Recreational cycling related injuries at the emergency department

Introduction Recreational cycling is gaining popularity in Singapore but there is a lack of literature regarding the spectrum and severity of these injuries and their impact on the utilisation of healthcare resources. We aim to characterise these injuries, as well as to review the healthcare resources required by injured cyclists. Methods A retrospective review of patients with recreational cycling-related injuries presenting to the Emergency Department (ED) between August 2018 and December 2020 was performed. Information about demographics, circumstances of injury, injuries sustained, clinical progress, and outcomes were collected and analysed. Results There were 214 patients, with an increase in monthly attendance towards the end of the study period. The median age was 48 years old (interquartile range (IQR) 31 to 60) and 165 (77.1%) patients were male. In the ED, 35 (16.4%), 142 (66.4%), and 37 (17.3%) patients were triaged as P1 (emergent), P2 (urgent), and P3 (ambulatory) respectively. Blunt injuries occurred in 210 (98.1%) patients. Soft tissue injuries involving the upper and lower limbs were most common. One hundred and eighty-one (84.6%) patients had a minor to moderate injury classified by an Injury Severity Score of 0 to 8. One hundred twenty-four (57.9%) patients were admitted to the hospital with 40 (18.7%) requiring surgery. Conclusion Recreational cycling-related injuries are increasingly encountered in the ED. These injuries are associated with morbidities which require utilisation of healthcare resources. Legislation and education efforts to promote safety in recreational cycling are required to reduce accidents and minimise the impact of the injuries sustained

Evolution of minimally invasive distal pancreatectomies at a single institution

Introduction: This study aims to study the changing trends and outcomes associated with the adoption of minimally invasive distal pancreatectomy (MIDP) at a single centre. Materials and Methods: Retrospective review of sixty consecutive patients who underwent MIDP from September 2006 to November 2016 at a single institution. To study the evolution of MIDP, the study population was divided into three groups consisting of twenty patients (Group I, Group II and Group III). Results: Sixty patients underwent MIDP with 11 (18.3%) requiring open conversions. The median operation time was 305 (range: 85–775) min and the median post-operative stay was 6 (range: 3–73) days. Fifteen procedures were spleen-saving pancreatectomies. Major post-operative morbidity (>Grade 2) occurred in 12 (20.0%) patients and there was no mortality or reoperations. There were 33 (55.0%) pancreatic fistulas, of which 15 (25.0%) were Grade B fistulas of which 12 (20.0%) required percutaneous drainage. Comparison between the three groups demonstrated a statistically significant increase in the frequency of procedures performed, increase in robotic-assisted procedures and proportion of asymptomatic tumours resected. There also tended to be non-significant decrease in open conversion rates from 25% to 5% between the three groups and increase in tumour size resected from 24 to 40 mm. Conclusion: Comparison between the three groups demonstrated that MIDP was performed with increased frequency. There was a statistically significant increase in the frequency of resections performed for asymptomatic tumours and resections performed through robotic assistance. There was also a non-significant trend towards a decrease in open conversions and increase in the size of tumours resected

Trajectory of immune evasion and cancer progression in hepatocellular carcinoma

Immune evasion is key to cancer initiation and later at metastasis, but its dynamics at intermediate stages, where potential therapeutic interventions could be applied, is undefined. Here we show, using multi-dimensional analyses of resected tumours, their adjacent non-tumour tissues and peripheral blood, that extensive immune remodelling takes place in patients with stage I to III hepatocellular carcinoma (HCC). We demonstrate the depletion of anti-tumoural immune subsets and accumulation of immunosuppressive or exhausted subsets along with reduced tumour infiltration of CD8 T cells peaking at stage II tumours. Corresponding transcriptomic modification occur in the genes related to antigen presentation, immune responses, and chemotaxis. The progressive immune evasion is validated in a murine model of HCC. Our results show evidence of ongoing tumour-immune co-evolution during HCC progression and offer insights into potential interventions to reverse, prevent or limit the progression of the disease.National Medical Research Council (NMRC)National Research Foundation (NRF)Published versionThis work was supported by the National Medical Research Council (NMRC), Singapore (ref numbers: NMRC/TCR/015-NCC/2016, NMRC/CIRG/1460/2016, NMRC/ CSA-SI/0013/2017, NMRC/CSA-SI/0018/2017, NMRC/OFLCG/003/2018, NMRC/ STaR/020/2013, NMRC/CG/M003/2017, LCG17MAY004 and NMRC/OFIRG/0064/ 2017) and National Research Foundation, Singapore (ref number: NRF-NRFF2015-04)

Multi-region sampling with paired sample sequencing analyses reveals sub-groups of patients with novel patient-specific dysregulation in Hepatocellular Carcinoma

Abstract Background Conventional differential expression (DE) testing compares the grouped mean value of tumour samples to the grouped mean value of the normal samples, and may miss out dysregulated genes in small subgroup of patients. This is especially so for highly heterogeneous cancer like Hepatocellular Carcinoma (HCC). Methods Using multi-region sampled RNA-seq data of 90 patients, we performed patient-specific differential expression testing, together with the patients’ matched adjacent normal samples. Results Comparing the results from conventional DE analysis and patient-specific DE analyses, we show that the conventional DE analysis omits some genes due to high inter-individual variability present in both tumour and normal tissues. Dysregulated genes shared in small subgroup of patients were useful in stratifying patients, and presented differential prognosis. We also showed that the target genes of some of the current targeted agents used in HCC exhibited highly individualistic dysregulation pattern, which may explain the poor response rate. Discussion/conclusion Our results highlight the importance of identifying patient-specific DE genes, with its potential to provide clinically valuable insights into patient subgroups for applications in precision medicine

Dynamic phenotypic heterogeneity and the evolution of multiple RNA subtypes in hepatocellular carcinoma: the PLANET study

Intra-tumor heterogeneity (ITH) is a key challenge in cancer treatment, but previous studies have focused mainly on the genomic alterations without exploring phenotypic (transcriptomic and immune) heterogeneity. Using one of the largest prospective surgical cohorts for hepatocellular carcinoma (HCC) with multi-region sampling, we sequenced whole genomes and paired transcriptomes from 67 HCC patients (331 samples). We found that while genomic ITH was rather constant across stages, phenotypic ITH had a very different trajectory and quickly diversified in stage II patients. Most strikingly, 30% of patients were found to contain more than one transcriptomic subtype within a single tumor. Such phenotypic ITH was found to be much more informative in predicting patient survival than genomic ITH and explains the poor efficacy of single-target systemic therapies in HCC. Taken together, we not only revealed an unprecedentedly dynamic landscape of phenotypic heterogeneity in HCC, but also highlighted the importance of studying phenotypic evolution across cancer types.National Medical Research Council (NMRC)National Research Foundation (NRF)Published versionThis work is supported in part by the Singapore National Medical Research Council grants (TCR/015-NCC/2016, CIRG18may-0057l, NMRC/CSA-SI/0018/2017, and NMRC/ OFIRG/0064/2017) and the National Research Foundation, Singapore (NRF-NRFF2015-04). W.Z. is supported in part by the National Key R&D Program of China (2018YFC1406902 and 2018YFC0910400), the National Natural Science Foundation of China (31970566), and the Strategic Priority Research Program of the Chinese Academy of Sciences (XDPB17). H.Y. is supported by the National Natural Science Foundation of China (32000407)