Displaying publications 1 - 20 of 140 in total

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  1. Thye CK, Lee YW, Jalalonmuhali M, Lim SK, Ng KP
    BMC Nephrol, 2023 Sep 11;24(1):267.
    PMID: 37691129 DOI: 10.1186/s12882-023-03057-w
    BACKGROUND: Assessment of donor renal function is made by the measurement of Glomerular Filtration Rate (GFR). Exogenous markers are preferred over creatinine clearance and are widely used for measuring GFR. However, they are difficult to obtain, costly and laborious. This is a study to look into the safety and accuracy of creatinine clearance for renal assessment among the living kidney donors in the Malaysian population.

    METHODS: This is a retrospective, single-centre study comprising 105 living kidney donor candidates from the year 2007 to 2020. By comparing against 51-Chromium ethylenediamine-tetraacetic acid (51Cr-EDTA), we analysed creatinine clearance for correlation, bias, precision and accuracy.

    RESULTS: The study group had a mean age of 45.68 ± 10.97 years with a mean serum creatinine of 64.43 ± 17.68 µmol/L and a urine volume of 2.06 ± 0.83 L. Mean measured GFR from 51Cr-EDTA was 124.37 ± 26.83 ml/min/1.73m2 whereas mean creatinine clearance was 132.35 ± 38.18 ml/min/1.73m2. Creatinine clearance overestimated 51Cr-EDTA significantly with a correlation coefficient of 0.48 (p 

  2. Kuan CS, Ng KP, Yew SM, Umar Meleh H, Seow HF, How KN, et al.
    Braz J Microbiol, 2023 Sep;54(3):1351-1372.
    PMID: 37351789 DOI: 10.1007/s42770-023-01032-z
    Neoscytalidium dimidiatum and Bipolaris species are fungal plant pathogens that have been reported to cause human diseases. Recently, we have isolated numerous N. dimidiatum and Bipolaris species from the skin scrapings and nails of different patients. In this work, we have sequenced the genome of one strain of N. dimidiatum. The sequenced genome was compared to that of a previously reported Bipolaris papendorfii genome for a better understanding of their complex lifestyle and broad host-range pathogenicity. Both N. dimidiatum UM 880 (~ 43 Mb) and B. papendorfii UM 226 (~ 33 Mb) genomes include 11,015-12,320 putative coding DNA sequences, of which 0.51-2.49% are predicted transposable elements. Analysis of secondary metabolism gene clusters revealed several genes involved in melanin biosynthesis and iron uptake. The arsenal of CAZymes related to plants pathogenicity is comparable between the species, including genes involved in hemicellulose and pectin decomposition. Several important gene encoding keratinolytic peptidases were identified in N. dimidiatum and B. papendorfii, reflecting their potential pathogenic role in causing skin and nail infections. In this study, additional information on the metabolic features of these two species, such as nutritional profiling, pH tolerance, and osmotolerant, are revealed. The genomic characterization of N. dimidiatum and B. papendorfii provides the basis for the future functional studies to gain further insights as to what makes these fungi persist in plants and why they are pathogenic to humans.
  3. Connelly K, Kandane-Rathnayake R, Hoi A, Louthrenoo W, Hamijoyo L, Cho J, et al.
    Lancet Rheumatol, 2022 Dec;4(12):e831-e841.
    PMID: 38261391 DOI: 10.1016/S2665-9913(22)00307-1
    BACKGROUND: The selection and categorisation of laboratory tests in disease activity measures used within systemic lupus erythematosus (SLE) trial endpoints lack strong evidence. We aimed to determine whether longitudinal improvements in routinely measured laboratory tests are associated with measures of clinical improvement in patients with baseline active SLE.

    METHODS: We included patients from a multicentre longitudinal cohort (recruited between May 1, 2013, and Dec 31, 2019) with active SLE (SLEDAI-2K ≥6) coinciding with an abnormality in at least one of 13 routine laboratory tests, at a visit designated as baseline. At 12 months, we analysed associations between thresholds of improvement in individual laboratory test results, measured as continuous variables, and five clinical outcomes using logistic regression. Primary outcomes were damage accrual and lupus low disease activity state (LLDAS), and secondary outcomes were modified SLE responder index (mSRI), physician global assessment (PGA) improvement of at least 0·3, and flare.

    FINDINGS: We included 1525 patients (1415 [93%] women and 110 [7%] men, 1328 [87%] Asian ethnicity) in separate subsets for each laboratory test. The strongest associations with LLDAS and damage protection were seen with improvements in proteinuria (complete response: adjusted odds ratio [OR] 62·48, 95% CI 18·79-208·31 for LLDAS, OR 0·22, 95% CI 0·10-0·49 for damage accrual), albumin (complete response: adjusted OR 6·46, 95% CI 2·20-18·98 for LLDAS, OR 0·42, 95% CI 0·20-1·22 for damage accrual), haemoglobin (complete response: adjusted OR 1·97, 95% CI 1·09-3·53 for LLDAS, OR 0·33, 95% CI 0·15-0·71 for damage accrual), erythrocyte sedimentation rate (complete response: adjusted OR 1·71, 95% CI 1·10-2·67 for LLDAS, OR 0·53, 95% CI 0·30-0·94 for damage accrual), and platelets (complete response: adjusted OR 4·82, 95% CI 1·54-15·07 for LLDAS, OR 0·49, 95% CI 0·20-1·19 for damage accrual). Improvement in serological tests were mainly associated with PGA and mSRI. White cell and lymphocyte count improvements were least predictive.

    INTERPRETATION: Improvements in several routine laboratory tests correspond with clinical outcomes in SLE over 12 months. Tests with the strongest associations were discrepant with laboratory tests included in current trial endpoints, and associations were observed across a range of improvement thresholds including incomplete resolution. These findings suggest the need to revise the use of laboratory test results in SLE trial endpoints.

    FUNDING: Abbvie.

  4. Jalalonmuhali M, Ng KP, Lee YW, Gan CC, Hing Wong A, Wan Md Adnan WAH, et al.
    Transplant Proc, 2022 Feb 15.
    PMID: 35181166 DOI: 10.1016/j.transproceed.2022.01.004
    BACKGROUND: Immunosuppressive therapy is the backbone of kidney transplantation in preventing acute rejection. T-cell depletion after doses of thymoglobulin is dose-dependent, as are their side effects. At the same time, basiliximab and other maintenance immunosuppressive drugs act at different signals on T lymphocytes. Therefore, studying the pattern of lymphocyte subset depletion depending on the induction regime given at transplantation could be an added tool in managing post-transplant recipients.

    METHODOLOGY: This prospective observational study recruited kidney transplant recipients from August 2019 through April 2021 at the University of Malaya Medical Centre. Blood tests for lymphocyte subsets were taken at pre-transplant, 1 week, 1 month, 3 months, and 6 months post-transplantation. At transplantation, recipients received either basiliximab, low-dose thymoglobulin (cumulative dose: 1.5 mg/kg), or standard-dose thymoglobulin (cumulative dose: 5 mg/kg).

    RESULTS: A total of 39 patients were recruited: 38.5% received basiliximab (15 of 39), 15.4% received low-dose thymoglobulin (6 of 39), and 46.2% received standard-dose thymoglobulin (18 of 39). Absolute lymphocyte counts 1 week post-transplantation were 1.5 ± 0.84 × 109/L for basiliximab, 0.7 ± 0.57 × 109/L for low-dose thymoglobulin, and 0.1 ± 0.08 × 109/L for standard-dose thymoglobulin (P < .001). The CD4+ and CD8+ counts were severely depleted in the standard-dose thymoglobulin group, with a statistically significant differenceup to 6 months post-transplantation. In the low-dose thymoglobulin group, the CD4+ and CD8+ counts were depleted at 1 week post-transplantation and recovered at 1 month post-transplantation. There was no difference in allograft function and incidence of allograft rejection across groups.

    CONCLUSIONS: The effects on lymphocyte counts, CD4+ and CD8+, vary depending on the type and dose of induction immunosuppression. This could be a guiding tool in managing immunosuppression post-transplantation depending on the patient's immunologic risk.

  5. Goh ET, Jalalonmuhali M, Ng KP, Wan Md Adnan AH, Hing Wong A, Cheng SF, et al.
    Transplant Proc, 2022 Feb 04.
    PMID: 35131101 DOI: 10.1016/j.transproceed.2021.12.039
    Living-kidney transplantation increases with years, however, the rate is comparatively low to support local needs. Marginal living donors like the elderly were used to increase the donor pool. We retrospectively evaluate the outcome of 25 elderly living kidney donors (eLKDs) who were ≥60 years old at the time of donation in our center. Their medical history and laboratory results were analyzed retrospectively from e-medical records. There are 16 females (64.0%) with a median age of 63 (60.5-66.0). The mean follow-up duration was 4.36 ± 2.46 years. Their mean body mass index increased from 23.70 ± 3.07 kg/m2 to 24.21 ± 2.93 kg/m2 (t[14] = -2.176, P = .047) post donation. Systolic blood pressure (SBP) increased from 133.33 ± 11.65 mm Hg to 140.56 ± 17.78 mm Hg (t[17] = -2.124, P = .049). However, the prevalence of overweight and hypertension were not significant. Only 5.56% of the eLKDs developed proteinuria post nephrectomy (P =1.000). Serum creatinine increased from 62.33 ± 14.39 mmol/L to 104.63 ± 28.53 mmol/L post 1-month donation (t[23] = -9.720, P = .000) and decreased to 99.67 ± 22.39 mmol/L post 1-year donation (t[17] = -8.415, P = .006), and latest results were 94.28 ± 20.74mmol/L (t[17] = -6.630, P = .033). Fasting blood glucose and HbA1c level recorded no significant changes post donation. We noted that 47.62% of the eLKDs had dyslipidemia pre donation, which increased to 76.20% post donation (P = .031). eLKDs with hyperuricemia increased significantly from 5.88% to 52.94%; with uric acid level from 306.12 ± 68.67 umol/L to 412.24 ± 74.14 umol/L (t[16] = -7.726, P = .000). None of the eLKDs were diagnosed with metabolic syndrome pre and post kidney donation. Postdonation kidney function of the eLKDs compensated well and were stable in the short term. We noted statistically significant increments of weight, body mass index, SBP, uric acid, and lipid levels, which did not translate to clinical significance post donation. Elderly living-kidney donation can be done safely with close monitoring post donation.
  6. Lau WP, Ng KP, Ganapathy SS, Tah PC, Ismail R, Jalalonmuhali M, et al.
    Transplant Proc, 2022 Feb 03.
    PMID: 35125235 DOI: 10.1016/j.transproceed.2021.12.019
    BACKGROUND: Proteinuria and metabolic acidosis adversely affect long term renal allograft outcome and are highly prevalent in reported studies. The role of dietary intake in influencing proteinuria and metabolic acidosis remained uncertain. This study aims to determine the prevalence rate of proteinuria and metabolic acidosis among kidney transplant recipients (KTRs) and to study their relationship with dietary intake.

    METHODS: We performed a cross-sectional study on KTRs with functioning renal allograft and at least 3 months post transplant. Dietary protein, salt, and dietary acid load were estimated using 24-hour urine collection. Demographic characteristics, concomitant medications, medical history, and laboratory results were obtained from electronic medical records.

    RESULTS: A total of 204 KTRs were recruited with median age of 48 years (interquartile range [IQR], 18 years); male to female ratio was 61:39. A total of 79.9% (n = 163) were living related kidney transplants. The median duration after transplant was 71 months (IQR, 131 months), and median eGFR was 65 mL/min/1.73 m2 (IQR, 25 mL/min/1.73 m2). The prevalence rates of proteinuria (defined as ≥ 0.5 g/d) and metabolic acidosis (defined as at least 2 readings of serum bicarbonate ≤ 22 mmol/L in the past 6 months) were 17.7 % and 6.2%, respectively. High dietary protein of > 1.2 g/kg ideal body weight (adjusted odds ratio, 3.13; 95% CI, 1.35-7.28; P = .008) was significantly associated with proteinuria. Dietary protein, salt, and acid load did not correlate with chronic metabolic acidosis.

    CONCLUSIONS: The prevalence rate of proteinuria is consistent with published literature, but metabolic acidosis rate is extremely low in our cohort. High protein intake (> 1.2 g/kg ideal body weight) is a risk factor of proteinuria and may have negative impact on KTR outcome.

  7. Thye CK, Lee YW, Jalalonmuhali M, Lim SK, Ng KP
    Transplant Proc, 2022 Feb 02.
    PMID: 35123793 DOI: 10.1016/j.transproceed.2021.12.023
    BACKGROUND: Evaluation of donor renal function as glomerular filtration rate (GFR) is a crucial part of pretransplant workup. Most guidelines recommend measured GFR (mGFR) using exogenous markers with creatinine clearance (CrCl) as an alternative. However, exogenous markers are difficult to obtain and perform, and CrCl may overestimate GFR.

    OBJECTIVE: We explore the use of CrCl and combined urea and creatinine clearance as an alternative for GFR assessment.

    METHODS: A retrospective study involving 81 kidney donors from 2007 to 2020, with mGFR collected by chromium 51-labeled ethylenediaminetetraacetic acid (51Cr-EDTA) and CrCl and combined urea and creatinine clearance. We analyzed the performance of CrCl and combined urea and creatinine clearance against 51Cr-EDTA. Adequacy of urine volume was taken into consideration.

    RESULTS: A total of 81 candidates with a mean age of 44.80 ± 10.77 years were enrolled. Mean mGFR from 51Cr-EDTA was 123.66 ± 26.91 mL/min/1.73 m2, and combined urea and creatinine clearance and CrCl were 122.13 ± 47.07 and 133.40 ± 36.32 mL/min/1.73 m2, respectively. CrCl overestimated 51Cr-EDTA. Though combined urea and creatinine clearance had minimal bias, it had a lower correlation coefficient (0.25 vs 0.43), lower precision (49.51 vs 38.10), and slightly lower accuracy within 30% of 51Cr-EDTA (74.07% vs 76.54%).

    CONCLUSIONS: Combined urea and creatinine clearance did not improve the performance of CrCl. Nevertheless, it can potentially be used as first-line GFR assessment, followed by mGFR in selected donors, to ascertain threshold of safe kidney donation. A stringent urine collection method is essential to ensure accurate measurement.

  8. Gan CC, Jalalonmuhali M, Nordin NZ, Abdul Wahab MZ, Yahya R, Ng KP, et al.
    Transplant Proc, 2021 Apr;53(3):856-864.
    PMID: 33487455 DOI: 10.1016/j.transproceed.2020.10.038
    Malaysia has a low deceased-donor donation rate and has not embarked on a paired kidney exchange program; therefore, ABO-incompatible and HLA-incompatible transplantation remain the main contributor to the sustainability of the national kidney transplantation (KT) program. There were 26 cases of ABO-incompatible KTs performed from 2011 to 2018 in 3 major transplant centers, namely, Hospital Kuala Lumpur, University Malaya Medical Centre, and Prince Court Medical Centre. We collected perioperative and follow-up data through June 2019. The desensitization protocol varies and is center specific: the localized Japanese protocol and Swedish protocol with a target anti-A/B isoagglutinin titer of 16 or 32 on the day of transplant. The induction and tacrolimus-based maintenance protocol was nearly identical. The median follow-up time was 62.3 months (interquartile range, 37.0-79.7). Fifteen subjects had the highest predesensitization anti-A/B titer of ≥32 (57.7%). The acute cellular rejection and antibody-mediated rejection incidence were 12.5% (3 cases) and 8.3% (2 cases), respectively. Patient, graft, and death-censored graft survival rates were 96.2%, 92.3%, and 96.0%, respectively, 1 year post-living-donor KT (LDKT) and 96.2%, 87.2%, and 90.7%, respectively, 5 years post-LDKT. Our experience shows that ABO-incompatible LDKT using a suitable desensitization technique could be a safe and feasible choice for LDKT even with varied desensitization regimens for recipients with relatively high baseline isoagglutinin titers.
  9. Jalalonmuhali M, Ng KP, Mohd Shariff NH, Lee YW, Wong AH, Gan CC, et al.
    Transplant Proc, 2020 05 21;52(6):1718-1722.
    PMID: 32448671 DOI: 10.1016/j.transproceed.2020.02.140
    The shortage of deceased donors led to an increase of living related renal transplant performed in the presence of donor-specific antibodies (DSAs) or ABO incompatibilities. There are various desensitization protocols that have been proposed. Here, we describe the outcome of these sensitized patients. This is a prospective cohort study recruiting all kidney transplant recipients from August 2016 until June 2018. Deceased donations, ABO incompatible patients, and sensitized patients who were not prescribed on our desensitization protocol were excluded. Recipients were screened for the presence of HLA-antibodies 1 month before transplant. Those with positive DSA will undergo flow cytometry (risk stratification). We are using a protocol that consisted of intravenous rituximab 200 mg (day -14), intravenous antithymocyte globulin 5mg/kg (day 0-4), plasma exchange post transplant for patients with mean fluorescent intensity (MFI) < 3000, and negative flow cytometry. Those patients with MFI ≥ 3000 or positive flow cytometry need extra cycles pretransplant. A total of 40 patients were recruited, and 20 were sensitized patients. Among the sensitized group 4 of 20 had flow cytometry crossmatch positive, while all had preformed HLA-DSA. A total of 8 of 20 had class I HLA-DSA, 11 of 20 had class II HLA-DSA, and 1of 20 was positive for both class I and II HLA-DSA. Mean immunodominant MFI was 2133.4 (standard deviation [SD], 4451.24) and 1383.7 (SD, 2979.02) for class I and class II, respectively. At 1 year, mean serum creatinine was 108.90 (SD, 25.95) and 118.42 (SD, 31.68) in sensitized and unsensitized patients, respectively. One of 20 unsensitized patients had Banff 1B rejection at 3 months, and there was no significant rejection in sensitized patients at 6 months and 1 year. There was no difference in the occurrence of de novo HLA-DSA between the groups. Desensitization protocols may help to overcome incompatibility barriers in living donor renal transplant. The combination of low-dose rituximab, antithymocyte globulin, and judicious use of plasma exchange has worked well for our cohort.
  10. Jalalonmuhali M, Ng KP, Ong CS, Lee YW, Wan Md Adnan WAH, Lim SK
    Transplant Proc, 2020 05 21;52(6):1709-1714.
    PMID: 32448669 DOI: 10.1016/j.transproceed.2020.02.139
    The aim of induction therapy in the management of kidney transplant is to reduce the incidence of acute rejection and delayed graft function after kidney transplant. The agent for induction therapy differs depending on the recipient risks. The regimen can be either polyclonal (rabbit antithymocyte globulin [rATG]) or monoclonal antibody (basiliximab). Basiliximab is commonly used in patients with low immunologic risk. However, to date we know that the use of rATG on T cell depletion is dose dependent and more potent antirejection therapy. Therefore, we would like to look at 1-year graft function of very low-dose rATG in low immunologic risk recipients. All low immunologic risk patients who received low-dose rATG (0.5 mg/kg of body weight daily) during transplant (day 0) and on days 1 and 2 were recruited. Their renal function, HLA donor-specific antibodies, lymphocyte counts, protocol biopsy results, and cytomegalovirus (CMV) polymerase chain reaction were monitored as per clinical practice. All 10 patients had immediate graft function. Low-dose rATG caused lymphocyte counts to deplete immediately on day 0, and the effect lasted about 1 month post-transplant. All the patients had stable graft function without any significance episode of rejection. Only one patient had de novo HLA-DQ antibody. It is good to know that without prophylaxis antiviral in CMV+ donor to CMV+ recipient, the incidence of CMV viremia is considerably low in our cohort. Very low-dose rATG is an effective induction immunosuppression in low immunologic risk patients with acceptable infection risk.
  11. Lo SG, Wong SF, Mak JW, Choo KK, Ng KP
    Med Mycol, 2020 Apr 01;58(3):333-340.
    PMID: 31309220 DOI: 10.1093/mmy/myz061
    Cladosporium is one of the most abundant spore. Fungi of this genus can cause respiratory allergy and intrabronchial lesion. We studied the differential expression of host genes after the interaction of Cladosporium sphaerospermum conidia with Human Bronchial Epithelial Cells (BEAS-2B) and Human Pulmonary Alveolar Epithelial Cells (HPAEpiC). C. sphaerospermum conidia were harvested and co-cultured with BEAS-2B cells or HPAEpiC cells for 48 hours respectively. This culture duration was chosen as it was associated with high germination rate. RNA was extracted from two biological replicates per treatment. RNA of BEAS-2B cells was used to assess changes in gene expression using AffymetrixGeneChip® Human Transcriptome Array 2.0. After co-culture with Cladosporium spores, 68 individual genes were found differentially expressed (P ≤ 0.05) and up-regulated ≥ 1.5 folds while 75 genes were found differentially expressed at ≤ -1.5 folds compared with controls. Reverse transcription and qPCR were performed on the RNA collected from both BEAS-2B cells and HPAEpiC cells to validate the microarray results with 7 genes. Based on the findings, infected pulmonary epithelial cells exhibited an increase in cell death-related genes and genes associated with innate immunity.
  12. Lo SG, Wong SF, Mak JW, Choo KK, Ng KP
    Trop Biomed, 2019 Dec 01;36(4):958-971.
    PMID: 33597466
    Cladosporium spores are ubiquitous in indoor and outdoor environment and may potentially trigger allergic responses upon inhalation. To date, there is limited investigation on the fate of Cladosporium spores after being inhaled into the respiratory tract. This study was conducted to investigate the interaction of Cladosporium sphaerospermum with Human Bronchial Epithelial Cells (BEAS-2B) and Human Pulmonary Alveolar Epithelial Cells (HPAEpiC). C. sphaerospermum conidia were harvested and co-cultured with BEAS-2B or HPAEpiC cells for 72 hours. At each time point (30 minutes, 2, 4, 24, 48 and 72 hours), adherence and invasion of the cells by C. sphaerospermum conidia (and hyphae) were investigated by immunofluorescence staining. This study demonstrated the adherence and internalization of C. sphaerospermum conidia within these epithelial cells. In addition, the conidia were able to germinate and invade the epithelial cells. The ability of the fungal conidia to adhere, internalize, germinate and invade both the bronchial and alveolar epithelial cells of the respiratory tract in vitro might contribute to the understanding of the pathogenesis of Cladosporium in respiratory infection and allergy in vivo.
  13. Guad RM, Ng KP, Lim SK, Hirayama K, Eng HS, Wan Md Adnan WAH
    Ann Acad Med Singap, 2019 Dec;48(12):403-411.
    PMID: 32112065
    INTRODUCTION: Studies have shown that a compatible human leukocyte antigen (HLA) match can confer a favourable effect on graft outcomes. We examined the outcomes of HLA matching in renal transplant donors in Malaysia.

    MATERIALS AND METHODS: A total of 140 patients who had compatible ABO blood type with negative T-cell lymphocytotoxicity crossmatch were included in the study and 25% of them were spousal transplant donors. No remarkable differences in acute rejection rate, graft survival, patient survival and serum creatinine level were observed between the spousal and living-related donor groups.

    RESULTS: The spousal donor group had a higher degree of HLA mismatch than the living-related donor group. HLA-A mismatch was associated with increased rejection risk at 6 months (odds ratio [OR], 2.75; P = 0.04), 1 year (OR, 2.54; P = 0.03) and 3 years (OR, 3.69; P = 0.001). It was also observed in the deleterious effects of HLA-B and HLA-DQ loci when the number of antigen mismatches increased. The risk was 7 times higher in patients with ≥1 mismatch at HLA-A, HLA-B and HLA-DR loci than those who did not have a mismatch at these loci at 6 months (P = 0.01), 1 year (P = 0.03) and 3 years (P = 0.003).

    CONCLUSION: A good match for HLA-A, HLA-B, HLA-DR and HLA-DQ can prevent acute rejection risk in renal transplant patients. Consequently, spousal donor transplants could be a safe intervention in renal patients.

  14. Yew SM, Tan KL, Yeo SK, Ng KP, Kuan CS
    J Thorac Dis, 2019 Nov;11(11):4626-4633.
    PMID: 31903251 DOI: 10.21037/jtd.2019.10.69
    BACKGROUND: In many developing countries, acute respiratory tract infections (ARTIs) are the main cause of morbidity and mortality among young children. This study aims to evaluate the molecular epidemiology of respiratory viruses among Malaysian children with confirmed respiratory infections between July 2014 and July 2015.

    METHODS: A total of 394 nasopharyngeal swabs were collected prospectively from children age 0-5 years old with ARTIs from hospitals in Kuala Lumpur. Respiratory viral panel (RVP) assay was used to identify the viral aetiology of respiratory infections.

    RESULTS: From a total of 394 samples, the positive detection rate was 79.9% (n=315). A total of 15 types of RNA viruses and a single type of DNA virus were detected. Enterovirus/rhinovirus (n=112, 28.4%), respiratory syncytial virus (RSV) (n=85, 21.6%), adenovirus (n=64, 16.2%), human bocavirus (n=34, 8.6%), and human metapneumovirus (n=29, 7.4%) were the five predominant viruses. Enterovirus/rhinovirus and RSV constituted most of the viral respiratory infections among young children, especially among children less than 1 year old. No coronavirus was detected among children between 3 and 5 years old. Co-infection caused by 2 or 3 respiratory viruses were detected in 52 patients (13.2%). Enterovirus/rhinovirus, adenovirus, and human bocavirus demonstrated pronounced seasonality. The infection rate peaked during mid-year, while the lowest activity occurred during early of the year.

    CONCLUSIONS: The use of molecular assay as a routine diagnostic in the hospitals can improve the diagnosis and management of respiratory tract infections among children.

  15. Peremalo T, Madhavan P, Hamzah S, Than L, Wong EH, Nasir MDM, et al.
    J Med Microbiol, 2019 Mar;68(3):346-354.
    PMID: 30724730 DOI: 10.1099/jmm.0.000940
    PURPOSE: Non-albicansCandida species have emerged as fungal pathogens that cause invasive infections, with many of these species displaying resistance to commonly used antifungal agents. This study was confined to studying the characteristics of clinical isolates of the C. rugosa complex and C. pararugosa species.

    METHODOLOGY: Seven isolates of the C. rugosa complex and one isolate of C. pararugosa were obtained from two tertiary referral hospitals in Malaysia. Their antifungal susceptibilities, biofilm, proteinase, phospholipase, esterase and haemolysin activities were characterized. Biofilms were quantified using crystal violet (CV) and tetrazolium (XTT) reduction assays at 1.5, 6, 18, 24, 48 and 72 h.Results/Key findings. The E-test antifungal tests showed that both species have elevated MICs compared to C. albicans and C. tropicalis. The highest biomass was observed in one of the C. rugosa isolates (0.237), followed by C. pararugosa (0.206) at 18 h of incubation. However, the highest bioactivity was observed in the C. rugosa ATCC 10571 strain at 24 h (0.075), followed by C. pararugosa at 48 h (0.048) and the same C. rugosa strain at 24 h (0.046), with P<0.05. All isolates exhibited high proteinase activity (+++) whereas six isolates showed very strong esterase activity (++++). All the isolates were alpha haemolytic producers. None of the isolates exhibited phospholipase activity.

    CONCLUSION: Elevated MICs were shown for the C. rugosa complex and C. pararugosa for commonly used antifungal drugs. Further studies to identify virulence genes involved in the pathogenesis and genes that confer reduced drug susceptibility in these species are proposed.

  16. Fu MS, Lim SJ, Jalalonmuhali M, Ng KS, Lim SK, Ng KP
    J Transplant, 2019;2019:9153875.
    PMID: 31186948 DOI: 10.1155/2019/9153875
    Background: The role of protocol renal allograft biopsy in kidney transplantation is controversial due to the concern with procedural-related complications; however, its role is slowly evolving. Recent evidence suggests that protocol biopsy is useful in detecting subclinical renal pathology. Early recognition and treatment of renal pathologies can improve long-term outcomes of renal allografts.

    Methodology: A total of 362 renal allograft protocol biopsies were performed in adult recipients of kidney transplantation between 2012 and 2017. After excluding those with poor quality or those performed with a baseline serum creatinine level >200 umol/L, we analyzed 334 (92.3%) biopsies. Histology reports were reviewed and categorized into histoimmunological and nonimmunological changes. The immunological changes were subcategorized into the following: (1) no acute rejection (NR), (2) borderline changes (BC), and (3) subclinical rejection (SCR). Nonimmunological changes were subcategorized into the following: (1) chronicity including interstitial fibrosis/tubular atrophy (IFTA), chronic T-cell-mediated rejection (TCMR), unspecified chronic lesions, and arterionephrosclerosis, (2) de novo glomerulopathy/recurrence of primary disease (RP), and (3) other clinically unsuspected lesions (acute pyelonephritis, calcineurin inhibitors toxicity, postinfective glomerulonephritis, and BK virus nephropathy). Risk factors associated with SCR were assessed.

    Results: For the histoimmunological changes, 161 (48.2%) showed NR, 145 (43.4%) were BC, and 28 (8.4%) were SCR. These clinical events were more pronounced for the first 5 years; our data showed BC accounted for 59 (36.4%), 64 (54.2%), and 22 (40.7%) biopsies within <1 year, 1-5 years, and > 5 years, respectively (p = 0.011). Meanwhile, the incidence for SCR was 6 (3.7%) biopsies in <1 year, 18 (15.3%) in 1-5 years, and 4 (7.4%) in >5 years after transplantation (p=0.003). For the nonimmunological changes, chronicity, de novo glomerulopathy/RP, and other clinically unsuspected lesions were seen in 40 (12%), 10 (3%), and 12 (3.6%) biopsies, respectively. Living-related donor recipients were associated with decreased SCR (p=0.007).

    Conclusions: Despite having a stable renal function, our transplant recipients had a significant number of subclinical rejection on renal allograft biopsies.

  17. Lotfalikhani A, Khosravi Y, Sabet NS, Na SL, Ng KP, Tay ST
    Trop Biomed, 2018 Dec 01;35(4):1123-1130.
    PMID: 33601859
    Candida glabrata has been reported as the second or third most common yeast species isolated from patients with vaginitis and invasive candidiasis. This study was aimed to determine the genetic diversity, antifungal susceptibility and enzymatic profiles of C. glabrata isolated from vaginal and blood samples in the Medical Microbiology Diagnostic Laboratory, University Malaya Medical Centre. A random amplified polymorphic DNA (RAPD) analysis method, using M13 and (GTG)5 primers, was used for strain differentiation of C. glabrata isolates. Antifungal susceptibility testing of C. glabrata isolates was determined using E-test against amphotericin B, caspofungin, fluconazole and voriconazole and microbroth dilution method against clotrimazole. The enzymic profiles of C. glabrata were determined using APIZYM semi-quantitation kit and egg-yolk agar method. A total of 14 RAPD patterns were identified amongst C. glabrata isolates investigated this study. Susceptibility to amphotericin B, caspofungin, fluconazole and voriconazole was noted. Approximately one third of the isolates demonstrated resistance to clotrimazole (MIC>=1 µg/ml). A single isolate of C. glabrata was resistant to caspofungin (MIC:1.5 µg/ml). Enzymatic activities of acid and alkaline phosphatase, aminopeptidases, esterase and lipase and phospholipase were detected in the C. glabrata isolates. The genetic diversity and antifungal susceptibility profiles of C. glabrata isolates were presented in this study. Continued surveillance and monitoring of the incidence and antifungal resistance in C. glabrata isolates is necessary.
  18. Madhavan P, Jamal F, Pei CP, Othman F, Karunanidhi A, Ng KP
    Mycopathologia, 2018 Jun;183(3):499-511.
    PMID: 29380188 DOI: 10.1007/s11046-018-0243-z
    Infections by non-albicans Candida species are a life-threatening condition, and formation of biofilms can lead to treatment failure in a clinical setting. This study was aimed to demonstrate the in vitro antibiofilm activity of fluconazole (FLU) and voriconazole (VOR) against C. glabrata, C. parapsilosis and C. rugosa with diverse antifungal susceptibilities to FLU and VOR. The antibiofilm activities of FLU and VOR in the form of suspension as well as pre-coatings were assessed by XTT [2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide] reduction assay. Morphological and intracellular changes exerted by the antifungal drugs on Candida cells were examined by scanning electron microscope (SEM) and transmission electron microscope (TEM). The results of the antibiofilm activities showed that FLU drug suspension was capable of killing C. parapsilosis and C. rugosa at minimum inhibitory concentrations (MICs) of 4× MIC FLU and 256× MIC FLU, respectively. While VOR MICs ranging from 2× to 32× were capable of killing the biofilms of all Candida spp tested. The antibiofilm activities of pre-coated FLU were able to kill the biofilms at ¼× MIC FLU and ½× MIC FLU for C. parapsilosis and C. rugosa strains, respectively. While pre-coated VOR was able to kill the biofilms, all three Candida sp at ½× MIC VOR. SEM and TEM examinations showed that FLU and VOR treatments exerted significant impact on Candida cell with various degrees of morphological changes. In conclusion, a fourfold reduction in MIC50 of FLU and VOR towards ATCC strains of C. glabrata, C. rugosa and C. rugosa clinical strain was observed in this study.
  19. Jalalonmuhali M, Elagel SMA, Tan MP, Lim SK, Ng KP
    Int J Nephrol, 2018;2018:3081518.
    PMID: 29862077 DOI: 10.1155/2018/3081518
    Background: To assess the performance of different GFR estimating equations, test the diagnostic value of serum cystatin-C, and compare the applicability of cystatin-C based equation with serum creatinine based equation for estimating GFR (eGFR) in comparison with measured GFR in the elderly Malaysian patients.

    Methods: A cross-sectional study recruiting volunteered patients 65 years and older attending medical outpatient clinic. 51 chromium EDTA (51Cr-EDTA) was used as measured GFR. The predictive capabilities of Cockcroft-Gault equation corrected for body surface area (CGBSA), four-variable Modification of Diet in Renal Disease (4-MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations using serum creatinine (CKD-EPIcr) as well as serum cystatin-C (CKD-EPIcys) were calculated.

    Results: A total of 40 patients, 77.5% male, with mean measured GFR 41.2 ± 18.9 ml/min/1.73 m2 were enrolled. Mean bias was the smallest for 4-MDRD; meanwhile, CKD-EPIcr had the highest precision and accuracy with lower limit of agreement among other equations. CKD-EPIcys equation did not show any improvement in GFR estimation in comparison to CKD-EPIcr and MDRD.

    Conclusion: The CKD-EPIcr formula appears to be more accurate and correlates better with measured GFR in this cohort of elderly patients.

    Study site: medical outpatient clinic. University of Malaya Medical Centre (UMMC)
  20. Jalalonmuhali M, Lim SK, Md Shah MN, Ng KP
    BMC Nephrol, 2017 Dec 13;18(1):363.
    PMID: 29237422 DOI: 10.1186/s12882-017-0776-2
    BACKGROUND: Accurate measurement of renal function is important: however, radiolabelled gold standard measurement of GFR is highly expensive and can only be used on a very limited scale. We aim to compare the performance of Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equations in the multi-ethnic population attending University Malaya Medical Centre (UMMC).
    METHODS: This is a cross-sectional study recruiting patients, who attend UMMC Nephrology clinics on voluntary basis. 51-Chromium EDTA (51Cr-EDTA) plasma level was used to measure the reference GFR. The serum creatinine was determined by IDMS reference modified Jaffe kinetic assay (CrJaffe). The predictive capabilities of MDRD and CKD-EPI based equations were calculated. Data was analysed using SPSS version 20 and correlation, bias, precision and accuracy were determined.
    RESULTS: A total of 113 subjects with mean age of 58.12 ± 14.76 years and BMI of 25.99 ± 4.29 kg/m2 were recruited. The mean reference GFR was 66.98 ± 40.65 ml/min/1.73m2, while the estimated GFR based on MDRD and CKD-EPI formula were 62.17 ± 40.40, and 60.44 ± 34.59, respectively. Both MDRD and CKD-EPI were well-correlated with reference GFR (0.806 and 0.867 respectively) and statistically significant with p 
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