Insights into the Classification of Myasthenia Gravis

Background and Purpose

Myasthenia gravis (MG) is often categorized into thymoma-associated MG, early-onset MG with onset age <50 years, and late-onset MG with onset age ≥50 years. However, the boundary age of 50 years old between early- and late-onset MG remains controversial, and each category contains further subtypes. We attempted to classify MG from a statistical perspective.

Methods

We analyzed 640 consecutive MG patients using two-step cluster analysis with clinical variables and discrimination analysis, using onset age as a variable.

Results

Two-step cluster analyses categorized MG patients into the following five subtypes: ocular MG; MG with thymic hyperplasia (THMG); generalized anti-acetylcholine receptor antibody (AChR-Ab)-negative MG; thymoma-associated MG; and generalized AChR-Ab-positive (SP) MG without thymic abnormalities. Among these 5 subtypes, THMG showed a distribution of onset age skewed toward a younger age (p<0.01), whereas ocular MG and SPMG without thymic abnormalities showed onset age skewed toward an older age (p<0.001 and p<0.0001, respectively). The other 2 subtypes showed normal distributions. THMG appeared as the main component of early-onset MG, and ocular MG and SPMG without thymic abnormalities as the main components of late-onset MG. Discrimination analyses between THMG and ocular MG and/or SPMG without thymic abnormalities demonstrated a boundary age of 45 years old.

Conclusions

From a statistical perspective, the boundary age between early- and late-onset MG is about 45 years old.     

Myasthenia Gravis: Analysis of Serum Autoantibody Reactivities to 1827 Potential Human Autoantigens by Protein Macroarrays

Background

Myasthenia gravis is a disorder of neuromuscular transmission associated with autoantibodies against the nicotinic acetylcholine receptor. We have previously developed a customized protein macroarray comprising 1827 potential human autoantigens, which permitted to discriminate sera of patients with different cancers from sera of healthy controls, but has not yet been evaluated in antibody-mediated autoimmune diseases.

Objective

To determine whether autoantibody signatures obtained by protein macroarray separate sera of patients with myasthenia gravis from healthy controls.

Methods

Sera of patients with acetylcholine receptor antibody-positive myasthenia gravis (n = 25) and healthy controls (n = 32) were analyzed by protein macroarrays comprising 1827 peptide clones.

Results

Autoantibody signatures did not separate patients with myasthenia gravis from controls with sufficient sensitivity, specificity, and accuracy. Intensity values of one antigen (poly A binding protein cytoplasmic 1, p = 0.0045) were higher in patients with myasthenia gravis, but the relevance of this and two further antigens, 40S ribosomal protein S13 (20.8% vs. 0%, p = 0.011) and proteasome subunit alpha type 1 (25% vs. 3.1%, p = 0.035), which were detected more frequently by myasthenia gravis than by control sera, currently remains uncertain.

Conclusion

Seroreactivity profiles of patients with myasthenia gravis detected by a customized protein macroarray did not allow discrimination from healthy controls, compatible with the notion that the autoantibody response in myasthenia gravis is highly focussed against the acetylcholine receptor.     

CTLA4 Variants and Haplotype Contribute Genetic Susceptibility to Myasthenia Gravis in Northern Chinese Population

Background

Cytotoxic T lymphocyte-associated antigen-4 (CTLA4), a critical negative regulator of the T-cell response, has been considered a candidate for many autoimmune diseases. Evidence from Caucasians supported a genetic predisposition of CTLA4 to myasthenia gravis (MG), but the contribution in East Asians has not been established.

Objectives

To investigate the role of CTLA4 variants in the susceptibility to MG and the contribution to subtypes of MG.

Methods

Six autoimmune disease-related risk alleles of CTLA4 (rs1863800, rs733618, rs4553808, rs5742909, rs231775, and rs3087243) were investigated for MG in northern Chinese. 168 patients with MG (mean age 37.1±20.5 years, 64 men and 104 women) and 233 healthy controls (mean age 53.3±8.7 years, 96 men and 137 women) were screened, and the contribution of CTLA4 to the general risk of MG and each subgroup was explored.

Results

rs1863800*C, rs733618*C, and rs231775*G were significantly associated with the whole cohort of patients with MG after permutation correction for multiple-testing adjustment (P = 0.027, 0.001, and 0.032, respectively). A risk haplotype (CCACG) [odds ratio (OR) = 1.535, range = 1.150–2.059, P = 0.004)] was also identified. The stratified subtype analysis indicated that the positive contribution was possibly derived from early onset MG (EOMG), seropositive MG (SPMG), female patients, and MG without thymoma. No association was observed in juvenile MG/LOMG, and MG coupled with thymoma.

Conclusion

A predisposing effect of rs1863800*C, rs733618*C, and rs231775*G of CTLA4 gene to general risk of MG in Chinese was demonstrated for the first time, which was likely derived from EOMG, SPMG, MG without thymoma and the female patients.     

Is Serum Zinc Associated with Pancreatic Beta Cell Function and Insulin Sensitivity in Pre-Diabetic and Normal Individuals? Findings from the Hunter Community Study

Aim

To determine if there is a difference in serum zinc concentration between normoglycaemic, pre-diabetic and type-2 diabetic groups and if this is associated with pancreatic beta cell function and insulin sensitivity in the former 2 groups.

Method

Cross sectional study of a random sample of older community-dwelling men and women in Newcastle, New South Wales, Australia. Beta cell function, insulin sensitivity and insulin resistance were calculated for normoglycaemic and prediabetes participants using the Homeostasis Model Assessment (HOMA-2) calculator.

Result

A total of 452 participants were recruited for this study. Approximately 33% (N = 149) had diabetes, 33% (N = 151) had prediabetes and 34% (N = 152) were normoglycaemic. Homeostasis Model Assessment (HOMA) parameters were found to be significantly different between normoglycaemic and prediabetes groups (p<0.001). In adjusted linear regression, higher serum zinc concentration was associated with increased insulin sensitivity (p = 0.01) in the prediabetic group. There was also a significant association between smoking and worse insulin sensitivity.

Conclusion

Higher serum zinc concentration is associated with increased insulin sensitivity. Longitudinal studies are required to determine if low serum zinc concentration plays a role in progression from pre-diabetes to diabetes.     

Increased HEV Seroprevalence in Patients with Autoimmune Hepatitis

Background

Hepatitis E virus (HEV) infection takes a clinically silent, self-limited course in the far majority of cases. Chronic hepatitis E has been reported in some cohorts of immunocompromised individuals. The role of HEV infections in patients with autoimmune hepatitis (AIH) is unknown.

Methods

969 individuals were tested for anti-HEV antibodies (MP-diagnostics) including 208 patients with AIH, 537 healthy controls, 114 patients with another autoimmune disease, rheumatoid arthritis (RA), and 109 patients with chronic HCV- or HBV-infection (HBV/HCV). Patients with AIH, RA and HBV/HCV were tested for HEV RNA. HEV-specific proliferative T cell responses were investigated using CFSE staining and in vitro stimulation of PBMC with overlapping HEV peptides.

Results

HEV-antibodies tested more frequently positive in patients with AIH (n = 16; 7.7%) than in healthy controls (n = 11; 2.0%; p = 0.0002), patients with RA (n = 4; 3.5%; p = 0.13) or patients with HBV/HCV infection (n = 2; 2.8%; p = 0.03). HEV-specific T cell responses could be detected in all anti-HEV-positive AIH patients. One AIH patient receiving immunosuppression with cyclosporin and prednisolone and elevated ALT levels had acute hepatitis E but HEV viremia resolved after reducing immunosuppressive medication. None of the RA or HBV/HCV patients tested HEV RNA positive.

Conclusions

Patients with autoimmune hepatitis but not RA or HBV/HCV patients are more likely to test anti-HEV positive. HEV infection should been ruled out before the diagnosis of AIH is made. Testing for HEV RNA is also recommended in AIH patients not responding to immunosuppressive therapy.     

Salt-Restriction-Spoon Improved the Salt Intake among Residents in China

Objective

To evaluate the effect of an improved salt-restriction spoon on the attitude of salt-restriction, the using rate of salt-restriction-spoon, the actual salt intake, and 24-hour urinary sodium excretion (24HUNa).

Design

A community intervention study.

Setting

Two villages in Beijing.

Participants

403 local adult residents being responsible for home cooking.

Intervention

Participants were randomly assigned to the intervention group or the control group. Those in the intervention group were provided with an improved salt-restriction-spoon and health education, and were informed of their actual salt intake and 24HUNa. Not any intervention was given to those in the control group.

Main Outcome Measures

The scores on the variables of Health Belief Model, the using rate of salt-restriction-spoon, the actual salt intake, and 24HUNa.

Analysis

Covariance analyses, Chi-square tests, Student’s t tests, and repeated measures analyses of variance.

Results

After 6 months of intervention, the intervention group felt significantly less objective barriers, and got access to significantly more cues to action as compared to the control group. The using rate and the correctly using rate of salt-restriction-spoon were significantly higher in the intervention group. The daily salt intake decreased by 1.42 g in the intervention group and by 0.28 g in the control group, and repeated measures analysis of variance showed significant change over time (F = 7.044, P<0.001) and significant difference between groups by time (F = 2.589, P = 0.041). The 24HUNa decreased by 34.84 mmol in the intervention group and by 33.65 mmol in the control group, and repeated measures analysis of variance showed significant change over time (F = 14.648, P<0.001) without significant difference between groups by time (F = 0.222, P = 0.870).

Conclusions

The intervention effect was acceptable, therefore, the improved salt-restriction-spoon and corresponding health education could be considered as an alternative for salt reduction strategy in China and other countries where salt intake comes mainly from home cooking.     

The Prognostic Value of SOX2 Expression in Non-Small Cell Lung Cancer: A Meta-Analysis

Objective

To investigate the association of SOX2 expression in tumor with clinicopathological features and survival of non-small-cell lung carcinoma (NSCLC) patients.

Methods

Publications assessing the clinicopathological characteristics and prognostic significance of SOX2 in NSCLC were identified up to May 2013. A meta-analysis of eligible studies was performed using standard statistical methods to clarify the association between SOX2 expression and these clinical parameters.

Results

A total of eight studies met the inclusion criteria. Analysis of these data showed that SOX2 expression was positively associated with squamous histology, (pooled OR = 5.26, 95% CI: 1.08–25.6, P = 0.040). Simultaneously, we also found that SOX2 expression was positively associated with overall survival (pooled HR = 0.65, 95% CI: 0.47–0.89, P = 0.007, random-effect).

Conclusions

SOX2 expression in tumor is a candidate positive prognostic biomarker for NSCLC patients.     

Predictors of Two Months Culture Conversion in Multidrug-Resistant Tuberculosis: Findings from a Retrospective Cohort Study

Background

Various studies have reported culture conversion at two months as a predictor of successful treatment outcome in multidrug-resistant tuberculosis (MDR-TB).

Objectives

The present study was conducted with the aim to evaluate the rate and predictors of culture conversion at two months in MDR-TB patients.

Methods

All confirmed pulmonary MDR-TB patients enrolled for treatment at Lady Reading Hospital Peshawar, Pakistan from 1 January to 31 December 2012 and met the inclusion criteria were reviewed retrospectively. Rate and predictors of culture conversion at two months were evaluated.

Results

Eighty seven (53.4%) out of 163 patients achieved culture conversion at two months. In a multivariate analysis lung cavitation at baseline chest X-ray (P = 0.006, OR = 0.349), resistance to ofloxacin (P = 0.041, OR = 0.193) and streptomycin (P = 0.017, OR = 0.295) had statistically significant (P<0.05) negative association with culture conversion at two months.

Conclusion

A reasonable proportion of patients achieved culture conversion at two months. Factors negatively associated with culture conversion at two months can be easily identified either before diagnosis or early in the course of MDR-TB treatment. This may help in better care of individual patients by identifying them early and treating them vigorously.     

Association between Exposure to Environmental Tobacco Smoke and Biomarkers of Oxidative Stress Among Patients Hospitalised with Acute Myocardial Infarction

Objective

To determine whether exposure to environmental tobacco smoke was associated with oxidative stress among patients hospitalised for acute myocardial infarction.

Design

An existing cohort study of 1,261 patients hospitalised for acute myocardial infarction.

Setting

Nine acute hospitals in Scotland.

Participants

Sixty never smokers who had been exposed to environmental tobacco smoke (admission serum cotinine ≥3.0 ng/mL) were compared with 60 never smokers who had not (admission serum cotinine ≤0.1 ng/mL).

Intervention

None.

Main outcome measures

Three biomarkers of oxidative stress (protein carbonyl, malondialdehyde (MDA) and oxidised low-density lipoprotein (ox-LDL)) were measured on admission blood samples and adjusted for potential confounders.

Results

After adjusting for baseline differences in age, sex and socioeconomic status, exposure to environmental tobacco smoke was associated with serum concentrations of both protein carbonyl (beta coefficient 7.96, 95% CI 0.76, 15.17, p = 0.031) and MDA (beta coefficient 10.57, 95% CI 4.32, 16.81, p = 0.001) but not ox-LDL (beta coefficient 2.14, 95% CI −8.94, 13.21, p = 0.703).

Conclusions

Exposure to environmental tobacco smoke was associated with increased oxidative stress. Further studies are requires to explore the role of oxidative stress in the association between environmental tobacco smoke and myocardial infarction.     

Endothelial Progenitor Cells and Cardiovascular Events in Patients with Chronic Kidney Disease – a Prospective Follow-Up Study

Background

Endothelial progenitor cells (EPCs) mediate vascular repair and regeneration. Their number in peripheral blood is related to cardiovascular events in individuals with normal renal function.

Methods

We evaluated the association between functionally active EPCs (cell culture) and traditional cardiovascular risk factors in 265 patients with chronic kidney disease stage V receiving hemodialysis therapy. Thereafter, we prospectively assessed cardiovascular events, e.g. myocardial infarction, percutaneous transluminal coronary angioplasty (including stenting), aorto-coronary bypass, stroke and angiographically verified stenosis of peripheral arteries, and cardiovascular death in this cohort.

Results

In our patients EPCs were related only to age (r = 0.154; p = 0.01). During a median follow-up period of 36 months 109 (41%) patients experienced a cardiovascular event. In a multiple Cox regression analysis, we identified EPCs (p = 0.03) and patient age (p = 0.01) as the only independent variables associated with incident cardiovascular events. Moreover, a total of 70 patients died during follow-up, 45 of those due to cardiovascular causes. Log rank test confirmed statistical significance for EPCs concerning incident cardiovascular events (p = 0.02).

Conclusions

We found a significant association between the number of functionally active EPCs and cardiovascular events in patients with chronic kidney disease. Thus, defective vascular repair and regeneration may be responsible, at least in part, for the enormous cardiovascular morbidity in this population.     

Prevention of Contrast-Induced Acute Kidney Injury: Is Simple Oral Hydration Similar To Intravenous? A Systematic Review of the Evidence

Background

Pre-procedural intravenous fluid administration is an effective prophylaxis measure for contrast-induced acute kidney injury. For logistical ease, the oral route is an alternative to the intravenous. The objective of this study was to compare the efficacy of the oral to the intravenous route in prevention of contrast-induced acute kidney injury.

Study Design

A systematic review and meta-analysis of randomised trials with a stratified analysis and metaregression. Databases included MEDLINE (1950 to November 23 2011), EMBASE (1947 to week 47 2011), Cochrane CENTRAL (3^rd quarter 2011). Two reviewers identified relevant trials and abstracted data.

Settings and Population

Trials including patients undergoing a contrast enhanced procedure.

Selection Criteria

Randomised controlled trial; adult (>18 years) population; comparison of oral versus intravenous volume expansion.

Intervention

Oral route of volume expansion compared to the intravenous route.

Outcomes

Any measure of acute kidney injury, need for renal replacement therapy, hospitalization and death.

Results

Six trials including 513 patients met inclusion criteria. The summary odds ratio was 1.19 (95% CI 0.46, 3.10, p = 0.73) suggesting no difference between the two routes of volume expansion. There was significant heterogeneity (Cochran’s Q = 11.65, p = 0.04; I² = 57). In the stratified analysis, inclusion of the five studies with a prespecified oral volume expansion protocol resulted in a shift towards oral volume expansion (OR 0.75, 95% CI 0.37, 1.50, p = 0.42) and also resolved the heterogeneity (Q = 3.19, P = 0.53; I² = 0).

Limitations

Small number of studies identified; lack of hard clinical outcomes.

Conclusion

The oral route may be as effective as the intravenous route for volume expansion for contrast-induced acute kidney injury prevention. Adequately powered trials with hard endpoints should be done given the potential advantages of oral (e.g. reduced patient burden and cost) over intravenous volume expansion.     

Cruciate Ligament Reconstruction and Risk of Knee Osteoarthritis: The Association between Cruciate Ligament Injury and Post-Traumatic Osteoarthritis. A Population Based Nationwide Study in Sweden, 1987–2009

Objective

To study the association between Cruciate Ligament (CL) injury and development of post-traumatic osteoarthritis in the knee in patients treated operatively with CL reconstruction compared with patients treated non-operatively.

Design

Population based cohort study; level of evidence II-2.

Setting

Sweden, 1987–2009.

Participants

All patients aged between 15–60 years being diagnosed and registered with a CL injury in The National Swedish Patient Register between 1987 and 2009.

Main Outcome Measures

Knee osteoarthritis.

Results

A total of 64,614 patients diagnosed with CL injury during 1987 to 2009 in Sweden were included in the study. Seven percent of the patients were diagnosed with knee OA in specialized healthcare during the follow-up (mean 9 years). Stratified analysis by follow-up showed that while those with shorter follow-up had a non-significant difference in risk (0.99, 95%CI 0.90–1.09 for follow-up less than five years compared with the non-operated cohort), those with longer follow-up had an increased risk of knee OA after CL reconstruction (HR = 1.42, 95%CI 1.27–1.58 for follow-up more than ten years compared with non-operated cohort). The risk to develop OA was not affected by sex.

Conclusion

CL reconstructive surgery does not seem to have a protective effect on long term OA in either men or women.     

Association between APOC1 Polymorphism and Alzheimer’s Disease: A Case-Control Study and Meta-Analysis

Background

Previous association studies examining the relationship between the APOC1 polymorphism and susceptibility to Alzheimer’s disease (AD) have shown conflicting results, and it is not clear if an APOC1 variant acts as a genetic risk factor in AD etiology across multiple populations.

Methods

To confirm the risk association between APOC1 and AD, we designed a case-control study and also performed a meta-analysis of previously published studies.

Results

Seventy-nine patients with AD and one hundred fifty-six unrelated controls were included in case-control study. No association was found between the variation of APOC1 and AD in stage 1 of our study. However, our meta-analysis pooled a total of 2092 AD patients and 2685 controls. The APOC1 rs11568822 polymorphism was associated with increased AD risk in Caucasians, Asians and Caribbean Hispanics, but not in African Americans. APOE ε4 carriers harboring the APOC1 insertion allele, were more prevalent in AD patients than controls (χ² = 119.46, OR = 2.79, 95% CI = 2.31–3.36, P<0.01).

Conclusions

The APOC1 insertion allele, in combination with APOE ε4, likely serves as a potential risk factor for developing AD.     

Pesticide Exposure as a Risk Factor for Myelodysplastic Syndromes: A Meta-Analysis Based on 1,942 Cases and 5,359 Controls

Objective

Pesticide exposure has been linked to increased risk of cancer at several sites, but its association with risk of myelodysplastic syndromes (MDS) is still unclear. A meta-analysis of studies published through April, 2014 was performed to investigate the association of pesticide exposure with the risk of MDS.

Methods

Studies were identified by searching the Web of Science, Cochrane Library and PubMed databases. Summary odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were calculated using random- or fixed-effect models.

Results

This meta-analysis included 11 case-control studies, all of which demonstrated a correlation between pesticide exposure and a statistically significant increased risk of MDS (OR = 1.95, 95% CI 1.23–3.09). In subgroup analyses, patients with pesticide exposure had increased risk of developing MDS if they were living in the Europe or Asia and had refractory anemia (RA) or RA with ringed sideroblasts (RARS). Moreover, in the analysis by specific pesticides, increased risk was associated with exposure to insecticides (OR = 1.71, 95% CI 1.22–2.40) but not exposure to herbicides or fungicides.

Conclusion

This meta-analysis supports the hypothesis that exposure to pesticides increases the risk of developing MDS. Further prospective cohort studies are warranted to verify the association and guide clinical practice in MDS prevention.     

Association between Irrigation Fluids,Washout Volumes and Risk of Local Recurrence of Anterior Resection for Rectal Cancer: A Meta-Analysis of 427 Cases and 492 Controls

Background

Rectal washout can prevent local recurrence after anterior resection of rectal cancer. Few studies have focused particularly on the association between irrigation fluids volume or agents and the risk of local recurrence after anterior resection of rectal cancer.

Objective

To estimate the association between irrigation fluids types, volumes of rectal washout and risk of local recurrence after anterior resection for cancer.

Data Sources

Relevant studies were identified by a search of Medline, Embase, Wiley Online Library, China National Knowledge Infrastructure, Cochrane Oral Health Group Specialized Register, Wanfang databases and Google Website from their inception until October 18,2013.

Study Selection

Studies reporting the association between rectal washout types and volumes and risk of local recurrence after anterior resection for cancer were included.

Interventions

Eligible studies used rectal washout. Control groups were defined as no washout.

Study Appraisal and Synthesis Methods

Random-effects model were used to obtain summary estimates of RR and 95% CI, with Stata version 11 and RevMan 5.2.5 softwares used. The quality of report was appraised in reference to the MINORS item.

Results

Of the 919 rectal cancer patients in 8 included studies, a total of 61(6.64%) cases of local recurrence were reported, with a pooled RR 0.51 (95%CI = 0.28–0.92, P = 0.03). The RRs 0.37 and 0.39 in normal saline and washout volume (≥1500 ml normal saline) subgroup, respectively, indicated that rectal washout with normal saline, or ≥1500 ml in volume could significantly reduce local recurrence (LR) rate (95% CI = 0.17–0.79, P = 0.01; 95% CI = 0.18–0.87, P = 0.02) after anterior resection for cancer.

Limitation

The included studies were non-randomized observational studies, with diversity of study designs.

Conclusion

Rectal washout with normal saline alone can reduce the risk of local recurrence in patients with resectable rectal cancer, and 1.5 liters rectal washout in volume is recommended.     

Sequence Variants of Toll Like Receptor 4 and Late-Onset Alzheimer's Disease

Background

Toll like receptor 4 (TLR4) has been related to inflammation and beta-amyloid deposition in Alzheimer''s disease (AD) brain. No study has explored the association between haplotype-tagging single nucleotide polymorphisms (htSNPs) of TLR4 and AD risk previously and ApoE e4 status alone showed low sensitivity in identifying late-onset AD (LOAD) patients.

Methods

A total of 269 LOAD patients were recruited from three hospitals in northern Taiwan (2007–2010). Controls (n = 449) were recruited from elderly health checkup and volunteers of the hospital during the same period of time. Five common (frequency≥5%) TLR4 htSNPs were selected to assess the association between TLR4 polymorphisms and the risk of LOAD in the Chinese ethnic population.

Results

Homozygosity of TLR4 rs1927907 was significantly associated with an increased risk of LOAD [TT vs. CC: adjusted odds ratio (AOR) = 2.45, 95% confidence interval (CI) = 1.30–4.64]. After stratification, the association increased further in ApoE e4 non-carriers (AOR = 3.07) and in hypertensive patients (AOR = 3.60). Haplotype GACGG was associated with a decreased risk of LOAD (1 vs. 0 copies: AOR = 0.59, 95% CI = 0.36–0.96; 2 vs. 0 copies: AOR = 0.31, 95% CI = 0.14–0.67) in ApoE e4 non-carriers. ApoE e4 status significantly modified this association (p _interaction = 0.01). These associations remained significant after correction for multiple tests.

Conclusions

Sequence variants of TLR4 were associated with an increased risk of LOAD, especially in ApoE e4 non-carriers and in hypertensive patients. The combination of TLR4 rs1927907 and ApoE e4 significantly increased the screening sensitivity in identifying LOAD patients from 0.4 to 0.7.     

Left Ventricular Hypertrophy and Insulin Resistance in Adults from an Urban Community in the Gambia: Cross-Sectional Study

Objective

To determine the association between left ventricular hypertrophy and insulin resistance in Gambians.

Design

Cross-sectional study.

Setting

Outpatient clinics of Royal Victoria Teaching Hospital and Medical Research Council Laboratories in Banjul.

Participants

Three hundred and sixteen consecutive patients were enrolled from outpatient clinics. The data of 275 participants (89 males) were included in the analysis with a mean (± standard deviation) age of 53.7 (±11.9) years.

Interventions

A questionnaire was filled and anthropometric measurements were taken. 2-D guided M-mode echocardiography, standard 12-1ead electrocardiogram, fasting insulin and the oral glucose tolerance test were performed.

Main Outcome Measures

The Penn formula was used to determine the left ventricular mass index, 125 g/m² in males and 110 g/m² in females as the cut-off for left ventricular hypertrophy. Using the fasting insulin and fasting glucose levels, the insulin resistance was estimated by the homeostatic model assessment formula. Logistic regression analysis was used to determine the association between left ventricular hypertrophy and insulin resistance.

Results

The mean Penn left ventricular mass index was 119.5 (±54.3) and the prevalence of Penn left ventricular mass index left ventricular hypertrophy was 41%. The mean fasting glucose was 5.6 (±2.5) mmol/l, fasting insulin was 6.39 (±5.49) μU/ml and insulin resistance was 1.58 (±1.45). There was no association between Penn left ventricular mass index left ventricular hypertrophy and log of insulin resistance in univariate (OR = 0.98, 95% CI = 0.80 – 1.19, p = 0.819) and multivariate logistic regression (OR = 0.93, 95% CI = 0.76–1.15, p = 0.516) analysis.

Conclusion

No association was found in this study between left ventricular hypertrophy and insulin resistance in Gambians and this does not support the suggestion that insulin is an independent determinant of left ventricular hypertrophy in hypertensives.     

The Association between Subclinical Atherosclerosis and Uterine Fibroids

Objective(s)

To explore the atherogenic hypothesis of uterine fibroids among Chinese women.

Methods

In a case-control study, 335 patients confirmed by ultrasound or hysterectomy surgery and 539 controls were enrolled between October 1, 2009 and April 1, 2012. Unconditional logistic regressions were used to calculate the odds ratios (ORs) for the associations of subclinical atherogenic and cardiovascular risk parameters with uterine fibroids in the overall case group and hysterectomy-confirmed case group, respectively.

Results

Higher level of ankle-brachial index (ABI) was independently associated with increased odds of uterine fibroids. The odds of UF among women in the highest tertile of ABI were 1.88 times higher (95%CI: 1.17, 3.02, P_trend = 0.008) compared to those in the lowest tertile. The serum concentration of homocysteine was inversely related to fibroids (middle vs. low: OR 0.56, 95%CI: 0.36, 0.85; high vs. low: OR 0.50, 95% CI: 0.32, 0.79; P_trend = 0.002). In the hysterectomy-confirmed group, an inverse association was suggested between high-density lipoprotein cholesterol (HDL-C) and fibroids (OR 0.46, 95% CI: 0.25, 0.84, P_trend = 0.014). Moreover, the effect of homocysteine concentration was not observed in this group.

Conclusion(s)

These findings suggest that women with uterine fibroids might have an increased risk of subclinical atherosclerosis.     

Relationship between Orthostatic Hypotension and White Matter Hyperintensity Load in Older Patients with Mild Dementia

Background/Objectives

White matter hyperintensities (WMH) in magnetic resonance imaging (MRI) scans of the brain, and orthostatic hypotension (OH) are both common in older people. We tested the hypothesis that OH is associated with WMH.

Design

Cross-sectional study.

Setting

Secondary care outpatient clinics in geriatric medicine and old age psychiatry in western Norway.

Participants

160 older patients with mild dementia, diagnosed according to standardised criteria.

Measurements

OH was diagnosed according to the consensus definition, measuring blood pressure (BP) in the supine position and within 3 minutes in the standing position. MRI scans were performed according to a common protocol at three centres, and the volumes of WMH were quantified using an automated method (n = 82), followed by manual editing. WMH were also quantified using the visual Scheltens scale (n = 139). Multiple logistic regression analyses were applied, with highest vs. lowest WMH quartile as response.

Results

There were no significant correlations between WMH volumes and systolic or diastolic orthostatic BP drops, and no significant correlations between Scheltens scores of WMH and systolic or diastolic BP drops. In the multivariate analyses, only APOEε4 status remained a significant predictor for WMH using the automated method (p = 0.037, OR 0.075 (0.007–0.851)), whereas only age remained a significant predictor for WMH scores (p = 0.019, OR 1.119 (1.018–1.230)).

Conclusion

We found no association between OH and WMH load in a sample of older patients with mild dementia.     

Prognostic Role of Pre-Treatment Serum AFP-L3% in Hepatocellular Carcinoma: Systematic Review and Meta-Analysis

Background

Serum lens culinaris agglutinin-reactive fraction of α-fetoprotein (AFP-L3%) has been widely used for HCC diagnosis and follow-up surveillance as tumor serologic marker. However, the prognostic value of high pre-treatment serum AFP-L3% in patients with hepatocellular carcinoma (HCC) remains controversial. We therefore conduct a meta-analysis to assess the relationship between high pre-treatment serum AFP-L3% and clinical outcome of HCC.

Methods

Eligible studies were identified through systematic literature searches. A meta-analysis of fifteen studies (4,465 patients) was carried out to evaluate the association between high pre-treatment serum AFP-L3% and overall survival (OS) and disease-free survival (DFS) in HCC patients. Sensitivity and subgroup analyses were also conducted in this meta-analysis.

Results

Our analysis results showed that high pre-treatment serum AFP-L3% implied poor OS (HR: 1.65, 95%CI: 1.45–1.89 p<0.00001) and DFS (HR: 1.80, 95% CI: 1.49–2.17 p<0.00001) of HCC. Subgroup analysis revealed that there was association between pre-treatment serum AFP-L3% and endpoint (OS and DFS) in low AFP concentration HCC patients (HR: 1.96, 95% CI: 1.24–3.10, p = 0.004; HR: 2.53, 95% CI: 1.09–5.89, p = 0.03, respectively).

Conclusion

The current evidence suggests that high pre-treatment serum AFP-L3% levels indicated a poor prognosis for patients with HCC and AFP-L3% may have significant prognostic value in HCC patients with low AFP concentration.