Detection of Intratumoral Susceptibility Signals Using T2*-Weighted Gradient Echo MRI in Patients with Clear Cell Renal Cell Carcinoma

Objective

To retrospectively evaluate whether T2*-weighted imaging can be used to grade clear cell renal cell carcinomas (ccRCC) based on intratumoral susceptibility signals (ISSs).

Materials and Methods

MR imaging from 37 patients with pathologically-proven ccRCCs was evaluated. ISSs on T2*WI were classified as linear or conglomerated linear structures (type I) and dot-like or patchy foci (type II). Two radiologists assessed the likelihood of the presence of ISS, dominant structure of ISS and ratio of ISS area to tumor area. Results were analyzed by nonparametric Mann-Whitney test.

Results

ISSs were seen in all patients except for four patients with low-grade ccRCCs and two patients with high-grade ccRCCs. There was no significant difference of the likelihood of the presence of ISS between low- and high-grade ccRCCs. More type I ISSs and less type II ISSs were predictive of low-grade tumors, whereas more conspicuity type II ISSs correlated with higher occurrence of high-grade tumors (P<0.05). The ratio of ISS area to tumor area was also significantly higher for the high-grade group (1.27±0.79) than that for the low-grade group (0.81±0.40) (P<0.05).

Conclusion

ISSs on T2*-weighted gradient-echo MR images can help grade ccRCCs before operations.     

Glioma: Application of Whole-Tumor Texture Analysis of Diffusion-Weighted Imaging for the Evaluation of Tumor Heterogeneity

Background and Purpose

To apply a texture analysis of apparent diffusion coefficient (ADC) maps to evaluate glioma heterogeneity, which was correlated with tumor grade.

Materials and Methods

Forty patients with glioma (WHO grade II (n = 8), grade III (n = 10) and grade IV (n = 22)) underwent diffusion-weighted imaging (DWI), and the corresponding ADC maps were obtained. Regions of interest containing the lesions were drawn on every section of the ADC map containing the tumor, and volume-based data of the entire tumor were constructed. Texture and first order features including entropy, skewness and kurtosis were derived from the ADC map using in-house software. A histogram analysis of the ADC map was also performed. The texture and histogram parameters were compared between low-grade and high-grade gliomas using an unpaired student’s t-test. Additionally, a one-way analysis of variance analysis with a post-hoc test was performed to compare the parameters of each grade.

Results

Entropy was observed to be significantly higher in high-grade gliomas than low-grade tumors (6.861±0.539 vs. 6.261±0.412, P  = 0.006). The fifth percentiles of the ADC cumulative histogram also showed a significant difference between high and low grade gliomas (836±235 vs. 1030±185, P = 0.037). Only entropy proved to be significantly different between grades III and IV (6.295±0.4963 vs. 7.119±0.3165, P<0.001). The diagnostic accuracy of ADC entropy was significantly higher than that of the fifth percentile of the ADC histogram (P = 0.0034) in distinguishing high- from low-grade glioma.

Conclusion

A texture analysis of the ADC map based on the entire tumor volume can be useful for evaluating glioma grade, which provides tumor heterogeneity.     

Finasteride Inhibits Human Prostate Cancer Cell Invasion through MMP2 and MMP9 Downregulation

Introduction

The use of the 5-alpha reductase inhibitors (5-ARIs) finasteride and dutasteride for prostate cancer prevention is still under debate. The FDA recently concluded that the increased prevalence of high-grade tumors among 5-ARI-treated patients must not be neglected, and they decided to disallow the use of 5-ARIs for prostate cancer prevention. This study was conducted to verify the effects of finasteride on prostate cell migration and invasion and the related enzymes/proteins in normal human and tumoral prostatic cell lines.

Materials and Methods

RWPE-1, LNCaP, PC3 and DU145 cells were cultivated to 60% confluence and exposed for different periods to either 10 µM or 50 µM finasteride that was diluted in culture medium. The conditioned media were collected and concentrated, and MMP2 and MMP9 activities and TIMP-1 and TIMP-2 protein expression were determined. Cell viability, migration and invasion were analyzed, and the remaining cell extracts were submitted to androgen receptor (AR) detection by western blotting techniques. Experiments were carried out in triplicate.

Results

Cell viability was not significantly affected by finasteride exposure. Finasteride significantly downregulated MMP2 and MMP9 activities in RWPE-1 and PC3 cells and MMP2 in DU145 cells. TIMP-2 expression in RWPE-1 cells was upregulated after exposure. The cell invasion of all four tested cell lines was inhibited by exposure to 50 µM of finasteride, and migration inhibition only occurred for RWPE-1 and LNCaP cells. AR was expressed by LNCaP, RWPE-1 and PC3 cells.

Conclusions

Although the debate on the higher incidence of high-grade prostate cancer among 5-ARI-treated patients remains, our findings indicate that finasteride may attenuate tumor aggressiveness and invasion, which could vary depending on the androgen responsiveness of a patient’s prostate cells.     

A Technique for Performing Electrical Impedance Myography in the Mouse Hind Limb: Data in Normal and ALS SOD1 G93A Animals

Objective

To test a method for performing electrical impedance myography (EIM) in the mouse hind limb for the assessment of disease status in neuromuscular disease models.

Methods

An impedance measuring device consisting of a frame with electrodes embedded within an acrylic head was developed. The head was rotatable such that data longitudinal and transverse to the major muscle fiber direction could be obtained. EIM measurements were made with this device on 16 healthy mice and 14 amyotrophic lateral sclerosis (ALS) animals. Repeatability was assessed in both groups.

Results

The technique was easy to perform and provided good repeatability in both healthy and ALS animals, with intra-session repeatability (mean ± SEM) of 5% ±1% and 12% ±2%, respectively. Significant differences between healthy and ALS animals were also identified (e.g., longitudinal mean 50 kHz phase was 18±0.6° for the healthy animals and 14±1.0° for the ALS animals, p = 0.0025).

Conclusions

With this simple device, the EIM data obtained is highly repeatable and can differentiate healthy from ALS animals.

Significance

EIM can now be applied to mouse models of neuromuscular disease to assess disease status and the effects of therapy.     

Combination of Intratumoral Invariant Natural Killer T Cells and Interferon-Gamma Is Associated with Prognosis of Hepatocellular Carcinoma after Curative Resection

Purpose

To investigate the prognostic value of intratumoral invariant natural killer T (iNKT) cells and interferon-gamma (IFN-γ) in hepatocellular carcinoma (HCC) after curative resection.

Experimental Design

Expression of TRAV10, encoding the Vα24 domain of iNKT cells, and IFN-γ mRNA were assessed by quantitative real-time polymerase chain reaction in tumor from 224 HCC patients undergoing curative resection. The prognostic value of these two and other clinicopathologic factors was evaluated.

Results

Either intratumoral iNKT cells and IFN-γ alone or their combination was an independent prognostic factor for OS (P = 0.001) and RFS (P = 0.001) by multivariate Cox proportional hazards analysis. Patients with concurrent low levels of iNKT cells and IFN-γ had a hazard ratio (HR) of 2.784 for OS and 2.673 for RFS. The areas under the curve of iNKT cells, IFN-γand their combination were 0.618 vs 0.608 vs 0.654 for death and 0.591 vs 0.604 vs 0.633 for recurrence respectively by receiver operating characteristic curve analysis. The prognosis was the worst for HCC patients with concurrent low levels of iNKT cells and IFN-γ, which might be related with more advanced pTNM stage and more vascular invasion.

Conclusions

Combination of intratumoral iNKT cells and IFN-γ is a promising independent predictor for recurrence and survival in HCC, which has a better power to predict HCC patients’ outcome compared with intratumoral iNKT cells or IFN-γ alone.     

Renal Function in Children Suffering from Sickle Cell Disease: Challenge of Early Detection in Highly Resource-Scarce Settings

Background

The prevalence of Sickle cell disease is extremely high in Democratic Republic of Congo. Despite this high prevalence of the disease, data on renal abnormalities in children are rare.

Method

The study proposed to assess blood pressure, glomerular function, urea and uric acid levels in 65 steady state Congolese children with homozygous sickle cell disease and 67 normal controls.

Results

In Hb-SS group, blood pressure level tended to be lower than Hb-AA groups but there was no statistically significant difference (p>0.05) between the two groups. The absolute values for GFR corrected for BSA were significantly higher in Hb-SS group compared to Hb-AA group (130.5±34.1 ml/min/1.73 m² vs 113.7±24.5 ml/min/1.73 m²; p = 0.004). Children with Hb-SS were more likely to hyperfiltrate (30.8% of subjects) than children with Hb-AA (6.1% of subjects). Proteinuria was found in 4 (6.2%) children with Hb-SS. Uric acid level was significantly increased in children with Hb-SS compared to corresponding values in control group (4.4±1.3 mg/dl vs 3.5±1.1 mg/dl; p<0.001). Urea level was significantly decreased compared to corresponding values in Hb-AA group (15.3±8.3 mg/dl vs 22.9±10.1 mg/dl; p<0.001).

Conclusion

Hyperfiltration, low creatinine, lower urea and high uric acid are more common in children with sickle cell disease than in normal controls.     

Hawthorne Effect with Transient Behavioral and Biochemical Changes in a Randomized Controlled Sleep Extension Trial of Chronically Short-Sleeping Obese Adults: Implications for the Design and Interpretation of Clinical Studies

Objective

To evaluate the effects of study participation per se at the beginning of a sleep extension trial between screening, randomization, and the run-in visit.

Design

Subjects were screened, returned for randomization (Comparison vs. Intervention) after 81 days (median), and attended run-in visit 121 days later.

Setting

Outpatient.

Patients

Obese (N = 125; M/F, 30/95; Blacks/Whites/Other, N = 73/44/8), mean weight 107.6±19.7 kg, <6.5 h sleep/night.

Intervention

Non-pharmacological sleep extension.

Measurements

Sleep duration (diaries and actigraphy watch), sleep quality (Pittsburgh Sleep Quality Index), daily sleepiness (Epworth Sleepiness Scale), fasting glucose, insulin and lipids.

Results

Prior to any intervention, marked improvements occurred between screening and randomization. Sleep duration increased (diaries: 357.4 ±51.2 vs. 388.1±48.6 min/night; mean±SD; P<0.001 screening vs. randomization; actigraphy: 344.3 ±41.9 vs. 358.6±48.2 min/night; P<0.001) sleep quality improved (9.1±3.2 vs. 8.2±3.0 PSQI score; P<0.001), sleepiness tended to improve (8.9±4.6 vs. 8.3±4.5 ESS score; P = 0.06), insulin resistance decreased (0.327±0.038 vs. 0.351±0.045; Quicki index; P<0.001), and lipids improved, except for HDL-C. Abnormal fasting glucose (25% vs. 11%; P = 0.007), and metabolic syndrome (42% vs. 29%; P = 0.007) both decreased. In absence of intervention, the earlier metabolic improvements disappeared at the run-in visit.

Limitations

Relatively small sample size.

Conclusions

Improvements in biochemical and behavioral parameters between screening and randomization changed the “true” study baseline, thereby potentially affecting outcome. While regression to the mean and placebo effect were considered, these findings are most consistent with the “Hawthorne effect”, according to which behavior measured in the setting of an experimental study changes in response to the attention received from study investigators. This is the first time that biochemical changes were documented with respect to the Hawthorne effect. The findings have implications for the design and conduct of clinical research.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00261898","term_id":"NCT00261898"}}NCT00261898.     

The Potential of a High Protein-Low Carbohydrate Diet to Preserve Intrahepatic Triglyceride Content in Healthy Humans

Background

Protein supplementation has been shown to reduce the increases in intrahepatic triglyceride (IHTG) content induced by acute hypercaloric high-fat and high-fructose diets in humans.

Objective

To assess the effect of a 12-wk iso-energetic high protein-low carbohydrate (HPLC) diet compared with an iso-energetic high carbohydrate-low protein (HCLP) diet on IHTG content in healthy non-obese subjects, at a constant body weight.

Design

Seven men and nine women [mean ± SD age: 24±5 y; BMI: 22.9±2.1 kg/m²] were randomly allocated to a HPLC [30/35/35% of energy (En%) from protein/carbohydrate/fat] or a HCLP (5/60/35 En%) diet by stratification on sex, age and BMI. Dietary guidelines were prescribed based on individual daily energy requirements. IHTG content was measured by ¹H-magnetic resonance spectroscopy before and after the dietary intervention.

Results

IHTG content changed in different directions with the HPLC (CH₂H₂O: 0.23±0.17 to 0.20±0.10; IHTG%: 0.25±0.20% to 0.22±0.11%) compared with the HCLP diet (CH₂H₂O: 0.34±0.20 vs. 0.38±0.21; IHTG%: 0.38±0.22% vs. 0.43±0.24%), which resulted in a lower IHTG content in the HPLC compared with the HCLP diet group after 12 weeks, which almost reached statistical significance (P = 0.055).

Conclusions

A HPLC vs. a HCLP diet has the potential to preserve vs. enlarge IHTG content in healthy non-obese subjects at a constant body weight.

Trial Registration

Clinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01551238","term_id":"NCT01551238"}}NCT01551238     

Reliability and Validity of the Multimedia Activity Recall in Children and Adults (MARCA) in People with Chronic Obstructive Pulmonary Disease

Objective

To determine the reliability and validity of the Multimedia Activity Recall for Children and Adults (MARCA) in people with chronic obstructive pulmonary disease (COPD).

Design

People with COPD and their carers completed the Multimedia Activity Recall for Children and Adults (MARCA) for four, 24-hour periods (including test-retest of 2 days) while wearing a triaxial accelerometer (Actigraph GT3X+®), a multi-sensor armband (Sensewear Pro3®) and a pedometer (New Lifestyles 1000®).

Setting

Self reported activity recalls (MARCA) and objective activity monitoring (Accelerometry) were recorded under free-living conditions.

Participants

24 couples were included in the analysis (COPD; age 74.4±7.9 yrs, FEV₁ 54±13% Carer; age 69.6±10.9 yrs, FEV₁ 99±24%).

Interventions

Not applicable.

Main Outcome Measure(s)

Test-retest reliability was compared for MARCA activity domains and different energy expenditure zones. Validity was assessed between MARCA-derived physical activity level (in metabolic equivalent of task (MET) per minute), duration of moderate to vigorous physical activity (min) and related data from the objective measurement devices. Analysis included intra-class correlation coefficients (ICC), Bland-Altman analyses, paired t-tests (p) and Spearman''s rank correlation coefficients (r_s).

Results

Reliability between occasions of recall for all activity domains was uniformly high, with test-retest correlations consistently >0.9. Validity correlations were moderate to strong (r_s = 0.43–0.80) across all comparisons. The MARCA yields comparable PAL estimates and slightly higher moderate to vigorous physical activity (MVPA) estimates.

Conclusion

In older adults with chronic illness, the MARCA is a valid and reliable tool for capturing not only the time and energy expenditure associated with physical and sedentary activities but also information on the types of activities.     

Systematic Review of Clinical Practice Guidelines Related to Multiple Sclerosis

Background

High quality clinical practice guidelines (CPGs) can provide clinicians with explicit recommendations on how to manage health conditions and bridge the gap between research and clinical practice. Unfortunately, the quality of CPGs for multiple sclerosis (MS) has not been evaluated.

Objective

To evaluate the methodological quality of CPGs on MS using the AGREE II instrument.

Methods

According to the inclusion and exclusion criteria, we searched four databases and two websites related to CPGs, including the Cochrane library, PubMed, EMBASE, DynaMed, the National Guideline Clearinghouse (NGC), and Chinese Biomedical Literature database (CBM). The searches were performed on September 20th 2013. All CPGs on MS were evaluated by the AGREE II instrument. The software used for analysis was SPSS 17.0.

Results

A total of 27 CPGs on MS met inclusion criteria. The overall agreement among reviews was good or substantial (ICC was above 0.70). The mean scores for each of all six domains were presented as follows: scope and purpose (mean ± SD: 59.05±16.13), stakeholder involvement (mean ± SD: 29.53±17.67), rigor of development (mean ± SD: 31.52±21.50), clarity of presentation (mean ± SD: 60.39±13.73), applicability (mean ± SD: 27.08±17.66), editorial independence (mean ± SD: 28.70±22.03).

Conclusions

The methodological quality of CPGs for MS was acceptable for scope, purpose and clarity of presentation. The developers of CPGs need to pay more attention to editorial independence, applicability, rigor of development and stakeholder involvement during the development process. The AGREE II instrument should be adopted by guideline developers.     

Endothelial Dysfunction and Specific Inflammation in Obesity Hypoventilation Syndrome

Background

Obesity hypoventilation syndrome (OHS) is associated with increased cardiovascular morbidity. What moderate chronic hypoventilation adds to obesity on systemic inflammation and endothelial dysfunction remains unknown.

Question

To compare inflammatory status and endothelial function in OHS versus eucapnic obese patients.

Methodology

14 OHS and 39 eucapnic obese patients matched for BMI and age were compared. Diurnal blood gazes, overnight polysomnography and endothelial function, measured by reactive hyperemia peripheral arterial tonometry (RH-PAT), were assessed. Inflammatory (Leptin, RANTES, MCP-1, IL-6, IL-8, TNFα, Resistin) and anti-inflammatory (adiponectin, IL-1Ra) cytokines were measured by multiplex beads immunoassays.

Principal Findings

OHS exhibited a higher PaCO₂, a lower forced vital capacity (FVC) and tended to have a lower PaO₂ than eucapnic obese patients. _HS-CRP, RANTES levels and glycated haemoglobin (HbA1c) were significantly increased in OHS (respectively 11.1±10.9 vs. 5.7±5.5 mg.l⁻¹ for _HS-CRP, 55.9±55.3 vs 23.3±15.8 ng/ml for RANTES and 7.3±4.3 vs 6.1±1.7 for HbA1c). Serum adiponectin was reduced in OHS (7606±2977 vs 13660±7854 ng/ml). Endothelial function was significantly more impaired in OHS (RH-PAT index: 0.22±0.06 vs 0.51±0.11).

Conclusions

Compared to eucapnic obesity, OHS is associated with a specific increase in the pro-atherosclerotic RANTES chemokine, a decrease in the anti-inflammatory adipokine adiponectin and impaired endothelial function. These three conditions are known to be strongly associated with an increased cardiovascular risk.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00603096","term_id":"NCT00603096"}}NCT00603096     

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.     

Effects of a Seven Day Overload-Period of High-Intensity Training on Performance and Physiology of Competitive Cyclists

Objectives

Competitive endurance athletes commonly undertake periods of overload training in the weeks prior to major competitions. This investigation examined the effects of two seven-day high-intensity overload training regimes (HIT) on performance and physiological characteristics of competitive cyclists.

Design

The study was a matched groups, controlled trial.

Methods

Twenty-eight male cyclists (mean ± SD, Age: 33±10 years, Mass 74±7 kg, VO₂ peak 4.7±0.5 L·min⁻¹) were assigned to a control group or one of two training groups for seven consecutive days of HIT. Before and after training cyclists completed an ergometer based incremental exercise test and a 20-km time-trial. The HIT sessions were ∼120 minutes in duration and consisted of matched volumes of 5, 10 and 20 second (short) or 15, 30 and 45 second (long) maximal intensity efforts.

Results

Both the short and long HIT regimes led to significant (p<0.05) gains in time trial performance compared to the control group. Relative to the control group, the mean changes (±90% confidence limits) in time-trial power were 8.2%±3.8% and 10.4%±4.3% for the short and long HIT regimes respectively; corresponding increases in peak power in the incremental test were 5.5%±2.7% and 9.5%±2.5%. Both HIT (short vs long) interventions led to non-significant (p>0.05) increases (mean ± SD) in VO₂ peak (2.3%±4.7% vs 3.5%±6.2%), lactate threshold power (3.6%±3.5% vs 2.9%±5.3%) and gross efficiency (3.2%±2.4% vs 5.1%±3.9%) with only small differences between HIT regimes.

Conclusions

Seven days of overload HIT induces substantial enhancements in time-trial performance despite non-significant increases in physiological measures with competitive cyclists.     

Molecular Imaging of Cell Death in Tumors. Increasing Annexin A5 Size Reduces Contribution of Phosphatidylserine-Targeting Function to Tumor Uptake

Objective

Annexin A5 is a phosphatidylserine binding protein that binds dying cells in vivo. Annexin A5 is a potential molecular imaging agent to determine efficacy of anti-cancer therapy in patients. Its rapid clearance from circulation limits tumor uptake and, hence, its sensitivity. The aim of this study is to determine if non-invasive imaging of cell death in tumors will benefit from increasing circulation time of annexin A5 by increasing its size.

Procedures

Annexin A5 size was increased by complexation of biotinylated annexin A5 with Alexa-Fluor680-labeled streptavidin. The non-binding variant of annexin A5, M1234, was used as negative control. The HT29 colon carcinoma xenograft model in NMRI nude mice was used to measure tumor uptake in vivo. Tumor uptake of fluorescent annexin A5-variants was measured using non-invasive optical imaging.

Results

The annexin A5-streptavidin complex (4∶1, moles:moles, M_w ∼200 kDa) binds phosphatidylserine-expressing membranes with a Hill-coefficient of 5.7±0.5 for Ca²⁺-binding and an EC50 of 0.9±0.1 mM Ca²⁺ (EC50 is the Ca²⁺ concentration required for half maximal binding)(annexin A5: Hill-coefficient 3.9±0.2, EC50 1.5±0.2 mM Ca²⁺). Circulation half-life of annexin A5-streptavidin is ±21 minutes (circulation half-life of annexin A5 is ±4 min.). Tumor uptake of annexin A5-streptavidin was higher and persisted longer than annexin A5-uptake but depended less on phosphatidylserine binding.

Conclusion

Increasing annexin A5 size prolongs circulation times and increases tumor uptake, but decreases contribution of PS-targeting to tumor uptake and abolishes power to report efficacy of therapy.     

Detection of Endogenous Iron Reduction during Hepatocarcinogenesis at Susceptibility-Weighted MR Imaging: Value for Characterization of Hepatocellular Carcinoma and Dysplastic Nodule in Cirrhotic Liver

Objective

To investigate the value of susceptibility-weighted imaging (SWI) for characterization of hepatocellular carcinoma (HCC) and dysplastic nodule (DN).

Materials and Methods

Sixty-eight cirrhotic patients with 89 hepatocellular nodules underwent SWI. The radiological features of hepatocellular nodules on SWI were classified into three types: type A (iso- or hypointensity, and background liver siderosis), type B (hyperintensity, and background liver siderosis), or type C (hyperintensity, and no background liver siderosis). Intranodular and background liver iron content was quantified and correlated with SWI pattern. Prussian blue staining was performed to quantify intranodular and background liver iron content.

Results

Type A pattern (n = 12) contained 11 (91.7%) DNs and 1 (8.3%) HCC, Type B pattern (n = 66) comprised 1 (1.5%) DN and 65 (98.5%) HCCs (including 12 DN-HCCs and 53 overt HCCs), and type C pattern (n = 11) was exclusively seen in HCCs. The iron scores of DN-HCCs and overt HCCs were significantly lower than those of background livers [(0.091±0.30) VS (2.18±0.87), P = 0.000; (0.11±0.41) VS (2.16±0.97), P = 0.000; respectively]. There was no significant difference between iron scores of DNs and those of background livers [(1.92±0.29) VS (2.17±039), P = 0.191]. For lesion-based and patient-based analysis of HCCs (DN-HCCs and overt HCCs), type B pattern showed a sensitivity, specificity, accuracy, positive predicative value (PPV), and negative predicative value (NPV) of 84.4% and 84.4%, 91.7% and 75%, 85.4% and 83.8%, 98.5% and 98.2%, 47.8% and 23.1%, respectively.

Conclusion

SWI can provide valuable information for characterization of HCC and DN based on endogenous iron reduction during hepatocarcinogenesis.     

The Value of Diffusion Tensor Imaging in Differentiating High-Grade Gliomas from Brain Metastases: A Systematic Review and Meta-Analysis

Purpose

Differentiation of high-grade gliomas and solitary brain metastases is an important clinical issue because the treatment strategies differ greatly. Our study aimed to investigate the potential value of diffusion tensor imaging (DTI) in differentiating high-grade gliomas from brain metastases using a meta-analytic approach.

Materials and Methods

We searched Pubmed, Embase and the Cochrane Library for relevant articles published in English. Studies that both investigated high-grade gliomas and brain metastases using DTI were included. Random effect model was used to compare fractional anisotropy (FA) and mean diffusivity (MD) values in the two tumor entities.

Results

Nine studies were included into the meta-analysis. In the peritumoral region, compared with brain metastases, high-grade gliomas had a significant increase of FA (SMD  = 0.47; 95% CI, 0.22–0.71; P<0.01) and a significant decrease of MD (SMD  = −1.49; 95% CI, −1.91 to −1.06; P<0.01). However, in the intratumoral area, no significant change in FA (SMD  = 0.16; 95% CI, −0.49 to 0.82; P = 0.73) or MD (SMD  = 0.34; 95% CI, −0.91 to 1.60; P = 0.59) was detected between gliomas and metastases.

Conclusions

High-grade gliomas may be distinguished from brain metastases by comparing the peritumoral FA and MD values. DTI appears to be a promising tool in diagnosing solitary intracranial lesions.     

Retinal Nerve Fibre Layer Thinning in Patients with Clinically Isolated Optic Neuritis and Early Treatment with Interferon-Beta

Background

Optic neuritis is associated with neurodegeneration leading to chronic impairment of visual functions.

Objective

This study investigated whether early treatment with interferon beta (IFN-β) slows retinal nerve fibre layer (RNFL) thinning in clinically isolated optic neuritis.

Methods

Twenty patients with optic neuritis and visual acuity decreased to ≤0.5 (decimal system) were included into this prospective, open-label, parallel group 4-month observation. After methylprednisolone pulse therapy, 10 patients received IFN-β from week 2 onwards. This group was compared to 10 patients free of any disease modifying treatment (DMT). The parameter of interest was change in RNFL thickness assessed at baseline and at weeks 4, 8, and 16. Changes in visual acuity, visual field, and visual evoked potentials (VEPs) served as additional outcome parameters.

Results

RNFL thinning did not differ between the groups with a mean reduction of 9.80±2.80 µm in IFN-β-treated patients (±SD) vs. 12.44±5.79 µm in patients who did not receive DMT (baseline non-affected eye minus affected eye at week 16; p = 0.67, t-test, 95% confidence interval: −15.77 to 10.48). Parameters of visual function did not show any differences between the groups either.

Conclusions

In isolated optic neuritis, early IFN-β treatment did not influence RNFL thinning nor had it any effect on recovery of visual functions.     

Technical Performance Evaluation of the MyT4 Point of Care Technology for CD4+ T Cell Enumeration

Objective

Though absolute CD4+ T cell enumeration is the primary gateway to antiretroviral therapy initiation for HIV-positive patients in all developing countries, patient access to this critical diagnostic test is relatively poor. We technically evaluated the performance of a newly developed point-of-care CD4+ T cell technology, the MyT4, compared with conventional CD4+ T cell testing technologies.

Design

Over 250 HIV-positive patients were consecutively enrolled and their blood tested on the MyT4, BD FACSCalibur, and BD FACSCount.

Results

Compared with the BD FACSCount, the MyT4 had an r² of 0.7269 and a mean bias of −23.37 cells/µl. Compared with the BD FACSCalibur, the MyT4 had an r² of 0.5825 and a mean bias of −46.58 cells/µl. Kenya currently uses a CD4+ T cell test threshold of 350 cells/µl to determine patient eligibility for antiretroviral therapy. At this threshold, the MyT4 had a sensitivity of 95.3% (95% CI: 88.4–98.7%) and a specificity of 87.9% (95% CI: 82.3–92.3%) compared with the BD FACSCount and sensitivity and specificity of 88.2% (95% CI: 79.4–94.2%) and 84.2% (95% CI: 78.2–89.2%), respectively, compared with the BD FACSCalibur. Finally, the MyT4 had a coefficient of variation of 12.80% compared with 14.03% for the BD FACSCalibur.

Conclusions

We conclude that the MyT4 performed well at the current 350 cells/µl ART initiation eligibility threshold when used by lower cadres of health care facility staff in rural clinics compared to conventional CD4+ T cell technologies.