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  1. Yu Chuah T, Loh TP, Loi HY, Lee KH
    West J Emerg Med, 2011 Nov;12(4):371.
    PMID: 22224121 DOI: 10.5811/westjem.2011.1.2193
  2. Tan RZ, C Thambiah S, Loh TP, Vasikaran S, Yeap SS
    Malays J Pathol, 2023 Dec;45(3):391-396.
    PMID: 38155380
    BACKGROUND: Well defined reference intervals are central to the utility of serum C-terminal telopeptide of type 1 collagen (CTX) and N-terminal propeptide of type I procollagen (P1NP), designated as reference markers in osteoporosis, and useful for monitoring therapeutic response in that condition. This study reports the reference intervals for plasma CTX and serum P1NP in a multi-ethnic Malaysian population.

    METHODS: Ethnic Malay, Chinese or Indian subjects aged 45-90 years old were recruited from Selangor, Malaysia from June 2016 to August 2018. Subjects with known medical conditions (e.g., bone disorders, malnutrition, immobilisation, renal impairment, hormonal disorders) and medications (including regular calcium or vitamin D supplements) that may affect CTX and P1NP were excluded. Additionally, subjects with osteoporosis or fracture on imaging studies were excluded. The blood samples were collected between 8 a.m. and 9 a.m. in fasting state. The CTX and P1NP were measured on Roche e411 platform in batches.

    RESULTS: The 2.5th-97.5th percentiles reference intervals (and bootstrapped 90%CI) for plasma CTX in men (n = 91) were 132 (94-175) - 775 (667-990) ng/L; in post-menopausal women (n = 132) 152 (134-177) - 1025 (834-1293) ng/L. The serum P1NP reference intervals in men were 23.7 (19.1-26.4) - 83.9 (74.0-105.0) µg/L, and in post-menopausal women, 25.9 (19.5-29.3) - 142.1 (104.7-229.7) µg/L.

    CONCLUSION: The reference intervals for plasma CTX and serum PINP for older Malaysian men and post-menopausal women are somewhat different to other published studies from the region, emphasising the importance of establishing specific reference intervals for each population.

  3. Chong YP, Lim SM, Loh TP, Mollee P, Wijeratne N, Choy KW
    J Clin Pathol, 2023 Nov;76(11):727-733.
    PMID: 37604683 DOI: 10.1136/jcp-2023-208774
    Monoclonal gammopathy is a spectrum of disorders characterised by clonal proliferation of plasma cells or lymphocytes, which produce abnormal immunoglobulin or its components (monoclonal proteins). Monoclonal gammopathies are often categorised as low-tumour-burden diseases (eg, amyloid light chain (AL) amyloidosis), premalignant disorders (such as monoclonal gammopathy of undetermined significance and smouldering multiple myeloma), and malignancies (eg, multiple myeloma and Waldenström's macroglobulinaemia). Such diversity of concentration and structure makes monoclonal protein a challenging clonal marker. This article provides an overview on initial laboratory testing of monoclonal gammopathy to guide clinicians and laboratory professionals in the selection and interpretation of appropriate investigations.
  4. Vasikaran S, Thambiah SC, Tan RZ, Loh TP, APFCB Harmonization of Reference Interval Working Group
    Ann Lab Med, 2024 Mar 01;44(2):126-134.
    PMID: 37869778 DOI: 10.3343/alm.2023.0214
    Bone-turnover marker (BTM) measurements in the blood or urine reflect the bone-remodeling rate and may be useful for studying and clinically managing metabolic bone diseases. Substantial evidence supporting the diagnostic use of BTMs has accumulated in recent years, together with the publication of several guidelines. Most clinical trials and observational and reference-interval studies have been performed in the Northern Hemisphere and have mainly involved Caucasian populations. This review focuses on the available data for populations from the Asia-Pacific region and offers guidance for using BTMs as diagnostic biomarkers in these populations. The procollagen I N-terminal propeptide and β-isomerized C-terminal telopeptide of type-I collagen (measured in plasma) are reference BTMs used for investigating osteoporosis in clinical settings. Premenopausal reference intervals (established for use with Asia-Pacific populations) and reference change values and treatment targets (used to monitor osteoporosis treatment) help guide the management of osteoporosis. Measuring BTMs that are not affected by renal failure, such as the bone-specific isoenzyme alkaline phosphatase and tartrate-resistant acid phosphatase 5b, may be advantageous for patients with advanced chronic kidney disease. Further studies of the use of BTMs in individuals with metabolic bone disease, coupled with the harmonization of commercial assays to provide equivalent results, will further enhance their clinical applications.
  5. Lim SM, Wijeratne N, Choy KW, Nguyen TTH, Setiawan L, Loh TP
    Crit Rev Clin Lab Sci, 2024 Mar;61(2):107-126.
    PMID: 37776896 DOI: 10.1080/10408363.2023.2257306
    Monoclonal gammopathy (MG) is a spectrum of diseases ranging from the benign asymptomatic monoclonal gammopathy of undetermined significance to the malignant multiple myeloma. Clinical guidelines and laboratory recommendations have been developed to inform best practices in the diagnosis, monitoring, and management of MG. In this review, the pathophysiology, relevant laboratory testing recommended in clinical practice guidelines and laboratory recommendations related to MG testing and reporting are examined. The clinical guidelines recommend serum protein electrophoresis, serum immunofixation and serum free light chain measurement as initial screening. The laboratory recommendations omit serum immunofixation as it offers limited additional diagnostic value. The laboratory recommendations offer guidance on reporting findings beyond monoclonal protein, which was not required by the clinical guidelines. The clinical guidelines suggested monitoring total IgA concentration by turbidimetry or nephelometry method if the monoclonal protein migrates in the non-gamma region, whereas the laboratory recommendations make allowance for involved IgM and IgG. Additionally, several external quality assurance programs for MG protein electrophoresis and free light chain testing are also appraised. The external quality assurance programs show varied assessment criteria for protein electrophoresis reporting and unit of measurement. There is also significant disparity in reported monoclonal protein concentrations with wide inter-method analytical variation noted for both monoclonal protein quantification and serum free light chain measurement, however this variation appears smaller when the same method was used. Greater harmonization among laboratory recommendations and reporting format may improve clinical interpretation of MG testing.
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