Displaying publications 561 - 580 of 659 in total

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  1. Appalanaido GK, Shukor SA, Fan AS, Chong SE, Hussin H, Karim NKA, et al.
    Rep Pract Oncol Radiother, 2021;26(4):647-653.
    PMID: 34434581 DOI: 10.5603/RPOR.a2021.0076
    Brachytherapy (BT) is an important local treatment of tumor and it can be applied to different anatomical sites either in a curative or palliative setting. BT can deliver large dose of radiation to the tumor while sparing the surrounding normal tissue which translates into a better therapeutic ratio compared to external beam radiotherapy. However, the evidence for the use of brachytherapy in the palliative setting is lacking in the literature. In this case report, we describe the brachytherapy technique and outcome of a patient with squamous cell carcinoma of the hypopharynx who underwent palliative brachytherapy to the hypopharynx and metastatic tumor at the right axilla.
  2. Yik LL, Ling LM, Ai LM, Ting AB, Capelle DP, Zainuddin SI, et al.
    Am J Hosp Palliat Care, 2021 Sep;38(9):1083-1090.
    PMID: 33078627 DOI: 10.1177/1049909120965944
    BACKGROUND: Mindfulness practices may have a role in reducing suffering and improving spiritual well-being among patients with serious illness. The efficacy, feasibility and acceptability of such interventions warrant further exploration in the palliative care population.

    OBJECTIVE: To investigate the effect of a brief mindfulness practice, the 5-minute mindfulness of peace intervention, on suffering and spiritual well-being among palliative care patients.

    METHODS: A randomized controlled study was conducted on adult palliative care patients with moderate to severe levels of suffering. Participants in the intervention arm were guided through a 5-minute mindfulness of peace exercise while participants in the control arm received 5 minutes of active listening. Pre- and post-intervention suffering and spiritual well-being were measured using the Suffering Pictogram and the FACIT-Sp-12 questionnaire, respectively.

    RESULTS: 40 participants completed the study. 5-minute mindfulness of peace significantly reduced suffering (median = -3.00, IQR = 2.00) more than 5 minutes of active listening (median = -1.00, IQR = 1.75), U = 73.50, z = -3.48, p = 0.001, η2 = 0.31. FACIT-Sp-12 score also significantly improved in the intervention arm (median = +5.00, IQR = 2.75) compared with the control arm after 5 minutes (median = +1.00, IQR = 3.00), U = 95.50, z = -2.85, p = 0.004, η2 = 0.21.

    CONCLUSIONS: A brief 5-minute mindfulness of peace exercise is effective in providing immediate relief of suffering and improving spiritual well-being. It is a useful and feasible intervention among patients receiving palliative care for rapidly and momentarily reducing spiritual suffering.

  3. Bujang MA, Adnan TH, Hashim NH, Mohan K, Kim Liong A, Ahmad G, et al.
    Int J Nephrol, 2017;2017:2735296.
    PMID: 28348890 DOI: 10.1155/2017/2735296
    Background. The incidence of patients with end-stage renal disease (ESRD) requiring dialysis has been growing rapidly in Malaysia from 18 per million population (pmp) in 1993 to 231 pmp in 2013. Objective. To forecast the incidence and prevalence of ESRD patients who will require dialysis treatment in Malaysia until 2040. Methodology. Univariate forecasting models using the number of new and current dialysis patients, by the Malaysian Dialysis and Transplant Registry from 1993 to 2013 were used. Four forecasting models were evaluated, and the model with the smallest error was selected for the prediction. Result. ARIMA (0, 2, 1) modeling with the lowest error was selected to predict both the incidence (RMSE = 135.50, MAPE = 2.85, and MAE = 87.71) and the prevalence (RMSE = 158.79, MAPE = 1.29, and MAE = 117.21) of dialysis patients. The estimated incidences of new dialysis patients in 2020 and 2040 are 10,208 and 19,418 cases, respectively, while the estimated prevalence is 51,269 and 106,249 cases. Conclusion. The growth of ESRD patients on dialysis in Malaysia can be expected to continue at an alarming rate. Effective steps to address and curb further increase in new patients requiring dialysis are urgently needed, in order to mitigate the expected financial and health catastrophes associated with the projected increase of such patients.
  4. Sivanandy P, Jun PH, Man LW, Wei NS, Mun NFK, Yii CAJ, et al.
    J Infect Public Health, 2022 Jan 21;15(3):285-292.
    PMID: 35085865 DOI: 10.1016/j.jiph.2022.01.005
    BACKGROUND: The Ebola virus has started to infect humans from time to time since then and has led to several outbreaks. Due to urbanisation growth, invasion of forested areas, and close interaction with wildlife animals, the spread of the Ebola virus has caused the deadliest diseases to animals and humans. To date, the Ebola virus disease (EVD) claimed many lives of human beings and a greater number of cases were observed in the African region. Hence, a review was carried out to analyse the trends in EVD outbreaks, morbidity and mortality among EVD patients, efficacy and safety of drugs approved for the treatment of EVD.

    METHOD: The literature on EVD outbreaks, safety, and efficacy of EVD drugs were searched on Science Direct, PubMed, and Google Scholar using the MeSH terms such as ̈Ebola, Ebola virus disease, Outbreak, Epidemic, Safety, Efficacy, for the period of 2016-2020. In addition to that. Centers for Disease Control & Prevention (CDC), World Health Organization (WHO), US Food & Drug Administration, and UpToDate websites also searched for the latest reports, guidelines, approved drugs, etc. RESULTS: There are only a few treatment options available for EVD to date, the most commonly used drugs for EVD are ZMapp, Inmazeb, and Ebanga. The review found that among these three drugs, ZMapp Plus is superior in the treatment of EVD with the current standard of care of 91.2%. INMAZEB when given at a 3 ml/kg IV dose reduced the mortality rate by 17% in subjects with EVD. Ebanga has shown a mortality rate of 35.1% when given a 50 mg/kg single IV dose. The most observed adverse effects were fever, tachycardia, diarrhoea, vomiting, hypotension, tachypnea, and chills.

    CONCLUSION: Overall, Inmazeb is the preferred drug of choice over ZMapp or other drugs for the treatment of EVD, and Ebanga is a choice in patients with cardiovascular complications. In addition to that, supportive care is very essential to control the mortality rate.

  5. Gani P, Apandi NM, Mohamed Sunar N, Matias-Peralta HM, Kean Hua A, Mohd Dzulkifli SN, et al.
    PMID: 35130096 DOI: 10.1080/15226514.2022.2033688
    Microalgae cultivation is well known as a sustainable method for eco-friendly wastewater phycoremediation and valuable biomass production. This study investigates the feasibility and kinetic removal of organic compounds and nutrients from food processing wastewater (FPW) using Botryococcus sp. in an enclosed photobioreactor. Simultaneously, response surface methodology (RSM) via face-centered central composite design (FCCCD) was applied to optimize the effects of alum and chitosan dosage and pH sensitivity on flocculation efficiency. The maximum growth rate of Botryococcus sp. cultivated in FPW was 1.83 mg day-1with the highest removal of chemical oxygen demand (COD), total organic carbon (TOC), and total phosphorus (TP) after 12 days of phycoremediation of 96.1%, 87.2%, and 35.4%, respectively. A second-order polynomial function fits well with the experimental results. Both coagulant dosage and pH significantly (p 
  6. Choi JR, Yong KW, Tang R, Gong Y, Wen T, Yang H, et al.
    Adv Healthc Mater, 2017 Jan;6(1).
    PMID: 27860384 DOI: 10.1002/adhm.201600920
    Paper-based devices have been broadly used for the point-of-care detection of dengue viral nucleic acids due to their simplicity, cost-effectiveness, and readily observable colorimetric readout. However, their moderate sensitivity and functionality have limited their applications. Despite the above-mentioned advantages, paper substrates are lacking in their ability to control fluid flow, in contrast to the flow control enabled by polymer substrates (e.g., agarose) with readily tunable pore size and porosity. Herein, taking the benefits from both materials, the authors propose a strategy to create a hybrid substrate by incorporating agarose into the test strip to achieve flow control for optimal biomolecule interactions. As compared to the unmodified test strip, this strategy allows sensitive detection of targets with an approximately tenfold signal improvement. Additionally, the authors showcase the potential of functionality improvement by creating multiple test zones for semi-quantification of targets, suggesting that the number of visible test zones is directly proportional to the target concentration. The authors further demonstrate the potential of their proposed strategy for clinical assessment by applying it to their prototype sample-to-result test strip to sensitively and semi-quantitatively detect dengue viral RNA from the clinical blood samples. This proposed strategy holds significant promise for detecting various targets for diverse future applications.
  7. Jafar A, Dollah R, Sakke N, Mapa MT, Hua AK, Eboy OV, et al.
    Sci Rep, 2022 Oct 15;12(1):17316.
    PMID: 36243784 DOI: 10.1038/s41598-022-22360-4
    The outbreak of the pandemic Covid-19 has transformed the education system in most countries worldwide. Following the lockdown measures in Malaysia, the Malaysian education system has fully transformed from conventional learning to online learning or known as e-learning as an alternative to minimize social contacts and physical communication to curb the transmission of Covid-19. In this regard, this study aims to identify the challenges faced by students in higher learning institutions throughout Malaysia during the implementation of the e-learning program. This study is based on a large sampling consisting of 2394 students from both public and private universities. The result from this study is analyzed through inferential methods such as the Spatial Analysis, the Principal Component Analysis, and the Mann-Whitney U test and through descriptive methods using the frequency analysis and the percentage analysis. Findings from this study suggest that location significantly influenced the challenges faced by students throughout the implementation of e-learning in higher learning institutions. For example, students in rural areas which can be identified as "vulnerable groups" are more likely to face both technical and connection with the internet access, tend to have a declining focus on learning and are prone to physical health problems, facing social isolation and low digital literacy compared to students in urban areas. Based on geographical analysis, students in Sabah, Perlis, and Melaka are most at risk of facing e-learning challenges. An anomaly case of students in Kuala Lumpur, however, posed another different result compared to other cities as they confront similar challenges with students in rural areas. This study provides the nuances of location and its implications for vulnerable groups that may put them at disadvantage in the e-learning program. Findings from this study will help to inform the relevant authorities and policymakers in improving the implementation of e-learning in Malaysia, especially towards the vulnerable groups so that it can be delivered more systematically and efficiently.
  8. Naing CM, Hakim M, Yee DA, Mun KR, Yung TC, Jian KK, et al.
    PMID: 21073071
    This study aimed to assess knowledge of and attitudes toward HIV/AIDS among a community in a semi-urban setting in Malaysia, to determine factors affecting perceptions toward people living with HIV in the community, and to provide baseline information for planning preventive measures against HIV/AIDS. This cross-sectional study was conducted in August 2009. Two hundred sixty-two household members were interviewed with a semi-structured questionnaire. Most respondents (232; 88.5%) had heard of HIV/AIDS. Only a few respondents (6; 2.6%) could correctly answer all the questionnaire items. Misconceptions about disease transmission were seen among surveyed participants, such as the belief HIV/AIDS can be contracted from saliva (104; 44.8%), mosquito bites (95; 40.9%) or casual touch (86; 37.1%). A multivariate linear regression model showed better perceptions towards people living with HIV depend on an improved knowledge of HIV/AIDS transmission. Current data emphasize the need to scale up HIV/AIDS education incorporating the mode of disease transmission.
  9. Toh HC, Yang MH, Wang HM, Hsieh CY, Chitapanarux I, Ho KF, et al.
    Ann Oncol, 2024 Dec;35(12):1181-1190.
    PMID: 39241963 DOI: 10.1016/j.annonc.2024.08.2344
    BACKGROUND: Epstein-Barr virus-specific cytotoxic T lymphocyte (EBV-CTL) is an autologous adoptive T-cell immunotherapy generated from the blood of individuals and manufactured without genetic modification. In a previous phase II trial of locally recurrent or metastatic nasopharyngeal carcinoma (R/M NPC) patients, first-line gemcitabine and carboplatin (GC) and EBV-CTL combination demonstrated objective antitumor EBV-CTL activity and a favorable safety profile. The present study explored whether this combined first-line chemo-immunotherapy strategy would produce superior clinical efficacy and better quality of life compared with conventional chemotherapy treatment.

    PATIENTS AND METHODS: This multicenter, randomized, phase III trial evaluated the efficacy and safety of GC followed by EBV-CTL versus GC alone as first-line treatment of R/M NPC patients. Thirty clinical sites in Singapore, Malaysia, Taiwan, Thailand, and the USA were included. Subjects were randomized to first-line GC (four cycles) and EBV-CTL (six cycles) or GC (six cycles) in a 1 : 1 ratio. The primary outcome was overall survival (OS) and secondary outcomes included progression-free survival, objective response rate, clinical benefit rate, quality of life, and safety.

    CLINICALTRIALS: gov identifier: NCT02578641.

    RESULTS: A total of 330 subjects with NPC were enrolled. Most subjects in both treatment arms received four or more cycles of chemotherapy and most subjects in the GC + EBV-CTL group received two or more infusions of EBV-CTL. The central Good Manufacturing Practices (GMP) facility produced sufficient EBV-CTL for 94% of GC + EBV-CTL subjects. The median OS was 25.0 months in the GC + EBV-CTL group and 24.9 months in the GC group (hazard ratio = 1.19; 95% confidence interval 0.91-1.56; P = 0.194). Only one subject experienced a grade 2 serious adverse event related to EBV-CTL.

    CONCLUSIONS: GC + EBV-CTL in subjects with R/M NPC demonstrated a favorable safety profile but no overall improvement in OS versus chemotherapy. This is the largest adoptive T-cell therapy trial reported in solid tumors to date.

  10. Fock KM, Talley N, Goh KL, Sugano K, Katelaris P, Holtmann G, et al.
    Gut, 2016 Sep;65(9):1402-15.
    PMID: 27261337 DOI: 10.1136/gutjnl-2016-311715
    OBJECTIVE: Since the publication of the Asia-Pacific consensus on gastro-oesophageal reflux disease in 2008, there has been further scientific advancement in this field. This updated consensus focuses on proton pump inhibitor-refractory reflux disease and Barrett's oesophagus.

    METHODS: A steering committee identified three areas to address: (1) burden of disease and diagnosis of reflux disease; (2) proton pump inhibitor-refractory reflux disease; (3) Barrett's oesophagus. Three working groups formulated draft statements with supporting evidence. Discussions were done via email before a final face-to-face discussion. We used a Delphi consensus process, with a 70% agreement threshold, using Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria to categorise the quality of evidence and strength of recommendations.

    RESULTS: A total of 32 statements were proposed and 31 were accepted by consensus. A rise in the prevalence rates of gastro-oesophageal reflux disease in Asia was noted, with the majority being non-erosive reflux disease. Overweight and obesity contributed to the rise. Proton pump inhibitor-refractory reflux disease was recognised to be common. A distinction was made between refractory symptoms and refractory reflux disease, with clarification of the roles of endoscopy and functional testing summarised in two algorithms. The definition of Barrett's oesophagus was revised such that a minimum length of 1 cm was required and the presence of intestinal metaplasia no longer necessary. We recommended the use of standardised endoscopic reporting and advocated endoscopic therapy for confirmed dysplasia and early cancer.

    CONCLUSIONS: These guidelines standardise the management of patients with refractory gastro-oesophageal reflux disease and Barrett's oesophagus in the Asia-Pacific region.

  11. Tan AH, Mahadeva S, Marras C, Thalha AM, Kiew CK, Yeat CM, et al.
    Parkinsonism Relat Disord, 2015 Mar;21(3):221-5.
    PMID: 25560322 DOI: 10.1016/j.parkreldis.2014.12.009
    BACKGROUND: Some studies have suggested that chronic Helicobacter pylori (HP) infection can aggravate the neurodegenerative process in Parkinson's disease (PD), and targeted intervention could potentially modify the course of this disabling disease. We aimed to study the impact of HP infection on motor function, gastrointestinal symptoms, and quality of life in a large cohort of PD patients.
    METHODS: 102 consecutive PD patients underwent (13)C urea breath testing and blinded evaluations consisting of the Unified Parkinson's Disease Rating Scale (UPDRS) including "On"-medication motor examination (Part III), objective and quantitative measures of bradykinesia (Purdue Pegboard and timed gait), Leeds Dyspepsia Questionnaire, and PDQ-39 (a health-related quality of life questionnaire).
    RESULTS: 32.4% of PD patients were HP-positive. HP-positive patients were older (68.4 ± 7.3 vs. 63.8 ± 8.6 years, P = 0.009) and had worse motor function (UPDRS Part III 34.0 ± 13.0 vs. 27.3 ± 10.0, P = 0.04; Pegboard 6.4 ± 3.3 vs. 8.0 ± 2.7 pins, P = 0.04; and timed gait 25.1 ± 25.4 vs. 15.5 ± 7.6 s, P = 0.08). In the multivariate analysis, HP status demonstrated significant main effects on UPDRS Part III and timed gait. The association between HP status and these motor outcomes varied according to age. Gastrointestinal symptoms and PDQ-39 Summary Index scores did not differ between the two groups.
    CONCLUSIONS: This is the largest cross-sectional study to demonstrate an association between HP positivity and worse PD motor severity.
    KEYWORDS: Gastrointestinal dysfunction; Helicobacter pylori; Parkinson's disease
  12. Tan AH, Mahadeva S, Thalha AM, Gibson PR, Kiew CK, Yeat CM, et al.
    Parkinsonism Relat Disord, 2014 May;20(5):535-40.
    PMID: 24637123 DOI: 10.1016/j.parkreldis.2014.02.019
    BACKGROUND: Recent studies reported a high prevalence of small intestinal bacterial overgrowth (SIBO) in Parkinson's disease (PD), and a possible association with gastrointestinal symptoms and worse motor function. We aimed to study the prevalence and the potential impact of SIBO on gastrointestinal symptoms, motor function, and quality of life in a large cohort of PD patients.
    METHODS: 103 Consecutive PD patients were assessed using the lactulose-hydrogen breath test; questionnaires of gastrointestinal symptoms and quality of life (PDQ-39); the Unified PD Rating Scale (UPDRS) including "on"-medication Part III (motor severity) score; and objective and quantitative measures of bradykinesia (Purdue Pegboard and timed test of gait). Patients and evaluating investigators were blind to SIBO status.
    RESULTS: 25.3% of PD patients were SIBO-positive. SIBO-positive patients had a shorter mean duration of PD (5.2 ± 4.1 vs. 8.1 ± 5.5 years, P = 0.007). After adjusting for disease duration, SIBO was significantly associated with lower constipation and tenesmus severity scores, but worse scores across a range of "on"-medication motor assessments (accounting for 4.2-9.0% of the variance in motor scores). There was no association between SIBO and motor fluctuations or PDQ-39 Summary Index scores.
    CONCLUSIONS: This is the largest study to date on SIBO in PD. SIBO was detected in one quarter of patients, including patients recently diagnosed with the disease. SIBO was not associated with worse gastrointestinal symptoms, but independently predicted worse motor function. Properly designed treatment trials are needed to confirm a causal link between SIBO and worse motor function in PD.
    KEYWORDS: Gastrointestinal dysfunction; Parkinson's disease/Parkinsonism; Small intestinal bacterial overgrowth
  13. Yam MF, Por LY, Peh KK, Ahmad M, Asmawi MZ, Ang LF, et al.
    Sensors (Basel), 2011;11(5):5058-70.
    PMID: 22163890 DOI: 10.3390/s110505058
    Behavioural assessment of experimental pain is an essential method for analysing and measuring pain levels. Rodent models, which are widely used in behavioural tests, are often subject to external forces and stressful manipulations that cause variability of the parameters measured during the experiment. Therefore, these parameters may be inappropriate as indicators of pain. In this article, a stepping-force analgesimeter was designed to investigate the variations in the stepping force of rats in response to pain induction. The proposed apparatus incorporates new features, namely an infrared charge-coupled device (CCD) camera and a data acquisition system. The camera was able to capture the locomotion of the rats and synchronise the stepping force concurrently so that each step could be identified. Inter-day and intra-day precision and accuracy of each channel (there were a total of eight channels in the analgesimeter and each channel was connected to one load cell and one amplifier) were studied using different standard load weights. The validation studies for each channel also showed convincing results whereby intra-day and inter-day precision were less than 1% and accuracy was 99.36-100.36%. Consequently, an in vivo test was carried out using 16 rats (eight females and eight males). The rats were allowed to randomly walk across the sensor tunnel (the area that contained eight channels) and the stepping force and locomotion were recorded. A non-expert, but from a related research domain, was asked to differentiate the peaks of the front and hind paw, respectively. The results showed that of the total movement generated by the rats, 50.27 ± 3.90% in the case of the male rats and 62.20 ± 6.12% in that of the female rats had more than two peaks, a finding which does not substantiate the assumptions made in previous studies. This study also showed that there was a need to use the video display frame to distinguish between the front and hind paws in the case of 48.80 ± 4.01% of the male rats and 66.76 ± 5.35% of the female rats. Evidently the assumption held by current researchers regarding stepping force measurement is not realistic in terms of application, and as this study has shown, the use of a video display frame is essential for the identification of the front and hind paws through the peak signals.
  14. Ma NH, Teh CL, Rapaee A, Lau KB, Fong AY, Hi S, et al.
    Int J Rheum Dis, 2010 Aug;13(3):223-9.
    PMID: 20704618 DOI: 10.1111/j.1756-185X.2010.01533.x
    INTRODUCTION: Rheumatoid arthritis (RA) patients who have active disease with longer disease duration have been reported to have increased risk of cardiovascular events compared to the normal population.
    OBJECTIVE: The primary aim of our study is to ascertain the prevalence of significant asymptomatic coronary artery disease (CAD) in Asian RA patients who are in remission using multi-detector computed tomography (MDCT). The secondary aims of our study are the usage of pulse wave velocity and the biomarkers N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-senstivity C-reactive protein (hs-CRP) to detect subclinical atherosclerosis in RA patients.
    METHODS: We performed a comparative cross-sectional study of 47 RA patients who were in remission with a control group of non-RA patients with a history of atypical chest pain in Sarawak General Hospital from November 2008 to February 2009. All patients underwent 64-slice MDCT, assessment of arterial stiffness using the SphygmoCor test and blood analysis for NT-proBNP and hsCRP.
    RESULTS: There were 94 patients in our study with a mean age of 50 +/- 8.8 years. The RA and control patients in each group were matched in terms of traditional CV risk factors. Our RA patients had a median disease duration of 3 years (IQR 5.5). MDCT showed evidence of CAD in nine (19.1%) RA patients and three (6.4%) control patients (P = 0.06). There was no significant association between pulse wave velocity (PWV) and presence of CAD in our RA group. There was no significant correlation between PWV with levels of proBNP or hsCRP in our RA patients.
    CONCLUSIONS: In our current pilot study with the limitation of small sample size, RA was not associated with an increased risk of CAD in our RA patients who were in remission. Larger studies of CAD in Asian RA patients are needed to confirm our current finding.
    Study site: Sarawak General Hospital, Kuching, Sarawak, Malaysia
  15. Hui DS, Ip M, Ling T, Chang SC, Liao CH, Yoo CG, et al.
    Respirology, 2011 Apr;16(3):532-9.
    PMID: 21299688 DOI: 10.1111/j.1440-1843.2011.01943.x
    Antimicrobial resistance is a global problem and the prevalence is high in many Asian countries.
  16. Noor Hafizah Y, Ang LC, Yap F, Nurul Najwa W, Cheah WL, Ruzita AT, et al.
    PMID: 31783477 DOI: 10.3390/ijerph16234722
    As there are few food frequency questionnaires (FFQ) to assess the dietary intake of preschool children, this study examined the validity and reliability of an FFQ for this purpose. A total of 210 preschoolers aged 4 to 6 years participated in the validation study, while a subsample of 66 participants joined the reliability study. The FFQ is modified from the ToyBox-study and South East Asian Nutrition Surveys (SEANUTS), and comprised 108 food items from 13 food groups. A three-day estimated dietary record (3DR) was used as reference and reliability was assessed through a second administration of the FFQ (FFQ2), four weeks after the first administration (FFQ1). For the validation study, Spearman's correlation coefficients showed moderate to high correlations (p < 0.001) between FFQ and 3DR. Cross-classification of quartile analysis showed moderate agreement between the two methods. As for reliability, Spearman's correlation coefficients showed moderate to high correlations (p < 0.001) between FFQ1 and FFQ2. Cronbach's alpha values (0.708 to 0.824) and intraclass correlation coefficients (0.710 to 0.826) showed good agreement between repeated FFQs. The results suggest that the FFQ has acceptable validity and good reliability. Hence, the FFQ can be used to assess preschool children's food intake.
  17. Tan AH, Chong CW, Lim SY, Yap IKS, Teh CSJ, Loke MF, et al.
    Ann Neurol, 2021 03;89(3):546-559.
    PMID: 33274480 DOI: 10.1002/ana.25982
    OBJECTIVE: Gut microbiome alterations in Parkinson disease (PD) have been reported repeatedly, but their functional relevance remains unclear. Fecal metabolomics, which provide a functional readout of microbial activity, have scarcely been investigated. We investigated fecal microbiome and metabolome alterations in PD, and their clinical relevance.

    METHODS: Two hundred subjects (104 patients, 96 controls) underwent extensive clinical phenotyping. Stool samples were analyzed using 16S rRNA gene sequencing. Fecal metabolomics were performed using two platforms, nuclear magnetic resonance (NMR) spectroscopy and liquid chromatography-mass spectrometry.

    RESULTS: Fecal microbiome and metabolome composition in PD was significantly different from controls, with the largest effect size seen in NMR-based metabolome. Microbiome and NMR-based metabolome compositional differences remained significant after comprehensive confounder analyses. Differentially abundant fecal metabolite features and predicted functional changes in PD versus controls included bioactive molecules with putative neuroprotective effects (eg, short chain fatty acids [SCFAs], ubiquinones, and salicylate) and other compounds increasingly implicated in neurodegeneration (eg, ceramides, sphingosine, and trimethylamine N-oxide). In the PD group, cognitive impairment, low body mass index (BMI), frailty, constipation, and low physical activity were associated with fecal metabolome compositional differences. Notably, low SCFAs in PD were significantly associated with poorer cognition and low BMI. Lower butyrate levels correlated with worse postural instability-gait disorder scores.

    INTERPRETATION: Gut microbial function is altered in PD, characterized by differentially abundant metabolic features that provide important biological insights into gut-brain pathophysiology. Their clinical relevance further supports a role for microbial metabolites as potential targets for the development of new biomarkers and therapies in PD. ANN NEUROL 2021;89:546-559.

  18. Ang YLE, Ho GF, Soo RA, Sundar R, Tan SH, Yong WP, et al.
    BMC Cancer, 2020 Nov 17;20(1):1118.
    PMID: 33203399 DOI: 10.1186/s12885-020-07616-4
    BACKGROUND: We previously reported that low-dose, short-course sunitinib prior to neoadjuvant doxorubicin-cyclophosphamide (AC) normalised tumour vasculature and improved perfusion, but resulted in neutropenia and delayed subsequent cycles in breast cancer patients. This study combined sunitinib with docetaxel, which has an earlier neutrophil nadir than AC.

    METHODS: Patients with advanced solid cancers were randomized 1:1 to 3-weekly docetaxel 75 mg/m2, with or without sunitinib 12.5 mg daily for 7 days prior to docetaxel, stratified by primary tumour site. Primary endpoints were objective-response (ORR:CR + PR) and clinical-benefit rate (CBR:CR + PR + SD); secondary endpoints were toxicity and progression-free-survival (PFS).

    RESULTS: We enrolled 68 patients from 2 study sites; 33 received docetaxel-sunitinib and 35 docetaxel alone, with 33 breast, 25 lung and 10 patients with other cancers. There was no difference in ORR (30.3% vs 28.6%, p = 0.432, odds-ratio [OR] 1.10, 95% CI 0.38-3.18); CBR was lower in the docetaxel-sunitinib arm (48.5% vs 71.4%, p = 0.027 OR 0.37, 95% CI 0.14-1.01). Median PFS was shorter in the docetaxel-sunitinib arm (2.9 vs 4.9 months, hazard-ratio [HR] 2.00, 95% CI 1.15-3.48, p = 0.014) overall, as well as in breast (4.2 vs 5.6 months, p = 0.048) and other cancers (2.0 vs 5.3 months, p = 0.009), but not in lung cancers (2.9 vs 4.1 months, p = 0.597). Median OS was similar in both arms overall (9.9 vs 10.5 months, HR 0.92, 95% CI 0.51-1.67, p = 0.789), and in the breast (18.9 vs 25.8 months, p = 0.354), lung (7.0 vs 6.7 months, p = 0.970) and other cancers (4.5 vs 8.8 months, p = 0.449) subgroups. Grade 3/4 haematological toxicities were lower with docetaxel-sunitinib (18.2% vs 34.3%, p = 0.132), attributed to greater discretionary use of prophylactic G-CSF (90.9% vs 63.0%, p = 0.024). Grade 3/4 non-haematological toxicities were similar (12.1% vs 14.3%, p = 0.792).

    CONCLUSIONS: The addition of sunitinib to docetaxel was well-tolerated but did not improve outcomes. The possible negative impact in metastatic breast cancer patients is contrary to results of adding sunitinib to neoadjuvant AC. These negative results suggest that the intermittent administration of sunitinib in the current dose and schedule with docetaxel in advanced solid tumours, particularly breast cancers, is not beneficial.

    TRIAL REGISTRATION: The study was registered ( NCT01803503 ) prospectively on clinicaltrials.gov on 4th March 2013.

  19. Goh SY, Ang E, Bajpai S, Deerochanawong C, Hong EG, Hussein Z, et al.
    J Diabetes Complications, 2016 08;30(6):973-80.
    PMID: 27288201 DOI: 10.1016/j.jdiacomp.2016.05.019
  20. Ang KC, Kathirgamanathan S, Ch'ng ES, Lee YY, Roslani AL, Naidu B, et al.
    J Assist Reprod Genet, 2017 Apr;34(4):517-524.
    PMID: 28108842 DOI: 10.1007/s10815-017-0871-0
    PURPOSE: The aim of this study was to evaluate a new predisposition factor, M2/ANXA5 (RPRGL3), in recurrent pregnancy loss (RPL) patients of Malay origin, since it was previously known that the prevalence of this condition is relatively high among the Malay population of Malaysia, where conventional hereditary thrombophilia factors have been generally ruled out.

    METHODS: A total of 232 women who had experienced ≥2 unexplained RPL and 141 available male partners were recruited, with 360 healthy Malay and 166 parous female controls. Prevalence of M2 carriage and RPL odds ratios were calculated in (a) control and patient groups; (b) clinically defined subgroups in categories of pregnancy loss, primary, secondary, and tertiary; and (c) timing of pregnancy loss in early, ≤15th gestation week and "late" fetal losses, and >15th gestation week subgroups.

    RESULTS: Both male and female subjects had similar M2/ANXA5 allele frequencies. The carrier rate of M2/ANXA5 for the general Malay population was 42.2 and 34.9% for parous controls. These carrier rates compared to Malay RPL subjects (52% M2 carriers) resulted in elevated odds ratios (95% confidence interval) of 1.53 (1.1 to 2.1) and 1.97 (1.3 to 3.1) accordingly for early fetal losses. Moreover, exceeding copy numbers of M2/ANXA5 alleles seemed to afflict a greater chance of RPL in couples, especially when both partners were M2 carriers.

    CONCLUSION: This study confirmed the proposed role of M2/ANXA5 as embryonic, genetically associated thrombophilia predisposition factor for early RPL among ethnic Malay of Malaysia.

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