3.The role of PIVKA-II in hepatocellular carcinoma surveillance in an Asian population.
Wai Yoong NG ; Daniel Yan Zheng LIM ; Si Yu TAN ; Jason Pik Eu CHANG ; Thinesh Lee KRISHNAMOORTHY ; Chee Hooi LIM ; Damien Meng Yew TAN ; Victoria Sze Min EKSTROM ; George Boon Bee GOH ; Mark Chang Chuen CHEAH ; Rajneesh KUMAR ; Chin Pin YEO ; Chee Kiat TAN
Annals of the Academy of Medicine, Singapore 2023;52(2):108-110
4.Global incidence and prevalence of nonalcoholic fatty liver disease
Margaret LP TENG ; Cheng Han NG ; Daniel Q. HUANG ; Kai En CHAN ; Darren JH TAN ; Wen Hui LIM ; Ju Dong YANG ; Eunice TAN ; Mark D. MUTHIAH
Clinical and Molecular Hepatology 2023;29(Suppl):S32-S42
Nonalcoholic fatty liver disease (NAFLD) is a leading cause of liver disease worldwide. The estimated global incidence of NAFLD is 47 cases per 1,000 population and is higher among males than females. The estimated global prevalence of NAFLD among adults is 32% and is higher among males (40%) compared to females (26%). The global prevalence of NAFLD has increased over time, from 26% in studies from 2005 or earlier to 38% in studies from 2016 or beyond. The prevalence of NAFLD varies substantially by world region, contributed by differing rates of obesity, and genetic and socioeconomic factors. The prevalence of NAFLD exceeds 40% in the Americas and South-East Asia. The prevalence of NAFLD is projected to increase significantly in multiple world regions by 2030 if current trends are left unchecked. In this review, we discuss trends in the global incidence and prevalence of NAFLD and discuss future projections.
5.Consensus and Diversity in the Management of Varicocele for Male Infertility: Results of a Global Practice Survey and Comparison with Guidelines and Recommendations
Rupin SHAH ; Ashok AGARWAL ; Parviz KAVOUSSI ; Amarnath RAMBHATLA ; Ramadan SALEH ; Rossella CANNARELLA ; Ahmed M. HARRAZ ; Florence BOITRELLE ; Shinnosuke KURODA ; Taha Abo-Almagd Abdel-Meguid HAMODA ; Armand ZINI ; Edmund KO ; Gokhan CALIK ; Tuncay TOPRAK ; Hussein KANDIL ; Murat GÜL ; Mustafa Emre BAKIRCIOĞLU ; Neel PAREKH ; Giorgio Ivan RUSSO ; Nicholas TADROS ; Ates KADIOGLU ; Mohamed ARAFA ; Eric CHUNG ; Osvaldo RAJMIL ; Fotios DIMITRIADIS ; Vineet MALHOTRA ; Gianmaria SALVIO ; Ralf HENKEL ; Tan V. LE ; Emrullah SOGUTDELEN ; Sarah VIJ ; Abdullah ALARBID ; Ahmet GUDELOGLU ; Akira TSUJIMURA ; Aldo E. CALOGERO ; Amr El MELIEGY ; Andrea CRAFA ; Arif KALKANLI ; Aykut BASER ; Berk HAZIR ; Carlo GIULIONI ; Chak-Lam CHO ; Christopher C.K. HO ; Ciro SALZANO ; Daniel Suslik ZYLBERSZTEJN ; Dung Mai Ba TIEN ; Edoardo PESCATORI ; Edson BORGES ; Ege Can SEREFOGLU ; Emine SAÏS-HAMZA ; Eric HUYGHE ; Erman CEYHAN ; Ettore CAROPPO ; Fabrizio CASTIGLIONI ; Fahmi BAHAR ; Fatih GOKALP ; Francesco LOMBARDO ; Franco GADDA ; Gede Wirya Kusuma DUARSA ; Germar-Michael PINGGERA ; Gian Maria BUSETTO ; Giancarlo BALERCIA ; Gianmartin CITO ; Gideon BLECHER ; Giorgio FRANCO ; Giovanni LIGUORI ; Haitham ELBARDISI ; Hakan KESKIN ; Haocheng LIN ; Hisanori TANIGUCHI ; Hyun Jun PARK ; Imad ZIOUZIOU ; Jean de la ROSETTE ; Jim HOTALING ; Jonathan RAMSAY ; Juan Manuel Corral MOLINA ; Ka Lun LO ; Kadir BOCU ; Kareim KHALAFALLA ; Kasonde BOWA ; Keisuke OKADA ; Koichi NAGAO ; Koji CHIBA ; Lukman HAKIM ; Konstantinos MAKAROUNIS ; Marah HEHEMANN ; Marcelo Rodriguez PEÑA ; Marco FALCONE ; Marion BENDAYAN ; Marlon MARTINEZ ; Massimiliano TIMPANO
The World Journal of Men's Health 2023;41(1):164-197
Purpose:
Varicocele is a common problem among infertile men. Varicocele repair (VR) is frequently performed to improve semen parameters and the chances of pregnancy. However, there is a lack of consensus about the diagnosis, indications for VR and its outcomes. The aim of this study was to explore global practice patterns on the management of varicocele in the context of male infertility.
Materials and Methods:
Sixty practicing urologists/andrologists from 23 countries contributed 382 multiple-choice-questions pertaining to varicocele management. These were condensed into an online questionnaire that was forwarded to clinicians involved in male infertility management through direct invitation. The results were analyzed for disagreement and agreement in practice patterns and, compared with the latest guidelines of international professional societies (American Urological Association [AUA], American Society for Reproductive Medicine [ASRM], and European Association of Urology [EAU]), and with evidence emerging from recent systematic reviews and meta-analyses. Additionally, an expert opinion on each topic was provided based on the consensus of 16 experts in the field.
Results:
The questionnaire was answered by 574 clinicians from 59 countries. The majority of respondents were urologists/ uro-andrologists. A wide diversity of opinion was seen in every aspect of varicocele diagnosis, indications for repair, choice of technique, management of sub-clinical varicocele and the role of VR in azoospermia. A significant proportion of the responses were at odds with the recommendations of AUA, ASRM, and EAU. A large number of clinical situations were identified where no guidelines are available.
Conclusions
This study is the largest global survey performed to date on the clinical management of varicocele for male infertility. It demonstrates: 1) a wide disagreement in the approach to varicocele management, 2) large gaps in the clinical practice guidelines from professional societies, and 3) the need for further studies on several aspects of varicocele management in infertile men.
6.Feasibility of corneal epithelial transplantation with polyethylene glycol hydrogel membrane as a carrier for limbal stem cell deficiency
Yiyuan GUO ; Huimin XIAN ; Tan SHEREEN ; Fu QIANG ; Xin JIN ; Daniel MARK ; Qiao GREG.G. ; Hong ZHANG
Chinese Journal of Experimental Ophthalmology 2022;40(12):1125-1133
Objective:To investigate whether polyethylene glycol hydrogel films (PHFs) can be used as a carrier for the expansion of corneal epithelial cells (CECs) in vitro and whether PHFs can be used in the treatment of limbal stem cell deficiency (LSCD). Methods:Sebacoyl chloride, dihydroxyl PCL and glycerol ethoxylate were used to synthesize PHFs.The thickness, transmittance and mechanical tensile properties of PHFs were measured.Four clean-grade New Zealand white rabbits were selected to culture primary limbal epithelial cells.The expression of keratin marker AE1/AE3 and stem cell marker p63 in the cultured cells were observed under a fluorescence microscope.The cells were divided into negative control group cultured with common cell culture solution, positive control group cultured with cell culture solution containing 100 μmol/L H 2O 2, and PHFs+ CECs group lined with PHFs cultured with common cell culture solution for 24 hours.The proliferation and apoptosis of cells in the three groups were observed by MTT and TUNEL staining, respectively.Fifteen clean-grade New Zealand white rabbits were divided into control group, PHFs group and PHFs+ CECs group by random number table method, with 5 rabbits in each group.LSCD model was constructed in the three groups.The control group was not given any treatment after modeling.In PHFs group, empty PHFs were placed on the corneal surface of rabbits.In PHFs+ CECs group, tissue-engineered grafts constructed with CECs after passage implanted on PHFs were placed on the corneal surface of rabbits.The corneal defect area of rabbits was detected and scored by fluorescein sodium staining.The histological characteristics of rabbits corneal epithelium was observed by hematoxylin-eosin staining.The use and care of animals complied with Guide for the Care and Use of Laboratory Animals by the U. S.National Research Council.The experimental protocol was approved by the Research and Clinical Trial Ethics Committee of The First Affiliated Hospital of Harbin Medical University (No.2021006). Results:The synthetic PHFs were with a thickness ≤150 μm, a tensile strength about 6 MPa, and a transmittance over than 99% in the range of 400-700 nm.Most of the cells from primary culture of limbal tissue were positive for AE1/AE3 and p63.MTT test results showed that the A490 value of PHFs+ CECs group, negative control group and positive control group was 0.59±0.01, 0.65±0.07 and 0.06±0.04, respectively, showing a statistically significant overall difference ( F=12.25, P<0.05). The A490 values of PHFs+ CECs group and negative control group were significantly higher than that of positive control group, and the differences were statistically significant (both at P<0.05). TUNEL test results showed that there was a significant difference in the TUNEL-positive cell rate among the three groups ( F=13.45, P<0.05), and the rates of TUNEL-positive cells in PHFs+ CECs group and negative control group were significantly lower than that in positive control group (both at P<0.05). Fluorescein sodium staining results showed that with the extension of postoperative period, the corneal fluorescein sodium staining score of the three groups decreased, which decreased successively in control group, PHFs group and PHFs+ CECs group.Hematoxylin-eosin staining showed fewer irregularly shaped corneal epithelial cells in the control group, and sparse single layer of corneal epithelial cells in some areas of the PHFs group.In PHFs+ CECs group, the corneal epithelium coverage was the largest, and the cell layers increased to 3-5, and the cells were with regular morphology and in close arrangement. Conclusions:PHFs have enough toughness, high transmittance and can expand corneal epithelium in vitro.PHFs are suitable for corneal epithelial transplantation and can promote the repair of corneal epithelium in rabbit model of LSCD.
7.Effective online large-group teaching in health professions education
Jie Ming Nigel FONG ; Li Ping Marianne TSANG ; Nigel Choon Kiat TAN ; Daniel SALCEDO ; Kevin TAN
Korean Journal of Medical Education 2022;34(2):155-166
Online large-group teaching (OLGT), employed to reach a large group of learners in separate physical locations, allows asynchronous learning and facilitates social distancing. While online large-groups can be a powerful and resource-lean means of health professions education, it has challenges and potential pitfalls that may affect the learning process and outcomes. Through a sociomateriality framework, this article describes strategies for effective online large-group teaching in health professions education in three key strands. Firstly, to optimize learning, OLGT sessions should match learning needs with appropriate OLGT platforms, incorporate strategies to sustain learner attention, and accommodate learners of different abilities. Secondly, to develop a learning culture, OLGT must not only focus on cognitive aspects of learning but also build a community of practice, nurture digital professionalism and professional identity. Thirdly, we discuss the avoidance of pitfalls such as cognitive overload of both tutors and learners, technical issues and security risks, mitigating inequities in access to online learning, and the use of program evaluation to plan for sustained improvements. We conclude with a case vignette that discusses the challenges of OLGT and the application of the above strategies in a teaching scenario.
8.Global prevalence of depression and anxiety in patients with hepatocellular carcinoma: Systematic review and meta-analysis
Darren Jun Hao TAN ; Sabrina Xin Zi QUEK ; Jie Ning YONG ; Adithya SURESH ; Kaiser Xuan Ming KOH ; Wen Hui LIM ; Jingxuan QUEK ; Ansel TANG ; Caitlyn TAN ; Benjamin NAH ; Eunice TAN ; Taisei KEITOKU ; Mark D. MUTHIAH ; Nicholas SYN ; Cheng Han NG ; Beom Kyung KIM ; Nobuharu TAMAKI ; Cyrus Su Hui HO ; Rohit LOOMBA ; Daniel Q. HUANG
Clinical and Molecular Hepatology 2022;28(4):864-875
Background/Aims:
Depression and anxiety are associated with poorer outcomes in patients with hepatocellular carcinoma (HCC). However, the prevalence of depression and anxiety in HCC are unclear. We aimed to establish the prevalence of depression and anxiety in patients with HCC.
Methods:
MEDLINE and Embase were searched and original articles reporting prevalence of anxiety or depression in patients with HCC were included. A generalized linear mixed model with Clopper-Pearson intervals was used to obtain the pooled prevalence of depression and anxiety in patients with HCC. Risk factors were analyzed via a fractional-logistic regression model.
Results:
Seventeen articles involving 64,247 patients with HCC were included. The pooled prevalence of depression and anxiety in patients with HCC was 24.04% (95% confidence interval [CI], 13.99–38.11%) and 22.20% (95% CI, 10.07–42.09%) respectively. Subgroup analysis determined that the prevalence of depression was lowest in studies where depression was diagnosed via clinician-administered scales (16.07%;95% CI, 4.42–44.20%) and highest in self-reported scales (30.03%; 95% CI, 17.19–47.01%). Depression in patients with HCC was lowest in the Americas (16.44%; 95% CI, 6.37–36.27%) and highest in South-East Asia (66.67%; 95% CI, 56.68–75.35%). Alcohol consumption, cirrhosis, and college education significantly increased risk of depression in patients with HCC.
Conclusions
One in four patients with HCC have depression, while one in five have anxiety. Further studies are required to validate these findings, as seen from the wide CIs in certain subgroup analyses. Screening strategies for depression and anxiety should also be developed for patients with HCC.
9.The effect of diabetes and prediabetes on the prevalence, complications and mortality in nonalcoholic fatty liver disease
Cheng Han NG ; Kai En CHAN ; Yip Han CHIN ; Rebecca Wenling ZENG ; Pei Chen TSAI ; Wen Hui LIM ; Darren Jun Hao TAN ; Chin Meng KHOO ; Lay Hoon GOH ; Zheng Jye LING ; Anand KULKARNI ; Lung-Yi Loey MAK ; Daniel Q HUANG ; Mark CHAN ; Nicholas WS CHEW ; Mohammad Shadab SIDDIQUI ; Arun J. SANYAL ; Mark MUTHIAH
Clinical and Molecular Hepatology 2022;28(3):565-574
Background/Aims:
Nonalcoholic fatty liver disease (NAFLD) is closely associated with diabetes. The cumulative impact of both diseases synergistically increases risk of adverse events. However, present population analysis is predominantly conducted with reference to non-NAFLD individuals and has not yet examined the impact of prediabetes. Hence, we sought to conduct a retrospective analysis on the impact of diabetic status in NAFLD patients, referencing non-diabetic NAFLD individuals.
Methods:
Data from the National Health and Nutrition Examination Survey 1999–2018 was used. Hepatic steatosis was defined with United States Fatty Liver Index (US-FLI) and FLI at a cut-off of 30 and 60 respectively, in absence of substantial alcohol use. A multivariate generalized linear model was used for risk ratios of binary outcomes while survival analysis was conducted with Cox regression and Fine Gray model for competing risk.
Results:
Of 32,234 patients, 28.92% were identified to have NAFLD. 36.04%, 38.32% and 25.63% were non-diabetic, prediabetic and diabetic respectively. Diabetic NAFLD significantly increased risk of cardiovascular disease (CVD), stroke, chronic kidney disease, all-cause and CVD mortality compared to non-diabetic NAFLD. However, prediabetic NAFLD only significantly increased the risk of CVD and did not result in a higher risk of mortality.
Conclusions
Given the increased risk of adverse outcomes, this study highlights the importance of regular diabetes screening in NAFLD and adoption of prompt lifestyle modifications to reduce disease progression. Facing high cardiovascular burden, prediabetic and diabetic NAFLD individuals can benefit from early cardiovascular referrals to reduce risk of CVD events and mortality.
10.Non-alcoholic fatty liver disease increases risk of carotid atherosclerosis and ischemic stroke: An updated meta-analysis with 135,602 individuals
Ansel Shao Pin TANG ; Kai En CHAN ; Jingxuan QUEK ; Jieling XIAO ; Phoebe TAY ; Margaret TENG ; Keng Siang LEE ; Snow Yunni LIN ; May Zin MYINT ; Benjamin TAN ; Vijay K SHARMA ; Darren Jun Hao TAN ; Wen Hui LIM ; Apichat KAEWDECH ; Daniel HUANG ; Nicholas WS CHEW ; Mohammad Shadab SIDDIQUI ; Arun J SANYAL ; Mark MUTHIAH ; Cheng Han NG
Clinical and Molecular Hepatology 2022;28(3):483-496
Background/Aims:
Non-alcoholic fatty liver disease (NAFLD) is associated with the development of cardiovascular disease. While existing studies have examined cardiac remodeling in NAFLD, there has been less emphasis on the development of carotid atherosclerosis and stroke. We sought to conduct a meta-analysis to quantify the prevalence, risk factors, and degree of risk increment of carotid atherosclerosis and stroke in NAFLD.
Methods:
Embase and Medline were searched for articles relating to NAFLD, carotid atherosclerosis, and stroke. Proportional data was analysed using a generalized linear mixed model. Pairwise meta-analysis was conducted to obtain odds ratio or weighted mean difference for comparison between patients with and without NAFLD.
Results:
From pooled analysis of 30 studies involving 7,951 patients with NAFLD, 35.02% (95% confidence interval [CI], 27.36–43.53%) had carotid atherosclerosis with an odds ratio of 3.20 (95% CI, 2.37–4.32; P<0.0001). Pooled analysis of 25,839 patients with NAFLD found the prevalence of stroke to be 5.04% (95% CI, 2.74–9.09%) with an odds ratio of 1.88 (95% CI, 1.23–2.88; P=0.02) compared to non-NAFLD. The degree of steatosis assessed by ultrasonography in NAFLD was closely associated with risk of carotid atherosclerosis and stroke. Older age significantly increased the risk of developing carotid atherosclerosis, but not stroke in NAFLD.
Conclusions
This meta-analysis shows that a stepwise increment of steatosis of NAFLD can significantly increase the risk of carotid atherosclerosis and stroke development in NAFLD. Patients more than a third sufferred from carotid atherosclerosis and routine assessment of carotid atherosclerosis is quintessential in NAFLD.

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