Gleneagles Hospital

Critically sized bone defects remain a global health and economic burden, and biomaterials associated with stem cell therapy have been widely applied as a significant strategy for bone regeneration. Due to limitations related to cell survivability, immune rejection, and transplantation at the defective bone site, the improved therapeutic outcomes of stem cells are achieved through paracrine actions, which involve the secretion of extracellular vesicles (EVs) and/or other factors. Ultra-small, nano-sized exosomes (Exos) of endosomal origin have demonstrated promising potential for bone regeneration through partially revealed intercellular communication. However, the real-time feasibility before clinical trials remains unknown. The current report aims to provide an overview of the various stem cell-derived exosomes in treating bone and cartilage defects, including osteoarthritis (OA) and osteochondral defect (OCD), and optimize the yield of Exos with enhanced tissue engineering potentials. Additionally, the encapsulation of Exos with various bioactive molecules to enhance therapeutic efficacy, their functionalization with biocompatible scaffolds to promote sustained release in the defective cellular microenvironment, and the molecular functions of Exos were investigated.

IntroductionNeutropenic fever (NF) has a crude mortality rate of 3–18%. International guidelines recommend that all patients with NF receive ultrabroad-spectrum antibiotics (UBSAs) within 1 hour of emergency department (ED) registration. However, over 70% patients presenting to hospital with suspected NF (sNF) cannot access absolute neutrophil count (ANC) result within 1 hour, do not have NF and do not require UBSAs. In ED and hospitalised patients with sNF, we hypothesise that the ASTERIC protocol effectively and safely reduces the use of UBSAs compared with standard care alone.Methods and analysisThis pragmatic, parallel, multicentre, type 1, hybrid effectiveness-implementation, stepped-wedge, before-and-after, cluster randomised controlled trial aims to evaluate whether antibiotic prescribing can be safely reduced through implementing a multifaceted antibiotic stewardship intervention (ASTERIC) in adult patients with sNF presenting to EDs. The sNF was defined as a fever with a single oral temperature of ≥38.3°C (101°F) within 24 hours before ED registration or a temperature of ≥38.0°C (100.4°F) sustained over a 1-hour period, following last chemotherapy or targeted therapy within 6 weeks for any solid tumour, or in any period following therapies against leucaemia, lymphoma, myelodysplastic syndrome, aplastic anaemia, multiple myeloma or recipient of HSCT. The study will involve eight hospitals in Hong Kong with variable baseline practice. We will include 704 adult patients (352 patients in pre-implementation and post-implementation periods, respectively) with sNF (tympanic temperature ≥38.3°C) and 48 staff participants (6 staff participants in each hospital). Healthcare professionals will receive a multifaceted stewardship intervention consisting of risk assessment tools, fast-track ANCs, a decision tool for patient management and antibiotic use, supported by an educational package and staff interaction programmes (ASTERIC protocol). Patients’ blood ANC, and cancer therapy and chronic illness therapy scores will be measured. The RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) and Proctor conceptual frameworks will be followed for evaluation of implementation. The main outcome measures are the mean total dose of UBSAs prescribed in 7 days and serious adverse events at 30 days. Data analysis will incorporate intention-to-treat, per-protocol and as-treated analyses for service outcomes (effectiveness, safety, quality of life assessments and cost-effectiveness) and mixed methods for implementation outcomes, informed by the Theoretical Domains Framework. We expect that the study results will inform health policy with improvement in hospital services in treating stable sNF, evidenced by improved safe antibiotic stewardship, early antibiotic de-escalation and reduced costs and length of stay.Ethics and disseminationThe institutional review boards of all study sites approved this study. This study will establish the ASTERIC protocol safely improves antibiotic stewardship and clinical management in adult patients with sNF. We will disseminate the findings through peer-reviewed publications, conference presentations and educational activities. All patients with sNF will be influenced by the new protocol which is agreed at hospital level. Randomisation is at hospital level, not patient level. Patient consent is sought for follow-up and data access, not for treatment. Staff consent is sought for interviewing.Trial registration numberNCT06794320.

Colorectal cancer(CRC) remains a significant global health challenge,ranking third in incidence and second in mortality among cancers worldwide.This review addresses the complex landscape of CRC, focusing on incidence,mortality trends, preventive strategies, and the evolving therapeuticapproaches, particularly highlighting the role of platinum-based drugslike oxaliplatin (OXP). It also underscores the increasing burdenof CRC, with factors such as westernized diets, aging populations,and genetic predispositions contributing to its prevalence. Therapeutically,early detection greatly enhances survival rates, emphasizing the importanceof regular colonoscopies and stool tests. For advanced CRC, chemotherapyremains pivotal, with OXP as a cornerstone treatment despite its associatedchemotherapy-induced peripheral neurotoxicity (CIPN). The review exploresinnovative strategies to overcome challenges related to chemotherapy,such as drug resistance and side effects, highlighting recent developmentsin the field, such as Pt­(IV) prodrugs and immunotherapeutic approachesto enhance efficacy while minimizing toxicity. Additionally, thismanuscript examines experimental models for drug screening, emphasizingthe role of murine models and advanced 3D in vitro systems in CRC research. Overall, the review advocates for a comprehensiveapproach, integrating prevention, early detection, and personalizedtreatments to alleviate the global burden of CRC.

BackgroundLung cancer is the most frequently diagnosed cancer globally. In Malaysia, it ranks as the second most common cancer among men and third among women. Presently, no local clinical practice guidelines exist for lung cancer care in Malaysia. Given the lack of consensus regarding the perioperative management of early-stage non-small cell lung cancer (NSCLC), this article seeks to harmonise surgical practices among thoracic physicians and surgeons in Malaysia by recommending best practices for screening, diagnosis and staging, as well as multimodal management and surveillance in early-stage disease (stages I to IIIB-N2).MethodsA local expert committee comprising nine high-volume actively practicing cardiothoracic or general thoracic surgeons gathered between February to July 2024 to deliberate existing evidence and formulate recommendations. A modified Delphi method comprising systematic review of published evidence and expert opinion based on local experience was utilised. The document was subsequently independently reviewed by two senior oncologists and two senior respiratory physicians, before incorporating their feedback into the final version.ResultsThis document comprises a surgical consensus of evidence-based guidelines to provide local recommendations on contemporary real-world best practices. The consensus statements were grouped into five domains of early-stage resectable NSCLC: (I) screening (3 statements); (II) diagnosis and staging (6 statements); (III) neoadjuvant/perioperative immunotherapy (3 statements); (IV) adjuvant therapy with tyrosine kinase inhibitors (TKIs) or immunotherapy (4 statements); and (V) operative metrics and post-operative surveillance (5 statements).ConclusionsThese consensus statement guidelines will elevate and standardise the perioperative management of early-stage NSCLC in Malaysia, serve as a valuable educational and training tool for relevant medical professionals, and promote an inclusive, comprehensive multidisciplinary approach to integrated holistic patient care, aimed at improving both clinical outcomes and patients’ quality of life with the best available evidence.

Aims: Strongyloidiasis is an asymptomatic disease caused by the intestinal helminth Strongyloides stercoralis in immunocompetent individuals and are present for decades. The rarity of our case presents in the facts that an elderly gentleman being immunocompetent before, being evaluated for a surgical condition, circumstances lead to sudden deterioration and within one day of the biopsy report succumbs to the condition. While undergoing retrospective evaluation it was diagnosed as hyper infection and disseminated strongyloidiasis. Presentation of the Case: 77 year old elderly male , a case of chronic idiopathic demyelinating neuropathy(recovered) , previously was on oral steroids for a period of 1-2 months; was admitted with persistent vomiting at other hospital, and on evaluation diagnosed with hiatus hernia with severe gastritis and referred to us, patient underwent Naso jejunal tube placement in view of gastric outlet obstruction and for feeding, post which, patient had initially loose stools and thereafter malena, upper Gi scopy with cessation of bleed done, to recur as hematemesis and within one day of diagnosis of duodenal biopsy suggestive of Strongyloides stercoralis, patient succumbed to the disease. Discussion: The case emphasizes on the importance of evaluation of various gastrointestinal infections especially caused by pathogens in our country with tropical climate and need to correlate the immunocompetency of patient especially on steroids with underlying infections. Conclusion: strongyloidiasis infection should be ruled out in all the immunodeficient patients especially on steroids for brief periods and presenting with gastrointestinal symptoms of vomiting and diarrhoea.