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Fulltext Central Nervous System Outcomes of Lazertinib Versus Gefitinib in EGFR-Mutated Advanced NSCLC: A LASER301 Subset Analysis

Soo RA, Cho BC, Kim JH, Ahn MJ, Lee KH, Zimina A, et al.

J Thorac Oncol, 2023 Dec;18(12):1756-1766.
PMID: 37865896 DOI: 10.1016/j.jtho.2023.08.017

INTRODUCTION: Lazertinib, a third-generation mutant-selective EGFR tyrosine kinase inhibitor, improved progression-free survival compared with gefitinib in the phase 3 LASER301 study (ClinicalTrials.gov Identifier: NCT04248829). Here, we report the efficacy of lazertinib and gefitinib in patients with baseline central nervous system (CNS) metastases.
METHODS: Treatment-naive patients with EGFR-mutated advanced NSCLC were randomized one-to-one to lazertinib (240 mg/d) or gefitinib (250 mg/d). Patients with asymptomatic or stable CNS metastases were included if any planned radiation, surgery, or steroids were completed more than 2 weeks before randomization. For patients with CNS metastases confirmed at screening or subsequently suspected, CNS imaging was performed every 6 weeks for 18 months, then every 12 weeks. End points assessed by blinded independent central review and Response Evaluation Criteria in Solid Tumors version 1.1 included intracranial progression-free survival, intracranial objective response rate, and intracranial duration of response.
RESULTS: Of the 393 patients enrolled in LASER301, 86 (lazertinib, n = 45; gefitinib, n = 41) had measurable and or non-measurable baseline CNS metastases. The median intracranial progression-free survival in the lazertinib group was 28.2 months (95% confidence interval [CI]: 14.8-28.2) versus 8.4 months (95% CI: 6.7-not reached [NR]) in the gefitinib group (hazard ratio = 0.42, 95% CI: 0.20-0.89, p = 0.02). Among patients with measurable CNS lesions, the intracranial objective response rate was numerically higher with lazertinib (94%; n = 17) versus gefitinib (73%; n = 11, p = 0.124). The median intracranial duration of response with lazertinib was NR (8.3-NR) versus 6.3 months (2.8-NR) with gefitinib. Tolerability was similar to the overall LASER301 population.
CONCLUSIONS: In patients with CNS metastases, lazertinib significantly improved intracranial progression-free survival compared with gefitinib, with more durable responses.
Fulltext Lazertinib Versus Gefitinib Tyrosine Kinase Inhibitors in Treatment-Naíve Patients With EGFR-Mutated Advanced NSCLC: Analysis of the Asian Subpopulation in LASER301

Reungwetwattana T, Cho BC, Lee KH, Pang YK, Fong CH, Kang JH, et al.

J Thorac Oncol, 2023 Oct;18(10):1351-1361.
PMID: 37702629 DOI: 10.1016/j.jtho.2023.06.016

INTRODUCTION: Lazertinib is a third-generation central nervous system-penetrant tyrosine kinase inhibitor targeting mutant EGFR in NSCLC. Lazertinib exhibited improved efficacy versus gefitinib in the LASER301 study; this subset analysis compared lazertinib with gefitinib among Asian patients.
METHODS: The phase 3 LASER301 study evaluated lazertinib efficacy and safety in treatment-naive patients with EGFR-mutated (exon 19 deletion or L858R) locally advanced or metastatic NSCLC. Patients were randomized one-to-one and received either lazertinib or gefitinib. The primary end point was investigator-assessed progression-free survival using Response Evaluation Criteria in Solid Tumors version 1.1. Secondary end points included overall survival, objective response rate, duration of response, and safety.
RESULTS: Between February 13, 2020, and July 29, 2022, among 258 patients of Asian descent, the median progression-free survival was significantly longer with lazertinib than gefitinib (20.6 versus 9.7 mo; hazard ratio: 0.46; 95% confidence interval [CI]: 0.34-0.63, p < 0.001), and the benefit was consistent across predefined subgroups (exon 19 deletion, L858R, baseline central nervous system metastases). Objective response rate and disease control rates were similar between treatment groups. The median duration of response was 19.4 months (95% CI: 16.6-24.9) versus 9.6 months (95% CI: 6.9-12.4) in the lazertinib versus gefitinib group. Adverse event rates in Asian patients were comparable with the overall LASER301 population. Adverse events leading to discontinuation in the lazertinib and gefitinib groups were 13% and 12%, respectively.
CONCLUSIONS: In LASER301, efficacy and safety results in Asian patients were consistent with the overall population. Lazertinib exhibited better efficacy than gefitinib in Asian patients with a tolerable safety profile.
A Rare Combination: Dengue Fever Complicated With Guillain-Barre Syndrome

Lim CS, Kaisbain N, Lim WJ

Cureus, 2023 Jun;15(6):e40957.
PMID: 37503499 DOI: 10.7759/cureus.40957

Guillain-Barre syndrome (GBS) is an uncommon neurological complication of dengue viral infection. It is more commonly reported with Campylobacter jejuni, Epstein-Barr virus, and Cytomegalovirus infection. We report an uncommon case of a 49-year-old man with dengue fever, who developed bilateral lower limb weakness and areflexia on day two of dengue illness. He was diagnosed with GBS as a sequel of dengue infection with the nerve conduction study showing evidence of demyelinating neuropathy. He recovered gradually without immunotherapy and was discharged after a week of hospitalization.
Association between dietary 3-monochloropropane-1,2-diol esters (3-MCPDE) and renal cancer in Peninsular Malaysia: exposure assessment and matched case-control study

Muhamad Rosli SH, Lau MS, Khalid T, Maarof SK, Jeyabalan S, Sirdar Ali S, et al.

Food Addit Contam Part A Chem Anal Control Expo Risk Assess, 2023 Apr;40(4):475-492.
PMID: 36947708 DOI: 10.1080/19440049.2023.2183068

3-Monochloropropane-1,2-diol esters (3-MCPDE) are food contaminants commonly found in refined vegetable oils and fats, which have possible carcinogenic implications in humans. To investigate this clinically, we conducted an occurrence level analysis on eight categories of retail and cooked food commonly consumed in Malaysia. This was used to estimate the daily exposure level, through a questionnaire-based case-control study involving 77 subjects with renal cancer, with 80 matching controls. Adjusted Odds Ratio (AOR) was calculated using the multiple logistic regression model adjusted for confounding factors. A pooled estimate of total 3-MCPDE intake per day was compared between both groups, to assess exposure and disease outcome. Among the food categories analysed, vegetable fats and oils recorded the highest occurrence levels (mean: 1.91 ± 1.90 mg/kg), significantly more than all other food categories (p
Oncologist-led BRCA counselling improves access to cancer genetic testing in middle-income Asian country, with no significant impact on psychosocial outcomes

Yoon SY, Wong SW, Lim J, Ahmad S, Mariapun S, Padmanabhan H, et al.

J Med Genet, 2022 Mar;59(3):220-229.
PMID: 33526602 DOI: 10.1136/jmedgenet-2020-107416

BACKGROUND: Identifying patients with BRCA mutations is clinically important to inform on the potential response to treatment and for risk management of patients and their relatives. However, traditional referral routes may not meet clinical needs, and therefore, mainstreaming cancer genetics has been shown to be effective in some high-income and high health-literacy settings. To date, no study has reported on the feasibility of mainstreaming in low-income and middle-income settings, where the service considerations and health literacy could detrimentally affect the feasibility of mainstreaming.
METHODS: The Mainstreaming Genetic Counselling for Ovarian Cancer Patients (MaGiC) study is a prospective, two-arm observational study comparing oncologist-led and genetics-led counselling. This study included 790 multiethnic patients with ovarian cancer from 23 sites in Malaysia. We compared the impact of different method of delivery of genetic counselling on the uptake of genetic testing and assessed the feasibility, knowledge and satisfaction of patients with ovarian cancer.
RESULTS: Oncologists were satisfied with the mainstreaming experience, with 95% indicating a desire to incorporate testing into their clinical practice. The uptake of genetic testing was similar in the mainstreaming and genetics arm (80% and 79%, respectively). Patient satisfaction was high, whereas decision conflict and psychological impact were low in both arms of the study. Notably, decisional conflict, although lower than threshold, was higher for the mainstreaming group compared with the genetics arm. Overall, 13.5% of patients had a pathogenic variant in BRCA1 or BRCA2, and there was no difference between psychosocial measures for carriers in both arms.
CONCLUSION: The MaGiC study demonstrates that mainstreaming cancer genetics is feasible in low-resource and middle-resource Asian setting and increased coverage for genetic testing.
Fulltext Correction to: A multicentre, multi-national, double-blind, randomised, active-controlled, parallel-group clinical study to assess the safety and efficacy of PDA10 (Epoetin-Alfa) vs. Eprex® in patients with anaemia of chronic renal failure

Lim SK, Goh BL, Visvanathan R, Kim SH, Jeon JS, Kim SG, et al.

BMC Nephrol, 2022 Jan 03;23(1):14.
PMID: 34979969 DOI: 10.1186/s12882-021-02651-0
Fulltext Device performances analysis of p-type doped silicene-based field effect transistor using SPICE-compatible model

Chuan MW, Riyadi MA, Hamzah A, Alias NE, Mohamed Sultan S, Lim CS, et al.

PLoS One, 2022;17(3):e0264483.
PMID: 35239699 DOI: 10.1371/journal.pone.0264483

Moore's Law is approaching its end as transistors are scaled down to tens or few atoms per device, researchers are actively seeking for alternative approaches to leverage more-than-Moore nanoelectronics. Substituting the channel material of a field-effect transistors (FET) with silicene is foreseen as a viable approach for future transistor applications. In this study, we proposed a SPICE-compatible model for p-type (Aluminium) uniformly doped silicene FET for digital switching applications. The performance of the proposed device is benchmarked with various low-dimensional FETs in terms of their on-to-off current ratio, subthreshold swing and drain-induced barrier lowering. The results show that the proposed p-type silicene FET is comparable to most of the selected low-dimensional FET models. With its decent performance, the proposed SPICE-compatible model should be extended to the circuit-level simulation and beyond in future work.
Fulltext A multicentre, multi-national, double-blind, randomised, active-controlled, parallel-group clinical study to assess the safety and efficacy of PDA10 (Epoetin-alpha) vs. Eprex® in patients with anaemia of chronic renal failure

Lim SK, Goh BL, Visvanathan R, Kim SH, Jeon JS, Kim SG, et al.

BMC Nephrol, 2021 Nov 25;22(1):391.
PMID: 34823497 DOI: 10.1186/s12882-021-02601-w

BACKGROUND: Erythropoietin stimulating agent (ESA) has been standard of care in treating renal anaemia for the past 20 years. Many patients have limited access to ESA in view of long-term costs leading to suboptimal ESA dosage. Biosimilar epoetin is a potential cost-effective alternative to originator for optimal renal anaemia management.
OBJECTIVE: To determine efficacy and safety of PDA10 in treating renal anaemia in haemodialysis patients, in comparison to the originator epoetin-α, Eprex®.
METHODS: A phase 3, multicentre, multi-national, double-blind, randomised, active-controlled and parallel group study conducted over 40 weeks in Malaysia and Korea. End stage kidney disease patients undergoing regular haemodialysis who were on erythropoietin treatment were recruited. The study has 3 phases, which included a 12-week titration phase, followed by 28-week double-blind treatment phase and 24-week open-label extension phase.
RESULTS: The PDA10 and Eprex® were shown to be therapeutically equivalent (p
Correction to: Prospective observational study on Pazopanib in patients treated for advanced or metastatic renal cell carcinoma in countries in Asia Pacific, North Africa, and Middle East regions: PARACHUTE study

Erman M, Biswas B, Danchaivijitr P, Chen L, Wong YF, Hashem T, et al.

BMC Cancer, 2021 Nov 09;21(1):1191.
PMID: 34753434 DOI: 10.1186/s12885-021-08848-8
Fulltext Plasmon-enhanced reduced graphene oxide photodetector with monometallic of Au and Ag nanoparticles at VIS-NIR region

Rohizat NS, Ripain AHA, Lim CS, Tan CL, Zakaria R

Sci Rep, 2021 Oct 04;11(1):19688.
PMID: 34608217 DOI: 10.1038/s41598-021-99189-w

Hybrids plasmonic nanoparticles (NPs) and unique 2D graphene significantly enhanced the photoresponse of the photodetectors. The metallic NPs that exhibit localized surface plasmon resonance (LSPR) improves strong light absorption, scattering and localized electromagnetic field by the incident photons depending on the optimum condition of NPs. We report high-performance photodetectors based on reduced graphene oxide (rGO) integrated with monometallic of Au and Ag nanoparticles via a familiar fabrication technique using an electron beam evaporation machine. Under 680 nm illumination of light, our rGO photodetector exhibited the highest performance for Au-rGO with the highest responsivity of 67.46 AW-1 and the highest specific detectivity (2.39 × 1013 Jones). Meanwhile, Ag-rGO achieved the highest responsivity of 17.23 AW-1, specific detectivity (7.17 × 1011 Jones) at 785 nm. The response time are 0.146 µs and 0.135 µs for Au-rGO and Ag-rGO respectively for both wavelengths. The proposed photodetector with combining monometallic and graphene provide a new strategy to construct reliable and next-generation optoelectronic devices at VIS-NIR region.
Fulltext Prospective observational study on Pazopanib in patients treated for advanced or metastatic renal cell carcinoma in countries in Asia Pacific, North Africa, and Middle East regions: PARACHUTE study

Erman M, Biswas B, Danchaivijitr P, Chen L, Wong YF, Hashem T, et al.

BMC Cancer, 2021 Sep 14;21(1):1021.
PMID: 34521387 DOI: 10.1186/s12885-021-08738-z

BACKGROUND: Clinical effectiveness and safety data of pazopanib in patients with advanced or mRCC in real-world setting from Asia Pacific, North Africa, and Middle East countries are lacking.
METHODS: PARACHUTE is a phase IV, prospective, non-interventional, observational study. Primary endpoint was the proportion of patients remaining progression free at 12 months. Secondary endpoints were ORR, PFS, safety and tolerability, and relative dose intensity (RDI).
RESULTS: Overall, 190 patients with a median age of 61 years (range: 22.0-96.0) were included. Most patients were Asian (70%), clear-cell type RCC was the most common (81%), with a favourable (9%), intermediate (47%), poor (10%), and unknown (34%) MSKCC risk score. At the end of the observational period, 78 patients completed the observational period and 112 discontinued the study; 60% of patients had the starting dose at 800 mg. Median RDI was 82%, with 52% of patients receiving 10%) TEAEs related to pazopanib included diarrhoea (30%), palmar-plantar erythrodysesthesia syndrome (15%), and hypertension (14%).
CONCLUSIONS: Results of the PARACHUTE study support the use of pazopanib in patients with advanced or mRCC who are naive to VEGF-TKI therapy. The safety profile is consistent with that previously reported by pivotal and real-world evidence studies.
Neuritin Protein Expression Is Positively Correlated with Neurite Outgrowth Induced by the Tiger Milk Mushroom, Lignosus rhinocerotis (Agaricomycetes), in PC12 Cells

Tan YH, Lim CS, Wong KH, Sabaratnam V

Int J Med Mushrooms, 2021;23(6):1-11.
PMID: 34369729 DOI: 10.1615/IntJMedMushrooms.2021038578

Neuritin is important in neuritogenesis, neurite arborization, and neurite extension. Lignosus rhinocerotis sclerotia extracts and nerve growth factor (NGF) have been well documented to possess positive neurite stimulatory effects. However, the correlation of neuritin expression with neurite outgrowth of L. rhinocerotis and NGF cotreatment of PC12 cells remains unknown. Thus, the present study investigated neuritin expression in PC12 cells treated with 5 ng/mL of NGF and L. rhinocerotis extracts (20-1280 μg/mL) concurrently for 48 h. The neurite outgrowth score was quantitated, and total protein was harvested for enzyme-linked immunosorbent assay. There was a significant difference (P = 0.051) in neuritin protein abundance in 640 μg/mL of L. rhinocerotis aqueous cotreatment with 5 ng/mL of NGF-treated cells (5 ± 0.39 ng/mL) and 50 ng/mL of NGF-treated PC12 cells (5 ± 0.48 ng/mL) compared to untreated cells (1.9 ± 0.65 ng/ mL), with an average neurite length of 98 ± 3.66, 106 ± 3.00, and 73 ± 4.79 μm, respectively. Expression of microtubule element β3 tubulin was increased in PC12 cells treated with 50 ng/mL of NGF (3.5 ± 0.21-fold) and also cells cotreated with 640 μg/mL of extract and 5 ng/mL of NGF (4.9 ± 0.29-fold) compared to untreated cells. Upregulation of β3 tubulin expression in this study confirmed the elongation of PC12 cell processes. Correlation analysis showed that neuritin protein abundance is positively proportional to the average neurite length in PC12 cells cotreated with L. rhinocerotis extract and 5 ng/mL of NGF. This study highlights that neuritin modulation is involved in neurite outgrowth induced by L. rhinocerotis treatment. To our knowledge, this is the first report to show that tiger milk mushroom extracts induce neuritin expression.
Fulltext Semi-analytical modelling and evaluation of uniformly doped silicene nanotransistors for digital logic gates

Chuan MW, Wong KL, Riyadi MA, Hamzah A, Rusli S, Alias NE, et al.

PLoS One, 2021;16(6):e0253289.
PMID: 34125874 DOI: 10.1371/journal.pone.0253289

Silicene has attracted remarkable attention in the semiconductor research community due to its silicon (Si) nature. It is predicted as one of the most promising candidates for the next generation nanoelectronic devices. In this paper, an efficient non-iterative technique is employed to create the SPICE models for p-type and n-type uniformly doped silicene field-effect transistors (FETs). The current-voltage characteristics show that the proposed silicene FET models exhibit high on-to-off current ratio under ballistic transport. In order to obtain practical digital logic timing diagrams, a parasitic load capacitance, which is dependent on the interconnect length, is attached at the output terminal of the logic circuits. Furthermore, the key circuit performance metrics, including the propagation delay, average power, power-delay product and energy-delay product of the proposed silicene-based logic gates are extracted and benchmarked with published results. The effects of the interconnect length to the propagation delay and average power are also investigated. The results of this work further envisage the uniformly doped silicene as a promising candidate for future nanoelectronic applications.
Coffee consumption revealed sex differences in host endogenous metabolism and gut microbiota in healthy adults

Chong CW, Wong LC, Teh CSJ, Ismail NH, Chan PQ, Lim CS, et al.

J Food Biochem, 2020 12;44(12):e13535.
PMID: 33103260 DOI: 10.1111/jfbc.13535

Coffee is rich in antioxidant and has been shown to confer various health benefits. Here, we investigated the effect of single-dose coffee consumption in healthy human subjects. About 30 healthy volunteers were recruited and given a serving of sugar free black coffee. Urine and fecal samples were collected and analyzed. Significant changes in urinary metabolites relating to coffee, gut microbial and host energy metabolisms were observed post-coffee consumption. Clear sex differences were also observed in the urinary metabolic profiles pre- and post-coffee consumption. Sex differences in richness and composition of gut microbiota were observed, however, the effect of single-dose coffee consumption on host gut microbiota were unremarkable. These findings indicated that single-dose coffee consumption affects sex-specific host metabolic responses that relates to gut-microbe and energy metabolism. This study demonstrated the utility of systems biology tools to unravel complexity of host-diet biology and gut microbial responses. PRACTICAL APPLICATIONS: This study demonstrated that integrated systems biology approach enabled efficient extractions of host biochemical and microbial information that allows food industry to ascertain the impact of diet and longitudinal assessment of potential functional food in humans.
Wilms tumour with poor response to pre-operative chemotherapy: A report of 2 cases

Tan HCL, Tan JH, Vellusamy VM, Vasavan Y, Lim CS

Malays J Pathol, 2020 Aug;42(2):267-271.
PMID: 32860380

INTRODUCTION: Majority of Wilms tumour (WT) responds well to pre-operative chemotherapy. In Malaysia, incidence of WT is rare with only two cases reported per one million populations yearly. This case report is to highlight on the awareness of WT in an Asian population and highlight two cases and challenges faced after pre-operative chemotherapy.
CASE REPORT: In this case series, we report on two cases of WT which had poor response to pre-operative chemotherapy. Both cases underwent surgery after pre-operative chemotherapy and recovery was uneventful during a two-year follow-up.
DISCUSSION: Both patients had chemotherapy prior planned surgery, but had unfortunate poor tumour response. The tumour progressed in size which required a radical nephrectomy. The histology report for the first case had more than 60% blastemal cells remaining despite giving pre-operative chemotherapy with no focal anaplasia. This showed poor response to chemotherapy evidenced by the high number of blastemal cells. The second case was a stromal type WT which is known for poor response and may lead to enhancement of growth and maturation induced by chemotherapy. These were the possible reason of poor response of WT in these two cases.
Fulltext Systematic comparison of plasma EBV DNA, anti-EBV antibodies and miRNA levels for early detection and prognosis of nasopharyngeal carcinoma

Tan LP, Tan GW, Sivanesan VM, Goh SL, Ng XJ, Lim CS, et al.

Int J Cancer, 2020 04 15;146(8):2336-2347.
PMID: 31469434 DOI: 10.1002/ijc.32656

Nasopharyngeal carcinoma (NPC) is originated from the epithelial cells of nasopharynx, Epstein-Barr virus (EBV)-associated and has the highest incidence and mortality rates in Southeast Asia. Late presentation is a common issue and early detection could be the key to reduce the disease burden. Sensitivity of plasma EBV DNA, an established NPC biomarker, for Stage I NPC is controversial. Most newly reported NPC biomarkers have neither been externally validated nor compared to the established ones. This causes difficulty in planning for cost-effective early detection strategies. Our study systematically evaluated six established and four new biomarkers in NPC cases, population controls and hospital controls. We showed that BamHI-W 76 bp remains the most sensitive plasma biomarker, with 96.7% (29/30), 96.7% (58/60) and 97.4% (226/232) sensitivity to detect Stage I, early stage and all NPC, respectively. Its specificity was 94.2% (113/120) against population controls and 90.4% (113/125) against hospital controls. Diagnostic accuracy of BamHI-W 121 bp and ebv-miR-BART7-3p were validated. Hsa-miR-29a-3p and hsa-miR-103a-3p were not, possibly due to lower number of advanced stage NPC cases included in this subset. Decision tree modeling suggested that combination of BamHI-W 76 bp and VCA IgA or EA IgG may increase the specificity or sensitivity to detect NPC. EBNA1 99 bp could identify NPC patients with poor prognosis in early and advanced stage NPC. Our findings provided evidence for improvement in NPC screening strategies, covering considerations of opportunistic screening, combining biomarkers to increase sensitivity or specificity and testing biomarkers from single sampled specimen to avoid logistic problems of resampling.
Fulltext Reefing Viability Index for Rigs-to-Reefs (R2R) in Malaysia

Mohd MH, Rahman MAA, Nazri MN, Tan CH, Mohamad Y, Lim CS, et al.

ScientificWorldJournal, 2020;2020:4695894.
PMID: 33223970 DOI: 10.1155/2020/4695894

Decommissioning of the offshore platform as an artificial reef, known as Rigs-to-Reefs (R2R), has become a sustainable approach for oil companies. The platform was reused to serve the underwater ecosystem as an artificial reef for a new marine ecosystem which helps to tackle food security issue. This paper presents the findings of the formulation of the reefing viability index to recognize an offshore region that can be used for R2R projects within the South China Sea. The combined effects of spatial data, numerical modelling, and geographic system (GIS) are proposed to study the relationship of spawning ground coral reefs, diversity, and planula larvae in the process of colonization to establish a map of the reef potential environment. Coral connectivity and spawning behaviour were studied to determine the possible source of coral seedling released during the spawning season, twice a year. A geographic reef viability index was established consisting of seven parameters which are coral larval density, pelagic larval length, sea currents, temperature, chlorophyll-a, depth, and substrate availability. The ocean hydrodynamic model was designed to resemble the pattern of larval scattering. By using the simulations and rankings, there were 95 (21%) sites which could probably be used for in situ reefing, whereas 358 (79%) sites were likely ideal for ex situ reefing. Validation of the viability index was carried out using media footage assessment of remotely operated vehicle (ROV).
Fulltext Management of advanced prostate cancer in a middle-income country: real-world consideration of the Advanced Prostate Cancer Consensus Conference 2017

Saad M, Alip A, Lim J, Abdullah MM, Chong FLT, Chua CB, et al.

BJU Int, 2019 09;124(3):373-382.
PMID: 31077523 DOI: 10.1111/bju.14807

OBJECTIVE: To examine the results of the Malaysian Advanced Prostate Cancer Consensus Conference (MyAPCCC) 2018, held for assessing the generalizability of consensus reached at the Advanced Prostate Cancer Consensus Conference (APCCC 2017) to Malaysia, a middle-income country.
METHODS: Six key sections were chosen: (1) high-risk localized and locally advanced prostate cancer, (2) oligometastatic prostate cancer, (3) castration-naïve prostate cancer, (4) castrate resistant prostate cancer, (5) use of osteoclast-targeted therapy and (6) global access to prostate cancer drugs. There were 101 consensus questions, consisting of 91 questions from APCCC 2017 and 10 new questions from MyAPCCC 2018, selected and modified by the steering committee; of which, 23 questions were assessed in both ideal world and real-world settings. A panel of 22 experts, comprising of 11 urologists and 11 oncologists, voted on 101 predefined questions anonymously. Final voting results were compared with the APCCC 2017 outcomes.
RESULTS: Most voting results from the MyAPCCC 2018 were consistent with the APCCC 2017 outcomes. No consensus was achieved for controversial topics with little level I evidence, such as management of oligometastatic disease. No consensus was reached on using high-cost drugs in castration-naïve or castration-resistant metastatic prostate cancer in real-world settings. All panellists recommended using generic drugs when available.
CONCLUSIONS: The MyAPCCC 2018 voting results reflect the management of advanced prostate cancer in a middle-income country in a real-world setting. These results may serve as a guide for local clinical practices and highlight the financial challenges in modern healthcare.
Fulltext Antibacterial activity of biosynthesized gold nanoparticles using biomolecules from Lignosus rhinocerotis and chitosan

Katas H, Lim CS, Nor Azlan AYH, Buang F, Mh Busra MF

Saudi Pharm J, 2019 Feb;27(2):283-292.
PMID: 30766441 DOI: 10.1016/j.jsps.2018.11.010

A simple, cost-effective, and environmentally friendly method is needed for synthesizing metal nanoparticles, including gold nanoparticles (AuNPs). In this study, AuNPs were synthesized with Lignosus rhinocerotis sclerotial extract (LRE) and chitosan (CS) as reducing and stabilizing agents, respectively. Different LRE concentrations from cold and hot water extraction (CWE and HWE, respectively) were used to reduce chloroauric acid (HAuCl4) to form AuNPs. Positively charged chitosan stabilized AuNPs (CS-AuNPs) mediated by LRE exhibited a surface plasmon resonance (SPR) band at 533 nm. The CS-AuNPs synthesized using CWE had a smaller particle size (49.5 ± 6.7-82.4 ± 28.0 nm) compared to that of the HWE samples (80.3 ± 23.4-125.3 ± 41.5 nm), depending on LRE concentration. FTIR results suggested protein and polysaccharides in LRE were the sources of reducing power, reducing gold ions to AuNPs. CS-AuNPs were mostly spherical with higher LRE concentrations, whereas some triangular, pentagonal, irregular, and rod shaped AuNPs were observed at lower LRE concentrations. CS-AuNPs mediated by LRE displayed effective antibacterial activity against gram-negative (Pseudomonas aeruginosa and Escherichia coli) and gram-positive bacteria (Staphylococcus aureus and Bacillus sp.). Thus, the biosynthesized AuNPs using LRE and chitosan provide opportunities for developing stable and eco-friendly nanoparticles with effective antibacterial properties.
Fulltext Bridging the gap between advancements in the evolution of diagnosis and treatment towards better outcomes in achalasia

Chuah SK, Lim CS, Liang CM, Lu HI, Wu KL, Changchien CS, et al.

Biomed Res Int, 2019;2019:8549187.
PMID: 30881999 DOI: 10.1155/2019/8549187

Over the past few decades, there was an encouraging breakthrough in bridging the gap between advancements in the evolution of diagnosis and treatment towards a better outcome in achalasia. The purpose of this review is to provide updated knowledge on how the current evidence has bridged the gap between advancements in the evolution of diagnosis and treatment of esophageal achalasia. The advent of high-resolution manometry and standardization based on the Chicago classification has increased early recognition of the disease. These 3 clinical subtypes of achalasia can predict the outcomes of patients, and the introduction of POEM has revolutionized the choice of treatment. Previous evidence has shown that laparoscopic Heller myotomy (LHM) and anterior fundoplication were considered the most durable treatments for achalasia. Based on the current evidence, POEM has been evolving as a promising strategy and is effective against all 3 types of achalasia, but the efficacy of POEM is based on short- and medium-term outcome studies from a limited number of centers. Types I and II achalasia respond well to POEM, LHM, and PD, while most studies have shown that type III achalasia responds better to POEM than to LHM and PD. In general, among the 3 subtypes of achalasia, type II achalasia has the most favorable outcomes after medical or surgical therapies. The long-term efficacy of POEM is still unknown. The novel ENDOFLIP measures the changes in intraoperative esophagogastric junction dispensability, which enables a quantitative assessment of luminal patency and sphincter distension; however, this technology is in its infancy with little data to date supporting its intraoperative use. In the future, identifying immunomodulatory drugs and the advent of stem cell therapeutic treatments, including theoretically transplanting neuronal stem cells, may achieve a functional cure. In summary, it is important to identify the clinical subtype of achalasia to initiate target therapy for these patients.

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