Displaying publications 1 - 20 of 38 in total

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  1. Gan CS, Wang CW, Tan KS
    Genet. Mol. Res., 2012;11(1):147-52.
    PMID: 22370881 DOI: 10.4238/2012.January.27.1
    Cerebral ischemia or ischemic stroke is mainly attributed to vascular and circulation disorders. Among protein biomarkers, RNA profiles have also been identified as markers of ischemic stroke. MicroRNA-145 expression is ostensibly recognized as marker and modulator of vascular smooth muscle cell phenotype; however, expression levels in ischemic stroke had not been investigated. Employing real-time quantitative PCR, we examined the expression profile of circulatory microRNA-145 in healthy control subjects (N = 14) and ischemic stroke patients (N = 32). Circulatory microRNA-145 expression was significantly higher in ischemic stroke patients than in control subjects. This demonstrates that hemostatic mechanisms are affected by ischemic stroke. We conclude that circulating microRNA-145 has potential as a biomarker for ischemic stroke.
  2. Gan CS, Yusof R, Othman S
    Acta Trop, 2015 Sep;149:8-14.
    PMID: 25981524 DOI: 10.1016/j.actatropica.2015.05.005
    Dengue virus (DV) infection demonstrates an intriguing virus-induced intracellular membrane alteration that results in the augmentation of major histocompatibility complex (MHC) class I-restricted antigen presentation. As oppose to its biological function in attracting CD8(+) T-cells, this phenomenon appears to facilitate the immune evasion. However, the molecular events that attribute to the dysregulation of the antigen presenting mechanism (APM) by DV remain obscure. In this study, we aimed to characterize the host cell APM upon infection with all serotypes of whole DV. Cellular RNA were isolated from infected cells and the gene expressions of LMP2, LMP7, TAP1, TAP2, TAPBP, CALR, CANX, PDIA3, HLA-A and HLA-B were analyzed via quantitative PCR. The profiles of the gene expression were further validated. We showed that all four DV serotypes modulate host APM at the proteasomal level with DV2 showing the most prominent expression profile.
  3. Lee WS, Gan CS, Chai PF, Harun F
    Med J Malaysia, 2008 Aug;63(3):229-36.
    PMID: 19248696
    We aimed to determine the outcome of nutritional intervention in children with moderate to severe malnutrition following persistent diarrhoea (PD), referred to a tertiary referral unit in Malaysia. Thirty-one (44%) of the 71 children (median age 19 months) with PD had moderate to severe malnutrition on admission. Fifty-three (75%) required dietary modification and 15 (21%) needed parenteral nutrition (PN, median duration 96 days). Of the 70 patients in whom remission of diarrhoea could be ascertained, 64 (91%) achieved remission. Three required home PN. At three months after discharge, there was a significant improvement in the mean weight-for-height z-score as compared to the original score at initial presentation (from -1.83 +/- -1.77 to -0.80 +/- -1.17; p < 0.001), although 12 (22%) of the 55 patients in whom nutritional status could be ascertained still had moderate to severe malnutrition. In conclusion, moderate to severe malnutrition was a common complication following PD resulting from diverse causes. With appropriate therapy, remission can be achieved in majority of patients, although a small number of patients needed home PN because of persistence of diarrhoea.
  4. Gan CS, Chong SY, Lum LC, Lee WS
    Singapore Med J, 2013 Feb;54(2):e35-7.
    PMID: 23462840
    An eight-month-old female infant with severe dengue disease, who was repeatedly given therapeutic paracetamol for severe dengue, developed fulminant liver failure with encephalopathy, gastrointestinal haemorrhage and severe coagulopathy. She responded to supportive measures and N-acetylcysteine infusion. This case highlights the potential danger of administering repeated therapeutic doses of paracetamol in childhood severe dengue disease with hepatitis.
  5. Lum LC, Abdel-Latif ME, de Bruyne JA, Nathan AM, Gan CS
    Pediatr Crit Care Med, 2011 Jan;12(1):e7-13.
    PMID: 20190672 DOI: 10.1097/PCC.0b013e3181d505f4
    To determine the factors that predict outcome of noninvasive ventilation (NIV) in critically ill children.
  6. Fong CY, Hashim N, Gan CS, Chow TK, Tay CG
    Eur. J. Paediatr. Neurol., 2016 Nov;20(6):957-961.
    PMID: 27524391 DOI: 10.1016/j.ejpn.2016.07.023
    Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare and potentially life-threatening acute drug-induced hypersensitivity reaction. Antiepileptic drugs (AEDs) predominantly aromatic AEDs are commonly reported in DRESS. To date there are no reports of sulthiame AED causing DRESS syndrome.
  7. Gan CS, Lim PJ, Razif MF, Yusof R, Othman S
    Rev Soc Bras Med Trop, 2017 Jan-Feb;50(1):99-103.
    PMID: 28327809 DOI: 10.1590/0037-8682-0207-2016
    INTRODUCTION:: Infection with all serotypes of dengue virus (DV) results in augmented antigen presentation by MHC class I molecules. However, the upregulation of immunoproteasome subunits only results from infection with two serotypes. This study aims to elucidate changes in the expression of immunoproteasome subunits resulting from infection with DV, particularly DV serotype 2 (DV2).

    METHODS:: HepG2 cells were grown in various culture milieu. Total cellular RNA and proteins were extracted and quantified.

    RESULTS:: Results demonstrated sequestration of immunoproteasome subunits LMP2 and LMP7 in DV2-infected cells.

    CONCLUSIONS:: This study provides insights into the mechanisms underlying immune evasion by DV.
  8. Tay CG, Fong CY, Li L, Ganesan V, Teh CM, Gan CS, et al.
    J Clin Neurosci, 2020 Feb;72:468-471.
    PMID: 31831253 DOI: 10.1016/j.jocn.2019.12.007
    Congenital myasthenic syndrome (CMS) is a heterogeneous group of inherited disorder which does not associate with anti-acetylcholine receptor (AChR) antibody. The presence of AChR autoantibody is pathogenic and highly sensitive and specific for autoimmune myasthenia gravis (MG). We describe 2 children from unrelated families who presented with hypotonia, ptosis and fatigability in early infancy with anti-AChR antibodies detected via ELISA on 2 separate occasions in the sera. Both were treated as refractory autoimmune MG due to poor clinical response to acetylcholinesterase inhibitor and immunotherapy. In view of the atypical clinical features, genetic studies of CMS were performed and both were confirmed to have novel pathogenic mutations in the COLQ gene. To the best of our knowledge, the presence of anti-AChR antibody in COLQ-related CMS has never been reported in the literature. The clinical presentation of early onset phenotype, and refractoriness to acetylcholinesterase inhibitor and immunotherapy should prompt CMS as a differential diagnosis.
  9. Fong CY, Saw MT, Li L, Lim WK, Ong LC, Gan CS
    Brain Dev, 2021 Apr;43(4):538-547.
    PMID: 33358123 DOI: 10.1016/j.braindev.2020.12.003
    OBJECTIVE: Describe the outcome of a Malaysian cohort of children with acute necrotising encephalopathy (ANE).

    METHOD: Retrospective study of children with ANE seen at University of Malaya Medical Centre from 2014 to 2019. All clinical details including ANE-severity score (ANE-SS), immunomodulation treatment and neurodevelopmental long-term outcome were collected.

    RESULTS: Thirteen patients had ANE and brainstem death occurred in 5. In 10 patients (77%) viruses were isolated contributing to ANE: 8 influenza virus, 1 acute dengue infection, and 1 acute varicella zoster infection. The ANE-SS ranged 2-7: 9 were high risk and 4 were medium risk. Among the 8 survivors; 1 was lost to follow-up. Follow-up duration was 1-6 years (median 2.2). At follow-up among the 4 high-risk ANE-SS: 2 who were in a vegetative state, 1 remained unchanged and 1 improved to severe disability; the other 2 with severe disability improved to moderate and mild disability respectively. At follow-up all 3 medium-risk ANE-SS improved: 2 with severe disability improved to moderate and mild disability respectively, while 1 in a vegetative state improved to severe disability. Early treatment with immunomodulation did not affect outcome.

    CONCLUSION: Our ANE series reiterates that ANE is a serious cause of encephalopathy with mortality of 38.5%. All survivors were in a vegetative state or had severe disability at discharge. Most of the survivors made a degree of recovery but good recovery was seen in 2. Follow-up of at least 12 months is recommended for accurate prognostication. Dengue virus infection needs to be considered in dengue endemic areas.

  10. Thambusamy E, Thambidorai CR, Nah SA, Gan CS, Wang J, Singaravel S, et al.
    J Pediatr Surg, 2022 Feb;57(2):199-202.
    PMID: 34857376 DOI: 10.1016/j.jpedsurg.2021.10.029
    BACKGROUND: Increased intra-abdominal pressure (IAP) is seen in patients after congenital diaphragmatic hernia (CDH) repair owing to reduction of thoracic contents into the relatively smaller abdominal cavity. In infants, IAP ≥11 mmHg is considered intra-abdominal hypertension (IAH). We aim to determine the incidence of IAH and its relationship with duration of ventilatory support, and gastrointestinal function post CDH repair.

    METHODS: We prospectively recruited all neonates who had CDH repair in four hospitals in Malaysia from June 2018 to October 2020. Intra vesical pressure was used as a proxy for IAP and was measured for 5 consecutive days post surgery. The daily median value was used for analysis. We categorized IAP as <11 mmHg (no IAH), 11-15 mmHg (IAH), and >15 mmHg (severe IAH). Incidence of IAH, its effects on the duration of ventilatory support, and gastrointestinal function were studied.

    RESULTS: There were 24 neonates included in this study. They were operated between day 1 and 6 of life (median: 4 days old). IAH was detected within the first 3 days post surgery, with 83% occurring on day one. Those requiring ventilatory support for more than 3 days contributed the largest proportion of IAH (n = 17, 71%). There was strong correlation between days of IAH and duration of ventilation (p 

  11. Gan CS, Lim SK, Chee CF, Yusof R, Heh CH
    Chem Biol Drug Des, 2018 02;91(2):448-455.
    PMID: 28834304 DOI: 10.1111/cbdd.13091
    Dengvaxia® (CTD-TDV), the only licensed tetravalent dengue vaccine by Sanofi Pasteur, was made available since 2015. However, administration of CTD-TDV, in general, has not received the prequalification recommendation from the World Health Organization. Having a universal antidengue agent for treatment will therefore beneficial. Accordingly, the development of nucleoside inhibitors specific to dengue viral polymerase that perturb dengue infection has been studied by many. Alternatively, we have used a marketed anti-HCV prodrug sofosbuvir to study its in silico and in vitro effects against dengue. As a result, the active metabolite of sofosbuvir (GS-461203) was predicted to bind to the catalytic motif (Gly-Asp-Asp) of dengue viral polymerase with binding affinity of -6.9 kcal/mol. Furthermore, sofosbuvir demonstrated excellent in vitro viral inhibition with an EC90 of 0.4 μm. In addition, this study demonstrated the requirement of specific liver enzymes to activate the prodrug into GS-461203 to exert its antidengue potential. All in all, sofosbuvir should be subjected to in-depth studies to provide information of its efficacy toward dengue and its lead potential as DENV polymerase inhibitor in human subjects. In conclusion, we have expended the potential of the clinically available drug sofosbuvir as treatment for dengue.
  12. Foo JC, Rahmat K, Mumin NA, Koh MT, Gan CS, Ramli N, et al.
    J Clin Neurosci, 2017 Sep 01.
    PMID: 28867361 DOI: 10.1016/j.jocn.2017.08.024
    We report a rare case of paediatric diphtheria complicated with encephalitis. A 6-year-old boy who did not receive his scheduled diptheria-tetanus-pertusis vaccination presented with one episode of generalised convulsive seizure. His illness was preceded by a 3day history of fever associated with enlarged exudative tonsils with a pseudomembrane. He was commenced on intravenous penicillin and oral erythromycin. However, he developed progressive encephalopathy with focal neurological deficit which required intubation on day 5 of illness. Throat swab polymerase chain reaction for diphtheria toxin A and B were positive and diphtheria antitoxin was given. Magnetic resonance imaging (MRI) of brain showed T2-weighted hyperintensities over the anterior cingulate gyri, insular cortex and cerebellum. This is the first reported MRI finding of diphtheric encephalitis. Our report highlights the importance of neuroimaging in diagnosing diphtheric encephalitis particularly in cases with unremarkable cerebrospinal findings.
  13. Fong CY, Aung HWW, Khairani A, Gan CS, Shahrizaila N, Goh KJ
    Brain Dev, 2018 Jun;40(6):507-511.
    PMID: 29459060 DOI: 10.1016/j.braindev.2018.02.001
    Bickerstaff's brainstem encephalitis (BBE) is a rare immune-mediated disorder characterized by ophthalmoplegia, ataxia and disturbance of consciousness, which may overlap with Guillain-Barré syndrome (GBS) if there is additional limb weakness. We report a 7-month-old boy presented with ophthalmoplegia followed by a rapidly ascending paralysis of all four limbs and disturbance of consciousness. The initial impression was BBE with overlapping GBS. This was supported by sequential nerve conduction study (NCS) findings compatible with an acute inflammatory demyelinating polyneuropathy (AIDP). He received intravenous pulse methylprednisolone, intravenous immunoglobulin and plasmapharesis with complete clinical recovery after 6 weeks of illness and improved NCS findings from week 16. This is the first case of paediatric BBE with overlapping GBS with an AIDP subtype of GBS. It expands the clinical spectrum of this condition in children. Our case highlights the importance of sequential NCS in paediatric BBE with overlapping GBS for accurate electrophysiological diagnosis and prognosis particularly if the first NCS findings are not informative.
  14. Ng YY, Abdel-Latif Mel-A, Gan CS, Siham A, Zainol H, Lum LC
    Singapore Med J, 2015 Sep;56(9):506-12.
    PMID: 26451053 DOI: 10.11622/smedj.2015135
    The present study aimed to determine the impact of an extended infection control training programme, which was conducted for all interns posted to the Department of Paediatrics, on the incidence of paediatric intensive care unit (PICU)-acquired bloodstream infections (BSIs) in University Malaya Medical Centre, Malaysia.
  15. Lee OPE, Kanesan N, Leow EH, Sultana R, Chor YK, Gan CS, et al.
    J Intensive Care Med, 2023 Jul;38(7):598-611.
    PMID: 37097910 DOI: 10.1177/08850666231170775
    OBJECTIVES: To summarize the role of therapeutic plasma exchange (TPE) in critically ill adults and children with severe sepsis.

    DATA COLLECTION: A systematic search was performed using the following databases: Medline, EMBASE, CINAHL, and Cochrane from January 1990 till December 2022. Comparative studies of TPE in severe sepsis were selected. Adult and pediatric data were analyzed separately.

    DATA SYNTHESIS: Eight randomized control trials and 6 observational studies (n = 50,142 patients) were included. Centrifugal TPE was the most common modality (209/280, 74.6% adults and 952/1026, 92.7% children). Every TPE study utilized different volume exchanges. Most TPE sessions (1173/1306, 89.8%) employed fresh frozen plasma (FFP) as replacement fluid and heparin as anticoagulant. Adults with severe sepsis supported with TPE using FFP had lower mortality (risk ratio, RR: 0.64 [95% confidence interval, CI: 0.49, 0.84]) compared to those who did not. In contrast, TPE was associated with increased mortality in septic children without thrombocytopenia-associated multiorgan failure (RR: 2.23, 95% CI: 1.93, 2.57). There was no difference in outcomes in patients supported with centrifugal and membrane TPE. In both populations, patients supported on TPE as a continuous regime had poorer outcome.

    CONCLUSION: Current evidence indicates that TPE is a potential adjunct therapy in adults with severe sepsis but not in children.

  16. Rajasegaran S, Nooraziz AN, Abdullah A, Sanmugam A, Singaravel S, Gan CS, et al.
    J Pediatr Surg, 2024 Apr;59(4):577-582.
    PMID: 38160184 DOI: 10.1016/j.jpedsurg.2023.12.007
    BACKGROUND: Congenital diaphragmatic hernia (CDH) survivors often experience long-term CDH-associated morbidities, including musculoskeletal, gastrointestinal and respiratory issues. This study evaluates parent-reported health-related quality of life (HRQOL) and family impact of the disease.

    METHODS: Electronic medical records (EMR) were reviewed and phone surveys performed with parents of CDH survivors who underwent repair at our institution from 2010 to 2019. They completed the following Pediatric Quality of Life Inventory™ (PedsQL™) questionnaires: Generic Core Scales 4.0 (parent-proxy report) and Family Impact (FI) Module 2.0. Age-matched and gender-matched healthy controls from an existing database were used for comparison. Subgroup analysis of CDH patients alone was also performed. Appropriate statistical analysis was used with p 

  17. Tan LT, Nathan AM, Jayanath S, Eg KP, Thavagnanam S, Lum LCS, et al.
    Pediatr Pulmonol, 2020 12;55(12):3477-3486.
    PMID: 33002341 DOI: 10.1002/ppul.25083
    BACKGROUND: Provision of home mechanical ventilation (HMV) to children with chronic respiratory insufficiency enhances growth and quality of life. The hypothesis was that health-related quality of life (HRQoL) and the development of these children were poorer than in healthy children.

    OBJECTIVES: To determine the HRQoL and developmental outcome of children on HMV.

    METHODS: This cross-sectional study used the TNO-AZL Preschool children's Quality Of Life (TAPQOL; <5 years old) and Health Utilities Index (HUI) 2/3 (≥5 years old) to assess the quality of life and the Schedule of Growing Skills-II to assess development. Instruments were used on children currently or previously on HMV (≥3 months) and compared with age and sex-matched controls.

    RESULTS: Sixty-five patients and 130 controls were recruited. Patients' median (interquartile range) age was 3.12 (1.65, 5.81) years. Patients had significantly lower TAPQOL scores in the domains of lung, liveliness, positive mood, social functioning, motor functioning, and communication, and lower HUI 2/3 scores in hearing, sensation, pain, speech, mobility, ambulatory, dexterity, and self-care domains. The developmental outcome of patients was poorer in all domains. However, patients had fewer behavioral problems. Those with respiratory tract disease and without comorbidities had better HRQoL and developmental scores. Having a parent as the primary caregiver was associated with better speech and language skills.

    CONCLUSIONS: HRQoL and the developmental outcome are lower in children on HMV compared to controls. Children with respiratory tract disease and without comorbidities have a better outcome. Parents play a crucial role in the acquisition of speech.

  18. Nathan AM, Loo HY, de Bruyne JA, Eg KP, Kee SY, Thavagnanam S, et al.
    Pediatr Pulmonol, 2017 04;52(4):500-507.
    PMID: 27712049 DOI: 10.1002/ppul.23569
    INTRODUCTION: Home ventilation (HV) for children is growing rapidly worldwide. The aim was to describe (1) the sociodemographic characteristics of children on HV and (2) the indications for, means and outcome of initiating HV in children from a developing country.

    METHODOLOGY: This retrospective study included patients sent home on noninvasive or invasive ventilation, over 13 years, by the pediatric respiratory unit in a single center. Children who declined treatment were excluded.

    RESULTS: Seventy children were initiated on HV: 85.7% on noninvasive ventilation, 14.3% on invasive ventilation. There was about a threefold increase from 2001-2008 (n = 18) to 2009-2014 (n = 52). Median (range) age of initiating HV was 11 (1-169) months and 73% of children were <2 years old. Common indications for HV were respiratory (57.2%), chest/spine anomalies (11.4%), and neuromuscular (10.0%). Fifty-two percent came off their devices with a median (interquartile range) usage duration of 12 (4.8, 21.6) months. Ten children (14.3%) died with one avoidable death. Children with neuromuscular disease were less likely to come off their ventilator (0.0%) compared to children with respiratory disease (62.1%). Forty-one percent of parents bought their equipment, whereas 58.6% borrowed their equipment from the medical social work department and other sources.

    CONCLUSION: HV in a resource-limited country is possible. Children with respiratory disease made up a significant proportion of those requiring HV and were more likely to be weaned off. The mortality rate was low. The social work department played an important role in facilitating early discharge. Pediatr Pulmonol. 2017;52:500-507. © 2016 Wiley Periodicals, Inc.

  19. Yao S, Chong SL, Allen JC, Dang H, Ming M, Chan LCN, et al.
    Transl Pediatr, 2023 Mar 31;12(3):344-353.
    PMID: 37035406 DOI: 10.21037/tp-22-443
    BACKGROUND: To study the association in moderate and severe pediatric traumatic brain injury (TBI) between hyperglycemia, hyperlactatemia, acidosis and unfavorable outcome, as assessed by Pediatric Cerebral Performance Category (PCPC) on discharge from the pediatric intensive care unit (PICU).

    METHODS: Children <16 years old with TBI and Glasgow Coma Scale (GCS) ≤13 in an Asian multi-center PICU TBI cohort from January 2014 to October 2017 were included in this study. We defined unfavorable outcome as PCPC ≥3-moderate disability, severe disability, vegetative state, and death. We performed logistic regression to investigate the association between metabolic changes with unfavorable outcome. We divided hyperglycemia (glucose >11.1 mmol/L) during PICU admission into early-onset (within 24 h), late-onset (beyond 48 h) and persistent (throughout first 72 h).

    RESULTS: Among the 305 children analyzed, 136 (44.6%) had unfavorable outcome. Children with unfavorable outcome were more likely to have early hyperglycemia (75/136, 55.1% vs. 33/169, 19.5%; P<0.001), high lactate levels >2.0 mmol/L (74/136, 54.4% vs. 56/169, 32.5%; P<0.001) and initial acidosis (85/136, 62.5% vs. 78/169, 56.1%; P=0.003) compared to those with favorable outcome. After adjusting for gender, GCS ≤8 and presence of polytrauma, early hyperglycemia [adjusted odds ratio (aOR) =3.68, 95% CI: 2.12-6.39, P<0.001] and late hyperglycemia (aOR =13.30, 95% CI: 1.64-107.8, P=0.015] were independently associated with unfavorable outcome. All children with persistent hyperglycemia died.

    CONCLUSIONS: We described unfavorable outcome in pediatric TBI especially with persistent hyperglycemia. Future trials should investigate the causal relationship between glycemic trends, early intervention and outcome in this cohort.

  20. Chong SL, Qian S, Yao SHW, Allen JC, Dang H, Chan LCN, et al.
    J Neurosurg Pediatr, 2022 Feb 01;29(2):225-231.
    PMID: 34715667 DOI: 10.3171/2021.8.PEDS21281
    OBJECTIVE: Early posttraumatic seizures (EPTSs) in children after traumatic brain injury (TBI) increase metabolic stress on the injured brain. The authors sought to study the demographic and radiographic predictors for EPTS, and to investigate the association between EPTS and death, and between EPTS and poor functional outcomes among children with moderate to severe TBI in Asia.

    METHODS: A secondary analysis of a retrospective TBI cohort among participating centers of the Pediatric Acute & Critical Care Medicine Asian Network was performed. Children < 16 years of age with a Glasgow Coma Scale (GCS) score ≤ 13 who were admitted to pediatric intensive care units between January 2014 and October 2017 were included. Logistic regression analysis was performed to study risk factors for EPTS and to investigate the association between EPTS and death, and between EPTS and poor functional outcomes. Poor functional outcomes were defined as moderate disability, severe disability, and coma as defined by the Pediatric Cerebral Performance Category scale.

    RESULTS: Overall, 313 children were analyzed, with a median age of 4.3 years (IQR 1.8-8.9 years); 162 children (51.8%) had severe TBI (GCS score < 8), and 76 children (24.3%) had EPTS. After adjusting for age, sex, and the presence of nonaccidental trauma (NAT), only younger age was significantly associated with EPTS (adjusted odds ratio [aOR] 0.85, 95% CI 0.78-0.92; p < 0.001). Forty-nine children (15.6%) in the cohort died, and 87 (32.9%) of the 264 surviving patients had poor functional outcomes. EPTS did not increase the risk of death. After adjusting for age, sex, TBI due to NAT, multiple traumas, and a GCS score < 8, the presence of EPTS was associated with poor functional outcomes (aOR 2.08, 95% CI 1.05-4.10; p = 0.036).

    CONCLUSIONS: EPTSs were common among children with moderate to severe TBI in Asia and were associated with poor functional outcomes among children who survived TBI.

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