Immunotherapy for NSCLC - addressing heterogeneity to improve clinical outcomes

( Darren Wan-teck Lim ) 대한결핵 및 호흡기학회 2019 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.127 No.-

Immunotherapy with checkpoint inhibitors has firmly entrenched itself as standard of care practice in NSCLC where EGFR/ALK testing is negative. Yet even within this group, heterogeneity exists, and the relative activity of immunotherapy in oncogene driven lung cancer is still not well defined. Even within EGFR/ALK positive NSCLC, there could exist subsets where immunotherapy may be useful. Recent updates from immunotherapy studies that address heterogeneity, and potential new approaches will be discussed.

Is it time for a paradigm shift in first line treatment of EGFR mutant NSCLC?

( Darren Wan-teck Lim ) 대한결핵 및 호흡기학회 2019 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.127 No.-

EGFR mutant NSCLC represents the majority of lung cancer in Asia. All generations of EGFR tyrosine kinase inhibitors have demonstrated excellent efficacy in advanced disease. Osimertinib was developed specifically to address T790M mutation, the dominant resistance mechanism following failure of 1st/2nd generation inhibitors. Moving the use of osimertinib to the first-line setting represents a paradigm shift in management of EGFR mt lung cancer, as it challenges current practice of sequencing EGFR inhibitors. The discussion will focus on recent overall survival data from FLAURA and its possible impact on existing practice in EGFR mutant NSCLC in Asia.

The US, China and ‘Technology War’

Darren Lim 동아시아재단 2019 Global Asia Vol.14 No.1

회전근 개 파열의 봉합에서 UU 봉합법은 변형된 MA(Mason-Allen) 봉합법을 대치할 수 있는가?

Darren J Friedman,고상훈(Sang-Hun Ko),박기봉(Ki-Bong Park),전형민(Hyung-Min Jun),김태원(Tae-Won Kim),임현우(Hyun-Woo Lim),염영진(Young-Jin Yum) 대한견주관절의학회 2009 대한견주관절의학회지 Vol.12 No.2

목적: 관절경 하 회전근 개 봉합에서 일반적으로 건-봉합간 접촉면 (tenon-suture interface) 에 약한부위 (weak link)가 형성되어 있어 관절경 하 회전근 개 봉합은 개방적 봉합술보다 높은 재파열율을 가진다. 이 연구의 목적은 봉합사를 뼈에 고정할 때 관절경으로 사용할 수 있는 UU(Ulsan University) 봉합과 개방적 변형 MA (Mason-Allen) 봉합의 강도를 비교하는 것이다. 대상 및 방법: 한 구의 사체 극상근 건을 채취하여 절반으로 나눈 후 다시 절반을 나누어 사체의 어깨 관절 한 구당 네 개의 건을 만들어 총 24개의 검체를 만들었다. 두 봉합 형태 (UU, MA)는 무작위로 선택하였으며 각각의 건에 시행하였다. 검체는 0.25 Hz에서 5~30N의 조절된 외력하에서 50회 주기 부하 (cyclic loading)를 받았다. 각 검체는 초당 1mm의 전이가 되는 상황하에서 파열이 발생할 때(ultimate tensile load)까지 부하를 받았다. 조건 이완 (condition elongation), peak-to-peak 전이(displacement), 기울기 (stiffness), 최대 인장력 (ultimate tensile load), 파열 양상 (mode of failure) 등을 기록하였다. 결과: 주기 부하 실험에서 두 봉합 형태 간 유의 있는 차이는 없었다. 최대 장력 실험에서 UU 봉합과 변형 MA (Mason-Allen) 봉합 간에 통계학적으로 유의한 차이는 없었다 (109.4 N, and 110.6 N). 양 봉합 형태에서 가장 흔한 파열 양상은 봉합의 빠짐 (suture pull-out)이었다. 결론: UU 봉합과 변형 MA 봉합은 유사한 생역학적 특성을 가진다. Purpose: In arthroscopic rotator cuff repairs there are generally weak link in tendon suture interface, arthroscopic rotator cuff repairs can have higher retear rates than open repairs. The purpose of this study was to compare the strength of UU (Ulsan University) suture than open modified MA (Mason-Allen) suture when suture anchored into bone. Materials and Methods: The human supraspinatus tendons were harvested from the shoulder of the cadaver and split in 2 times, producing four tendons per one shoulder, for a total of 24 specimens. Two suture configurations (UU, MA) were randomized and checked on each set of tendons. Specimens were cyclically loaded under force control between 5 and 30 N at 0.25 Hz for fifty cycles. Each specimen was loaded to failure under displacement control at 1 mm/sec. Cyclic elongation, peak to peak displacement, stiffness, ultimate tensile load, mode of failure were checked. Results: No significant difference was found between two suture configuration with respect to peak to peak displacement, cyclic elongation, and stiffness. With regard to ultimate failure load, there were no significant difference statistically between the UU suture and modified MA suture (109.4 N, 110.6 N). The most common mode of failure between both sutures was suture pull-out through the tendon. Conclusion: The UU suture and modified MA suture produced similar biomechanical properties.

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,Nichola 대한간학회 2022 Clinical and Molecular Hepatology(대한간학회지) Vol.28 No.4

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.

Durability Properties and Microstructure of Ground Granulated Blast Furnace Slag Cement Concrete

Bahador Sabet Divsholi,Tze Yang Darren Lim,Susanto Teng 한국콘크리트학회 2014 International Journal of Concrete Structures and M Vol.8 No.2

Ground granulated blast-furnace slag (GGBS) is a green construction material used to produce durable concrete. The secondary pozzolanic reactions can result in reduced pore connectivity; therefore, replacing partial amount of Portland cement (PC) with GGBS can significantly reduce the risk of sulfate attack, alkali?silica reactions and chloride penetration. However, it may also reduce the concrete resistance against carbonation. Due to the time consuming process of concrete carbonation, many researchers have used accelerated carbonation test to shorten the experimental time. However, there are always some uncertainties in the accelerated carbonation test results. Most importantly, the moisture content and moisture profile of the concrete before the carbonation test can significantly affect the test results. In this work, more than 200 samples with various water?cementitious material ratios and various replacement percentages of GGBS were cast. The compressive strength, electrical resistivity, chloride permeability and carbonation tests were conducted. The moisture loss and microstructure of concrete were studied. The partial replacement of PC with GGBS produced considerable improvement on various properties of concrete.

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 대한간학회 2023 Clinical and Molecular Hepatology(대한간학회지) Vol.29 No.-

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.

Protein Tyrosine Phosphatase 1B (PTP1B) Inhibitors from <i>Morinda citrifolia</i> (Noni) and Their Insulin Mimetic Activity

Nguyen, Phi-Hung,Yang, Jun-Li,Uddin, Mohammad N.,Park, So-Lim,Lim, Seong-Il,Jung, Da-Woon,Williams, Darren R.,Oh, Won-Keun American Chemical Society and American Society of 2013 Journal of natural products Vol.76 No.11

<P>As part of our ongoing search for new antidiabetic agents from medicinal plants, we found that a methanol extract of <I>Morinda citrifolia</I> showed potential stimulatory effects on glucose uptake in 3T3-L1 adipocyte cells. Bioassay-guided fractionation of this active extract yielded two new lignans (<B>1</B> and <B>2</B>) and three new neolignans (<B>9</B>, <B>10</B>, and <B>14</B>), as well as 10 known compounds (<B>3</B>–<B>8</B>, <B>11</B>–<B>13</B>, and <B>15</B>). The absolute configurations of compounds <B>9</B>, <B>10</B>, and <B>14</B> were determined by ECD spectra analysis. Compounds <B>3</B>, <B>6</B>, <B>7</B>, and <B>15</B> showed inhibitory effects on PTP1B enzyme with IC<SUB>50</SUB> values of 21.86 ± 0.48, 15.01 ± 0.20, 16.82 ± 0.42, and 4.12 ± 0.09 μM, respectively. Furthermore, compounds <B>3</B>, <B>6</B>, <B>7</B>, and <B>15</B> showed strong stimulatory effects on 2-NBDG uptake in 3T3-L1 adipocyte cells. This study indicated the potential of compounds <B>3</B>, <B>6</B>, <B>7</B>, and <B>15</B> as lead molecules for antidiabetic agents.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jnprdf/2013/jnprdf.2013.76.issue-11/np400533h/production/images/medium/np-2013-00533h_0002.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/np400533h'>ACS Electronic Supporting Info</A></P>

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 C 대한간학회 2022 Clinical and Molecular Hepatology(대한간학회지) Vol.28 No.3

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.

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 Kaewd 대한간학회 2022 Clinical and Molecular Hepatology(대한간학회지) Vol.28 No.3

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.