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Fulltext A study protocol: spinal morphology, physical performance, quality of life and biochemical markers in adults at risk of osteoporotic fractures

Chua, S.K., Singh, Devinder K.A., Rajaratnam, B.S., Mokhtar, Sabarul A., Sridharan, R., Gan, K.B., et al.

Pertanika Journal of Science & Technology, 2017;25(4):1123-1134.
MyJurnal

Older adults are at risk of osteoporotic fractures. Osteoporotic vertebral fractures are associated with a reduced cross-sectional area and muscle strength of the back extensor muscles, increased intramuscular fat infiltration and thoracic and lumbar curvature alterations. This study proposed a protocol to examine in more detail the contributions of altered spinal morphological, physical performance and biochemical markers to the risk of developing osteoporotic vertebral fractures. In this cross-sectional study, we plan to recruit 100 adults aged 50 years and above from an orthopaedic clinic, Hospital Canselor Tuanku Muhriz, Universiti Kebangsaan Malaysia. The fracture prediction tool (FRAX) will be used to categorise high and low risk groups. Back muscle strength will be quantified using a load cell system. Thoracolumbar curvatures will be examined using an electromagnetic tracking system and intramuscular fat infiltration in the lumbar muscles will be measured using Magnetic Resonance Imaging. The Short Physical Performance Battery and JAMA dynamometer will quantify physical performance and the European Quality of Life Questionnaire will be used to assess self-perceived quality of life. Biochemical markers of serum C terminal telopeptide and N terminal propeptide of type I procollagen will be assessed using an enzyme-linked immunosorbent assays kit. A spine-specific model using regression analysis will be developed to predict osteoporotic vertebral fractures using the measured parameters in the present study.
Fulltext Giant epidermal cyst with intramuscular extension: a rare occurrence

Low SF, Sridharan R, Ngiu CS

BMJ Case Rep, 2015 Feb 06;2015.
PMID: 25661748 DOI: 10.1136/bcr-2013-202534

An epidermal cyst is the most common type of cyst to occur in subcutaneous tissue. When its size is greater than 5 cm, it is recognised as a giant epidermal cyst. A subcutaneous giant epidermal cyst with intramuscular extension is extremely rare. The authors report a case of a 74-year-old man who presented with a painless, slow-growing left gluteal mass of 6-month duration. Examination revealed a large left gluteal mass that was fixed to the underlying structures. A small epidermal cyst with visible punctum was noted at the medial aspect of the mass. MRI demonstrated a large, lobulated left gluteal lesion measuring 20 cm×16 cm×10 cm. The lesion was partly within the gluteal maximus muscle and partly within the subcutaneous tissue. MRI and ultrasound features of the lesion were consistent with a giant epidermal cyst with intramuscular extension. The lesion was excised and histology confirmed the diagnosis.
Juvenile spondyloarthropathy: an important clinical lesson to remember

Sridharan R, Ngiu CS, Shaharir SS, Said MS

BMJ Case Rep, 2015;2015.
PMID: 26677159 DOI: 10.1136/bcr-2015-213220

Spondyloarthropathy (SpA) is a group of inflammatory conditions that include spondylitis, sacroiliitis, asymmetrical peripheral arthritis and enthesitis. This condition is known as juvenile SpA when the diagnosis is made in patients up to 16 years of age. Enthesitis is a highly specific feature that occurs more often in juvenile SpA than in the adult form. In contrast to adult onset SpA, the initial manifestation of juvenile SpA rarely presents as inflammatory back pain. Peripheral arthritis is the more common presenting feature. We report a case of a 12-year-old boy who presented with a 1-year history of progressive low back pain, gluteal pain and thigh pain. There were no clinical symptoms of arthropathy of the distal extremities. MRI of the whole spine was performed twice, which, unfortunately, was unyielding. Finally, MRI of the sacroiliac joints revealed asymmetric sacroiliitis as well as enthesitis of the hips and pelvis. Further laboratory data showed negative rheumatoid factor and positive human leucocyte antigen (HLA) B27. A diagnosis of juvenile SpA with sacroiliitis and enthesitis was made. The imaging characteristics of juvenile SpA are highlighted.
Fulltext Osseous haemophilic pseudotumour and concurrent primary hyperparathyroidism: a diagnostic conundrum

Low SF, Sridharan R, Ngiu CS, Haflah NH

BMJ Case Rep, 2014;2014.
PMID: 24729114 DOI: 10.1136/bcr-2013-203282

Pseudotumours are rare, occurring in 1-2% of severe haemophiliacs. Osseous locations are far less frequent than soft tissue location. We report a case of a 43-year-old man with haemophilia A, who presented with a gradually enlarging left thigh mass for 8 months. There were no constitutional symptoms. Plain radiograph showed an expansile lytic lesion with 'soap-bubble' appearance arising from the left femur diaphysis. On MRI, it appeared as a non-enhancing, multilobulated lesion expanding the medullary and subperiosteal spaces. The mass exhibited concentric ring sign with heterogeneous intermediate signal intensity in the core lesion, reflective of chronic haematoma with blood degradation products of different stages. A diagnosis of haemophilic pseudotumour was made. Hypercalcaemia, however, raised a diagnostic dilemma as bone malignancy needed to be considered. An open excisional biopsy and subsequent amputation confirmed the diagnosis of osseous haemophilic pseudotumour. Nuclear medicine study later revealed a concurrent parathyroid adenoma.
Fulltext Midgut malrotation with congenital peritoneal band: a rare cause of small bowel obstruction in adulthood

Low SF, Ngiu CS, Sridharan R, Lee YL

BMJ Case Rep, 2014;2014.
PMID: 24717859 DOI: 10.1136/bcr-2013-202690

Midgut malrotation commonly presents in the neonatal period, and rarely manifests its symptoms in adulthood with an estimated incidence of 0.2-0.5%. Nevertheless, the symptoms are non-specific with no strong pointers towards the clinical diagnosis. Consequently, the diagnosis is usually disclosed with imaging or surgery. We report a case of small bowel obstruction secondary to a congenital peritoneal band with underlying midgut malrotation in a 48-year-old man.
Fulltext Spinal neurocytoma with extensive syringohydromyelia

Hanafiah M, Low SF, Sridharan R, Young B

BMJ Case Rep, 2013;2013.
PMID: 24132448 DOI: 10.1136/bcr-2013-201285
Fulltext NOMID: the radiographic and MRI features and review of literature

Zaki FM, Sridharan R, Pei TS, Ibrahim S, Ping TS

J Radiol Case Rep, 2012 Mar;6(3):1-8.
PMID: 22690285 DOI: 10.3941/jrcr.v6i3.745

Neonatal onset multisystem inflammatory disease (NOMID) is a rare autoinflammatory disorder, which manifests early in infancy. We describe a case of a 10-year-old boy who has been unwell since infancy. He presented with urticarial rash, intermittent fever and hepatosplenomegaly followed by progressive arthropathy. His joint symptoms started at two years of age, which progressively involved multiple joints, resulting in bone and joint deformities. A series of joint radiographs demonstrated bizarre enlarging physeal mass with heterogenous calcification. Magnetic resonance imaging (MRI) of the involved right ankle and knee showed characteristic thickened and calcified physeal lesions, which enhanced post-gadolinium. This debilitating disease is also known to involve the central nervous system and eyes. This case report aims to highlight the conventional radiographic and magnetic resonance imaging (MRI) findings of this physeal abnormality in NOMID syndrome.
Fulltext The clinical significance of interleukin-1 receptor antagonist +2018 polymorphism in rheumatoid arthritis

Ismail E, Nofal OK, Sakthiswary R, Shaharir SS, Sridharan R

PLoS One, 2016;11(4):e0153752.
PMID: 27105431 DOI: 10.1371/journal.pone.0153752

OBJECTIVE: Interleukin-1 receptor antagonist (IL-1Ra) acts as an inhibitor of IL-1; which is one of the culprit cytokines in rheumatoid arthritis (RA). Although +2018 polymorphism of IL-1Ra has been implicated in the pathogenesis of RA, its importance remains poorly understood. Hence, the purpose of this study was to determine the clinical significance of interleukin-1 receptor antagonist (IL-1Ra) +2018 polymorphism in RA.
METHODS: Polymerase chain reaction (PCR) and sequencing were used to determine the genotypes of the IL-1Ra +2018 for 77 RA patients and 18 healthy controls. All RA patients were assessed for the disease activity score that includes 28 joints (DAS28) and radiographic disease damage based on Modified Sharp Score (MSS).
RESULTS: The frequency of the T/T and C/T genotypes did not differ significantly (p = 0.893) between the RA patients and the controls. The C/T genotype had significantly higher mean disease activity (DAS 28) and disease damage (MSS) scores with p values of 0.017 and 0.004, respectively. Additionally, the ESR (erythrocyte sedimentation rate), CRP (C-reactive protein), the number of swollen and tender joints were higher for the C/T individuals. On multivariate analysis the CRP, swollen joint count and MSS remained significant with the following p values i.e. 0.045, 0.046 and less than 0.05.
CONCLUSIONS: C/T genotype of IL-1Ra +2018 prognosticates more aggressive disease in RA.
Study site: Outpatient clinic, Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM), Kuala Lumpur, Malaysia
Fulltext Focal uptake at the rotator interval or inferior capsule of shoulder on18F-FDG PET/CT is associated with adhesive capsulitis

Sridharan R, Engle MP, Garg N, Wei W, Amini B

Skeletal Radiol, 2017 Apr;46(4):533-538.
PMID: 28161721 DOI: 10.1007/s00256-017-2587-8

OBJECTIVE: To determine if focal increased uptake at the rotator interval (RI) and/or inferior capsule (IC) on18F-FDG PET/CT ("positive PET") predicts the presence of adhesive capsulitis (AC).
MATERIALS AND METHODS: Three populations were retrospectively examined. Group 1 included 1,137 consecutive18F-FDG PET/CT studies and was used to determine the prevalence of focal uptake at the RI or IC. Group 2 included 361 cases from a 10-year period with18F-FDG PET/CT and MRI of shoulder performed within 45 days of each other and was used to enrich the study group. Group 3 included 109 randomly selected patients from the same time frame as groups 1 and 2 and was used to generate the control group. The study group consisted of 15 cases from the three groups, which had positive PET findings. PET/CT images were assessed in consensus by two musculoskeletal radiologists. The reference standard for a diagnosis of AC was clinical and was made by review of the medical record by a pain medicine physician.
RESULTS: The prevalence of focal activity at either the RI or IC ("positive PET") was 0.53%. Nine patients had a clinical diagnosis of AC and 15 patients had a positive PET. The sensitivity and specificity of PET for detection of AC was 56% and 87%, respectively. PET/CT had a positive likelihood ratio for AC of 6.3 (95% CI: 2.8-14.6).
CONCLUSIONS: Increased uptake at the RI or IC on PET/CT confers a moderate increase in the likelihood of AC.
Fulltext Serum matrix metalloproteinase-3 predicts radiographic joint damage and functional disability in rheumatoid arthritis

Sakthiswary R, Omimah KJN, Endom I, Shaharir SS, Sridharan R

Medicine & Health, 2016;11(2):209-217.
MyJurnal

The search for novel biomarkers has taken centre stage in the past decades of research in Rheumatoid Arthritis (RA). The purpose of the present study was to determine the correlation of serum matrix metalloproteinase-3 (MMP-3) with disease activity, joint damage and functional disability in patients with RA. We consecutively recruited RA patients who were under follow-up at the Universiti Kebangsaan Malaysia Medical Centre (UKMMC). Information on the RA disease characteristics were obtained from the medical records and all RA patients were
assessed for DAS28 (disease activity score based on 28 joints) and Stanford Health Assessment Questionnaire (HAQ) 8-item Disability Index (HAQ-DI). The hand radiographs of the RA patients were assessed for joint damage using the Modified Sharp Score (MSS). Serum MMP-3 levels from RA patients and healthy controls were measured using the ELISA method. We recruited a total of 77 RA patients and 18 healthy controls. The serum MMP-3 levels were significantly higher among the RA patients (p<0.05). There were significant correlations between the serum MMP3 levels and MSS (r =0.327) and HAQ-DI (r=0.256), both p<0.05. The mean serum MMP levels in RA patients with radiographic joint erosions was significantly higher than in patients without erosions (p<0.05). Likewise, the subjects with significant functional impairment i.e HAQ-DI ≥1; had significantly higher mean MMP-3 levels compared to RA patients without significant disability (p<0.05). Using multivariate analysis, HAQ-DI remained the independent predictor of serum MMP-3 in RA patients. Serum MMP-3 is a potential biomarker and predictor of radiographic joint damage and functional disability in RA.
Keywords: acquired joint deformity, matrix metalloproteinases, rheumatoid arthritis
Cartilage oligomeric matrix protein (COMP) in rheumatoid arthritis and its correlation with sonographic knee cartilage thickness and disease activity

Sakthiswary R, Rajalingam S, Hussein H, Sridharan R, Asrul AW

Clin Rheumatol, 2017 Dec;36(12):2683-2688.
PMID: 28889184 DOI: 10.1007/s10067-017-3817-0

The aim of the study is to investigate the correlation of serum cartilage oligomeric matrix protein (COMP) levels with articular cartilage damage based on sonographic knee cartilage thickness (KCT) and disease activity in rheumatoid arthritis (RA). A total of 61 RA patients and 27 healthy controls were recruited in this study. Serum samples were obtained from all subjects to determine the serum COMP levels. All subjects had bilateral ultrasound scan of their knees. The KCT was based on the mean of measurements at three sites: the medial condyle, lateral condyle and intercondylar notch. Besides, the RA patients were assessed for their disease activity based on 28-joint-based Disease Activity Score (DAS 28). Serum COMP concentrations were significantly elevated in the RA patients compared to the controls (p = 0.001). The serum COMP levels had an inverse relationship with bilateral KCT in RA subjects and the healthy controls. COMP correlated significantly with disease activity based on DAS 28 (r = 0.299, p = 0.010), disease duration (r = 0.439, p = r = - 0.285, p = 0.014) in RA. The correlation between serum COMP and DAS 28 scores was comparable to the traditional markers of inflammation: erythrocyte sedimentation rate (ESR) (r = 0.372, p = 0.003) and C-reactive protein (CRP) (r = 0.305, p = 0.017). The serum COMP is a promising biomarker in RA which reflects disease activity and damage to the articular cartilage.
Study site: Putrajaya Hospital, Malaysia
Fulltext Intracavernous internal carotid artery pseudoaneurysm

Sridharan R, Low SF, Mohd MR, Kew TY

Singapore Med J, 2014 Oct;55(10):e165-8.
PMID: 25631906

Epistaxis is commonly encountered in otorhinolaryngologic practice. However, severe and recurrent epistaxis is rarely seen, especially that originating from a pseudoaneurysm of the intracavernous internal carotid artery (ICA). We herein present the case of a 32-year-old man who was involved in a motor vehicle accident and subsequently developed recurrent episodes of profuse epistaxis for the next three months, which required blood transfusion and nasal packing to control the bleeding. Computed tomography angiography revealed a large intracavernous ICA pseudoaneurysm measuring 1.7 cm × 1.2 cm × 1.0 cm. The patient underwent emergent four-vessel angiography and coil embolisation and was discharged one week later without any episode of bleeding. He remained asymptomatic after three-month and one‑year intervals. This case report highlights a large intracavernous ICA pseudoaneurysm as a rare cause of epistaxis, which requires a high index of suspicion in the right clinical setting and emergent endovascular treatment to prevent mortality.
Fulltext Non Secretory Multiple Myeloma With Extensive Extramedullary Plasmacytoma: A Diagnostic Dilemma

Low SF, Mohd Tap NH, Kew TY, Ngiu CS, Sridharan R

Iran J Radiol, 2015 Jul;12(3):e11760.
PMID: 26528383 DOI: 10.5812/iranjradiol.11760v2

Multiple myeloma (MM) is characterized by progressive proliferation of malignant plasma cells, usually initiating in the bone marrow. MM can affect any organ; a total of 7 - 18% of patients with MM demonstrate extramedullary involvement at diagnosis. Non-secretory multiple myeloma (NSMM) is a rare variant that accounts for 1 - 5% of all cases of multiple myeloma. The disease is characterized by the absence of monoclonal gammopathy in serum and urine electrophoresis. Our case report highlights the diagnostic challenge of a case of NSMM with extensive extramedullary involvement in a young female patient who initially presented with right shoulder pain and bilateral breasts lumps. Skeletal survey showed multiple lytic bony lesions. The initial diagnosis was primary breast carcinoma with osseous metastases. No monoclonal gammopathy was found in the serum or urine electrophoresis. Bone marrow and breast biopsies revealed marked plasmacytosis. The diagnosis was delayed for a month in view of the lack of clinical suspicion of multiple myeloma in a young patient and scant biochemical expression of non-secretory type of multiple myeloma.
Fulltext Comparison on the use of semi-automated and automated core biopsy needle in ultrasound guided breast biopsy

Sridharan R, Yunos SM, Aziz S, Hussain RI, Alhabshi SM, Suria Hayati MP, et al.

Med J Malaysia, 2015 Dec;70(6):326-33.
PMID: 26988204 MyJurnal

OBJECTIVE: The aim of this study was to compare the use of semi-automated (Medax Velox 2; Poggio Rusco, Italy) and automated (Bard Magnum Biopsy Instrument; Covington, GA, USA) core biopsy needles, for ultrasound guided breast biopsy.
MATERIALS AND METHODS: A 14G semi-automatic spring loaded core biopsy needle with a 22-mm-throw (Medax Velox 2; Poggio Rusco, Italy) and 14-gauge automated needle device with a 22-mm-throw biopsy gun (Bard-Magnum Biopsy Instrument, Covington, GA, USA) were used for breast biopsies under ultrasound guidance on alternate months during the study period between July 2009 and May 2011. One hundred and sixty lesions were biopsied and specimens were sent for histological evaluation.
RESULTS: The automated needle obtained a higher number of histology reports at 84% (67/80) as compared with the semiautomated needle at 60% (48/80) (Fisher exact test, p value=0.023). Inadequate samples with the automated needle were much less at 9% (7/60) than with the semiautomated needle at 23% (18/60) (Fisher exact test, p value=0.028). The semi-automated needle showed slightly less fragmented samples. However, the number of fragmented samples with definitive diagnosis was slightly higher with the automated compared with the semiautomated needle, at 16% (13/80) and 13% (10/80) respectively. Compared with histology of 29 lesions that were excised, the semi-automated needle had higher sensitivity (100%) but lower specificity (75%) and accuracy (90%) compared with the automated needle (88% sensitivity, 100% specificity, 95% accuracy).
CONCLUSION: Definitive diagnosis from the study samples slightly favours the use of automated core biopsy needle as compared to semi-automated core biopsy needle.
Study site: Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur
Fulltext Interpretation time for screening mammography as a function of the number of computer-aided detection marks

Schwartz TM, Hillis SL, Sridharan R, Lukyanchenko O, Geiser W, Whitman GJ, et al.

J Med Imaging (Bellingham), 2020 Mar;7(2):022408.
PMID: 32042859 DOI: 10.1117/1.JMI.7.2.022408

Purpose: Computer-aided detection (CAD) alerts radiologists to findings potentially associated with breast cancer but is notorious for creating false-positive marks. Although a previous paper found that radiologists took more time to interpret mammograms with more CAD marks, our impression was that this was not true in actual interpretation. We hypothesized that radiologists would selectively disregard these marks when present in larger numbers. Approach: We performed a retrospective review of bilateral digital screening mammograms. We use a mixed linear regression model to assess the relationship between number of CAD marks and ln (interpretation time) after adjustment for covariates. Both readers and mammograms were treated as random sampling units. Results: Ten radiologists, with median experience after residency of 12.5 years (range 6 to 24) interpreted 1832 mammograms. After accounting for number of images, Breast Imaging Reporting and Data System category, and breast density, the number of CAD marks was positively associated with longer interpretation time, with each additional CAD mark proportionally increasing median interpretation time by 4.35% for a typical reader. Conclusions: We found no support for our hypothesis that radiologists will selectively disregard CAD marks when they are present in larger numbers.
Sarcoid Myopathy Mimicking Polymyositis: A Case Report and Pool Analysis of the Literature Reviews

Sazliyana Shaharir S, Jamil A, Kosasih S, Soo Fin L, Sridharan R, Hayati Md Pauzi S

Acta Med Iran, 2017 Dec;55(12):800-806.
PMID: 29373888

A 59-year-old man presented with proximal myopathy, myalgia, and weight loss, with the initial markedly elevated serum creatine kinase at 11,000 U/L. Due to his refusal for muscle biopsy, he was initially treated as inflammatory myositis and responded well with the corticosteroids. However, he subsequently had a relapse of the symptoms with more extensive systemic involvement, i.e., hypercalcemia, lymphadenopathy and subcutaneous nodules. Finally, a biopsy of the thigh and subcutaneous nodule revealed non-caseating granulomatous inflammation, consistent with sarcoidosis. He responded well to the corticosteroids, and finally, azathioprine was added as a steroid-sparing agent. Including our series, there are 103 cases of symptomatic muscle involvement in sarcoidosis patients published in the English literature to date. Further pool analysis of the cases will be reported in this review.
Fulltext Ureteral stricture formation after ureteroscope treatment of impacted calculi: a prospective study

Fam XI, Singam P, Ho CC, Sridharan R, Hod R, Bahadzor B, et al.

Korean J Urol, 2015 Jan;56(1):63-7.
PMID: 25598938 DOI: 10.4111/kju.2015.56.1.63

Urinary calculi is a familiar disease. A well-known complication of endourological treatment for impacted ureteral stones is the formation of ureteral strictures, which has been reported to occur in 14.2% to 24% of cases.

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