Tan Jun Hao
Email Address
gmstanjh@nus.edu.sg
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Publication A novel hospital capacity versus clinical justification triage score (CCTS) for prioritization of spinal surgeries in the "new normal state" of the COVID-19 pandemic(SPRINGER, 2021-01-02) Liu, Gabriel; Tan, Jun-Hao; Hey, Hwee Weng Dennis; Lau, Leok Lim; Thambiah, Joseph; Kumar, Naresh; Tan, Jonathan; Ruiz, John; Nga, Vincent; Lwin, Sein; Teo, Kejia; Ning, Chou; Agrawal, Rohit Vijay; NG, Bryan; Wong, Weng Hoa; Yeo, Tseng Tsai; Wong, Hee-Kit; Dr Weng Hoa Wong; SURGERY; ORTHOPAEDIC SURGERY; ANAESTHESIA; DUKE-NUS MEDICAL SCHOOLIntroduction: During the Coronavirus disease 2019 outbreak, while healthcare systems and hospitals are diverting their resources to combat the pandemic, patients who require spinal surgeries continue to accumulate. The aim of this study is to describe a novel hospital capacity versus clinical justification triage score (CCTS) to prioritize patients who require surgery during the “new normal state” of the COVID-19 pandemic. Methodology: A consensus study using the Delphi technique was carried out among clinicians from the Orthopaedic Surgery, Neurosurgery, and Anaesthesia departments. Three rounds of consensus were carried out via survey and Webinar discussions. Results: A 50-points score system consisting of 4 domains with 4 subdomains was formed. The CCTS were categorized into the hospital capacity, patient factors, disease severity, and surgery complexity domains. A score between 30 and 50 points indicated that the proposed operation should proceed without delay. A score of less than 20 indicates that the proposed operation should be postponed. A score between 20 and 29 indicates that the surgery falls within a grey area where further discussion should be undertaken to make a joint justification for approval of surgery. Conclusion: This study is a proof of concept for the novel CCTS scoring system to prioritize surgeries to meet the rapidly changing demands of the COVID-19 pandemic. It offers a simple and objective method to stratify patients who require surgery and allows these complex and difficult decisions to be unbiased and made transparently among surgeons and hospital administrators.Publication Application of a targeted-enrichment methodology for full-genome sequencing of Dengue 1-4, Chikungunya and Zika viruses directly from patient samples(Public Library of Science, 2019) Kamaraj, U.S.; Tan, J.H.; Mei, O.X.; Pan, L.; Chawla, T.; Uehara, A.; Wang, L.-F.; Ooi, E.E.; Gubler, D.J.; Tissera, H.; Ng, L.C.; Wilder-Smith, A.; de Sessions, P.F.; Barkham, T.; Anderson, D.E.; Sessions, O.M.; DUKE-NUS MEDICAL SCHOOLThe frequency of epidemics caused by Dengue viruses 1–4, Zika virus and Chikungunya viruses have been on an upward trend in recent years driven primarily by uncontrolled urbanization, mobility of human populations and geographical spread of their shared vectors, Aedes aegypti and Aedes albopictus. Infections by these viruses present with similar clinical manifestations making them challenging to diagnose; this is especially difficult in regions of the world hyperendemic for these viruses. In this study, we present a targeted-enrichment methodology to simultaneously sequence the complete viral genomes for each of these viruses directly from clinical samples. Additionally, we have also developed a customized computational tool (BaitMaker) to design these enrichment baits. This methodology is robust in its ability to capture diverse sequences and is amenable to large-scale epidemiological studies. We have applied this methodology to two large cohorts: a febrile study based in Colombo, Sri Lanka taken during the 2009–2015 dengue epidemic (n = 170) and another taken during the 2016 outbreak of Zika virus in Singapore (n = 162). Results from these studies indicate that we were able to cover an average of 97.04% ± 0.67% of the full viral genome from samples in these cohorts. We also show detection of one DENV3/ZIKV co-infected patient where we recovered full genomes for both viruses. © 2019 Kamaraj et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Publication Comparative whole-genome sequence analysis of Mycobacterium tuberculosis isolated from tuberculous meningitis and pulmonary tuberculosis patients(2018) Faksri, K; Xia, E; Ong, R.T.-H; Tan, J.H; Nonghanphithak, D; Makhao, N; Thamnongdee, N; Thanormchat, A; Phurattanakornkul, A; Rattanarangsee, S; Ratanajaraya, C; Suriyaphol, P; Prammananan, T; Teo, Y.-Y; Chaiprasert, A; SAW SWEE HOCK SCHOOL OF PUBLIC HEALTH; DUKE-NUS MEDICAL SCHOOLTuberculous meningitis (TBM) is a severe form of tuberculosis with a high mortality rate. The factors associated with TBM pathogenesis are still unclear. Using comparative whole-genome sequence analysis we compared Mycobacterium tuberculosis (Mtb) isolates from cerebrospinal fluid of TBM cases (n = 73) with those from sputum of pulmonary tuberculosis (PulTB) patients (n = 220) from Thailand. The aim of this study was to seek genetic variants of Mtb associated with TBM. Regardless of Mtb lineage, we found 242 variants that were common to all TBM isolates. Among these variants, 28 were missense SNPs occurring mainly in the pks genes (involving polyketide synthesis) and the PE/PPE gene. Six lineage-independent SNPs were commonly found in TBM isolates, two of which were missense SNPs in Rv0532 (PE-PGRS6). Structural variant analysis revealed that PulTB isolates had 14 genomic regions containing 2-3-fold greater read depth, indicating higher copy number variants and half of these genes belonged to the PE/PPE gene family. Phylogenetic analysis revealed only two small clusters of TBM clonal isolates without support from epidemiological data. This study reported genetic variants of Mtb commonly found in TBM patients compared to PulTB patients. Variants associated with TBM disease warrant further investigation. © 2018 The Author(s).Publication A systematic approach to the development of a safe live attenuated Zika vaccine(Nature Publishing Group, 2018) Kwek, S.S; Watanabe, S; Chan, K.R; Ong, E.Z; Tan, H.C; Ng, W.C; Nguyen, M.T.X; Gan, E.S; Zhang, S.L; Chan, K.W.K; Tan, J.H; Sessions, O.M; Manuel, M; Pompon, J; Chua, C; Hazirah, S; Tryggvason, K; Vasudevan, S.G; Ooi, E.E; DUKE-NUS MEDICAL SCHOOLZika virus (ZIKV) is a flavivirus that can cause congenital disease and requires development of an effective long-term preventative strategy. A replicative ZIKV vaccine with properties similar to the yellow fever 17D (YF17D) live-attenuated vaccine (LAV) would be advantageous, as a single dose of YF17D produces lifelong immunity. However, a replicative ZIKV vaccine must also be safe from causing persistent organ infections. Here we report an approach to ZIKV LAV development. We identify a ZIKV variant that produces small plaques due to interferon (IFN)-restricted viral propagation and displays attenuated infection of endothelial cells. We show that these properties collectively reduce the risk of organ infections and vertical transmission in a mouse model but remain sufficiently immunogenic to prevent wild-type ZIKV infection. Our findings suggest a strategy for the development of a safe but efficacious ZIKV LAV. © 2018 The Author(s).Publication A Zika virus from America is more efficiently transmitted than an Asian virus by Aedes aegypti mosquitoes from Asia(2017) Pompon, J; Morales-Vargas, R; Manuel, M; Tan, C.H; Vial, T; Tan, J.H; Sessions, O.M; Vasconcelos, P.D.C; Ng, L.C; Missé, D; DUKE-NUS MEDICAL SCHOOLZika is a mosquito-borne disease associated with neurological disorders that causes an on-going pandemic. The first outbreak was recorded in Micronesia in 2007, then in French Polynesia in 2014 from which it spread to South America in 2015 and ignited a widespread epidemic. Interestingly, Zika outbreaks in Asia remained of moderate intensity although the virus is circulating. To understand these epidemiological variations, we investigated the entomological determinants of ZIKV transmission in Asia. We used oral infection of mosquitoes collected in Singapore to identify the vector species, to quantify the blood infection threshold and to compare transmissibility between an Asian ZIKV strain (H/PF13) and an American strain collected in Brazil (BE H 815744). We have confirmed the vector status of Aedes aegypti and determined that 103 pfu/ml of blood is sufficient to infect mosquitoes. We showed that only the American strain was present in the saliva 3 days post-infection, and that this strain had a 30-40% higher rate of saliva infection in Ae. aegypti from 3 to 14 days post-infection than the Asian strain. Our data suggests that American strains are more efficiently transmitted than Asian strains, which raises concerns about the introduction of American strains in Asia. © 2017 The Author(s).Publication Alterations to DNA methylation and expression of CXCL14 are associated with suboptimal birth outcomes(2014) Cheong C.Y.; Chng K.; Lim M.K.; Amrithraj A.I.; Joseph R.; Sukarieh R.; Chee Tan Y.; Chan L.; Tan J.H.; Chen L.; Pan H.; Holbrook J.D.; Meaney M.J.; Seng Chong Y.; Gluckman P.D.; Stünkel W.; MICROBIOLOGY AND IMMUNOLOGY; DUKE-NUS MEDICAL SCHOOL; PAEDIATRICS; BIOCHEMISTRY; OBSTETRICS & GYNAECOLOGYCXCL14 is a chemokine that has previously been implicated in insulin resistance in mice. In humans, the role of CXCL14 in metabolic processes is not well established, and we sought to determine whether CXCL14 is a risk susceptibility gene important in fetal programming of metabolic disease. For this purpose, we investigated whether CXCL14 is differentially regulated in human umbilical cords of infants with varying birth weights. We found an elevated expression of CXCL14 in human low birth weight (LBW) cords, as well as in cords from nutritionally restricted Macaca fascicularis macaques. To further analyze the regulatory mechanisms underlying the expression of CXCL14, we examined CXCL14 in umbilical cord-derived mesenchymal stem cells (MSCs) that provide an in vitro cell-based system amenable to experimental manipulation. Using both whole frozen cords and MSCs, we determined that site-specific CpG methylation in the CXCL14 promoter is associated with altered expression, and that changes in methylation are evident in LBW infant-derived umbilical cords that may indicate future metabolic compromise through CXCL14.