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  1. Samsudin I, Vasikaran SD
    Clin Biochem Rev, 2017 Apr;38(2):59-68.
    PMID: 29332972
    Procalcitonin (PCT), regarded as a biomarker specific for bacterial infections, is used in a variety of clinical settings including primary care, emergency department and intensive care. PCT measurement aids in the diagnosis of sepsis and to guide and monitor antibiotic therapy. This article gives a brief overview of PCT and its use in guiding antibiotic therapy in various clinical settings, as well as its limitations. PCT performance in comparison with other biomarkers of infection in particular CRP is also reviewed. Owing to its greater availability, CRP has been widely used as a biomarker of infection and sepsis. PCT is often reported to be more superior to CRP, being more specific for sepsis and bacterial infection. PCT starts to rise earlier and returns to normal concentration more rapidly than CRP, allowing for an earlier diagnosis and better monitoring of disease progression.
  2. Kathiravelu Z, Thambiah SC, Mat Salleh MJ, Samsudin IN
    Malays J Pathol, 2021 Apr;43(1):101-107.
    PMID: 33903313
    INTRODUCTION: Haemolytic specimens are a frequent occurrence in clinical laboratories, and they interfere with the analysis of many tests.

    CASE REPORT: We describe here an unusual case of leptospirosis complicated by haemolytic anaemia in a 70-year-old man with established kidney failure. He presented with an abrupt onset of shortness of breath, flushing and erythematous rash after completing haemodialysis. The patient's biochemistry test samples were however rejected twice as they were grossly haemolysed. The integrated auto-verification alert system implemented in the hospital's laboratory information system alerted the staff of the possibility of in vivo haemolysis.

    DISCUSSION: The auto-verification alert system effectively distinguishes between in vitro and in vivo haemolysis and as such can be utilised as a diagnostic aid in patients with suspected intravascular haemolysis.

  3. Abdul Rahim FH, Thambiah CS, Samsudin IN, Mohamed Mokhtar N
    Malays J Pathol, 2020 Aug;42(2):297-300.
    PMID: 32860386
    INTRODUCTION: Cystic fibrosis (CF) is a life-limiting autosomal recessive disorder as a result of CF transmembrane conductance regulator gene mutation. It has a wide range of disease severity in patients with the same genotype.

    CASE REPORT: A 5-year-old Malay boy with a history of recurrent pneumonia, presented with productive cough, fever and worsening tachypnoea. Physical examination revealed coarse crepitations, reduced breath sounds and clubbing. Biochemical investigations showed that he had respiratory type 2 failure as a result of bronchiectasis. Sweat conductivity done twice was raised supporting a diagnosis of CF. Other investigations such as bronchoscopy to look for congenital anomaly of the lung, infectious disease screening and tuberculosis, fungal and viral culture and sensitivity were negative. Further cascade screening revealed high sweat conductivity results in his siblings.

    DISCUSSION: Although CF prevalence is low in Malaysia, it is nevertheless an important diagnosis to be recognised as it is associated with increased morbidity.

  4. Zahari Sham SY, C Thambiah S, Samsudin IN, Lim SM
    Malays J Pathol, 2017 Dec;39(3):311-315.
    PMID: 29279596 MyJurnal
    Multiple myeloma is a type of plasma cell dyscrasia, characterised by presence of paraprotein or monoclonal (M)-protein in serum or urine. The M-protein may consist of an intact immunoglobulin, the heavy chain only or the light chain only. The latter, designated as light chain multiple myeloma (LCMM) makes up almost 20% of myelomas. Clinical manifestation is often heralded by hypercalcaemia, renal impairment, normocytic normochromic anaemia and bone lesions, reflecting end-organ damage, collectively known as the acronym CRAB. In particular, free light chain nephrotoxicity accounts for the high prevalence of renal impairment seen in LCMM. This case illustrates a typical presentation of LCMM with focal discussion on its initial and diagnostic, as well as prognostic biochemical investigations.
  5. Lai YY, Thambiah SC, Mohamed Mokhtar N, Samsudin IN
    Malays J Pathol, 2024 Apr;46(1):109-113.
    PMID: 38682851
    INTRODUCTION: Persistently elevated thyroid stimulating hormone (TSH) despite levothyroxine (LT4) treatment that exceeds the standard weight-adjusted dose is a common clinical presentation. This may lead to additional testing for LT4 malabsorption or poor LT4 adherence, the latter of which is challenging to confirm because it is predicated on accurate patient accountability.

    CASE REPORT: A 35-year-old lady, post-radioactive iodine therapy for Graves' disease remained euthyroid for a year on oral LT4. Two years later, she was clinically and biochemically hypothyroid despite claiming LT4 compliance. As all laboratory investigations were within the reference range, pseudomalabsorption was suspected and a LT4 absorption test was done. During the test, her free thyroxine increased significantly at 4 hours, reaching a peak of more than 50% from baseline while TSH decreased appropriately from 0 minute to 360 minutes. This was followed by normalisation of TSH with LT4 treatment under direct observation.

    DISCUSSION: The LT4 absorption test is a prompt and economical means to rule out true malabsorption, decrease unwarranted subspecialty referrals and validate the weight-adjusted LT4 dose reduction.

  6. Zahari Sham SY, Hanif E, Thambiah SC, Samsudin IN, Mohd Noor S, Osman M, et al.
    Malays J Pathol, 2021 04;43(1):33-40.
    PMID: 33903303
    INTRODUCTION: Cardiovascular disease (CVD) remains the leading cause of death in Malaysia. Identification of asymptomatic at-risk individuals is often achieved by means of a risk prediction algorithm. Traditional CVD risk factors and their associated algorithms are, however, limited by residual CVD risk. High sensitivity C-reactive protein (hsCRP) has emerged as a novel CVD risk factor. This study aimed to evaluate hsCRP as an adjunct CVD risk marker among the adult Malaysian population by determining its correlation with the Framingham Risk Score (FRS). Comparison analyses were done according to sociodemographic, clinical and laboratory factors and between subjects with and without Metabolic Syndrome (MetS).

    METHOD: This cross-sectional study involved eighty-three (n=83) adults attending a health screening program at Universiti Putra Malaysia (UPM). Demographic data, anthropometric measurements and blood samples for fasting blood glucose (FBG), fasting lipid profile (FSL), glycated haemoglobin (HbA1c) and hsCRP were taken. Respondents were grouped according to FRS and the Joint Interim Statement into 10-year CVD risk categories (low, intermediate and high) and MetS, respectively.

    RESULTS: hsCRP was significantly increased in patients with high body mass index (BMI) (p=0.001), at-risk waist circumference (WC) (p=0.001) and MetS (p=0.009). Spearman's correlation coefficient showed a significant positive correlation between hsCRP level and total FRS score (r=0.26, p<0.05) and HDL-C score (r=0.22, p<0.05).

    CONCLUSION: The significant difference of hsCRP levels across obesity levels and MetS with its modest correlation with FRS scores supported the adjunctive role of hsCRP in CVD risk prediction, most likely capturing the inflammatory pathological aspect and thus partly accounting for the residual CVD risk.

  7. Thambiah CS, Mohamed Pesri NA, Mazalan N, Samsudin IN, Mohamad Ismuddin S, Appannah G, et al.
    Malays J Pathol, 2020 Aug;42(2):215-225.
    PMID: 32860374
    INTRODUCTION: Dyslipidaemia is a recognised conventional risk factor for cardiovascular disease (CVD). However, even when traditional lipid parameters are normal, CVD risk can exist. Small dense lowdensity lipoprotein cholesterol (sdLDL) has appeared as a significant risk marker for CVD. This study aimed to determine the prevalence and associated factors of atherogenic lipoprotein Pattern B in the Malaysian population.

    MATERIALS AND METHODS: This cross-sectional study included 150 subjects aged 30 years and above who attended a health screening in a Malaysian tertiary institution. Sociodemographics, clinical characteristics and laboratory parameters (lipids, glucose, and sdLDL) were obtained. Lipoprotein subfraction was analysed using the polyacrylamide gel electrophoresis method.

    RESULTS: Malays and females made up the majority of subjects and the median age was 37 years. Normolipidaemic Pattern B was significantly higher in women (p=0.008). Significant independent predictors of Pattern B were gender (p=0.02), race (p=0.01), body mass index (BMI) [p=0.02] and lipid status (p=0.01). Triglyceride was the only independent predictor of sdLDL (p=0.001).

    CONCLUSION: The prevalence of Pattern B of 33% in this study was comparatively high, of which 6.7% were normolipidaemic. Chinese males with dyslipidaemia and increased BMI independently predicted Pattern B. Differences in triglyceride levels alone among these ethnic groups do not fully explain the differences in the prevalence of Pattern B although it was the only lipid parameter to independently predict sdLDL. Individuals with atherogenic normolipidaemia are at greater risk for a CVD event as they are not included in the protective measures of primary CVD prevention.

  8. Choo JE, Samsudin IN, Mat Salleh MJ, Zahari Sham SY, Thambiah SC
    Malays J Pathol, 2020 Dec;42(3):433-437.
    PMID: 33361725
    INTRODUCTION: Salivary cortisol is used as an indicator of stress level and a recommended screening test for Cushing syndrome. The normal reference interval for salivary cortisol is dependent on the analytical methodology and the population studied and hence, establishment of a local population-based reference interval is recommended.

    MATERIALS AND METHODS: A total of 129 healthy blood donors and staffs of Penang General Hospital were recruited from June 2018-May 2019. Paired (morning and late-night) saliva samples were collected from individuals aged between 18 and 60 years old with no history of chronic medical illness. Salivary cortisol was assayed using electrochemiluminescence immunoassay technique. Non-parametric statistics were used for calculation of reference interval and 90% confidence intervals (90% CIs).

    RESULTS: The reference interval for morning and latenight salivary cortisol was 2.09 - 22.63 nmol/L and <12.00 nmol/L, respectively.

    CONCLUSION: The locally-derived adult reference intervals for morning and late-night salivary cortisol concentration was determined and varied with previous studies emphasising the need in establishing individual laboratory reference interval.

  9. Samsudin I, Page MM, Hoad K, Chubb P, Gillett M, Glendenning P, et al.
    Ann. Clin. Biochem., 2018 Nov;55(6):679-684.
    PMID: 29660998 DOI: 10.1177/0004563218774590
    Background Plasma-free metanephrines (PFM) or urinary fractionated metanephrines (UFM) are the preferred biochemical tests for the diagnosis of phaeochromocytoma and paraganglioma (PPGL). Borderline increased results should be followed up to either exclude or confirm diagnosis. Methods We extracted all PFM and UFM results reported by our laboratory over a six-month period from the laboratory information system. We categorized patients with borderline increased results according to whether follow-up testing had been performed as suggested in the initial laboratory report. Questionnaires were then sent to all requesting doctors and medical notes reviewed where available. Results Two hundred and four patients with borderline increased PFM or UFM were identified. Sixty-five (38.5%) of 169 patients with borderline increased PFM had a repeat test out of which 36 were normal and 29 did not normalize. Of 35 patients with borderline increased UFM, 17 (48.6%) had subsequent PFM measurement, out of which 15 were normal. Questionnaires were returned to 106 (52%) patients. Of these, the most frequent indication for testing was hypertension ( n = 50); 15 patients had an incidental adrenal mass and two of these patients were diagnosed with a phaeochromocytoma. Conclusion Only 38% of patients with borderline increased PFM had a repeat PFM measurement. This was not significantly higher when compared with the 28% in a previous audit that we reported in 2010 ( P = 0.10). Forty-nine per cent of patients with a borderline increased UFM had a repeat UFM or PFM measurement. There remains a substantial possibility of missed detection of PPGL.
  10. Tengku Ibrahim TZ, Thambiah SC, Samsudin IN, Nasuruddin AN, Zakaria MH
    Malays J Pathol, 2019 Dec;41(3):355-358.
    PMID: 31901922
    INTRODUCTION: Thyroid storm (TS) is an endocrine emergency. Early diagnosis for prompt treatment is essential as it has a high mortality rate.

    CASE REPORT: A 31-year-old lady with underlying hyperthyroidism, dilated cardiomyopathy with severe mitral regurgitation presented with shortness of breath. She was intubated and admitted due to decreasing Glasgow Coma Score. Her blood investigations revealed increased white cell count, raised free thyroxine with suppressed thyroid stimulating hormone, deranged liver, renal and coagulation profiles. As her condition did not improve with initial treatment, plasmapheresis was commenced on day 4. Biochemically, her thyroid function test (TFT) showed improvement; however, she succumbed due to multi-organ failure.

    DISCUSSION: Plasmapheresis is considered in TS if there is no clinical improvement within 24-48 hours of initial treatment. The improvement in patient's TFT post plasmapheresis signifies its role in treating TS. Unfortunately, there was a delay in commencing plasmapheresis due to haemodynamic instability in this patient.

  11. Ramachandran M, Loi B, Mat Ariff N, Ng OC, Zahari Sham SY, Thambiah SC, et al.
    Malays J Pathol, 2020 Apr;42(1):71-76.
    PMID: 32342933
    INTRODUCTION: Metformin is the first-line pharmacological therapy for type 2 diabetes mellitus (T2DM). Guidelines recommend metformin to be given at reduced dosages for those with an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m2 and omitted in those with eGFR<30 mL/min/1.73m2. Lactic acidosis is a known complication of those on metformin. This study aimed to determine the appropriateness of metformin prescription in T2DM patients with chronic kidney disease (CKD) stages 3-5 in a tertiary centre in Malaysia.

    MATERIALS AND METHODS: A cross-sectional design using retrospective secondary data of T2DM patients on metformin attending nephrology and diabetic clinics in the year 2017. eGFR calculated using the CKD-EPI formula identified those in CKD stage 3-5 defined using the National Kidney Foundation-Kidney Disease Outcomes Quality Initiative criteria. Metformin prescription was considered appropriate when the metformin maximum daily dosage does not exceed 1500 mg in CKD stage 3a and 1000 mg in CKD stage 3b and metformin stopped in CKD stages 4 and 5.

    RESULTS: A total of 143 patients were included. Majority were in the elderly age group (62.9%), male (60.8%) and had concurrent hypertension (85.3%). Median HbA1c was 8.3% (67 mmol/mol) with most patients (88.8%) having HbA1c above 6.5% (48 mmol/ mol). Majority (92.3%) were categorised as stage 3 CKD. Eleven (7.7%) subjects had inappropriate metformin prescription. Seven of nine (78%) subjects in CKD stage 4 were on metformin with a maximum daily dose of 500 mg to1000 mg. Three patients had serum lactate measured.

    CONCLUSION: The majority of CKD patients had appropriate metformin prescription. However, a considerable number of CKD stage 4 patients continued to be on metformin. The many benefits of metformin may be a reason why it is still continued against recommendations. Only three patients had lactate measured which, although may suggest that lactic acidosis is not a common occurrence, the potential for metformin-associated lactic acidosis especially in those at risk should be considered.

  12. Aizamddin MF, Mahat MM, Zainal Ariffin Z, Samsudin I, Razali MSM, Amir M'
    Polymers (Basel), 2021 Nov 05;13(21).
    PMID: 34771378 DOI: 10.3390/polym13213822
    Silver (Ag) particles have sparked considerable interest in industry and academia, particularly for health and medical applications. Here, we present the "green" and simple synthesis of an Ag particle-based silicone (Si) thin film for medical device applications. Drop-casting and peel-off techniques were used to create an Si thin film containing 10-50% (v/v) of Ag particles. Electro impedance spectroscopy (EIS), X-ray diffraction analysis (XRD), scanning electron microscopy (SEM), energy dispersive X-ray (EDX), and tensile tests were used to demonstrate the electrical conductivity, crystallinity, morphology-elemental, and mechanical properties, respectively. The oriented crystalline structure and excellent electronic migration explained the highest conductivity value (1.40 × 10-5 S cm-1) of the 50% Ag-Si thin film. The findings regarding the evolution of the conductive network were supported by the diameter and distribution of Ag particles in the Si film. However, the larger size of the Ag particles in the Si film resulted in a lower tensile stress of 68.23% and an elongation rate of 68.25% compared to the pristine Si film. The antibacterial activity of the Ag-Si film against methicillin-resistant Staphylococcus aureus (MRSA), Bacillus cereus (B. cereus), Klebsiella pneumoniae (K. pneumoniae), and Pseudomonas aeruginosa (P. aeruginosa) was investigated. These findings support Si-Ag thin films' ability to avoid infection in any medical device application.
  13. Lim SM, Thambiah SC, Zahari Sham SY, Omar R, Hambali Z, Samsudin IN
    Malays J Pathol, 2017 Aug;39(2):135-140.
    PMID: 28866694
    Introduction of high-sensitivity cardiac troponin I (hscTn I) assays for routine clinical use in Malaysia requires determination of the 99(th) percentile upper reference limit (URL) for each assay to suit local context. Hence, this study aimed to determine the 99(th) percentile URL for hscTn I in the Malaysian population. A total of 250 (120 males and 130 females) healthy Malaysian blood donors aged 18 to 60 years old were recruited. Blood samples for hscTn I were measured using Abbott Diagnostics hscTn I assay on Architect i2000sr analyser. The 99(th) percentile was calculated using a non-parametric method and gender specific results were compared. The 99(th) percentile URL for hscTn I for the overall population was 23.7 ng/L, with gender specific values being 29.9 ng/L and 18.6 ng/L for male and female, respectively. Females had significantly lower hscTn I compared to males. This study confirms the use of gender specific 99(th) percentile URL for hscTn I for clinical use in a multi-ethnic Malaysian population.
  14. Thambiah SC, Samsudin IN, George E, Zahari Sham SY, Lee HM, Muhamad MA, et al.
    Malays J Pathol, 2016 Aug;38(2):123-30.
    PMID: 27568669 MyJurnal
    The risk of coronary heart disease (CHD) is dramatically increased in diabetic patients due to their atherogenic lipid profile. The severity of CHD in diabetic patients has been found to be directly associated with glycated haemoglobin (HbA1c). According to the Malaysian Clinical Practice Guidelines on diabetes mellitus (DM), HbA1c level less than 6.5% reduces the risk of microvascular and macrovascular complications. Hence, this study aimed to determine the relationship between dyslipidaemia and glycaemic status in patients with type 2 DM (T2DM) patients in Hospital Putrajaya, a tertiary endocrine centre in Malaysia. This was a cross sectional, retrospective study of 214 T2DM patients with dyslipidaemia who had visited the endocrine clinic between January 2009 and December 2012. Significant correlations were found between fasting blood glucose (FBG) and HbA1c with total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL), non-high density lipoprotein cholesterol (non-HDL), LDL/HDL ratio and TC/HDL ratio; greater correlation being with HbA1c than FBG. In patients with HbA1c ≥ 6.5%, TC, TG, non-HDL and TC/HDL ratio were significantly higher than in patients with HbA1c < 6.5%. Non-HDL, LDL/HDL ratio, TC/HDL ratio and HbA1c were significantly lower in patients on statin treatment than nontreated patients (p<0.05). This significant association between glycaemic status and dyslipidaemia emphasises the additional possible use of HbA1c as a biomarker for dyslipidaemia as well as a potential indirect predictor of cardiovascular disease (CVD) risk in T2DM patients.
  15. Mohamad Ismuddin S, Thambiah SC, Appannah G, Samsudin IN, Md Said S, Yeap SS, et al.
    Malays J Pathol, 2022 Dec;44(3):477-490.
    PMID: 36591715
    INTRODUCTION: Cardiovascular disease and osteoporosis (OP) have been shown to have similar risk factors but studies have demonstrated contradictory results with regards to their associations. This study evaluated relationships between bone characteristics and cardiovascular risk factors among adults in selected urban areas in Malaysia.

    MATERIALS AND METHODS: A cross-sectional study was performed involving 331 subjects between 45-90 years recruited at a health screening programme. Sociodemographic and clinical characteristics were recorded. Biochemical analyses on fasting blood samples and dual energy X-ray absorptiometry scan to determine bone mineral density (BMD) were performed.

    RESULTS: Increased waist circumference (WC) was protective for abnormal BMD status (osteopenia and OP). Males with increased high-density lipoprotein cholesterol (HDL) were more likely to be osteoporotic. WC, fasting blood glucose (FBG) and triglyceride (TG) were positively associated with BMD at all sites but was gender specific. In contrast, WC was negatively associated with trabecular bone score (TBS) for females but this association became attenuated when adjusted for fat percentage. HDL and MetS were negatively and positively associated with BMD, respectively in males.

    CONCLUSION: The cardiovascular risk factors of raised WC, FBG, TG and low HDL were significantly associated with increased BMD with skeletal site and gender specific differences after adjusting for confounders. However, a higher WC was associated with a weaker skeletal microstructure reflected by lower TBS in females driven by fat percentage. A higher BMD was demonstrated among MetS individuals. These findings suggest that adiposity may have a protective effect on BMD.

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