698 results on '"Lim TH"'
Search Results
2. Combination treatments including the small-interfering RNA JNJ-3989 induce rapid and sometimes prolonged viral responses in patients with CHB
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Yuen, M-F, Locarnini, S, Lim, TH, Strasser, S, Sievert, W, Cheng, W, Thompson, AJ, Given, BD, Schluep, T, Hamilton, J, Biermer, M, Kalmeijer, R, Beumont, M, Lenz, O, De Ridder, F, Cloherty, G, Wong, DK-H, Schwabe, C, Jackson, K, Lai, CL, Gish, RG, Gane, E, Yuen, M-F, Locarnini, S, Lim, TH, Strasser, S, Sievert, W, Cheng, W, Thompson, AJ, Given, BD, Schluep, T, Hamilton, J, Biermer, M, Kalmeijer, R, Beumont, M, Lenz, O, De Ridder, F, Cloherty, G, Wong, DK-H, Schwabe, C, Jackson, K, Lai, CL, Gish, RG, and Gane, E
- Abstract
BACKGROUND & AIMS: RNA interference therapy has been shown to reduce hepatitis B surface antigen (HBsAg) levels in preclinical models, which could confer functional cure in patients with chronic hepatitis B. This phase IIa trial (ClinicalTrials.gov Identifier: NCT03365947) assessed the safety and efficacy of the small-interfering RNA JNJ-73763989 (JNJ-3989) plus a nucleos(t)ide analogue (NA), with/without the capsid assembly modulator JNJ-56136379 (JNJ-6379) in patients with chronic hepatitis B. METHODS: Treatment-naïve and NA-suppressed patients received 3 subcutaneous JNJ-3989 doses every week (QW; 100, 200, or 300 mg), 2 weeks (Q2W; 100 mg) or 4 weeks (Q4W; 25, 50, 100, 200, 300, or 400 mg), or JNJ-3989 Q4W (200 mg) plus oral JNJ-6379 250 mg daily for 12 weeks. Patients received NAs throughout. RESULTS: Eighty-four patients were recruited. All treatments were well tolerated, with all 5 serious adverse events considered unrelated to study drugs. JNJ-3989 100 to 400 mg Q4W resulted in HBsAg reductions ≥1 log10 IU/ml from baseline in 39/40 (97.5%) patients at the nadir. All patients receiving the triple combination (n = 12) had HBsAg reductions ≥1 log10 IU/ml from baseline at the nadir. HBsAg reductions were similar for HBeAg-positive (n = 21) and HBeAg-negative (n = 47) patients in all JNJ-3989 Q4W treatment arms, including the triple combination (n = 68). Smaller HBsAg reductions were seen with 25 mg (n = 8) and 50 mg (n = 8) than with 100 to 400 mg (n = 40). Shorter dosing intervals (QW [n = 12] and Q2W [n = 4]) did not improve response vs. Q4W dosing. HBsAg reductions ≥1 log10 IU/ml from baseline persisted in 38% of patients 336 days after the last JNJ-3989 dose. CONCLUSIONS: JNJ-3989 plus an NA, with/without JNJ-6379, was well tolerated and resulted in HBsAg reductions up to 336 days after the last JNJ-3989 Q4W dose. CLINICAL TRIAL NUMBER: NCT03365947. LAY SUMMARY: Hepatitis B virus affects people's livers and produces particles called hepatitis B surface antig
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- 2022
3. Endoscopic therapy for treatment of staple line leaks post Laparoscopic Sleeve Gastrectomy (LSG): Experience from a large bariatric surgery centre in New Zealand
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SOUTHWELL, T, LIM, TH, and OGRA, R
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- 2015
4. A Case of Severe Falciparum Malaria in a Returned Traveler
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Low, QJ, Lau, WK, Lim, TH, Lee, RA, and Cheo, SW
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Case Report ,human activities - Abstract
Primary care providers should be alert to travel-related infections. Around 10-40% of returning travelers from all destinations and 15-70% of travelers from tropical settings experience ill health, either overseas or upon returning home.(1) A systematic approach concentrating on possible infections should be undertaken based on the patient’s travel location, immunization history, presence of malaria chemoprophylaxis at the destination, other potential exposures, incubation period, and clinical presentation.(2–3) The World Health Organization (WHO) website is constantly being updated on specific travel-related infections and recent geographical outbreaks. In this paper, we report a case of severe falciparum malaria in a returned traveler.
- Published
- 2020
5. Incomplete Retinal Pigment Epithelial and Outer Retinal Atrophy in Age-Related Macular Degeneration Classification of Atrophy Meeting Report 4
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Guymer, RH, Rosenfeld, PJ, Curcio, CA, Holz, FG, Staurenghi, G, Freund, KB, Schmitz-Valckenberg, S, Sparrow, J, Spaide, RF, Tufail, A, Chakravarthy, U, Jaffe, GJ, Csaky, K, Sarraf, D, Mones, JM, Tadayoni, R, Grunwald, J, Bottoni, F, Liakopoulos, S, Pauleikhoff, D, Pagliarini, S, Chew, EY, Viola, F, Fleckenstein, M, Blodi, BA, Lim, TH, Chong, V, Lutty, J, Bird, AC, Sadda, SR, Guymer, RH, Rosenfeld, PJ, Curcio, CA, Holz, FG, Staurenghi, G, Freund, KB, Schmitz-Valckenberg, S, Sparrow, J, Spaide, RF, Tufail, A, Chakravarthy, U, Jaffe, GJ, Csaky, K, Sarraf, D, Mones, JM, Tadayoni, R, Grunwald, J, Bottoni, F, Liakopoulos, S, Pauleikhoff, D, Pagliarini, S, Chew, EY, Viola, F, Fleckenstein, M, Blodi, BA, Lim, TH, Chong, V, Lutty, J, Bird, AC, and Sadda, SR
- Abstract
PURPOSE: To describe the defining features of incomplete retinal pigment epithelium (RPE) and outer retinal atrophy (iRORA), a consensus term referring to the OCT-based anatomic changes often identified before the development of complete RPE and outer retinal atrophy (cRORA) in age-related macular degeneration (AMD). We provide descriptive OCT and histologic examples of disease progression. DESIGN: Consensus meeting. PARTICIPANTS: Panel of retina specialists, including retinal imaging experts, reading center leaders, and retinal histologists. METHODS: As part of the Classification of Atrophy Meeting (CAM) program, an international group of experts analyzed and discussed longitudinal multimodal imaging of eyes with AMD. Consensus was reached on a classification system for OCT-based structural alterations that occurred before the development of atrophy secondary to AMD. New terms of iRORA and cRORA were defined. This report describes in detail the CAM consensus on iRORA. MAIN OUTCOME MEASURES: Defining the term iRORA through OCT imaging and longitudinal cases showing progression of atrophy, with histologic correlates. RESULTS: OCT was used in cases of early and intermediate AMD as the base imaging method to identify cases of iRORA. In the context of drusen, iRORA is defined on OCT as (1) a region of signal hypertransmission into the choroid, (2) a corresponding zone of attenuation or disruption of the RPE, and (3) evidence of overlying photoreceptor degeneration. The term iRORA should not be used when there is an RPE tear. Longitudinal studies confirmed the concept of progression from iRORA to cRORA. CONCLUSIONS: An international consensus classification for OCT-defined anatomic features of iRORA are described and examples of longitudinal progression to cRORA are provided. The ability to identify these OCT changes reproducibly is essential to understand better the natural history of the disease, to identify high-risk signs of progression, and to study early interventi
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- 2020
6. Facile synthesis of Ge1-x Snx nanowires
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Xu, Y, primary, Al-Salim, N, primary, Lim, TH, primary, Bumby, Christopher, primary, Cheong, S, primary, and Tilley, RD, primary
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- 2021
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7. Human pharyngeal microbiota in age-related macular degeneration.
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Clark, SJ, Ho, EXP, Cheung, CMG, Sim, S, Chu, CW, Wilm, A, Lin, CB, Mathur, R, Wong, D, Chan, CM, Bhagarva, M, Laude, A, Lim, TH, Wong, TY, Cheng, CY, Davila, S, Hibberd, M, Clark, SJ, Ho, EXP, Cheung, CMG, Sim, S, Chu, CW, Wilm, A, Lin, CB, Mathur, R, Wong, D, Chan, CM, Bhagarva, M, Laude, A, Lim, TH, Wong, TY, Cheng, CY, Davila, S, and Hibberd, M
- Abstract
BACKGROUND: While the aetiology of age-related macular degeneration (AMD)-a major blinding disease-remains unknown, the disease is strongly associated with variants in the complement factor H (CFH) gene. CFH variants also confer susceptibility to invasive infection with several bacterial colonizers of the nasopharyngeal mucosa. This shared susceptibility locus implicates complement deregulation as a common disease mechanism, and suggests the possibility that microbial interactions with host complement may trigger AMD. In this study, we address this possibility by testing the hypothesis that AMD is associated with specific microbial colonization of the human nasopharynx. RESULTS: High-throughput Illumina sequencing of the V3-V6 region of the microbial 16S ribosomal RNA gene was used to comprehensively and accurately describe the human pharyngeal microbiome, at genus level, in 245 AMD patients and 386 controls. Based on mean and differential microbial abundance analyses, we determined an overview of the pharyngeal microbiota, as well as candidate genera (Prevotella and Gemella) suggesting an association towards AMD health and disease conditions. CONCLUSIONS: Utilizing an extensive study population from Singapore, our results provided an accurate description of the pharyngeal microbiota profiles in AMD health and disease conditions. Through identification of candidate genera that are different between conditions, we provide preliminary evidence for the existence of microbial triggers for AMD. Ethical approval for this study was obtained through the Singapore Health Clinical Institutional Review Board, reference numbers R799/63/2010 and 2010/585/A.
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- 2018
8. Systemic, Ocular and Genetic Risk Factors for Age-related Macular Degeneration and Polypoidal Choroidal Vasculopathy in Singaporeans.
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Cheung, CMG, Laude, A, Yeo, I, Tan, S-P, Fan, Q, Mathur, R, Lee, SY, Chan, CM, Tan, G, Lim, TH, Cheng, C-Y, Wong, TY, Cheung, CMG, Laude, A, Yeo, I, Tan, S-P, Fan, Q, Mathur, R, Lee, SY, Chan, CM, Tan, G, Lim, TH, Cheng, C-Y, and Wong, TY
- Abstract
To examine the association of systemic, ocular and genetic risk factors in neovascular age-related macular degeneration (nAMD) in a large cohort of Asian patients, and to further compare risk factors between those with typical AMD and polypoidal choroidal vasculoapthy (PCV) subtypes. We recruited 456 cases and 1,824 controls matched for age, gender and ethnicity. Data on systemic and ocular risk factors were collected on questionnaires. In a subgroup of subjects, we included genetic data on four AMD-associated single nucleotide polymorphisms (SNPs). Risk factors for nAMD and subtypes were analyzed. Systemic risk factors for nAMD included older age, male gender, higher BMI and higher HDL-cholesterol. Ocular risk factors included pseudophakic and shorter axial length. Risk factors common to both typical AMD and PCV subtypes included age, BMI and HDL-cholesterol. Shorter axial length was only associated with PCV, while male gender and pseudophakia were only associated with typical AMD. In the subgroup with genotype data, ARMS2 rs10490924 and CFH rs800292 were associated with nAMD. None of the risk factors were significantly different between PCV and typical AMD. Systemic, ocular and genetic risk factors were largely similar for typical AMD and PCV subtypes in this Asian population based in Singapore.
- Published
- 2017
9. HDL-cholesterol levels and risk of age-related macular degeneration: a multiethnic genetic study using Mendelian randomization.
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Fan, Q, Maranville, JC, Fritsche, L, Sim, X, Cheung, CMG, Chen, LJ, Gorski, M, Yamashiro, K, Ahn, J, Laude, A, Dorajoo, R, Lim, TH, Teo, Y-Y, Blaustein, RO, Yoshimura, N, Park, K-H, Pang, CP, Tai, ES, Khor, CC, Wong, TY, Runz, H, Cheng, C-Y, Fan, Q, Maranville, JC, Fritsche, L, Sim, X, Cheung, CMG, Chen, LJ, Gorski, M, Yamashiro, K, Ahn, J, Laude, A, Dorajoo, R, Lim, TH, Teo, Y-Y, Blaustein, RO, Yoshimura, N, Park, K-H, Pang, CP, Tai, ES, Khor, CC, Wong, TY, Runz, H, and Cheng, C-Y
- Abstract
BACKGROUND: Dyslipidemia, particularly high-density lipoprotein cholesterol (HDL-C), has recently been implicated in the pathogenesis of age-related macular degeneration (AMD), the leading cause of vision loss. However, epidemiological studies have yielded conflicting results. METHODS: We investigated the causal role of plasma lipid levels in AMD in multiethnic populations comprising 16 144 advanced AMD cases and 17 832 controls of European descent, together with 2219 cases and 5275 controls of Asian descent, using Mendelian randomization in three models. Model 1 is a conventional meta-analysis which does not account for pleiotropy of instrumental variable (IV) effects. Model 2 is a univariate, inverse variance weighted regression analysis that accounts for potential unbalanced pleiotropy using MR-Egger method. Finally, Model 3 is a multivariate regression analysis that addresses pleiotropy by MR-Egger method and by adjusting for effects on other lipid traits. RESULTS: A 1 standard deviation (SD) higher HDL-cholesterol level was associated with an odds ratio (OR) for AMD of 1.17 (95% confidence interval: 1.07-1.29) in Europeans (P = 6.88 × 10-4) and of 1.58 (1.24-2.00) in Asians (P = 2.92 × 10-4) in Model 3. The corresponding OR estimates were 1.30 (1.09-1.55) in Europeans (P = 3.18 × 10-3) and 1.42 (1.11-1.80) in Asians (P = 4.42 × 10-3) in Model 1, and 1.21 (1.11-1.31) in Europeans (P = 3.12 × 10-5) and 1.51 (1.20-1.91) in Asians (P = 7.61 × 10-4) in Model 2. Conversely, neither LDL-C (Europeans: OR = 0.96, P = 0.272; Asians: OR = 1.02, P = 0.874; Model 3) nor triglyceride levels (Europeans: OR = 0.91, P = 0.102; Asians: OR = 1.06, P = 0.613) were associated with AMD. We also assessed the association between lipid levels and polypoidal choroidal vasculopathy (PCV) in Asians, a subtype of AMD, and found a similar trend for association of PCV with HDL-C levels. CONCLUSIONS: Our study shows that high levels of plasma HDL-C are causally associated with an increased ri
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- 2017
10. PRESUMED RHEGMATOGENOUS RETINAL DETACHMENT IN PATIENTS WITH RETINOBLASTOMA
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Robertson Dm and Lim Th
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Male ,medicine.medical_specialty ,Adolescent ,genetic structures ,Retinal Neoplasms ,medicine.medical_treatment ,Cryotherapy ,Malignancy ,Eye Enucleation ,Radiotherapy, High-Energy ,Ophthalmology ,Humans ,Medicine ,In patient ,Child ,Retrospective Studies ,business.industry ,Retinoblastoma ,Retinal Detachment ,Infant ,Retinal detachment ,General Medicine ,medicine.disease ,eye diseases ,Scleral Buckling ,Female ,Special care ,Subretinal fluid ,business ,After treatment - Abstract
PURPOSE To review the characteristics, treatment, and outcome of presumed rhegmatogenous retinal detachment (RD) in patients with retinoblastoma. METHODS Descriptive consecutive case series study from 1970 to 1996. RESULTS Of 45 eyes with retinoblastoma that received various modalities of eye-sparing treatment and adequate follow-up, five developed presumed rhegmatogenous RD after treatment. All five eyes had previous treatment with external beam radiation, four of which also had been treated with cryotherapy. To minimize the potential spread of the malignancy intraoperatively, long disease-free intervals were ensured before scleral buckling surgeries were performed, and special care was taken during subretinal fluid drainage. The RDs were totally reattached in three eyes and partially reattached in the other two. CONCLUSION Presumed rhegmatogenous RD may occur after external beam radiation or cryotherapy for retinoblastoma. It poses special challenges in management.
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- 2000
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11. Burden Of Wet Age-Related Macular Degeneration In Singapore In The Year 2030
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Saxena, N, primary, George, PP, additional, Heng, BH, additional, Yong, SO, additional, and Lim, TH, additional
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- 2016
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12. New loci and coding variants confer risk for age-related macular degeneration in East Asians.
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Cheng, C-Y, Yamashiro, K, Chen, LJ, Ahn, J, Huang, L, Cheung, CMG, Miyake, M, Cackett, PD, Yeo, IY, Laude, A, Mathur, R, Pang, J, Sim, KS, Koh, AH, Chen, P, Lee, SY, Wong, D, Chan, CM, Loh, BK, Sun, Y, Davila, S, Nakata, I, Nakanishi, H, Akagi-Kurashige, Y, Gotoh, N, Tsujikawa, A, Matsuda, F, Mori, K, Yoneya, S, Sakurada, Y, Iijima, H, Iida, T, Honda, S, Lai, TYY, Tam, POS, Chen, H, Tang, S, Ding, X, Wen, F, Lu, F, Zhang, X, Shi, Y, Zhao, P, Zhao, B, Sang, J, Gong, B, Dorajoo, R, Yuan, J-M, Koh, W-P, van Dam, RM, Friedlander, Y, Lin, Y, Hibberd, ML, Foo, JN, Wang, N, Wong, CH, Tan, GS, Park, SJ, Bhargava, M, Gopal, L, Naing, T, Liao, J, Ong, PG, Mitchell, P, Zhou, P, Xie, X, Liang, J, Mei, J, Jin, X, Saw, S-M, Ozaki, M, Mizoguchi, T, Kurimoto, Y, Woo, SJ, Chung, H, Yu, H-G, Shin, JY, Park, DH, Kim, IT, Chang, W, Sagong, M, Lee, S-J, Kim, HW, Lee, JE, Li, Y, Liu, J, Teo, YY, Heng, CK, Lim, TH, Yang, S-K, Song, K, Vithana, EN, Aung, T, Bei, JX, Zeng, YX, Tai, ES, Li, XX, Yang, Z, Park, K-H, Pang, CP, Yoshimura, N, Wong, TY, Khor, CC, Cheng, C-Y, Yamashiro, K, Chen, LJ, Ahn, J, Huang, L, Cheung, CMG, Miyake, M, Cackett, PD, Yeo, IY, Laude, A, Mathur, R, Pang, J, Sim, KS, Koh, AH, Chen, P, Lee, SY, Wong, D, Chan, CM, Loh, BK, Sun, Y, Davila, S, Nakata, I, Nakanishi, H, Akagi-Kurashige, Y, Gotoh, N, Tsujikawa, A, Matsuda, F, Mori, K, Yoneya, S, Sakurada, Y, Iijima, H, Iida, T, Honda, S, Lai, TYY, Tam, POS, Chen, H, Tang, S, Ding, X, Wen, F, Lu, F, Zhang, X, Shi, Y, Zhao, P, Zhao, B, Sang, J, Gong, B, Dorajoo, R, Yuan, J-M, Koh, W-P, van Dam, RM, Friedlander, Y, Lin, Y, Hibberd, ML, Foo, JN, Wang, N, Wong, CH, Tan, GS, Park, SJ, Bhargava, M, Gopal, L, Naing, T, Liao, J, Ong, PG, Mitchell, P, Zhou, P, Xie, X, Liang, J, Mei, J, Jin, X, Saw, S-M, Ozaki, M, Mizoguchi, T, Kurimoto, Y, Woo, SJ, Chung, H, Yu, H-G, Shin, JY, Park, DH, Kim, IT, Chang, W, Sagong, M, Lee, S-J, Kim, HW, Lee, JE, Li, Y, Liu, J, Teo, YY, Heng, CK, Lim, TH, Yang, S-K, Song, K, Vithana, EN, Aung, T, Bei, JX, Zeng, YX, Tai, ES, Li, XX, Yang, Z, Park, K-H, Pang, CP, Yoshimura, N, Wong, TY, and Khor, CC
- Abstract
Age-related macular degeneration (AMD) is a major cause of blindness, but presents differently in Europeans and Asians. Here, we perform a genome-wide and exome-wide association study on 2,119 patients with exudative AMD and 5,691 controls, with independent replication in 4,226 patients and 10,289 controls, all of East Asian descent, as part of The Genetics of AMD in Asians (GAMA) Consortium. We find a strong association between CETP Asp442Gly (rs2303790), an East Asian-specific mutation, and increased risk of AMD (odds ratio (OR)=1.70, P=5.60 × 10(-22)). The AMD risk allele (442Gly), known to protect from coronary heart disease, increases HDL cholesterol levels by 0.17 mmol l(-1) (P=5.82 × 10(-21)) in East Asians (n=7,102). We also identify three novel AMD loci: C6orf223 Ala231Ala (OR=0.78, P=6.19 × 10(-18)), SLC44A4 Asp47Val (OR=1.27, P=1.08 × 10(-11)) and FGD6 Gln257Arg (OR=0.87, P=2.85 × 10(-8)). Our findings suggest that some of the genetic loci conferring AMD susceptibility in East Asians are shared with Europeans, yet AMD in East Asians may also have a distinct genetic signature.
- Published
- 2015
13. Peak-Dose Ballism Associated with Declining Implantable Pulse Generator Battery Life in Deep Brain Stimulation for Parkinson’s Disease
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Denzel Chong Jen-Rei, Lim Thien Thien, Lee Hock Keong, Hoe Wei Leng, Onanong Phokaewvarangkul, and Roongroj Bhidayasiri
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Neurology. Diseases of the nervous system ,RC346-429 - Published
- 2021
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14. Bilateral optic nerve infiltration in tuberculous meningitis: A diagnostic dilemma
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Lim Thiam-Hou, Ibrahim Mohtar, Wan Hazabbah Wan Hitam, and Sanihah Abdul Halim
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tuberculous meningitis ,infiltrative optic neuropathy ,tuberculoma ,Medical emergencies. Critical care. Intensive care. First aid ,RC86-88.9 - Abstract
Rationale: Tuberculous meningitis (TBM) is severe extrapulmonary tuberculosis that can cause poor outcomes without timely treatment. We report a case of presumed TBM that presented solely ocular complaints without other neurological features. Patient’s concerns: A 71-year-old man presented with a sudden central visual defect in both eyes for 10 days. Fundoscopy showed bilateral hyperaemic swelling disc with infiltrates. Diagnosis: A diagnosis of presumptive TBM was made with Mantoux test reading 15 mm, elevated erythrocyte sedimentation rate, subdural effusion on CT scan, and high opening pressure. Intervention: Anti-tuberculous treatment. Outcomes: Bilateral vision improved and optic discs swelling resolved. Lessons: Early recognition of TBM with optic nerve infiltration is crucial for prompt treatment that may lead to a good prognosis. Neuroimaging will facilitate the diagnosis when other investigations show a borderline result.
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- 2021
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15. Future of Cardiac-CT
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Lim, TH, primary
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- 2014
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16. Synthesis of CeO2-Fe2O3 Mixed Oxides for Low-Temperature Carbon Monoxide Oxidation
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Chuc Ngoc Pham, Quyen Van Trinh, Dang Van Thai, Nhiem Ngoc Dao, Bac Quang Nguyen, Dung Trung Doan, Hung Bao Le, Vinh Van Nguyen, Lim Thi Duong, and Lam Dai Tran
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Physical and theoretical chemistry ,QD450-801 - Abstract
In this study, the CeO2-Fe2O3 mixed oxide catalysts have been prepared by combustion method using gel-created tartaric acid. The ability of effective carbon monoxide (CO) oxidation to carbon dioxide (CO2) by CeO2-Fe2O3 catalyst under low-temperature conditions was also demonstrated. The calcined CeO2-Fe2O3 material has a porous honeycomb structure and good gaseous absorption-desorption ability. The solid solution of CeO2-Fe2O3 mixed oxides was formed by the substitution of Fe+3 ions at some Ce4+ ion sites within the CeO2 crystal lattice. The results also showed that the calcination temperature and the molar ratio of Ce3+ ions to Fe3+ ions (CF) affected the formation of the structural phase and the catalytic efficiency. The catalytic properties of the CeO2-Fe2O3 mixed oxide were good at the CF ratio of 1 : 1, the average crystal size was near 70 nm, and the specific surface area was about 20.22 m2.g-1. The full conversion of CO into CO2 has been accomplished at a relatively low temperature of 270 °C under insufficient O2 conditions.
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- 2022
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17. PSS7 - Burden Of Wet Age-Related Macular Degeneration In Singapore In The Year 2030
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Saxena, N, George, PP, Heng, BH, Yong, SO, and Lim, TH
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- 2016
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18. Infective crystalline keratopathy due to Citrobacter koseri
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Lim Thiam-Hou, Evelyn Li Min Tai, Shamel Sonny Teo Khairy, and Ibrahim Mohtar
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infectious crystalline keratopathy ,citrobacter koseri ,gram-negative bacteria ,Medical emergencies. Critical care. Intensive care. First aid ,RC86-88.9 - Abstract
Rationale: Infectious keratopathy is an ocular emergency with the potential to cause irreversible blindness. Patient's concerns: A 63-year-old diabetic man presented with a 3-day history of painful red right eye. He had a history of multiple ocular surgeries in the affected eye without recent ocular trauma. Diagnosis: Infective crystalline keratopathy secondary to Citrobacter koseri. Interventions: Topical corticosteroids were discontinued, and dual topical antibiotic therapy of moxifloxacin 5% and gentamycin 0.3% were applied. Outcomes: Twelve hours after the start of treatment, the crystalline nature of the infiltrate disappeared, with enlargement of the epithelial defect. The antibiotic regime was continued and the lesion healed within a week of presentation with residual scarring. Lessons: Infective crystalline keratopathy classically presents with intrastromal branching fern-like opacities and minimal anterior segment inflammation in an immunosuppressed eye. The mainstay of management is corticosteroid discontinuation and the administration of empirical antibiotics until the results of the culture and sensitivity are available. In Citrobacter-related cases, treatment may result in a suppurative appearance before healing of the lesion.
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- 2021
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19. Isolation and Production of Human Monoclonal Antibody Proteins against a Toxocara canis Excretory–Secretory Recombinant Antigen
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Zamrina Baharudeen, Rahmah Noordin, Lim Theam Soon, Dinesh Balachandra, Nor Suhada Anuar, Fatin Hamimi Mustafa, and Anizah Rahumatullah
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Toxocara canis ,phage display technology ,recombinant monoclonal antibodies ,antigen-antibody binding assays ,antigen detection ELISA ,Medicine - Abstract
Toxocariasis is a widespread zoonotic parasitic disease with a significant socioeconomic impact, particularly on underprivileged communities. Limitations of existing diagnostic tools and vague presenting symptoms may lead to misdiagnosis, thus underestimating the actual global impact of the disease. The present study describes the isolation and production of novel recombinant monoclonal antibodies against Toxocara canis recombinant TES-26 antigen (rTES-26) utilizing a human helminth scFv phage display library. The isolated antibody clones were characterized based on their gene sequences and binding characteristics. Three clones representing unique gene families (clone 48: IgHV3-LV1; clone 49: IgHV3-LV3; clone 50: IgHV6-LV3) were isolated, but only clones 48 and 49 showed successful insertion of the full-length scFv antibody sequence after sub-cloning. Both clones produced antibody proteins of good solubility and satisfactory yield and purity. Binding assays via Western blot and ELISA using rTES-26 and Toxocara canis native protein showed that both monoclonal antibodies were highly specific and sensitive to the target antigen. A preliminary antigen detection ELISA showed the diagnostic potential of the monoclonal antibody proteins. The proteins can also be useful in studying host–parasite interactions and therapeutic applications.
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- 2022
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20. Tele-ophthalmology research in post-phacoemulsification diagnostic outcomes (TORPEDO) study - preliminary results
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YANG, FP, primary and LIM, TH, additional
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- 2012
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21. PSS1 BEVACIZUMAB FOR NEO-VASCULAR AGE RELATED MACULAR DEGENERATION—EVIDENCE SUMMARY
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George, PP, primary, Molina, JAD, additional, Heng, BH, additional, Tan, NWH, additional, and Lim, TH, additional
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- 2010
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22. Quality Management in Radiology in Korea
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Lim, TH, primary
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- 2006
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23. Prediction of Farmers’ Income in Hebei Province Based on the Fractional Grey Model (1,1)
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Yongqiang Xu, Lim Thien Sang, and Kun Wang
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Mathematics ,QA1-939 - Abstract
The problem of increasing farmers’ income has been a hot issue of social concern. Understanding the farmers’ income and the overall development trend is conducive to the rational layout of the social economy and promotes the steady development of a well-off society. Based on this, the paper selects the per capita disposable income (PCDI) of farmers’ households from 2012 to 2019 in 11 cities of Hebei Province as the research object and applies the fractional grey model (FGM (1,1)) to predict farmers’ income from 2020 to 2024. The results show that the farmers’ income will increase in the next five years. However, the growth rate of farmers’ income is slow in the areas with a large base of farmers’ income and strong in the areas with a small base of farmers’ income. The area with the highest trend in the growth rate of farmers’ income is Zhangjiakou and the lowest place is Handan. Only Shijiazhuang’s income growth rate is on the rise. Finally, suggestions are given to promote farmers’ income in Hebei Province.
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- 2021
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24. Central serous retinopathy complicating systemic lupus erythematosus: a case series
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Khng, CGYW, primary, Yap, EY, additional, Au-Eong, KG, additional, Lim, TH, additional, and Leong, KH, additional
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- 2000
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25. A method for covering surfaces of reflective gait markers
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Abuzzahab, FS, primary, Lim, TH, additional, Harris, GF, additional, Hasegawa, T, additional, and Kidder, SM, additional
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- 1995
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26. Evaluation of contrast-enhanced magnetic resonance angiography (MRA) using Gd-DOTA compared with time-of-flight MRA in the diagnosis of clinically significant non-coronary arterial disease.
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Kang JW, Lim TH, Choi CG, Ko GY, Kim JK, Kwon TW, Kang, Joon-Won, Lim, Tae-Hwan, Choi, Choong-Gon, Ko, Gi-Young, Kim, Jeong-Kon, and Kwon, Tae-Won
- Abstract
Objectives: This trial assessed diagnostic accuracy of contrast-enhanced magnetic resonance angiography (MRA) with meglumine gadoterate (Gd-DOTA) at 3 Tesla (T) over unenhanced MRA at 3 T in non-coronary arterial diseases by comparing their accuracy with that of the gold standard, x-ray angiography.Methods: Ninety-two patients with suspected non-coronary arterial disease underwent in fixed sequence unenhanced time-of flight (TOF) MRA, contrast-enhanced MRA using a Gd-DOTA bolus (intravenous bolus 0.1 mmol/kg) and x-ray angiography.Results: Eighty-four patients (71 male, 13 female; median age 64.5 years) were included in an intent-to-treat efficacy analysis. Targeted vascular areas were aorto-iliac, calf, carotid, femoral, popliteal and renal. Within-patient accuracy was significantly higher with contrast-enhanced MRA using Gd-DOTA than with unenhanced MRA (p = 0.0003). There was 84.4 +/- 17.5% agreement between contrast-enhanced MRA (Gd-DOTA) and x-ray angiography, compared with 76.8 +/- 20.4% between non-enhanced MRA and x-ray angiography. Sensitivity and specificity were also better with Gd-DOTA compared with non-enhanced MRA at the segment level. Duration of the MRA procedure was 3.5 times shorter with Gd-DOTA compared with non-enhanced MRA. Six patients reported six mild or moderate adverse events. No serious adverse events occurred.Conclusions: Contrast-enhanced MRA using Gd-DOTA at 3 T was superior to unenhanced TOF MRA in the vascular territories investigated. [ABSTRACT FROM AUTHOR]- Published
- 2010
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27. Outcomes of patients with acute type a aortic intramural hematoma.
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Song JK, Yim JH, Ahn JM, Kim DH, Kang JW, Lee TY, Song JM, Choo SJ, Kang DH, Chung CH, Lee JW, and Lim TH
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- 2009
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28. Investigation of T2-weighted signal intensity of infarcted myocardium and its correlation with delayed enhancement magnetic resonance imaging in a porcine model with reperfused acute myocardial infarction.
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Choi SH, Kang JW, Kim ST, Lee BH, Chun EJ, Schuleri KH, Choi SI, Lim TH, Choi, Seong Hoon, Kang, Joon-Won, Kim, Sang-Tae, Lee, Byung Han, Chun, Eun Ju, Schuleri, Karl H, Choi, Sang Il, and Lim, Tae-Hwan
- Abstract
To assess the signal pattern in T2-weighted images (T2WI) and determine its relation to persistent microvascular obstruction (PMO) and intramyocardial hemorrhage in a porcine model with reperfused acute myocardial infarction. Left anterior descending artery was occluded (90 or 180 min) and reperfused (90 min). T2WI and delayed-enhanced magnetic resonance images (DE-MRI) were acquired. The T2WI signal pattern, T2WI contrast ratio, PMO, and intramyocardial hemorrhage were evaluated, and their interrelationships were analyzed. The infarct area on T2WI was recorded as a homogeneous high-intensity signal or as low- or iso-intensity signals. The contrast ratio of the T2WI in the cases with PMO was significantly lower than that in those without PMO (1.38 +/- 0.25 vs. 1.89 +/- 0.31, P < 0.05), and it showed significant inverse correlation with the extent of PMO observed in DE-MRI images (r =-0.8, P < 0.05). The extent of PMO correlated strongly with that of intramyocardial hemorrhage (r = 0.97, P < 0.05). The abnormal signal area in the T2WI was larger than the infarct area in the DE-MRI images (47.0 +/- 9.9% vs. 37.8 +/- 9.9%, P < 0.05) and the infarct area observed after TTC staining (47.0 +/- 9.9% vs. 37.4 +/- 8.4%, P < 0.05). We observed variable T2WI signal patterns for the infarcted myocardium. Lower T2WI contrast ratios significantly correlated with the extent of PMO in DE-MRI and intramyocardial hemorrhage in the gross specimen. [ABSTRACT FROM AUTHOR]
- Published
- 2009
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29. Incidental cardiac and pericardial abnormalities on chest CT.
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Lee SH, Seo JB, Kang JW, Chae EJ, Park SH, Lim TH, Lee, Soo-Hyun, Seo, Joon Beom, Kang, Joon-Won, Chae, Eun Jin, Park, Seong Hoon, and Lim, Tae-Hwan
- Published
- 2008
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30. Some existence results for advanced backward stochastic differential equations with a jump time
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Jeanblanc Monique, Lim Thomas, and Agram Nacira
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Applied mathematics. Quantitative methods ,T57-57.97 ,Mathematics ,QA1-939 - Abstract
In this paper, we are interested by advanced backward stochastic differential equations (ABSDEs), in a probability space equipped with a Brownian motion and a single jump process, with a jump at time τ. ABSDEs are BSDEs where the driver depends on the future paths of the solution. We show, that under immersion hypothesis between the Brownian filtration and its progressive enlargement with τ, assuming that the conditional law of τ is equivalent to the unconditional law of τ, and a Lipschitz condition on the driver, the ABSDE has a solution.
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- 2017
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31. Endotracheal intubation using a GlideScope video laryngoscope by emergency physicians: a multicentre analysis of 345 attempts in adult patients.
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Choi HJ, Kang H, Lim TH, Chung HS, Cho J, Oh Y, Kim Y, and Korean Emergency Airway Management Registry (KEAMR) Investigators
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OBJECTIVE: To investigate the use and success rates of the GlideScope (GVL) by emergency physicians (EPs) during the initial two years after its introduction. METHODS: We performed an observational study using registry data of five emergency departments. The success rates in adult patients were evaluated and compared with those of conventional laryngoscope (CL). RESULTS: The GVL was used in 345 (10.7%) of 3233 intubation attempts by EPs. The overall success rate of the GVL was not higher than a CL (79.1% vs 77.6%, p=0.538). The success rate for the patients with difficult airway was higher in the GVL than a CL (80.0% vs 50.4%, p<0.001). CONCLUSION: The GVL was not used frequently by EPs during the initial two years after its introduction. Although the GVL provides a better glottic view, the overall success rates were similar to a CL. The GVL may be useful in patients with difficult airway. [ABSTRACT FROM AUTHOR]
- Published
- 2010
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32. Use of Stretch Expanded Polytetrafluoroethylene as a Microvascular Graft in a Low-pressure Situation
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Marcus T.C. Wong, Jane Lim, and Lim Thiam Chye
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low pressure ,microvascular ,polytetrafluoroethylene ,Surgery ,RD1-811 - Abstract
Microvascular reconstruction is often limited by the availability and length of the pedicle. The harvesting of autologous vein grafts adds morbidity and may not provide a good match. Expanded polytetrafluoroethylene (ePTFE) grafts have been used routinely in macrovascular surgery. However, there are no conclusive data on the performance of small-diameter PTFE grafts for pedicle lengthening in free flaps in a low-pressure situation. In this study, we evaluated the efficacy of 3-mm diameter stretch ePTFE grafts to lengthen the venous pedicle of a free flap. Methods: Fifteen male New Zealand white rabbits were operated on under sterile conditions. Using an operating microscope, an epigastric flap was raised and the pedicle was exposed and dissected to its origin from the superficial femoral vessels. A segment of the vein of 1cm to 3cm was replaced with a stretch ePTFE graft. Microsurgical anastomoses were performed using 9-0 nylon sutures. Four weeks postoperatively, the flaps were raised again with the pedicles re-explored. The graft was then removed and examined histologically. Results: All the grafts demonstrated immediate patency. There were no cases of flap loss on the control side at 4 weeks postoperatively. When re-explored, the patent ePTFE grafts appeared to be covered by connective tissue. Light microscopy showed neoendothelialization with fibrovascular ingrowth. Conclusion: From this study, we can conclude that 3-mm diameter stretch ePTFE grafts can be used successfully as an alternative to bridging autologous vein grafts in free-flap pedicles.
- Published
- 2007
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33. Quantitative cardiac-cineangiography in acquired valvular heart disease
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Han, MC, primary and Lim, TH, additional
- Published
- 1980
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34. Two-chambered right ventricle resulting from aberrant muscle bundles a case report
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Lim, TH, primary, Ko, KH, additional, Im, CK, additional, and Han, MC, additional
- Published
- 1979
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35. Transpositions and malpositions of the great arteries
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Yoo, SJ, primary, Park, JH, additional, Han, MC, additional, and Lim, TH, additional
- Published
- 1980
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36. Biomechanical comparison of anterior, posterior, and circumferential fixation after one-level anterior cervical corpectomy in the human cadaveric spine.
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Karam YR, Dahdaleh NS, Magnetta MJ, Kim BS, Lim TH, Serhan H, Torner JC, and Hitchon PW
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- 2011
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37. Pulsatile To-and-Fro Flow Detected by Contrast-Enhanced Electrocardiogram-Gated Computed Tomography: A Novel Method for Detecting the Leakage Point of a Pseudoaneurysm.
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Kim B, Kang JW, Lee CW, Chul Suh D, Lee JW, and Lim TH
- Published
- 2010
38. VIR-2218 (elebsiran) plus pegylated interferon-alfa-2a in participants with chronic hepatitis B virus infection: a phase 2 study.
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Yuen MF, Lim YS, Yoon KT, Lim TH, Heo J, Tangkijvanich P, Tak WY, Thanawala V, Cloutier D, Mao S, Arizpe A, Cathcart AL, Gupta SV, Hwang C, and Gane E
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- Humans, Adult, Female, Male, Middle Aged, Young Adult, DNA, Viral blood, DNA, Viral analysis, Treatment Outcome, Adolescent, Aged, Hepatitis B virus drug effects, Hepatitis B virus immunology, Hepatitis B virus genetics, Interferon-alpha therapeutic use, Interferon-alpha administration & dosage, Interferon-alpha adverse effects, Polyethylene Glycols adverse effects, Polyethylene Glycols administration & dosage, Polyethylene Glycols therapeutic use, Hepatitis B, Chronic drug therapy, Antiviral Agents therapeutic use, Antiviral Agents adverse effects, Antiviral Agents administration & dosage, Recombinant Proteins administration & dosage, Recombinant Proteins therapeutic use, Recombinant Proteins adverse effects, Drug Therapy, Combination, Hepatitis B Surface Antigens blood, Hepatitis B Surface Antigens immunology
- Abstract
Background: Chronic hepatitis B virus (HBV) remains a global concern, with current treatments achieving low rates of HBsAg seroclearance. VIR-2218 (elebsiran), a small interfering RNA agent against HBV transcripts, reduces HBsAg concentrations. We aimed to evaluate the safety and antiviral activity of VIR-2218 with and without pegylated interferon-alpha-2a treatment in participants with chronic HBV., Methods: This open-label, phase 2 study was conducted at 23 sites in six countries (New Zealand, Australia, Hong Kong, Thailand, South Korea, and Malaysia). Adults (aged 18-65 years) with chronic HBV infection without cirrhosis and with HBsAg more than 50 IU/mL and HBV DNA less than 90 IU/mL who were on continued nucleoside or nucleotide reverse transcriptase inhibitor (NRTI) therapy for 2 months or longer were eligible. Participants were enrolled into one of six cohorts to receive VIR-2218 200 mg subcutaneously every 4 weeks, with or without 180 μg subcutaneous pegylated interferon-alfa-2a once per week. Cohort 1 received six doses of VIR-2218 (total 20 weeks); cohort 2 received six doses of VIR-2218 starting at day 1, plus 12 doses of pegylated interferon-alfa-2a starting at week 12 (total 24 weeks); cohort 3 received six doses of VIR-2218 and 24 doses of pegylated interferon-alfa-2a (total 24 weeks); cohort 4 received six doses of VIR-2218 and up to 48 doses of pegylated interferon-alfa-2a (total 48 weeks); cohort 5 received up to 13 doses of VIR-2218 and up to 44 doses of pegylated interferon-alfa-2a (total 48 weeks); and cohort 6 received three doses of VIR-2218 and 12 doses of pegylated interferon-alfa-2a (total 12 weeks). The primary endpoints were the incidence of adverse events and clinical assessments (including results of laboratory tests). Secondary endpoints were the mean maximum reduction of serum HBsAg at any timepoint; the proportion of participants with serum HBsAg seroclearance at any timepoint and for more than 6 months after the end of treatment; and the proportion of participants with anti-HBs seroconversion at any timepoint. For patients who were HBeAg-positive, we also assessed the proportion with HBeAg seroclearance or anti-HBe seroconversion at any timepoint. This study is registered with ClinicalTrials.gov, NCT03672188, and is ongoing., Findings: Between July 2, 2020, and Nov 2, 2021, 124 individuals were screened for eligibility, 84 of whom were enrolled (15 in cohort 1, 15 in cohort 2, 18 in cohort 3, 18 in cohort 4, 13 in cohort 5, and five in cohort 6). Participants were predominantly HBeAg-negative, Asian, and male (66 [79%] participants were male and 18 [21%] were female). Most treatment emergent adverse events were grades 1-2. Three (20%) participants in cohort 1, four (27%) in cohort 2, eight (44%) in cohort 3, seven (39%) in cohort 4, six (46%) in cohort 5, and two (40%) in cohort 6 reported treatment-emergent adverse events related to VIR-2218. 12 (80%) participants in cohort 2, 12 (67%) in cohort 3, 14 (78%) in cohort 4, 13 (100%) in cohort 5, and three (60%) in cohort 6 reported treatment-emergent adverse events related to pegylated interferon-alfa-2a. Two (13%) participants in cohort 1 had elevations in alanine aminotransferase, compared with 13 (87%) participants in cohort 2, 15 (83%) in cohort 3, 17 (94%) in cohort 4, 11 (85%) in cohort 5, and three (60%) in cohort 6. The mean maximum change from baseline at any timepoint in HBsAg concentration was -2·0 log
10 IU/mL (95% CI -2·1 to -1·8) in cohort 1, -2·2 log10 IU/mL (-2·5 to -1·8) in cohort 2, -2·5 log10 IU/mL (-2·8 to -2·1) in cohort 3, -2·4 log10 IU/mL (-3·1 to -1·8) in cohort 4, -3·0 log10 IU/mL (-3·7 to -2·3) in cohort 5, and -1·7 log10 IU/mL (-2·1 to -1·4) in cohort 6. 11 participants (one in cohort 2, one in cohort 3, five in cohort 4, and four in cohort 5) receiving VIR-2218 plus pegylated interferon-alfa-2a had HBsAg seroclearance at any timepoint. Of these, ten (91%; one in cohort 2, five in cohort 4, and four in cohort 5) had anti-HBs seropositivity. Six participants (one in cohort 2, three in cohort 4, and two in cohort 5) had sustained HBsAg seroclearance through to 24 weeks after the end of treatment. No participants receiving VIR-2218 monotherapy (cohort 1) or VIR-2218 plus pegylated interferon-alfa-2a 12-week regimen (cohort 6) had HBsAg seroclearance. 12 (42%) of 26 participants (one of four in cohort 1, two of six in cohort 2, four of seven in cohort 3, four of six in cohort 4, and one of three in cohort 5) who were HBeAg positive at baseline had HBeAg seroclearance or anti-HBe seroconversion., Interpretation: The results of this phase 2 study support further development of VIR-2218 as a potential therapy for patients with chronic HBV infection. Additional clinical trials of VIR-2218 with and without pegylated interferon-alfa-2a in combination with an HBsAg-targeting monoclonal antibody are ongoing., Funding: Vir Biotechnology., Competing Interests: Declaration of interests M-FY is a consultant for AbbVie, Arbutus Biopharma, Bristol Myers Squibb, ClearB Therapeutics, Dicerna Pharmaceuticals, GlaxoSmithKline, Gilead Sciences, Janssen, Merck Sharp & Dohme, Spring Bank Pharmaceuticals, Roche, and Vir Biotechnology, and has received grant support from Arrowhead Pharmaceuticals, Assembly Biosciences, Bristol Myers Squibb, Fujirebio Incorporation, Gilead Sciences, Merck Sharp & Dohme, Spring Bank Pharmaceuticals, and Sysmex Corporation. Y-SL has received grant support from Gilead Sciences, has received consultant fees from AbbVie, Assembly Biosciences, GlaxoSmithKline, Gilead Sciences, Janssen, Olix Pharmaceuticals, Roche, Vaccitech, and Vir Biotechnology, and has received honoraria from AbbVie, Gilead Sciences, and Vaccitech. JH has received grant support from Gilead Sciences and Roche, has received consultant fees from Roche and lecture fees from AbbVie Korea, Roche, Yuhan Korea, Oncolys, and Gilead, and is a member of an AstraZeneca steering committee. VT, SM, AA, ALC, SVG, and CH are employees of Vir Biotechnology. DC is a former employee of Vir Biotechnology. EG has served on scientific advisory boards for Gilead Sciences, ALIGOS, Janssen, Roche, and Assembly and has received unrestricted grant support from AbbVie. EG is an associate editor of the Journal of Hepatology and is a sponsored lecturer for the HCV Elimination Leaders Conference series for AbbVie. All other authors declare no competing interests., (© 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)- Published
- 2024
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39. Total cholesterol and bilirubin levels are associated with neurologic outcomes in patients with out-of-hospital cardiac arrest.
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Lee SH, Cho Y, Oh J, Kang H, Lim TH, Ko BS, Yoo KH, and Lee J
- Abstract
Background: Assessing the neurologic outcomes of patients who experience out of hospital cardiac arrest (OHCA) is challenging. Neurologic outcomes were evaluated using initial nutrition related biochemical markers., Methods: We used data from a multicentre retrospective observational study, the Korean Cardiac Arrest Resuscitation Consortium (KoCARC) registry. Among the 666 patients, 217 had good neurologic outcomes, while 449 had poor neurologic outcomes. Multivariate logistic regression and classification and regression tree (CART) analyses were employed., Result: In the multivariate logistic regression analysis, total cholesterol ≥ 158.5 mg/dL, total bilirubin ≥ 0.265 mg/dL, Sodium < 142.1 mEq/L, AST < 200.5 U/L and were identified as significant biomarkers for good neurologic outcomes. In the CART analysis, total cholesterol ≥ 158.5 mg/dL and total bilirubin ≥ 0.365 mg/dL were found to be significant indicators. In additional analysis, when the total bilirubin level ranged from 0.6 to 0.7 mg/dL, the highest rate of a good neurologic outcome was observed at 44.6%, whereas levels below or above this range gradually indicated a lower rate of a good neurologic outcome., Conclusion: We propose that total cholesterol and total bilirubin levels could serve as valuable indicators for predicting neurologic outcomes in patients with OHCA., (© 2024. The Author(s), under exclusive licence to Società Italiana di Medicina Interna (SIMI).)
- Published
- 2024
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40. A Catalogue of Structural Variation across Ancestrally Diverse Asian Genomes.
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Tan JHJ, Li Z, Porta MG, Rajaby R, Lim WK, Tan YA, Jimenez RT, Teo R, Hebrard M, Ow JL, Ang S, Jeyakani J, Chong YS, Lim TH, Goh LL, Tham YC, Leong KP, Chin CWL, Davila S, Karnani N, Cheng CY, Chambers J, Tai ES, Liu J, Sim X, Sung WK, Prabhakar S, Tan P, and Bertin N
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- Humans, Linkage Disequilibrium, Polymorphism, Single Nucleotide, Genetic Variation, Singapore, Genetics, Population, Asian People genetics, Genome, Human genetics, Whole Genome Sequencing, Genomic Structural Variation, Genome-Wide Association Study
- Abstract
Structural variants (SVs) are significant contributors to inter-individual genetic variation associated with traits and diseases. Current SV studies using whole-genome sequencing (WGS) have a largely Eurocentric composition, with little known about SV diversity in other ancestries, particularly from Asia. Here, we present a WGS catalogue of 73,035 SVs from 8392 Singaporeans of East Asian, Southeast Asian and South Asian ancestries, of which ~65% (47,770 SVs) are novel. We show that Asian populations can be stratified by their global SV patterns and identified 42,239 novel SVs that are specific to Asian populations. 52% of these novel SVs are restricted to one of the three major ancestry groups studied (Indian, Chinese or Malay). We uncovered SVs affecting major clinically actionable loci. Lastly, by identifying SVs in linkage disequilibrium with single-nucleotide variants, we demonstrate the utility of our SV catalogue in the fine-mapping of Asian GWAS variants and identification of potential causative variants. These results augment our knowledge of structural variation across human populations, thereby reducing current ancestry biases in global references of genetic variation afflicting equity, diversity and inclusion in genetic research., (© 2024. The Author(s).)
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- 2024
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41. Long-term mortality of adult patients with carbon monoxide poisoning presenting to the emergency department in Korea: a population-based cohort study.
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Lee SH, Ryu SR, Yoo KH, Lee J, Cho Y, Lim TH, Kang H, Oh J, and Ko BS
- Abstract
Background: Carbon monoxide (CO) poisoning can lead to significant morbidity and mortality. However, relatively few studies have investigated its long-term mortality impact. This nationwide population-based cohort study examined the association between CO poisoning and long-term mortality., Methods: This retrospective study utilized data from the National Health Insurance Service database in South Korea. We compared the patients with CO poisoning to those without CO poisoning. Inverse probability treatment weights were applied to both groups to control for potential confounding factors. Subsequently, mortality was assessed using the incidence rate and Cox proportional hazard ratios., Results: This study included 23,387 patients with CO poisoning and 359,851 without it. Over a median follow-up period of 7.6 years after CO poisoning diagnosis, the mortality risk was 2.6 times higher in patients with CO poisoning compared to that in the control group. In a long-term follow-up of patients surviving beyond 30 days, mortality remained 2.18 times higher. Additionally, a higher mortality risk was observed in the relatively younger age group (18-39 years) and the group with fewer underlying diseases, as indicated by a Charlson Comorbidity Index score of 0., Conclusions: CO poisoning is associated with an elevated long-term mortality rate particularly in a relatively young and healthy population.
- Published
- 2024
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42. Diagnostic Accuracy of Plasma Renin Concentration and Renin Activity in Predicting Mortality and Kidney Outcomes in Patients With Septic Shock and Hypoperfusion or Hypotension: A Multicenter, Prospective, Observational Study.
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Lee GT, Ko BS, Kim DS, Kim M, Park JE, Hwang SY, Jeong D, Chung CR, Kang H, Oh J, Lim TH, Chae B, Kim WY, and Shin TG
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- Humans, Prospective Studies, Male, Female, Aged, Middle Aged, Renin blood, Shock, Septic mortality, Shock, Septic blood, Shock, Septic diagnosis, Shock, Septic complications, Acute Kidney Injury diagnosis, Acute Kidney Injury mortality, Acute Kidney Injury blood, Hypotension diagnosis, Hypotension blood, Hypotension complications, Hypotension mortality, ROC Curve, Biomarkers blood, Area Under Curve, Lactic Acid blood
- Abstract
Background: Lactate is a commonly used biomarker for sepsis, although it has limitations in certain cases, suggesting the need for novel biomarkers. We evaluated the diagnostic accuracy of plasma renin concentration and renin activity for mortality and kidney outcomes in patients with sepsis with hypoperfusion or hypotension., Methods: This was a multicenter, prospective, observational study of 117 patients with septic shock treated at three tertiary emergency departments between September 2021 and October 2022. The accuracy of renin activity, renin, and lactate concentrations in predicting 28-day mortality, acute kidney injury (AKI), and renal replacement requirement was assessed using the area under the ROC curve (AUC) analysis., Results: The AUCs of initial renin activity, renin, and lactate concentrations for predicting 28-day mortality were 0.66 (95% confidence interval [CI], 0.55-0.77), 0.63 (95% CI, 0.52-0.75), and 0.65 (95% CI, 0.53-0.77), respectively, and those at 24 hrs were 0.74 (95% CI, 0.62-0.86), 0.70 (95% CI, 0.56-0.83), and 0.67 (95% CI, 0.54-0.79). Renin concentrations and renin activity outperformed initial lactate concentrations in predicting AKI within 14 days. The AUCs of renin and lactate concentrations were 0.71 (95% CI, 0.61-0.80) and 0.57 (95% CI, 0.46-0.67), respectively ( P =0.030). The AUC of renin activity (0.70; 95% CI, 0.60-0.80) was also higher than that of lactate concentration ( P =0.044)., Conclusions: Renin concentration and renin activity show comparable performance to lactate concentration in predicting 28-day mortality in patients with septic shock but superior performance in predicting AKI.
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- 2024
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43. Early Mortality Stratification with Serum Albumin and the Sequential Organ Failure Assessment Score at Emergency Department Admission in Septic Shock Patients.
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Kim SM, Ryoo SM, Shin TG, Jo YH, Kim K, Lim TH, Chung SP, Choi SH, Suh GJ, and Kim WY
- Abstract
Background: Early risk stratification is crucial due to septic patients' heterogeneity. Serum albumin level may reflect the severity of sepsis and host status. This study aimed to evaluate the prognostic ability of the initial sequential organ failure assessment (SOFA) score alone and combined with serum albumin levels for predicting 28-day mortality in patients with septic shock. Methods: We conducted an observational study using a prospective, multicenter registry of septic shock patients between October 2015 and May 2022 from 12 emergency departments in the Korean Shock Society and the results were validated by examining those from the septic shock cohort in Asan Medical Center. The primary outcome was 28-day mortality. The area under the receiver operating characteristic (ROC) curve was used to compare the predictive values of SOFA score alone and SOFA score combined with serum albumin level. Results: Among 5805 septic shock patients, 1529 (26.3%) died within 28 days. Mortality increased stepwise with decreasing serum albumin levels (13.6% in albumin ≥3.5, 20.7% in 3.5-3.0, 29.7% in 3.0-2.5, 44.0% in 2.5-2.0, 56.4% in <2.0). The albumin SOFA score was calculated by adding the initial SOFA score to the 4 points assigned for albumin levels. ROC analysis for predicting 28-day mortality showed that the area under the curve for the albumin SOFA score was 0.71 (95% CI 0.70-0.73), which was significantly higher than that of the initial SOFA score alone (0.68, 95% CI: 0.67-0.69). Conclusions: The combination of the initial SOFA score with albumin can improve prognostic accuracy for patients with septic shock, suggesting the albumin SOFA score may be used as an early mortality stratification tool.
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- 2024
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44. The impact of pulmonary tuberculosis on SARS-CoV-2 infection: a nationwide cohort study.
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Lee SH, Kim YJ, Oh J, Kang H, Yoo KH, Ko BS, Lim TH, Kim BG, Lee H, Kim SH, Sohn JW, Yoon HJ, Choi H, Cho Y, and Park DW
- Abstract
Background: The interaction between COVID-19 and tuberculosis (TB) is not yet fully understood, and large-scale research on the mortality outcome of such dual infection has been limited. This study aimed to investigate the impact of PTB on mortality among patients with COVID-19 within a Korean population by conducting an extensive analysis of a nationwide large dataset., Method: We investigated the mortality and disease severity among COVID-19 patients who had PTB in South Korea. This study analyzed 462,444 out of 566,494 COVID-19 patients identified between January 2020 and December 2021., Result: A total of 203 COVID-19 with PTB patients and 812 matched COVID-19 without PTB were analyzed using 1:4 propensity score matching. COVID-19 patients with PTB exhibited higher in-hospital mortality (odds ratio (OR) 3.02, 95% confidence interval (CI) 1.45-6.27, p -value = 0.003) and were at increased risk of requiring conventional oxygen therapy (OR 1.57, 95% CI 1.10-2.25, p -value = 0.013) as well as high flow nasal cannula (HFNC) or noninvasive ventilation (NIV) oxygen therapy (OR 1.91, 95 CI 1.10-3.32, p -value = 0.022) compared to those without PTB. Compared to matched COVID-19 without PTB, co-infected patients showed increased mortality rates across various timeframes, including during hospitalization, and at 30 day and 90 day intervals. In-hospital mortality rates were particularly elevated among women, individuals with malignancy, and those with lower incomes. Furthermore, the increased in-hospital mortality among PTB patients persisted irrespective of the timing of TB diagnosis or vaccination status against COVID-19., Conclusion: We suggest that physicians be aware of the risk of mortality and severity among COVID-19 patients with PTB; coinfection with COVID-19 is a critical situation that remains to be further explored and needs more attention in countries with an intermediate to high PTB burden., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lee, Kim, Oh, Kang, Yoo, Ko, Lim, Kim, Lee, Kim, Sohn, Yoon, Choi, Cho and Park.)
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- 2024
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45. Synergistic Effect of SARS-CoV-2 Infection and COVID-19 Vaccination on the Risk of Venous Thromboembolism.
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Yoo KH, Lee SH, Cho Y, Kim YJ, Kim JG, Lim TH, Kang H, Oh J, Ko BS, and Lee J
- Abstract
Background: Previous studies have reported a greater risk of venous thromboembolism among patients infected with SARS-CoV-2 and those who received COVID-19 vaccination. Nevertheless, there is a lack of understanding regarding the interaction effect on the risk of venous thromboembolism occurrence between SARS-CoV-2 infection and COVID-19 vaccination., Methods: This was a retrospective cohort study including adult patients with confirmed SARS-CoV-2 infection between October 2020 and September 2021. Patients with confirmed SARS-CoV-2 infection were selected and matched 1:1 by age and sex with individuals who were not infected during the same period. A Cox proportional hazards model was used to analyze the venous thromboembolism risk., Results: The study included 422546 individuals who were divided into 4 groups; the interaction group defined by having SARS-CoV-2 infection within 90 days following COVID-19 vaccination, the infection group defined by no vaccination before 90 days of SARS-CoV-2 infection, the vaccination group defined by COVID-19 vaccination without SARS-CoV-2 infection, and the reference group defined by neither COVID-19 vaccination nor SARS-CoV-2 infection. The results showed that the adjusted hazard ratio (aHR) of the interaction group was 29.71 (95% confidence interval [CI], 22.95-38.47), while the aHRs of the infection group and the vaccination group were 6.66 (95% CI, 5.18-8.58) and 2.31 (95% CI, 1.78-3.00), respectively., Conclusions: A synergistic effect on the risk of venous thromboembolism was suggested when individuals were infected with SARS-CoV-2 within 90 days following COVID-19 vaccination., (Copyright © 2024 Elsevier Inc. All rights reserved.)
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- 2024
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46. Association Between QRS Characteristics in Pulseless Electrical Activity and Survival Outcome in Cardiac Arrest Patients: A Systematic Review and Meta-Analysis.
- Author
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Kim JH, Lee J, Shin H, Lim TH, Jang BH, Cho Y, Kim W, Choi KS, Kim JG, Ahn C, Lee H, Namgung M, Na MK, and Kwon SM
- Abstract
Objective: Recent studies have shown inconsistent results regarding the association between QRS characteristics and survival outcomes in patients with cardiac arrest and pulseless electrical activity (PEA) rhythms. This meta-analysis aimed to identify the usefulness of QRS width and frequency as prognostic tools for outcomes in patients with cardiac arrest and PEA rhythm., Methods: Extensive searches were conducted using Medline, Embase, and the Cochrane Library to find articles published from database inception to 4 June 2023. Studies that assessed the association between the QRS characteristics of cardiac arrest patients with PEA rhythm and survival outcomes were included. The Newcastle-Ottawa Scale was used to assess the methodological quality of the included studies., Results: A total of 9727 patients from seven observational studies were included in this systematic review and meta-analysis. The wide QRS group (QRS ≥ 120 ms) was associated with significantly higher odds of mortality than the narrow QRS group (QRS < 120 ms) (odds ratio (OR) = 1.86, 95% confidence interval (CI) = 1.11-3.11, I
2 = 58%). The pooled OR for mortality was significantly higher in patients with a QRS frequency of < 60/min than in those with a QRS frequency of ≥ 60/min (OR = 1.90, 95% CI = 1.19-3.02, I2 = 65%)., Conclusions: Wide QRS width or low QRS frequency is associated with increased odds of mortality in patients with PEA cardiac arrest. These findings may be beneficial to guide the disposition of cardiac arrest patients with PEA during resuscitation.- Published
- 2024
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47. Targeting Heme Oxygenase 2 (HO2) with TiNIR, a Theragnostic Approach for Managing Metastatic Non-Small Cell Lung Cancer.
- Author
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Mun SK, Sim HB, Lee JH, Kim H, Park DH, Lee YA, Han JY, Choi YJ, Son JS, Park J, Lim TH, Yee ST, Chang YT, Lee S, Chang DJ, and Kim JJ
- Abstract
Despite notable advancements in cancer therapeutics, metastasis remains a primary obstacle impeding a successful prognosis. Our prior study has identified heme oxygenase 2 (HO2) as a promising therapeutic biomarker for the aggressive subsets within tumor. This study aims to systematically evaluate HO2 as a therapeutic target of cancer, with a specific emphasis on its efficacy in addressing cancer metastasis. Through targeted inhibition of HO2 by TiNIR (tumor-initiating cell probe with near infrared), we observed a marked increase in reactive oxygen species. This, in turn, orchestrated the modulation of AKT and cJUN activation, culminating in a substantial attenuation of both proliferation and migration within a metastatic cancer cell model. Furthermore, in a mouse model, clear inhibition of cancer metastasis was unequivocally demonstrated with an HO2 inhibitor administration. These findings underscore the therapeutic promise of targeting HO2 as a strategic intervention to impede cancer metastasis, enhancing the effectiveness of cancer treatments., Competing Interests: Competing interests: The authors declare that they have no competing interests., (Copyright © 2024 Seul-Ki Mun et al.)
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- 2024
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48. Generalizability of Deep Neural Networks for Vertical Cup-to-Disc Ratio Estimation in Ultra-Widefield and Smartphone-Based Fundus Images.
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Yap BP, Kelvin LZ, Toh EQ, Low KY, Rani SK, Goh EJH, Hui VYC, Ng BK, and Lim TH
- Subjects
- Artificial Intelligence, Smartphone, Neural Networks, Computer, Ophthalmology, Telemedicine
- Abstract
Purpose: To develop and validate a deep learning system (DLS) for estimation of vertical cup-to-disc ratio (vCDR) in ultra-widefield (UWF) and smartphone-based fundus images., Methods: A DLS consisting of two sequential convolutional neural networks (CNNs) to delineate optic disc (OD) and optic cup (OC) boundaries was developed using 800 standard fundus images from the public REFUGE data set. The CNNs were tested on 400 test images from the REFUGE data set and 296 UWF and 300 smartphone-based images from a teleophthalmology clinic. vCDRs derived from the delineated OD/OC boundaries were compared with optometrists' annotations using mean absolute error (MAE). Subgroup analysis was conducted to study the impact of peripapillary atrophy (PPA), and correlation study was performed to investigate potential correlations between sectoral CDR (sCDR) and retinal nerve fiber layer (RNFL) thickness., Results: The system achieved MAEs of 0.040 (95% CI, 0.037-0.043) in the REFUGE test images, 0.068 (95% CI, 0.061-0.075) in the UWF images, and 0.084 (95% CI, 0.075-0.092) in the smartphone-based images. There was no statistical significance in differences between PPA and non-PPA images. Weak correlation (r = -0.4046, P < 0.05) between sCDR and RNFL thickness was found only in the superior sector., Conclusions: We developed a deep learning system that estimates vCDR from standard, UWF, and smartphone-based images. We also described anatomic peripapillary adversarial lesion and its potential impact on OD/OC delineation., Translational Relevance: Artificial intelligence can estimate vCDR from different types of fundus images and may be used as a general and interpretable screening tool to improve community reach for diagnosis and management of glaucoma.
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- 2024
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49. The usefulness of lactate/albumin ratio, C-reactive protein/albumin ratio, procalcitonin/albumin ratio, SOFA, and qSOFA in predicting the prognosis of patients with sepsis who presented to EDs.
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Yoo KH, Choi SH, Suh GJ, Chung SP, Choi HS, Park YS, Jo YH, Shin TG, Lim TH, Kim WY, and Lee J
- Subjects
- Humans, Male, Female, Lactic Acid, C-Reactive Protein, Organ Dysfunction Scores, Retrospective Studies, Prognosis, ROC Curve, Albumins, Procalcitonin metabolism, Sepsis
- Abstract
Purpose: Early identification of sepsis with a poor prognosis in the emergency department (ED) is crucial for prompt management and improved outcomes. This study aimed to examine the predictive value of sequential organ failure assessment (SOFA), quick SOFA (qSOFA), lactate to albumin ratio (LAR), C-reactive protein to albumin ratio (CAR), and procalcitonin to albumin ratio (PAR), obtained in the ED, as predictors for 28-day mortality in patients with sepsis and septic shock., Materials and Methods: We included 3499 patients (aged ≥19 years) from multicenter registry of the Korean Shock Society between October 2015 and December 2019. The SOFA score, qSOFA score, and lactate level at the time of registry enrollment were used. Albumin, C-reactive protein, and procalcitonin levels were obtained from the initial laboratory results measured upon ED arrival. We evaluated the predictive accuracy for 28-day mortality using the area under the receiver operating characteristic (AUROC) curve. A multivariable logistic regression analysis of the independent predictors of 28-day mortality was performed. The SOFA score, LAR, CAR, and PAR were converted to categorical variables using Youden's index and analyzed. Adjusting for confounding factors such as age, sex, comorbidities, and infection focus, adjusted odds ratios (aOR) were calculated., Results: Of the 3499 patients, 2707 (77.4%) were survivors, whereas 792 (22.6%) were non-survivors. The median age of the patients was 70 (25th-75th percentiles, 61-78), and 2042 (58.4%) were male. LAR for predicting 28-day mortality had the highest AUROC, followed by the SOFA score (0.715; 95% confidence interval (CI): 0.69-0.74 and 0.669; 95% CI: 0.65-0.69, respectively). The multivariable logistic regression analysis revealed that the aOR of LAR >1.52 was 3.75 (95% CI: 3.16-4.45), and the aOR, of SOFA score at enrollment >7.5 was 2.67 (95% CI: 2.25-3.17)., Conclusion: The results of this study showed that LAR is a relatively strong predictor of sepsis prognosis in the ED setting, indicating its potential as a straightforward and practical prognostic factor. This finding may assist healthcare providers in the ED by providing them with tools to risk-stratify patients and predict their mortality., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)
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- 2024
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50. Comparison of an amplicon-based large panel next generation sequencing (NGS) assay with conventional testing methods for MET and HER2 amplification in lung and breast cancers.
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Tay TKY, Tan GS, Lee SH, Sam XX, Lim TH, Ng JWK, Tan DSW, and Lim TKH
- Subjects
- Humans, Female, Receptor, ErbB-2 genetics, Receptor, ErbB-2 metabolism, High-Throughput Nucleotide Sequencing, Gene Amplification, Lung metabolism, Breast Neoplasms diagnosis, Breast Neoplasms genetics
- Abstract
The frequency of MET and HER2 amplification being detected by next generation sequencing (NGS) is increasing due to NGS being increasingly adopted for molecular profiling of cancers. However, the accuracy of NGS in detecting these gene amplifications remains uncertain due to conflicting reports in the scientific literature. We studied the accuracy of an amplicon-based large panel NGS assay in detecting MET and HER2 amplification in lung and breast cancers, respectively, by comparing it against conventional testing methods. Amongst 48 lung cancers, four of five cancers that were MET amplified on fluorescence in situ hybridisation (FISH) were classified as amplified on NGS while 42 of the remaining 43 non-amplified cancers were classified as non-amplified on NGS, giving a sensitivity of 80%, specificity of 97.7% and overall concordance of 95.8%. Of the 46 breast cancers tested, only six of the nine cancers that were HER2-positive on immunohistochemistry (IHC)/FISH were HER2-positive on NGS, while all the remaining HER2-negative cases were negative on NGS, giving a sensitivity of 66.7%, specificity of 100% and overall concordance of 93.5%. All the false-negative cases had low level gene amplification (MET:CEP7 or HER2:CEP17 FISH ratio of <3). The low sensitivity for HER2 amplification may be confounded by the small sample size and disproportionate number of cases with low level amplification. In summary, the NGS assay has good concordance with conventional testing methods but may be less sensitive in detecting low level gene amplification., (Copyright © 2023 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.)
- Published
- 2024
- Full Text
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