Introduction: Current prognostic markers have improved survival prediction, however, it has not advanced treatment strategies. Gene expression profiling may identify biological markers suitable as therapeutic targets. Leukaemia stem cell is associated with adverse outcome, however, its biological characteristics are still being investigated. We observed higher in vitro cell viability in acute myeloid leukaemia (AML) samples with poor prognosis, which may be stem cell related. Objective: The objective of this study was to profile highly expressed genes in an AML sample of poor prognosis/high viability and compare with a sample of good prognosis/low viability. Method: Subtractive hybridization was performed on two AML samples with high blast counts (>80%), a poor prognosis, PP (disease free survival, DFS<12 months) and a good prognosis, GP (DFS>12 months) sample. The PP sample had higher CD34+ counts (73% vs 46%) and higher cell viability than the GP sample. cDNA libraries were subsequently cloned and sequenced. Results: cDNA subtracted from the PP samples was identified as genes active during fetal/embryonic development (LCOR, CNOT1, ORMDL1), HOX- related genes (HOXA3, PBX3, SF3B1), hematopoiesis (SELL, IL-3RA) and aerobic glycolysis/hypoxia (PGK1, HIGD1A) -associated genes. Majority of GP clones isolated contained genes involved in oxidative phosphorylation, OXPHOS (COXs, ATPs, MTND4 and MTRNR2), protein synthesis (including ribosomal proteins, initiating and elongation factors), chromatin remodeling (H2AFZ, PTMA), cell motility (MALAT1, CALM2, TMSB4X), and mitochondria (HSPA9, MPO) genes. Conclusion: Thus, the PP sample exhibited stem cell-like features while the GP sample showed cells at a high level of cell activity. These genes are potential prognostic markers and targets for therapy.
Leukemia, Myeloid, Acute

Aged, 80 and over ; Community Health Services ; Female ; Humans ; Male ; Pilot Projects ; Terminal Care ; organization & administration

INTRODUCTION: Institutional surgical antibiotic prophylaxis (SAP) guidelines are in place at all public hospitals in Singapore, but variations exist and adherence to guidelines is not tracked consistently. A national point prevalence survey carried out in 2020 showed that about 60% of surgical prophylactic antibiotics were administered for more than 24 hours. This guideline aims to align best practices nationally and provides a framework for audit and surveillance. METHOD: This guideline was developed by the National Antimicrobial Stewardship Expert Panel's National Surgical Antibiotic Prophylaxis Guideline Development Workgroup Panel, which comprises infectious diseases physicians, pharmacists, surgeons and anaesthesiologists. The Workgroup adopted the ADAPTE methodology framework with modifications for the development of the guideline. The recommended duration of antibiotic prophylaxis was graded according to the strength of consolidated evidence based on the scoring system of the Singapore Ministry of Health Clinical Practice Guidelines. RESULTS: This National SAP Guideline provides evidence-based recommendations for the rational use of antibiotic prophylaxis. These include recommended agents, dose, timing and duration for patients undergoing common surgeries based on surgical disciplines. The Workgroup also provides antibiotic recommendations for special patient population groups (such as patients with β-lactam allergy and patients colonised with methicillin-resistant Staphylococcus aureus), as well as for monitoring and surveillance of SAP. CONCLUSION This evidence-based National SAP Guideline for hospitals in Singapore aims to align practices and optimise the use of antibiotics for surgical prophylaxis for the prevention of surgical site infections while reducing adverse events from prolonged durations of SAP.
Humans ; Antibiotic Prophylaxis ; Anti-Bacterial Agents/therapeutic use* ; Methicillin-Resistant Staphylococcus aureus ; Singapore ; Surgeons ; Hospitals, Public

Purpose: To investigate the effect of androgen deprivation therapy (ADT) on health-related quality of life (HRQOL) in Asian men with all stages of prostate cancer. Materials and Methods: READT (real-life evaluation of the effect of ADT in prostate cancer patients in Asia) was a multi-center, prospective observational study involving six sites across four Asian populations. We enrolled eligible prostate cancer patients, who opted for ADT alone or in combination without prior neoadjuvant or adjuvant ADT within 12 months. The EuroQoL-5 dimensions, 5 level scale (EQ-5D-5L) utility index scores and visual analog scale (VAS) were evaluated at baseline, month 6 and month 12. Results: A total of 504 patients were recruited into READT between September 2016 and May 2020 with 52.9% diagnosed with metastatic prostate cancer. The EQ-5D-5L was evaluable in 442/504 (87.7%) of patients. Overall baseline EQ-5D-5L utility index score was 0.924 (interquartile range [IQR] 0.876–1.000). We observed a statistically significant difference in baseline EQ-5D-5L utility index score among different populations with a median EQ-5D-5L utility index score of 1 for Taiwan & Hong Kong, 0.897 for China and 0.838 for Malaysia. Similar trend was observed throughout multiple treatment time-points. Stage IV prostate cancer were significantly associated with a lower baseline EQ-5D-5L utility index score compared to stage I–III prostate cancer, producing a median disutility value of -0.080. Participants had a high median VAS (80, IQR 70–90), indicating good overall health on average during ADT initiation. Conclusions The study highlights the differences in health state utility index scores among various Asian prostate cancer patients receiving ADT at real-world setting. Our findings will be informative and useful in cost-effectiveness evaluation and policy decision making.