0.001), Bai (P<0.001) or Yi (P<0.001) ethnicity, greater body mass index (P<0.001), higher systolic blood pressure (P<0.001), greater corneal curvature (P<0.001), deeper anterior chamber (P < 0.001), and thicker lens (P<0.001). Ethnicity contributed significantly to presence of thin cornea (60%; P< 0.001) compared with other factors. CCT had similar impact on intraocular pressure readings across all ethnic groups.

Conclusions

This study of more than 6500 multiethnic participants demonstrates significant ethnic variations in CCT, with Han ethnicity having the thinnest cornea compared with ethnic minorities. These data are essential to guide future multiethnic clinical trials on CCT-related ocular conditions such as glaucoma.