Reproductive factors and mammographic density within the International Consortium of Mammographic Density: A cross-sectional study.

BACKGROUND: Elevated mammographic density (MD) for a woman's age and body mass index (BMI) is an established breast cancer risk factor. The relationship of parity, age at first birth, and breastfeeding with MD is less clear. We examined the associations of these factors with MD within the International Consortium of Mammographic Density (ICMD). METHODS: ICMD is a consortium of 27 studies with pooled individual-level epidemiological and MD data from 11,755 women without breast cancer aged 35-85 years from 22 countries, capturing 40 country-& ethnicity-specific population groups. MD was measured using the area-based tool Cumulus. Meta-analyses across population groups and pooled analyses were used to examine linear regression associations of square-root (√) transformed MD measures (percent MD (PMD), dense area (DA), and non-dense area (NDA)) with parity, age at first birth, ever/never breastfed and lifetime breastfeeding duration. Models were adjusted for age at mammogram, age at menarche, BMI, menopausal status, use of hormone replacement therapy, calibration method, mammogram view and reader, and parity and age at first birth when not the association of interest. RESULTS: Among 10,988 women included in these analyses, 90.1% (n = 9,895) were parous, of whom 13% (n = 1,286) had ≥ five births. The mean age at first birth was 24.3 years (Standard deviation = 5.1). Increasing parity (per birth) was inversely associated with √PMD (ß: - 0.05, 95% confidence interval (CI): - 0.07, - 0.03) and √DA (ß: - 0.08, 95% CI: - 0.12, - 0.05) with this trend evident until at least nine births. Women who were older at first birth (per five-year increase) had higher √PMD (ß:0.06, 95% CI:0.03, 0.10) and √DA (ß:0.06, 95% CI:0.02, 0.10), and lower √NDA (ß: - 0.06, 95% CI: - 0.11, - 0.01). In stratified analyses, this association was only evident in women who were post-menopausal at MD assessment. Among parous women, no associations were found between ever/never breastfed or lifetime breastfeeding duration (per six-month increase) and √MD. CONCLUSIONS: Associations with higher parity and older age at first birth with √MD were consistent with the direction of their respective associations with breast cancer risk. Further research is needed to understand reproductive factor-related differences in the composition of breast tissue and their associations with breast cancer risk.

Epidemiological and ES cell-based functional evaluation of BRCA2 variants identified in families with breast cancer.

The discovery of high-risk breast cancer susceptibility genes, such as Breast cancer associated gene 1 (BRCA1) and Breast cancer associated gene 2 (BRCA2) has led to accurate identification of individuals for risk management and targeted therapy. The rapid decline in sequencing costs has tremendously increased the number of individuals who are undergoing genetic testing world-wide. However, given the significant differences in population-specific variants, interpreting the results of these tests can be challenging especially for novel genetic variants in understudied populations. Here we report the characterization of novel variants in the Malaysian and Singaporean population that consist of different ethnic groups (Malays, Chinese, Indian, and other indigenous groups). We have evaluated the functional significance of 14 BRCA2 variants of uncertain clinical significance by using multiple in silico prediction tools and examined their frequency in a cohort of 7840 breast cancer cases and 7928 healthy controls. In addition, we have used a mouse embryonic stem cell (mESC)-based functional assay to assess the impact of these variants on BRCA2 function. We found these variants to be functionally indistinguishable from wild-type BRCA2. These variants could fully rescue the lethality of Brca2-null mESCs and exhibited no sensitivity to six different DNA damaging agents including a poly ADP ribose polymerase inhibitor. Our findings strongly suggest that all 14 evaluated variants are functionally neutral. Our findings should be valuable in risk assessment of individuals carrying these variants.

Microstructural Integrity of Peripheral Nerves in Charcot-Marie-Tooth Disease: An MRI Evaluation Study.

BACKGROUND: Charcot-Marie-Tooth (CMT) disease is diagnosed through clinical findings and genetic testing. While there are neurophysiological tools and clinical functional scales in CMT, objective disease biomarkers that can facilitate in monitoring disease progression are limited. PURPOSE: To investigate the utility of diffusion tensor imaging (DTI) in determining the microstructural integrity of sciatic and peroneal nerves and its correlation with the MRI grading of muscle atrophy severity and clinical function in CMT as determined by the CMT neuropathy score (CMTNS). STUDY TYPE: Prospective case-control. SUBJECTS: Nine CMT patients and nine age-matched controls. FIELD STRENGTH/SEQUENCE: 3 T T1 -weighted in-/out-of phase spoiled gradient recalled echo (SPGR) and DTI sequences. ASSESSMENT: Fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD) values for sciatic and peroneal nerves were obtained from DTI. Muscle atrophy was graded according to the Goutallier classification using in-/out-of phase SPGRs. DTI parameters and muscle atrophy grades were compared between CMT and controls, and the relationship between DTI parameters, muscle atrophy grades, and CMTNS were assessed. STATISTICAL TESTS: The Wilcoxon Signed Ranks test was used to compare DTI parameters between CMT and controls. The relationship between DTI parameters, muscle atrophy grades, and CMTNS were analyzed using the Spearman correlation. Receiver operating characteristic (ROC) analyses of DTI parameters that can differentiate CMT from healthy controls were done. RESULTS: There was a significant reduction in FA and increase in RD of both nerves (P < 0.05) in CMT, with significant correlations between FA (negative; P < 0.05) and RD (positive; P < 0.05) with muscle atrophy grade. In the sciatic nerve, there was significant correlation between FA and CMTNS (r = -0.795; P < 0.05). FA and RD could discriminate CMT from controls with high sensitivity (77.8-100%) and specificity (88.9-100%). DATA CONCLUSION: There were significant differences of DTI parameters between CMT and controls, with significant correlations between DTI parameters, muscle atrophy grade, and CMTNS. Level of Evidence 2 Technical Efficacy Stage 2 J. MAGN. RESON. IMAGING 2021;53:437-444.

Physical activity and mammographic density in an Asian multi-ethnic cohort.

BACKGROUND: Physical activity is a modifiable lifestyle factor associated with reduced breast cancer risk. Mammographic density is a strong, independent risk factor for breast cancer, and some breast cancer risk factors have been shown to modify mammographic density. However, the effect of physical activity on mammographic density, studied predominantly among Caucasians, has yielded conflicting results. In this study, we examined, in an Asian population, the association between physical activity and mammographic density. METHODS: We conducted a cross-sectional study of 2,377 Malaysian women aged 40-74 years. Physical activity information was obtained at screening mammogram and mammographic density was measured from mammograms by the area-based STRATUS method (n = 1,522) and the volumetric Volpara™ (n = 1,200) method. Linear regression analyses were performed to evaluate the association between physical activity and mammographic density, adjusting for potential confounders. RESULTS: We observed that recent physical activity was associated with area-based mammographic density measures among postmenopausal women, but not premenopausal women. In the fully adjusted model, postmenopausal women with the highest level of recent physical activity had 8.0 cm2 [95% confidence interval: 1.3, 14.3 cm2] lower non-dense area and 3.1% [0.1, 6.3%] higher area-based percent density, compared to women with the lowest level of recent physical activity. Physical activity was not associated to volumetric mammographic density. CONCLUSIONS: Our findings suggest that the beneficial effects of physical activity on breast cancer risk may not be measurable through mammographic density. Future research is needed to identify appropriate biomarkers to assess the effect of physical activity on breast cancer risk.

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.

Opportunistic mammography screening provides effective detection rates in a limited resource healthcare system.

BACKGROUND: Breast cancer is the leading cause of cancer deaths in women world-wide. In low and middle income countries, where there are no population-based mammographic screening programmes, late presentation is common, and because of inadequate access to optimal treatment, survival rates are poor. Mammographic screening is well-studied in high-income countries in western populations, and because it has been shown to reduce breast cancer mortality, it has become part of the healthcare systems in such countries. However the performance of mammographic screening in a developing country is largely unknown. This study aims to evaluate the performance of mammographic screening in Malaysia, a middle income country, and to compare the stage and surgical treatment of screen-detected and symptomatic breast cancer. METHODS: A retrospective review of 2510 mammograms performed from Jan to Dec 2010 in a tertiary medical centre is carried out. The three groups identified are the routine (opportunistic) screening group, the targeted (high risk) screening group and the diagnostic group. The performance indicators of each group is calculated, and stage at presentation and treatment between the screening and diagnostic group is analyzed. RESULTS: The cancer detection rate in the opportunistic screening group, targeted screening group, and the symptomatic group is 0.5 %, 1.25 % and 26 % respectively. The proportion of ductal carcinoma in situ is 23.1 % in the two screening groups compared to only 2.5 % in the diagnostic group. Among the opportunistic screening group, the cancer detection rate was 0.2 % in women below 50 years old compared to 0.65 % in women 50 years and above. The performance indicators are within international standards. Early-staged breast cancer (Stage 0-2) were 84.6 % in the screening groups compared to 61.1 % in the diagnostic group. CONCLUSION: From the results, in a setting with resource constraints, targeted screening of high risk individuals will give a higher yield, and if more resources are available, population-based screening of women 50 and above is effective. Opportunistic mammographic screening is feasible and effective in a middle income country with performance indicators within international standards. Waiting until women are symptomatic will lead to more advanced cancers.

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

BACKGROUND: Intraventricular haemorrhage is the most common cause of hydrocephalus in a pre-term baby and may require surgical intervention depending on severity. CLINICAL CASE: This 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. CONCLUSION: 3D-FIESTA sequence is recommended for investigating children with hydrocephalus secondary to intraventricular haemorrhage due to its diagnostic potential and implications on surgical technique.

Imaging of an atypical pericardial cyst.

Pericardial cysts are uncommon mediastinal lesions that are usually congenital in origin. Patients are usually asymptomatic and the cysts are generally discovered on routine radiography for unrelated purposes. This case illustrates a symptomatic presentation of a haemorrhagic pericardial cyst in which radiographic, echocardiographic and multislice (MRI and CT) imaging were performed. The imaging findings were not typical of pericardial cysts leading to a diagnostic quandary despite the varied imaging techniques. In conclusion, it is important to appreciate that the imaging findings of pericardial cysts can be varied. Radiologists and clinicians alike should be aware of this variability.

Spindle Cell Metaplastic Breast Carcinoma.

INTRODUCTION: Metaplastic breast carcinoma is an uncommon malignancy that constitutes < 5% of all breast cancers. There are 5 subtypes which are spindle cell, squamous cell, carcinosarcoma, matrix-producing and metaplastic with osteoclastic giant cells. Spindle cell carcinoma represents approximately <0.3% of invasive breast carcinomas. It is typically a triple-negative cancer with distinct pathological characteristics, but relatively a non-conclusive on imaging findings. CASE REPORT: An elderly lady presented with an enlarging painful left breast lump for one year. Palpable left breast lump was found on clinical examination. Mammography demonstrated a high density, oval lesion with a partially indistinct margin. Corresponding ultrasound showed a large irregular heterogeneous lesion with solid-cystic areas. Histopathology showed atypical spindle-shaped cells that stained positive for cytokeratins and negative for hormone and human epidermal growth factor receptors, which favoured spindle cell metaplastic carcinoma. Left mastectomy and axillary dissection were performed, and the final diagnosis was consistent with metaplastic spindle cell carcinoma. CONCLUSION: Spindle cell carcinoma of the breast is a rare and aggressive histological type of carcinoma, which may present with benign features on imaging. Tissue diagnosis is essential for prompt diagnosis with multidisciplinary team discussion to guide management and improve patient's outcomes.

Impact of preoperative magnetic resonance imaging on surgery and eligibility for intraoperative radiotherapy in early breast cancer.

We looked at the usefulness of magnetic resonance imaging (MRI) in decision-making and surgical management of patients selected for intraoperative radiotherapy (IORT). We also compared lesion size measurements in different modalities (ultrasound (US), mammogram (MMG), MRI) against pathological size as the gold standard. 63 patients eligible for IORT based on clinical and imaging criteria over a 34-month period were enrolled. All had MMG and US, while 42 had additional preoperative MRI for locoregional preoperative staging. Imaging findings and pathological size concordances were analysed across the three modalities. MRI changed the surgical management of 5 patients (11.9%) whereby breast-conserving surgery (BCS) and IORT was cancelled due to detection of satellite lesion, tumor size exceeding 30mm and detection of axillary nodal metastases. Ten of 42 patients (23.8%) who underwent preoperative MRI were subjected to additional external beam radiotherapy (EBRT); 7 due to lymphovascular invasion (LVI), 2 due to involved margins, and 1 due to axillary lymph node metastatic carcinoma detected in the surgical specimen. Five of 21 (23.8%) patients without prior MRI were subjected to additional EBRT post-surgery; 3 had LVI and 2 had involved margins. The rest underwent BCS and IORT as planned. MRI and MMG show better imaging-pathological size correlation. Significant increase in the mean 'waiting time' were seen in the MRI group (34.1 days) compared to the conventional imaging group (24.4 days). MRI is a useful adjunct to conventional imaging and impacts decision making in IORT. It is also the best imaging modality to determine the actual tumour size.

Is pre-operative axillary ultrasound alone sufficient to determine need for axillary dissection in early breast cancer patients?

ABSTRACT: Pre-operative status of axillary lymph node (ALN) in early breast cancer is usually initially assessed by pre-operative ultrasound, followed by ultrasound-guided needle biopsy (UNB) confirmation. Patients with positive nodal status will undergo axillary lymph node dissection (ALND), while those with negative nodal status will have sentinel lymph node biopsy. ALND is associated with higher morbidity than Sentinel lymph node biopsy. The objective of this study is to determine if axillary ultrasound alone without UNB is predictive enough to assign patients to ALND and to identify ultrasound features that are significantly associated with pathologically positive ALN.383 newly diagnosed primary breast cancer patients between 2012 and 2014, and who had undergone pre-operative axillary ultrasound in University Malaya Medical Centre with a complete histopathology report of the axillary surgery were retrospectively reviewed. ALN was considered positive if it had any of these features: cortical thickening > 3 mm, loss of fatty hilum, hypoechoic solid node, mass-like appearance, round shape and lymph node size > 5 mm. Post-operative histopathological reports were then analyzed for nodal involvement.The overall sensitivity, specificity, and accuracy of pre-operative axillary ultrasound in detecting diseased nodes were 45.5%, 80.7%, and 60.3% respectively. The positive (PPV) and negative predictive values were 76.5% and 51.8%. Round shape, loss of fatty hilum and mass-like appearance had the highest PPVs of 87%, 83% and 81.6% respectively and significant odds ratios (ORs) of 5.22 (95% confidence interval [CI]: 1.52 - 17.86), ORs of 4.77 (95% CI: 2.62 - 8.70) and ORs of 4.26 (95% CI: 2.37 - 7.67) respectively (P-value < .05). Cortical thickness of > 3 mm was identified to have low PPV at 69.1%, ORs of 1.71 (95% CI: 0.86 - 3.41, P = .126).There are features on axillary ultrasound that confer high PPV for axillary involvement i.e. round shape, loss of fatty hilum, and mass-like appearance. In a low resource setting, these features may benefit from ALND without further pre-operative biopsies. However, pre-operative UNB for features with low PPV that is, cortical thickness > 3 mm should be considered to obviate the unnecessary morbidity associated with ALND.

Spectrum of imaging findings of papillary breast disease: A radiopathological review in a tertiary center.

ABSTRACT: To evaluate the clinical and imaging findings of papillary breast neoplasm and review the pathologic correlation at a tertiary center.Retrospective study of patients diagnosed with benign and malignant papillary lesions between 2008 to 2018. 147 patients were identified with histology diagnosis of papillary lesions. The clinical, imaging, and pathological characteristics were reviewed.Patient cohort included 147 women diagnosed with papillary lesions (mean age at diagnosis 53.8 years) and were divided into 3 histology groups (benign, atypical, and malignant). Common clinical presentations were breast lump (n = 60) and nipple discharge (n = 29), 48 patients were asymptomatic.Only 37 were detected as a mass lesion on mammogram. The presence of mass lesion on mammogram was the most common feature in all 3 papillary lesion groups, and with the presence of asymmetric density, were the 2 mammographic features significantly associated (P < .05) with malignancy.All lesions were detected on ultrasound. The most common sonographic features for all 3 groups were the presence of a mass and irregular shape. Among all the sonographic features assessed, larger size, presence of vascularity and absence of dilated ducts were significantly associated (P < .05) with malignancy.Feature pattern recognition of the variety of benign, atypical and malignant papillary neoplasm on ultrasound and mammogram, with emphasis on size, presence of vascularity and dilated ducts on ultrasound and presence of mass, and architectural distortion on mammogram, is important in the assessment of patients with suspected ductal lesions to facilitate optimal treatment and surgical care.

Diagnostic accuracy of digital breast tomosynthesis in combination with 2D mammography for the characterisation of mammographic abnormalities.

This study aims to assess the diagnostic accuracy of digital breast tomosynthesis in combination with full field digital mammography (DBT + FFDM) in the charaterisation of Breast Imaging-reporting and Data System (BI-RADS) category 3, 4 and 5 lesions. Retrospective cross-sectional study of 390 patients with BI-RADS 3, 4 and 5 mammography with available histopathology examination results were recruited from in a single center of a multi-ethnic Asian population. 2 readers independently reported the FFDM and DBT images and classified lesions detected (mass, calcifications, asymmetric density and architectural distortion) based on American College of Radiology-BI-RADS lexicon. Of the 390 patients recruited, 182 malignancies were reported. Positive predictive value (PPV) of cancer was 46.7%. The PPV in BI-RADS 4a, 4b, 4c and 5 were 6.0%, 38.3%, 68.9%, and 93.1%, respectively. Among all the cancers, 76% presented as masses, 4% as calcifications and 20% as asymmetry. An additional of 4% of cancers were detected on ultrasound. The sensitivity, specificity, PPV and NPV of mass lesions detected on DBT + FFDM were 93.8%, 85.1%, 88.8% and 91.5%, respectively. The PPV for calcification is 61.6% and asymmetry is 60.7%. 81.6% of cancer detected were invasive and 13.3% were in-situ type. Our study showed that DBT is proven to be an effective tool in the diagnosis and characterization of breast lesions and supports the current body of literature that states that integrating DBT to FFDM allows good characterization of breast lesions and accurate diagnosis of cancer.

Evaluation of automated volumetric breast density software in comparison with visual assessments in an Asian population: A retrospective observational study.

This study aims to compare Quantra, as an automated volumetric breast density (Vbd) tool, with visual assessment according to ACR BI-RADS density categories and to determine its potential usage in clinical practice.Five hundred randomly selected screening and diagnostic mammograms were included in this retrospective study. Three radiologists independently assigned qualitative ACR BI-RADS density categories to the mammograms. Quantra automatically calculates the volumetric density data into the system. The readers were blinded to the Quantra and other readers assessment. Inter-reader agreement and agreement between Quantra and each reader were tested. Region under the curve (ROC) analysis was performed to obtain the cut-off value to separate dense from a non-dense breast. Results with P value <.05 was taken as significant.There were 40.4% Chinese, 27% Malays, 19% Indian and 3.6% represent other ethnicities. The mean age of the patients was 57. 15%, 45.6%, 30.4%, and 9% of patients fall under BI-RADS A, B, C and D density category respectively. Fair agreement with Kappa (κ) value: 0.49, 0.38, and 0.30 were seen for Reader 1, 2 and 3 versus Quantra. Moderate agreement with κ value: 0.63, 0.64, 0.51 was seen when the data were dichotomized (density A and B to "non-dense", C and D to "dense"). The cut-off Vbd value was 13.5% to stratify dense from non-dense breasts with a sensitivity of 86.2% and specificity of 83.1% (AUC 91.4%; confidence interval: 88.8, 94.1).Quantra showed moderate agreement with radiologists visual assessment. Hence, this study adds to the available evidence to support the potential use of Quantra as an adjunct tool for breast density assessment in routine clinical practice in the Asian population. We found 13.5% is the best cut-off value to stratify dense to non-dense breasts in our study population. Its application will provide an objective, consistent and reproducible results as well as aiding clinical decision-making on the need for supplementary breast ultrasound in our screening population.

Radiopathological characteristics and outcomes of phyllodes tumor of the breast in Malaysian women.

Phyllodes tumor or cystosarcoma phyllodes is a rare fibroepithelial neoplasm which arises from the periductal stroma of the breast. They are classified as benign, borderline, and malignant based on the histologic features. However, all phyllodes tumor (PT) subtypes are regarded as having malignant potential and correct diagnosis is important for surgical management and optimal care. This study is a retrospective review of 76 women diagnosed as PT with highlights on the imaging characteristics, pathology, and surgical treatment over a 7-year period in a tertiary medical center of urban population in Malaysia. There were 45 benign, 16 borderline, and 15 malignant PT. The median age for benign PT was 43, borderline 48.5, and malignant 42 years. The Malay ethnic group constitute 52.6% of cases, with 27.6% and 18.4% in Chinese and Indian ethnic groups, respectively. On mammograms, most benign (64.3%) and 33.3% of malignant PT showed high-density lesions. Calcifications were only seen in 2 benign PT. On ultrasound, 86% of benign PT was well-circumscribed whilst 50.0% of malignant PT had irregular outline. Cystic spaces were seen in 40.0% of malignant and 9.5% of benign PT. 80% of malignant PT lesions were heterogenous. Malignant PT demonstrates tumor heterogeneity, cystic spaces, and posterior acoustic enhancement on ultrasound. Half of malignant PT showed regular borders on ultrasound and appear well circumscribed on mammogram. A total of 46 patients had wide local excision or excision biopsy whilst 30 underwent mastectomy as primary treatment. The majority of the borderline and malignant PTs in our study (75.0% and 85.7% respectively) and only 5 out of the 43 (11.6%) benign PT underwent mastectomy. There were 2 tumor recurrence in the benign PT group and 1 case in the borderline and malignant group respectively.

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.

BACKGROUND: Osteoarthritis (OA) is considered an established risk factor for falls. Published studies evaluating secondary falls prevention strategies among individuals with OA are limited. OBJECTIVE: To evaluate the effect of a personalized home-based exercise program to improve postural balance, fear of falling, and falls risk in older fallers with knee OA and gait and balance problems. DESIGN: Randomized controlled trial. SETTING: University of Malaya Medical Centre. PARTICIPANTS: Fallers who had both radiological OA and a Timed Up and Go (TUG) score of over 13.5 seconds. MAIN OUTCOME MEASURE: Postural sway (composite sway) was quantified with the Modified Clinical Test of Sensory Interaction on Balance (mCTSIB) under 4 different sensory conditions: eyes open on firm surface, eyes closed on firm surface, eyes open on unstable foam surface, and eyes closed on unstable foam surface. Participants were asked to stand upright and to attempt to hold their position for 10 seconds for each test condition. The average reading for all conditions were calculated. METHODS: Participants randomized to the intervention arm received a home-based modified Otago Exercise Program (OEP) as part of a multifactorial intervention, whereas control participants received general health advice and conventional treatment. This was a secondary subgroup analysis from an original randomized controlled trial, the Malaysian Falls Assessment and Intervention Trial (MyFAIT) (trial registration number: ISRCTN11674947). Posturography using a long force plate balance platform (Balancemaster, NeuroCom, USA), the Knee injury and Osteoarthritis Outcome Score (KOOS) and the short-form Falls Efficacy Scale-International (short FES-I) were assessed at baseline and 6 months. RESULTS: Results of 41 fallers with radiological evidence of OA and impaired TUG (intervention, 17; control, 24) were available for the final analysis. Between-group analysis revealed significant improvements in the Modified Clinical Test of Sensory Interaction on Balance (mCTSIB), Limits of Stability (LOS), and short FES-I scores by the intervention group compared to the control group at 6 months. No significant difference in time to first fall or in fall-free survival between the intervention and control groups was found. CONCLUSION: Home-based balance and strength exercises benefited older fallers with OA and gait and balance disorders by improving postural control, with no observable trend in reduction of fall recurrence. Our findings will now inform a future, adequately powered, randomized controlled study using fall events as definitive outcomes. LEVEL OF EVIDENCE: I.

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

INTRODUCTION: Low body weight in Parkinson's 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 ±â€¯8.5 vs. 62.4 ±â€¯8.4years, P = 0.003). Mean body mass index (24.0 ±â€¯0.4 vs. 25.6 ±â€¯0.5kg/m2, Padjusted = 0.016), fat mass index (7.4 ±â€¯0.3 vs. 9.0 ±â€¯0.3kg/m2, Padjusted<0.001), and whole-body fat percentage (30.7 ±â€¯0.8 vs. 35.7 ±â€¯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.

A case-control study of breast cancer risk factors in 7,663 women in Malaysia.

BACKGROUND: Breast cancer risk factors have been examined extensively in Western setting and more developed Asian cities/countries. However, there are limited data on developing Asian countries. The purpose of this study was to examine breast cancer risk factors and the change of selected risk factors across birth cohorts in Malaysian women. METHODS: An unmatched hospital based case-control study was conducted from October 2002 to December 2016 in Selangor, Malaysia. A total of 3,683 cases and 3,980 controls were included in this study. Unconditional logistic regressions, adjusted for potential confounding factors, were conducted. The breast cancer risk factors were compared across four birth cohorts by ethnicity. RESULTS: Ever breastfed, longer breastfeeding duration, a higher soymilk and soy product intake, and a higher level of physical activity were associated with lower risk of breast cancer. Chinese had the lowest breastfeeding rate, shortest breastfeeding duration, lowest parity and highest age of first full term pregnancy. CONCLUSIONS: Our study shows that breastfeeding, soy intake and physical activity are modifiable risk factors for breast cancer. With the increasing incidence of breast cancer there is an urgent need to educate the women about lifestyle intervention they can take to reduce their breast cancer risk.

There is less MRI brain lesions and no characteristic MRI Brain findings in IIDDs patients with positive AQP4 serology among Malaysians.

BACKGROUND AND OBJECTIVE: The recently introduced International Consensus diagnostic criteria for diagnosis of neuromyelitis spectrum disorder include patients who are seronegative for AQP4 antibody. The criteria are dependent on typical MRI changes in the spinal cord, optic nerve and brain. This study aims to determine whether there are significant differences in the MRI brain images between AQP4 positive and negative patients with IIDDs. METHOD: MRI brain of patients with a diagnosis of IIDDs presented to the Hospital from 2010 to 2015 was analysed. The MRI was assessed by 2 radiologists blinded to the AQP4 status, on features said to be typical of NMOSD and MS. RESULTS: Thirty nine patients fulfilled the criteria and were included in the study. They consisted of 19 AQP4 seropositive and 20 AQP4 seronegative patients. The mean age was older (37.0 vs. 28.8 years) among the AQP4 positive group. The majority of the patients were ethnic Chinese (72%), followed by the Malays and Indians. Those with AQP4 seropositive status generally has less brain lesions, and significantly less fulfilling the McDonald DIS criteria as compared to those with AQP4 seronegative status (15.8% vs. 60.0%, p=0.005). None of the seven cerebral MRI features highlighted in NMOSD 2015 diagnostic criteria, said to be characteristic of NMOSD was more common among the AQP4 positive patients. These features were in fact seen less frequently among the AQP4 seropositive patients. An example was the extensive hemispheric lesion seen in 10.5% of AQP4 seropositive patients vs. 45% of that AQP4 seronegative group. CONCLUSION: There was no characteristic MRI brain features in the Malaysian AQP4 seropositive IIDD patients versus those who are seronegative. This could be a reflection of ethnical difference.