Farhana Fadzli

Shearwave Elastography Increases Diagnostic Accuracy in Characterization of Breast Lesions.

AbstractThe purpose of this study was to investigate the diagnostic efficacy of shearwave elastography (SWE) in differentiating between benign and malignant breast lesions.One hundred and fifty-nine lesions were assessed using B-mode ultrasound (US) and SWE parameters were recorded (Emax, Emean, Emin, Eratio, SD). SWE measurements were then correlated with histopathological diagnosis.The final sample contained 85 benign and 74 malignant lesions. The maximum stiffness (Emax) with a cutoff point of ≥ 56.0 kPa (based on ROC curves) provided sensitivity of 100.0%, specificity of 97.6%, positive predictive value (PPV) of 97.4%, and negative predictive value (NPV) of 100% in detecting malignant lesions. A cutoff of ≥80 kPa managed to downgrade 95.5% of the Breast Imaging-Reporting and Data System (BI-RADS) 4a lesions to BI-RADS 3, negating the need for biopsy. Using a combination of BI-RADS and SWE, the authors managed to improve the PPV from 2.3% to 50% in BI-RADS 4a lesions.SWE of the breast provides highly specific and sensitive quantitative values that are beneficial in the characterization of breast lesions. Our results showed that Emax is the most accurate value for differentiating benign from malignant lesions.

Mammographic density and ageing: A collaborative pooled analysis of cross-sectional data from 22 countries worldwide

Background Mammographic density (MD) is one of the strongest breast cancer risk factors. Its age-related characteristics have been studied in women in western countries, but whether these associations apply to women worldwide is not known. Methods and findings We examined cross-sectional differences in MD by age and menopausal status in over 11,000 breast-cancer-free women aged 35–85 years, from 40 ethnicity- and location-specific population groups across 22 countries in the International Consortium on Mammographic Density (ICMD). MD was read centrally using a quantitative method (Cumulus) and its square-root metrics were analysed using meta-analysis of group-level estimates and linear regression models of pooled data, adjusted for body mass index, reproductive factors, mammogram view, image type, and reader. In all, 4,534 women were premenopausal, and 6,481 postmenopausal, at the time of mammography. A large age-adjusted difference in percent MD (PD) between post- and premenopausal women was apparent (–0.46 cm [95% CI: −0.53, −0.39]) and appeared greater in women with lower breast cancer risk profiles; variation across population groups due to heterogeneity (I2) was 16.5%. Among premenopausal women, the √PD difference per 10-year increase in age was −0.24 cm (95% CI: −0.34, −0.14; I2 = 30%), reflecting a compositional change (lower dense area and higher non-dense area, with no difference in breast area). In postmenopausal women, the corresponding difference in √PD (−0.38 cm [95% CI: −0.44, −0.33]; I2 = 30%) was additionally driven by increasing breast area. The study is limited by different mammography systems and its cross-sectional rather than longitudinal nature. Conclusions Declines in MD with increasing age are present premenopausally, continue postmenopausally, and are most pronounced over the menopausal transition. These effects were highly consistent across diverse groups of women worldwide, suggesting that they result from an intrinsic biological, likely hormonal, mechanism common to women. If cumulative breast density is a key determinant of breast cancer risk, younger ages may be the more critical periods for lifestyle modifications aimed at breast density and breast cancer risk reduction.

Unmasking Heavily O-Glycosylated Serum Proteins Using Perchloric Acid: Identification of Serum Proteoglycan 4 and Protease C1 Inhibitor as Molecular Indicators for Screening of Breast Cancer

Heavily glycosylated mucin glycopeptides such as CA 27.29 and CA 15–3 are currently being used as biomarkers for detection and monitoring of breast cancer. However, they are not well detected at the early stages of the cancer. In the present study, perchloric acid (PCA) was used to enhance detection of mucin-type O-glycosylated proteins in the serum in an attempt to identify new biomarkers for early stage breast cancer. Sensitivity and specificity of an earlier developed sandwich enzyme-linked lectin assay were significantly improved with the use of serum PCA isolates. When a pilot case-control study was performed using the serum PCA isolates of normal participants (n = 105) and patients with stage 0 (n = 31) and stage I (n = 48) breast cancer, higher levels of total O-glycosylated proteins in sera of both groups of early stage breast cancer patients compared to the normal control women were demonstrated. Further analysis by gel-based proteomics detected significant inverse altered abundance of proteoglycan 4 and plasma protease C1 inhibitor in both the early stages of breast cancer patients compared to the controls. Our data suggests that the ratio of serum proteoglycan 4 to protease C1 inhibitor may be used for screening of early breast cancer although this requires further validation in clinically representative populations.

Mild Joint Symptoms are Associated with Lower Risk of Falls than Asymptomatic Individuals with Radiological Evidence of Osteoarthritis

Osteoarthritis (OA) exacerbates skeletal muscle functioning, leading to postural instability and increased falls risk. However, the link between impaired physical function, OA and falls have not been elucidated. We investigated the role of impaired physical function as a potential mediator in the association between OA and falls. This study included 389 participants [229 fallers (≥2 falls or one injurious fall in the past 12 months), 160 non-fallers (no history of falls)], age (≥65 years) from a randomized controlled trial, the Malaysian Falls Assessment and Intervention Trial (MyFAIT). Physical function was assessed using Timed Up and Go (TUG) and Functional Reach (FR) tests. Knee and hip OA were diagnosed using three methods: Clinical, Radiological and Self-report. OA symptom severity was assessed using the Western Ontario and McMaster Universities Arthritis Index (WOMAC). The total WOMAC score was categorized to asymptomatic, mild, moderate and severe symptoms. Individuals with radiological OA and ‘mild’ overall symptoms on the WOMAC score had reduced risk of falls compared to asymptomatic OA [OR: 0.402(0.172–0.940), p = 0.042]. Individuals with clinical OA and ‘severe’ overall symptoms had increased risk of falls compared to those with ‘mild’ OA [OR: 4.487(1.883–10.693), p = 0.005]. In individuals with radiological OA, mild symptoms appear protective of falls while those with clinical OA and severe symptoms have increased falls risk compared to those with mild symptoms. Both relationships between OA and falls were not mediated by physical limitations. Larger prospective studies are needed for further evaluation.

Neonatal post-hemorrhagic hydrocephalus resulting in foraminal septae—radiological technique and surgical implications

BackgroundIntraventricular haemorrhage is the most common cause of hydrocephalus in a pre-term baby and may require surgical intervention depending on severity.Clinical caseThis case illustrates foraminal septae as a subtle cause of progressive quadriventricular hydrocephalus in a child born pre-term with a history of grade III intraventricular haemorrhage. The septae within the fourth ventricular exits were clearly demonstrated with 3D-FIESTA (fast imaging employing steady-state acquisition) MRI acquisitions and assisted in differentiation from communicating hydrocephalus. This finding guided the decision to a successful endoscopic third ventriculostomy.Conclusion3D-FIESTA sequence is recommended for investigating children with hydrocephalus secondary to intraventricular haemorrhage due to its diagnostic potential and implications on surgical technique.

Effect of Modified Otago Exercises on Postural Balance, Fear of Falling, and Fall Risk in Older Fallers With Knee Osteoarthritis and Impaired Gait and Balance: A Secondary Analysis

Osteoarthritis (OA) is considered an established risk factor for falls. Published studies evaluating secondary falls prevention strategies among individuals with OA are limited.

Altered body composition, sarcopenia, frailty, and their clinico-biological correlates, in Parkinson's disease.

INTRODUCTION Low body weight in Parkinsons disease (PD) is poorly understood despite the associated risks of malnutrition, fractures, and death. Sarcopenia (loss of muscle bulk and strength) and frailty are geriatric syndromes that are likewise associated with adverse health outcomes, yet have received scant attention in PD. We studied body composition, sarcopenia, frailty, and their clinico-biological correlates in PD. METHODS 93 patients and 78 spousal/sibling controls underwent comprehensive assessment of diet, clinical status, muscle strength/performance, frailty, body composition (using dual-energy X-ray absorptiometry), and serum levels of neurogastrointestinal hormones and inflammatory markers. RESULTS PD patients were older than controls (66.0 ± 8.5 vs. 62.4 ± 8.4years, P = 0.003). Mean body mass index (24.0 ± 0.4 vs. 25.6 ± 0.5kg/m2, Padjusted = 0.016), fat mass index (7.4 ± 0.3 vs. 9.0 ± 0.3kg/m2, Padjusted<0.001), and whole-body fat percentage (30.7 ± 0.8 vs. 35.7 ± 0.9%, Padjusted<0.001) were lower in patients, even after controlling for age and gender. There were no between-group differences in skeletal muscle mass index and whole-body bone mineral density. Body composition parameters did not correlate with disease duration or motor severity. Reduced whole-body fat percentage was associated with higher risk of motor response complications as well as higher levels of insulin-growth factor-1 and inflammatory markers. PD patients had a higher prevalence of sarcopenia (17.2% vs. 10.3%, Padjusted = 0.340) and frailty (69.4% vs. 24.2%, Padjusted = 0.010). Older age and worse PD motor severity were predictors of frailty in PD. CONCLUSIONS We found reduced body fat with relatively preserved skeletal muscle mass, and a high prevalence of frailty, in PD. Further studies are needed to understand the patho-mechanisms underlying these alterations.

Shear wave elastography for characterization of breast lesions

Shear wave elastography (SWE) examination using ultrasound elastography (USE) is a popular imaging procedure for obtaining elasticity information of breast lesions. Elasticity parameters obtained through SWE can be used as biomarkers that can distinguish malignant breast lesions from benign ones. Furthermore, the elasticity parameters extracted from SWE can speed up the diagnosis and possibly reduce human errors. In this paper, Shearlet transform and local binary pattern histograms (LBPH) are proposed as an original algorithm to differentiate malignant and benign breast lesions. First, Shearlet transform is applied on the SWE images to acquire low frequency, horizontal and vertical cone coefficients. Next, LBPH features are extracted from the Shearlet transform coefficients and subjected to dimensionality reduction using locality sensitivity discriminating analysis (LSDA). The reduced LSDA components are ranked and then fed to several classifiers for the automated classification of breast lesions. A probabilistic neural network classifier trained only with seven top ranked features performed best, and achieved 98.08% accuracy, 98.63% sensitivity, and 97.59% specificity in distinguishing malignant from benign breast lesions. The high sensitivity and specificity of our system indicates that it can be employed as a primary screening tool for faster diagnosis of breast malignancies, thereby possibly reducing the mortality rate due to breast cancer.

The mediating role of psychological symptoms on falls risk among older adults with osteoarthritis

The purpose of this study was to investigate the role of fear of falling (FoF) and psychological symptoms in explaining the relationship between osteoarthritis (OA) symptom severity and falls. Individuals aged ≥65 years with ≥2 falls or ≥1 injurious fall over the past 12 months were included in the falls group, while volunteers aged ≥65 years with no history of falls over 12 months were recruited as controls. The presence of lower extremity OA was determined radiologically and clinically. Severity of symptoms was assessed using the Western Ontario and McMaster Universities Arthritis Index (WOMAC) questionnaire. FoF and psychological status were measured with the shortened version of the Falls Efficacy Scale-International and the 21-item Depression, Anxiety and Stress Scale (DASS-21), respectively. Of 389 (229 fallers, 160 non-fallers) potential participants, mean (SD) age: 73.74 (6.60) years, 141 had clinical OA and 171 had radiological OA. Fallers with both radiological OA and clinical OA had significantly higher FoF and DASS-21 scores than non-fallers. FoF was significantly positively correlated with symptom severity in fallers and non-fallers with radiological and clinical OA. Depression, anxiety, and stress scores were only significantly correlated with symptom severity among fallers but not non-fallers in both clinical and radiological OA. The relationship between mild symptoms and reduced risk of falls compared to no symptoms in those with radiological OA was attenuated by increased anxiety. The increased falls risk associated with severe symptoms compared to mild symptoms in clinical OA was attenuated by FoF. FoF may, therefore, be a potentially modifiable risk factor for OA-associated falls which could be considered in future intervention studies.

Is Volumetric Breast Density Related to Body Mass Index, Body Fat Mass, Waist-Hip Ratio, Age and Ethnicity for Malaysian Women?

Previous studies have shown that breast cancer has been linked to breast density as well as obesity. We aim to investigate the relationships between body mass index (BMI), body fat mass (BFM), waist-hip ratio (WHR), age and ethnicity with volumetric breast density (VBD) among Malaysian women. In this context, VBD is defined as the ratio of fibroglandular tissue volume to total breast volume. We collected anthropomorphic and body composition data for 2457 subjects undergoing mammographic examination at the University of Malaya Medical Centre, Kuala Lumpur. The data included weight, height, BMI and BFM which were measured with a body composition analyzer. We also measured waist and hip circumferences for 500 of these subjects. A VBD assessment system (Volpara) was used to analyze mammograms. Our results showed that VBD is not significantly correlated with BMI (r2 = 0.17), BFM (r2 = 0.19), WHR (r2 = 0.11). We also noted that VBD is highest among Malaysian women below 40 years old. VBD is highest for Chinese (mean = 11.3%), followed by Malay (mean = 10.1%) and Indian (mean = 9.4%). In conclusion, VBD is dependent on age and ethnicity (ANOVA, p<0.05) but not on BMI, BFM and WHR.