Gene expression profile of immune-check point in response to Trastuzumab therapy in patients with HER-2 positive breast cancer.

OBJECTIVE: Aim: To clarify the association between response to Trastuzumab and molecular expression of TIM-3 and FOXP-3 immune checkpoints. PATIENTS AND METHODS: Materials and Methods: FOXP-3 and TIM-3 expression in peripheral blood was analyzed using qPCR, and the serum level of Trastuzumab was estimated using an immune sorbent enzyme assay. RESULTS: Results: During treatment with Trastuzumab, the FOXP-3 gene expression showed a significant decline throughout one year of treatment, going from 0.85 at cycle 9 to 0.75 at cycle 17. While the TIM-3 gene expression showed a significant up regulation at cycle 9 to 2.8 fold, followed by a reduction in the fold change from 2.8 to 1.7 in the font of reference gene expression. CONCLUSION: Conclusions:FOXP-3 and TIM-3 have the potential to be suggestive markers that can anticipate the response to Trastuzumab, but they are not capable of predicting the likelihood of recurrence.

Stunting and Its Associated Factors among Children Below 5 Years Old on the East Coast of Peninsular Malaysia: Evidence from the National Health and Morbidity Survey.

Background: Child malnutrition problems still occur in Malaysia, particularly stunting. This study aimed to determine the proportion of stunting among children below 5 years old and investigate the factors associated with stunting on the East Coast of Peninsular Malaysia. Methods: This study utilised data from the 2016 National Health and Morbidity Survey (NHMS). Multiple logistic regression was used to determine the factors associated with malnutrition among non-stunted and stunted children. Results: The proportion of stunting among children below 5 years old in this East Coast region was 26.2%. When divided by state, Kelantan had the highest proportion of stunting, followed by Pahang and Terengganu, at 28.8%, 26.2% and 23.4%, respectively. In this study, the factors associated with stunting were children aged 24 months old-59 months old (adjusted odds ratio [aOR]: 1.52; 95% CI: 1.26, 1.83; P < 0.001), male children (aOR: 1.47; 95% CI: 1.23, 1.76; P < 0.001), Orang Asli children (aOR: 2.84; 95% CI: 1.86, 4.32; P < 0.001), children with low birth weight from 1,500 g to 2,499 g (aOR: 1.86; 95% CI: 1.36, 2.55; P < 0.001) and children from households that practice unsanitary waste disposal (aOR: 1.42; 95% CI: 1.16, 1.74; P = 0.001). Conclusion: Stunting among children under the age of 5 years old on the East Coast of Peninsular Malaysia remains a public health problem. To reduce the prevalence of stunting in this region, intervention programmes should be intensified. Emphasis should be placed on public health programmes that target the associated factors, such as dietary habits, Orang Asli children, low birth weight and unsanitary waste disposal.

Willingness to receive a COVID-19 booster vaccine and its associated factors among adults with chronic disease: A cross-sectional study in Putrajaya, Malaysia.

Introduction: Booster vaccination has been shown to reduce transmission and serious infection with COVID-19. This study examined the willingness to receive a COVID-19 booster vaccine and its associated factors among high-risk patients at Klinik Kesihatan Putrajaya Presint 9. Method: A cross-sectional study was conducted among patients aged >18 years attending Klinik Kesihatan Putrajaya Presint 9 with a high risk of contracting COVID-19 recruited via systematic random sampling. Data were collected using a self-administered questionnaire. A multiple logistic regression analysis was performed to identify the associated factors. Results: The response rate for this study was 97.4% (N=489). The median patient age was 55 years. Approximately 51.7% were men, and 90.4% were Malays. Approximately 81.2% were willing to receive a COVID-19 booster vaccine. The patients who perceived COVID-19 as a serious illness (Adjusted Odd Ratio, AOR=2.414), those who perceived COVID-19 booster vaccines as beneficial (AOR=7.796), those who disagreed that COVID-19 booster vaccines have many side effects (AOR=3.266), those who had no doubt about the content of COVID-19 vaccines (AOR=2.649) and those who were employed (AOR=2.559) and retired (AOR=2.937) were more likely to be willing to receive a booster vaccine than those who were unemployed and those who did not have close friends or family members who contracted severe COVID-19 (AOR=2.006). Conclusion: The majority of the participants were willing to receive a COVID-19 booster vaccine. Healthcare authorities should take initiatives to design targeted public intervention programmes to increase the willingness for COVID-19 booster vaccination.

Ramadan fasting in people with diabetes and chronic kidney disease (CKD) during the COVID-19 pandemic: The DaR global survey.

BACKGROUND AND AIMS: The DaR Global survey was conducted to observe the impact of the COVID-19 pandemic on the intentions to fast and the outcomes of fasting in people with diabetes and chronic kidney disease (CKD). METHODS: Muslim people with diabetes and CKD were surveyed in 13 countries shortly after the end of Ramadan 2020, using a simple Survey Monkey questionnaire. RESULTS: This survey recruited 6736 people with diabetes, of which 707 (10.49%) had CKD. There were 118 (16.69%) people with type1 diabetes (T1D), and 589 (83.31%) were with type2 diabetes (T2D). 62 (65.24%) people with T1D and 448 (76.06%) people with T2D had fasted with CKD. Episodes of hypoglycaemia and hyperglycaemia were more frequent among people with T1D compared to T2D, 64.52% and 43.54% vs 25.22% and 22.32% respectively. Visits to the emergency department and hospitalization were more frequent among people with CKD, however no significant difference was found between people with T1D and T2D. CONCLUSION: The COVID-19 pandemic had only a minor effect on the intention to fast during Ramadan in people with diabetes and CKD. However, hypoglycaemia and hyperglycaemia were found to be more frequent, as well as emergency visits and hospital admissions among people with diabetic kidney disease. Prospective studies are needed in future to evaluate the risk indicators of hypoglycaemia and hyperglycaemia among fasting people with CKD, especially in the context of different stages of kidney disease.

Carbon dots labeled Lactiplantibacillus plantarum: a fluorescent multifunctional biocarrier for anticancer drug delivery.

A carbon dots (CDs)-biolabeled heat-inactivated Lactiplantibacillus plantarum (HILP) hybrid was investigated as a multifunctional probiotic drug carrier with bioimaging properties using prodigiosin (PG) as anticancer agent. HILP, CDs and PG were prepared and characterized using standard methods. CDs-labeled HILP (CDs/HILP) and PG loaded CDs/HILP were characterized by transmission electron microscopy (TEM), laser scanning confocal microscopy (LSCM) and for entrapment efficiency (EE%) of CDs and PG, respectively. PG-CDs/HILP was examined for stability and PG release. the anticancer activity of PG-CDs/HILP was assessed using different methods. CDs imparted green fluorescence to HILP cells and induced their aggregation. HILP internalized CDs via membrane proteins, forming a biostructure with retained fluorescence in PBS for 3 months at 4°C. Loading PG into CDs/HILP generated a stable green/red bicolor fluorescent combination permitting tracking of both drug carrier and cargo. Cytotoxicity assay using Caco-2 and A549 cells revealed enhanced PG activity by CDs/HILP. LCSM imaging of PG-CDs/HILP-treated Caco-2 cells demonstrated improved cytoplasmic and nuclear distribution of PG and nuclear delivery of CDs. CDs/HILP promoted PG-induced late apoptosis of Caco-2 cells and reduced their migratory ability as affirmed by flow cytometry and scratch assay, respectively. Molecular docking indicated PG interaction with mitogenic molecules involved in cell proliferation and growth regulation. Thus, CDs/HILP offers great promise as an innovative multifunctional nanobiotechnological biocarrier for anticancer drug delivery. This hybrid delivery vehicle merges the physiological activity, cytocompatibility, biotargetability and sustainability of probiotics and the bioimaging and therapeutic potential of CDs.

International consensus recommendations for the optimal prioritisation and distribution of surgical services in low-income and middle-income countries: a modified Delphi process.

OBJECTIVES: To develop consensus statements regarding the regional-level or district-level distribution of surgical services in low and middle-income countries (LMICs) and prioritisation of service scale-up. DESIGN: This work was conducted using a modified Delphi consensus process. Initial statements were developed by the International Standards and Guidelines for Quality Safe Surgery and Anesthesia Working Group of the Global Alliance for Surgical, Obstetric, Trauma and Anesthesia Care (G4 Alliance) and the International Society of Surgery based on previously published literature and clinical expertise. The Guidance on Conducting and REporting DElphi Studies framework was applied. SETTING: The Working Group convened in Suva, Fiji for a meeting hosted by the Ministry of Health and Medical Services to develop the initial statements. Local experts were invited to participate. The modified Delphi process was conducted through an electronically administered anonymised survey. PARTICIPANTS: Expert LMIC surgeons were nominated for participation in the modified Delphi process based on criteria developed by the Working Group. PRIMARY OUTCOME MEASURES: The consensus panel voted on statements regarding the organisation of surgical services, principles for scale-up and prioritisation of scale-up. Statements reached consensus if there was ≥80% agreement among participants. RESULTS: Fifty-three nominated experts from 27 LMICs voted on 27 statements in two rounds. Ultimately, 26 statements reached consensus and comprise the current recommendations. The statements covered three major themes: which surgical services should be decentralised or regionalised; how the implementation of these services should be prioritised; and principles to guide LMIC governments and international visiting teams in scaling up safe, accessible and affordable surgical care. CONCLUSIONS: These recommendations represent the first step towards the development of international guidelines for the scaling up of surgical services in LMICs. They constitute the best available basis for policymaking, planning and allocation of resources for strengthening surgical systems.

Evaluating Cataract Surgical Rate through Smart Partnership between Ministry of Health, Malaysia and Federal Territory Islamic Religious Council.

INTRODUCTION: Cataract is the leading cause of blindness. About 90% of cataract blindness occurs in low- and middle-income countries. The prevalence of blindness and low vision in any country depends on the socioeconomic status, the availability of medical and healthcare facilities, and the literacy of the population. AIM: This paper aims to estimate the cataract surgery rate (CSR) at Pusat Pembedahan Katarak, MAIWP-Hospital Selayang (Cataract Operation Centre), and provide descriptive assessments of the patients who received eye treatments in the center. METHODS: The data were retrieved from the clinical database from 2013 to 2016. Information on the patient's sociodemographic and clinical and treatment history was collected. RESULTS: The cataract surgery rate for 2013 was about 27 and increased to 37.3 in 2014. However, it declined to 25 in 2015 before it resumed to 36 in 2016. For female patients who received eye treatments at Pusat Pembedahan Katarak, MAIWP-Hospital Selayang, the rate was higher (53.7%) compared to male patients (46.3%). The mean duration of cataract surgery from 2013 to 2016 was 21.25 ± 11.071 min. CONCLUSION: The increased cataract surgery rate for MAIWP-HS through smart partnerships for day care cataract surgery proved that better accessibility makes the short- and long-term strategies for the reduction and prevention of blindness in Malaysia possible to achieve.

Early phase oncology clinical trials in Malaysia: current status and future perspectives.

Historically, the majority of oncology clinical trials are conducted in Western Europe and North America. Globalization of drug development has resulted in sponsors shifting their focus to the Asia-Pacific region. In Malaysia, implementation of various government policies to promote clinical trials has been initiated over a decade ago and includes the establishment of Clinical Research Malaysia, which functions as a facilitator and enabler of industry-sponsored clinical trials on a nationwide basis. Although oncology clinical trials in Malaysia have seen promising growth, there are still only a limited number of early phase oncology studies being conducted. Hence, the Phase 1 Realization Project was initiated to develop Malaysia's early phase clinical trial capabilities. In addition, the adaptation of good practices from other countries contribute to the effective implementation of existing initiatives to drive progress in the development of early phase drug development set up in Malaysia. Furthermore, holistic approaches with emphasis in training and education, infrastructure capacities, strategic alliances, reinforcement of upstream activities in the value chain of drug development, enhanced patient advocacy, coupled with continued commitment from policy makers are imperative in nurturing a resilient clinical research ecosystem in Malaysia.

Molecular and serological biomarkers to predict trastuzumab responsiveness in HER-2 positive breast cancer.

HER-2-positive breast cancer is characterized by its aggressive nature, poor prognosis, and reduced overall survival. The emergence of trastuzumab resistance is currently considered a global problem. The immune system plays a pivotal role in tumor progression and development. Cytotoxic T lymphocyte-associated protein-4 (CTLA-4) and other immune checkpoint proteins may be potential prognostic factors and therapeutic targets for breast cancer. This study aimed to determine the correlation between CTLA-4 expression in peripheral blood and insulin-like growth factor-1 (IGF-1) serum levels and their impact on trastuzumab responsiveness in HER-2-positive patients with breast cancer. CTLA-4 expression was analyzed in peripheral blood cells using quantitative PCR, while IGF-1 serum levels were assessed through electrochemiluminescence assays. There was a significant increase in CTLA-4 expression at cycle 9, which continued to increase until it reached 4.6 at cycle 17. High IGF-1 levels were observed in newly diagnosed HER-2 positive patients before trastuzumab therapy, significantly decreasing post-therapy (p=0.001). Co-targeting HER-2 and IGF-1 receptors may reduce the risk of recurrence and improve outcomes. In addition, targeted CTLA-4 molecules may improve patient survival and prevent recurrence.

Prognostic Factor of Lower Limb Amputation among Diabetic Foot Ulcer Patients in North-East Peninsular Malaysia.

Lower limb amputation (LLA) is a common complication of diabetic foot ulcer (DFU), which can lead to a higher 5-year mortality rate compared to all cancers combined. This study aimed to determine the prognostic factors of LLA among DFU patients in Kelantan from 2014 to 2018. A population-based study was conducted using secondary data obtained from the National Diabetic Registry (NDR). There were 362 cases that fulfilled the study criteria and were further analysed. The prognostic factors were determined by Multiple Cox Proportional Hazards Regression. There were 66 (18.2%) DFU patients who underwent LLA in this study, while 296 (81.8%) were censored. The results revealed that the factor leading to a higher risk of LLA was abnormal HDL-cholesterol levels (Adj. HR 2.18; 95% CI: 1.21, 3.92). Factors that led to a lower risk of LLA include DFU in patients aged 60 or more (Adj. HR 0.48; 95% CI: 0.27, 0.89) and obesity (Adj. HR 0.45; 95% CI: 0.22, 0.89). In conclusion, our model showed that abnormal HDL cholesterol was associated with a 2 times higher risk of LLA when adjusted for age and BMI. Any paradoxical phenomena should be addressed carefully to avoid wrong clinical decision making that can harm the patient.

The effects of super spreading events and movement control measures on the COVID-19 pandemic in Malaysia.

This paper aims to develop an automated web application to generate validated daily effective reproduction numbers (Rt) which can be used to examine the effects of super-spreading events due to mass gatherings and the effectiveness of the various Movement Control Order (MCO) stringency levels on the outbreak progression of COVID-19 in Malaysia. The effective reproduction number, Rt, was estimated by adopting and modifying an Rt estimation algorithm using a validated distribution mean of 3.96 and standard deviation of 4.75 with a seven-day sliding window. The Rt values generated were validated using thea moving window SEIR model with a negative binomial likelihood fitted using methods from the Bayesian inferential framework. A Pearson's correlation between the Rt values estimated by the algorithm and the SEIR model was r = 0.70, p < 0.001 and r = 0.81, p < 0.001 during the validation period The Rt increased to reach the highest values at 3.40 (95% CI 1.47, 6.14) and 1.72 (95% CI 1.54, 1.90) due to the Sri Petaling and Sabah electoral process during the second and third waves of COVID-19 respectively. The MCOs was able to reduce the Rt values by 63.2 to 77.1% and 37.0 to 47.0% during the second and third waves of COVID-19, respectively. Mass gathering events were one of the important drivers of the COVID-19 outbreak in Malaysia. However, COVID-19 transmission can be fuelled by noncompliance to Standard Operating Procedure, population mobility, ventilation and environmental factors.

Yield of a second right colon examination during colonoscopy after a first examination using a mucosal exposure device.

BACKGROUND AND AIMS: Double right colon examination during colonoscopy has been advocated to reduce the risk of interval cancer in the right colon. Whether 2 examinations are necessary when the first examination is performed with a mucosal exposure device is uncertain. We documented the rates of missed adenomas, sessile serrated lesions, and hyperplastic polyps after an initial right colon examination by a high-level detector using a mucosal exposure device. METHODS: At a single tertiary hospital outpatient practice, we prospectively collected data on the yield of a second examination of the right colon after an initial examination by a single high-detecting colonoscopist using a mucosal exposure device. RESULTS: During the study period, 1331 eligible consecutive patients underwent colonoscopy. Right colon adenoma, sessile serrated lesion, and hyperplastic polyp miss rates were 15.8%, 14.1%, and 16.7%, respectively. Four percent of patients had adenomas detected in the right colon only with a second examination. CONCLUSIONS: A second examination of the right colon is warranted, even when using a distal mucosal exposure device to perform colonoscopy.

PICK-ing Malaysia's Epidemic Apart: Effectiveness of a Diverse COVID-19 Vaccine Portfolio.

Malaysia rolled out a diverse portfolio of predominantly three COVID-19 vaccines (AZD1222, BNT162b2, and CoronaVac) beginning 24 February 2021. We evaluated vaccine effectiveness with two methods, covering 1 April to 15 September 2021: (1) the screening method for COVID-19 (SARS-CoV-2) infection and symptomatic COVID-19; and (2) a retrospective cohort of confirmed COVID-19 cases for COVID-19 related ICU admission and death using logistic regression. The screening method estimated partial vaccination to be 48.8% effective (95% CI: 46.8, 50.7) against COVID-19 infection and 33.5% effective (95% CI: 31.6, 35.5) against symptomatic COVID-19. Full vaccination is estimated at 87.8% effective (95% CI: 85.8, 89.7) against COVID-19 infection and 85.4% effective (95% CI: 83.4, 87.3) against symptomatic COVID-19. Among the cohort of confirmed COVID-19 cases, partial vaccination with any of the three vaccines is estimated at 31.3% effective (95% CI: 28.5, 34.1) in preventing ICU admission, and 45.1% effective (95% CI: 42.6, 47.5) in preventing death. Full vaccination with any of the three vaccines is estimated at 79.1% effective (95% CI: 77.7, 80.4) in preventing ICU admission and 86.7% effective (95% CI: 85.7, 87.6) in preventing deaths. Our findings suggest that full vaccination with any of the three predominant vaccines (AZD1222, BNT162b2, and CoronaVac) in Malaysia has been highly effective in preventing COVID-19 infection, symptomatic COVID-19, COVID-19-related ICU admission, and death.

Modelling infectious diseases with herd immunity in a randomly mixed population.

The conventional susceptible-infectious-recovered (SIR) model tends to magnify the transmission dynamics of infectious diseases, and thus the estimated total infections and immunized population may be higher than the threshold required for infection control and eradication. The study developed a new SIR framework that allows the transmission rate of infectious diseases to decline along with the reduced risk of contact infection to overcome the limitations of the conventional SIR model. Two new SIR models were formulated to mimic the declining transmission rate of infectious diseases at different stages of transmission. Model A utilized the declining transmission rate along with the reduced risk of contact infection following infection, while Model B incorporated the declining transmission rate following recovery. Both new models and the conventional SIR model were then used to simulate an infectious disease with a basic reproduction number (r0) of 3.0 and a herd immunity threshold (HIT) of 0.667 with and without vaccination. Outcomes of simulations were assessed at the time when the total immunized population reached the level predicted by the HIT, and at the end of simulations. Further, all three models were used to simulate the transmission dynamics of seasonal influenza in the United States and disease burdens were projected and compared with estimates from the Centers for Disease Control and Prevention. For the simulated infectious disease, in the initial phase of the outbreak, all three models performed expectedly when the sizes of infectious and recovered populations were relatively small. As the infectious population increased, the conventional SIR model appeared to overestimate the infections even when the HIT was achieved in all scenarios with and without vaccination. For the same scenario, Model A appeared to attain the level predicted by the HIT and in comparison, Model B projected the infectious disease to be controlled at the level predicted by the HIT only at high vaccination rates. For infectious diseases with high r0, and at low vaccination rates, the level at which the infectious disease was controlled cannot be accurately predicted by the current theorem. Transmission dynamics of infectious diseases with herd immunity can be accurately modelled by allowing the transmission rate of infectious diseases to decline along with the reduction of contact infection risk after recovery or vaccination. Model B provides a credible framework for modelling infectious diseases with herd immunity in a randomly mixed population.

RACS and its Fellows: a contribution to sustainable healthcare improvement in South East Asia.

The question of whether small non-government organizations with comparatively small budgets can make a substantial contribution to sustainable improvement in health care in low- and middle-income countries is crucial to funding global surgical projects. The Royal Australasian College of Surgeons and its Fellows have partnered with local organizations and clinicians to deliver a wide range of projects in South East Asia. These projects have proved sustainable and have increased healthcare capacity in these nations. This provides strong evidence that small non-government organizations such as the Royal Australasian College of Surgeons can make a major contribution to global surgeryI.

Adverse events and residual lesion rate after cold endoscopic mucosal resection of serrated lesions ≥10 mm.

BACKGROUND AND AIMS: Cold EMR is being increasingly used for large serrated lesions. We sought to measure residual lesion rates and adverse events after cold EMR of large serrated lesions. METHODS: In a single academic center, we retrospectively examined a database of serrated class lesions ≥10 mm removed with cold EMR for safety and efficacy. RESULTS: Five hundred sixty-six serrated lesions ≥10 mm in size were removed from 312 patients. We successfully contacted 223 patients (71.5%) with no reported serious adverse events that required hospitalization, repeat endoscopy, or transfusion. The residual lesion rate per lesion at first follow-up colonoscopy was 18 of 225 (8%; 95% confidence interval, 5-12.1). Lesions with residual were larger at polypectomy compared with lesions without recurrence (median, 23 mm versus 16 mm, P = .017). CONCLUSION: Cold EMR appears to be safe and effective for the removal of large serrated lesions.

Tracking the early depleting transmission dynamics of COVID-19 with a time-varying SIR model.

The susceptible-infectious-removed (SIR) model offers the simplest framework to study transmission dynamics of COVID-19, however, it does not factor in its early depleting trend observed during a lockdown. We modified the SIR model to specifically simulate the early depleting transmission dynamics of COVID-19 to better predict its temporal trend in Malaysia. The classical SIR model was fitted to observed total (I total), active (I) and removed (R) cases of COVID-19 before lockdown to estimate the basic reproduction number. Next, the model was modified with a partial time-varying force of infection, given by a proportionally depleting transmission coefficient, [Formula: see text] and a fractional term, z. The modified SIR model was then fitted to observed data over 6 weeks during the lockdown. Model fitting and projection were validated using the mean absolute percent error (MAPE). The transmission dynamics of COVID-19 was interrupted immediately by the lockdown. The modified SIR model projected the depleting temporal trends with lowest MAPE for I total, followed by I, I daily and R. During lockdown, the dynamics of COVID-19 depleted at a rate of 4.7% each day with a decreased capacity of 40%. For 7-day and 14-day projections, the modified SIR model accurately predicted I total, I and R. The depleting transmission dynamics for COVID-19 during lockdown can be accurately captured by time-varying SIR model. Projection generated based on observed data is useful for future planning and control of COVID-19.