Salmonella exploits membrane reservoirs for invasion of host cells.

Salmonella utilizes a type 3 secretion system to translocate virulence proteins (effectors) into host cells during infection1. The effectors modulate host cell machinery to drive uptake of the bacteria into vacuoles, where they can establish an intracellular replicative niche. A remarkable feature of Salmonella invasion is the formation of actin-rich protuberances (ruffles) on the host cell surface that contribute to bacterial uptake. However, the membrane source for ruffle formation and how these bacteria regulate membrane mobilization within host cells remains unclear. Here, we show that Salmonella exploits membrane reservoirs for the generation of invasion ruffles. The reservoirs are pre-existing tubular compartments associated with the plasma membrane (PM) and are formed through the activity of RAB10 GTPase. Under normal growth conditions, membrane reservoirs contribute to PM homeostasis and are preloaded with the exocyst subunit EXOC2. During Salmonella invasion, the bacterial effectors SipC, SopE2, and SopB recruit exocyst subunits from membrane reservoirs and other cellular compartments, thereby allowing exocyst complex assembly and membrane delivery required for bacterial uptake. Our findings reveal an important role for RAB10 in the establishment of membrane reservoirs and the mechanisms by which Salmonella can exploit these compartments during host cell invasion.

Aberrant non-canonical NF-κB signalling reprograms the epigenome landscape to drive oncogenic transcriptomes in multiple myeloma.

In multiple myeloma, abnormal plasma cells establish oncogenic niches within the bone marrow by engaging the NF-κB pathway to nurture their survival while they accumulate pro-proliferative mutations. Under these conditions, many cases eventually develop genetic abnormalities endowing them with constitutive NF-κB activation. Here, we find that sustained NF-κB/p52 levels resulting from such mutations favours the recruitment of enhancers beyond the normal B-cell repertoire. Furthermore, through targeted disruption of p52, we characterise how such enhancers are complicit in the formation of super-enhancers and the establishment of cis-regulatory interactions with myeloma dependencies during constitutive activation of p52. Finally, we functionally validate the pathological impact of these cis-regulatory modules on cell and tumour phenotypes using in vitro and in vivo models, confirming RGS1 as a p52-dependent myeloma driver. We conclude that the divergent epigenomic reprogramming enforced by aberrant non-canonical NF-κB signalling potentiates transcriptional programs beneficial for multiple myeloma progression.

Towards a better preclinical cancer model - human immune aging in humanized mice.

BACKGROUND: Preclinical models are often used for cancer studies and evaluation of novel therapeutics. The relevance of these models has vastly improved with mice bearing a human immune system, especially in the context of immunotherapy. Nonetheless, cancer is an age-related disease, and studies often overlook the effects of aging. Here we have established a humanized mouse model of human immune aging to investigate the role of this phenomenon on liver tumor dynamics. METHODS: Multiple organs and tissues (blood, thymus, lung, liver, spleen and bone marrow) were harvested from NOD-scid IL2rγ-/- (NIKO) mice reconstituted with human immune cells, over a period of 60 weeks post-birth, for immune profiling. Young and aging immune cells were compared for transcriptomic changes and functional differences. Effect of immune aging was investigated in a liver cancer humanized mouse model. RESULTS: Focusing on the T cell population, which is central to cancer immunosurveillance and immunotherapy, we showed that the proportion of naïve T cells declined while memory subsets and senescent-like cells increased with age. RNA-sequencing revealed that downregulated genes were related to immune responses and processes, and this was corroborated by reduced cytokine production in aging T cells. Finally, we showed faster liver tumor growth in aging than younger humanized mice, which could be attributed to specific pathways of aging T cell exhaustion. CONCLUSION: Our work improves on existing humanized (immune) mouse model and highlights the importance of considering immune aging in liver cancer modeling.

Sensing in Soft Robotics.

Soft robotics is an exciting field of science and technology that enables robots to manipulate objects with human-like dexterity. Soft robots can handle delicate objects with care, access remote areas, and offer realistic feedback on their handling performance. However, increased dexterity and mechanical compliance of soft robots come with the need for accurate control of the position and shape of these robots. Therefore, soft robots must be equipped with sensors for better perception of their surroundings, location, force, temperature, shape, and other stimuli for effective usage. This review highlights recent progress in sensing feedback technologies for soft robotic applications. It begins with an introduction to actuation technologies and material selection in soft robotics, followed by an in-depth exploration of various types of sensors, their integration methods, and the benefits of multimodal sensing, signal processing, and control strategies. A short description of current market leaders in soft robotics is also included in the review to illustrate the growing demands of this technology. By examining the latest advancements in sensing feedback technologies for soft robots, this review aims to highlight the potential of soft robotics and inspire innovation in the field.

Cell Granularity Reflects Immune Cell Function and Enables Selection of Lymphocytes with Superior Attributes for Immunotherapy.

In keeping with the rule of "form follows function", morphological aspects of a cell can reflect its role. Here, it is shown that the cellular granularity of a lymphocyte, represented by its intrinsic side scatter (SSC), is a potent indicator of its cell state and function. The granularity of a lymphocyte increases from naïve to terminal effector state. High-throughput cell-sorting yields a SSChigh population that can mediate immediate effector functions, and a highly prolific SSClow population that can give rise to the replenishment of the memory pool. CAR-T cells derived from the younger SSClow population possess desirable attributes for immunotherapy, manifested by increased naïve-like cells and stem cell memory (TSCM )-like cells together with a balanced CD4/CD8 ratio, as well as enhanced target-killing in vitro and in vivo. Altogether, lymphocyte segregation based on biophysical properties is an effective approach for label-free selection of cells that share collective functions and can have important applications for cell-based immunotherapies.

SLIT2/ROBO1 signaling suppresses mTORC1 for organelle control and bacterial killing.

SLIT/ROBO signaling impacts many aspects of tissue development and homeostasis, in part, through the regulation of cell growth and proliferation. Recent studies have also linked SLIT/ROBO signaling to the regulation of diverse phagocyte functions. However, the mechanisms by which SLIT/ROBO signaling acts at the nexus of cellular growth control and innate immunity remain enigmatic. Here, we show that SLIT2-mediated activation of ROBO1 leads to inhibition of mTORC1 kinase activity in macrophages, leading to dephosphorylation of its downstream targets, including transcription factor EB and ULK1. Consequently, SLIT2 augments lysosome biogenesis, potently induces autophagy, and robustly promotes the killing of bacteria within phagosomes. Concordant with these results, we demonstrate decreased lysosomal content and accumulated peroxisomes in the spinal cords of embryos from Robo1 -/- , Robo2 -/- double knockout mice. We also show that impediment of auto/paracrine SLIT-ROBO signaling axis in cancer cells leads to hyperactivation of mTORC1 and inhibition of autophagy. Together, these findings elucidate a central role of chemorepellent SLIT2 in the regulation of mTORC1 activity with important implications for innate immunity and cancer cell survival.

Intraoperative cell-salvaged autologous blood transfusion is safe in metastatic spine tumour surgery: early outcomes of prospective clinical study.

PURPOSE: Allogeneic blood transfusion (ABT) is current standard of blood replenishment despite known complications. Salvaged blood transfusion (SBT) addresses majority of such complications. Surgeons remain reluctant to employ SBT in metastatic spine tumour surgery (MSTS), despite ample laboratory evidence. This prompted us to conduct a prospective clinical study to ascertain safety of intraoperative cell salvage (IOCS), in MSTS. METHODS: Our prospective study included 73 patients who underwent MSTS from 2014 to 2017. Demographics, tumour histology and burden, clinical findings, modified Tokuhashi score, operative and blood transfusion (BT) details were recorded. Patients were divided based on BT type: no blood transfusion (NBT) and SBT/ABT. Primary outcomes assessed were overall survival (OS), and tumour progression was evaluated using RECIST (v1.1) employing follow-up radiological investigations at 6, 12 and 24 months, classifying patients with non-progressive and progressive disease. RESULTS: Seventy-three patients [39:34(M/F)] had mean age of 61 years. Overall median follow-up and survival were 26 and 12 months, respectively. All three groups were comparable for demographics and tumour characteristics. Overall median blood loss was 500 mL, and BT was 1000 mL. Twenty-six (35.6%) patients received SBT, 27 (37.0%) ABT and 20 (27.4%) NBT. Females had lower OS and higher risk of tumour progression. SBT had better OS and reduced risk of tumour progression than ABT group. Total blood loss was not associated with tumour progression. Infective complications other than SSI were significantly (p = 0.027) higher in ABT than NBT/SBT groups. CONCLUSIONS: Patients of SBT had OS and tumour progression better than ABT/NBT groups. This is the first prospective study to report of SBT in comparison with control groups in MSTS.

Angle-independent solar radiation capture by 3D printed lattice structures for efficient photoelectrochemical water splitting.

Photoelectrochemical water splitting is one of the sustainable routes to renewable hydrogen production. One of the challenges to deploying photoelectrochemical (PEC) based electrolyzers is the difficulty in the effective capture of solar radiation as the illumination angle changes throughout the day. Herein, we demonstrate a method for the angle-independent capture of solar irradiation by using transparent 3 dimensional (3D) lattice structures as the photoanode in PEC water splitting. The transparent 3D lattice structures were fabricated by 3D printing a silica sol-gel followed by aging and sintering. These transparent 3D lattice structures were coated with a conductive indium tin oxide (ITO) thin film and a Mo-doped BiVO4 photoanode thin film by dip coating. The sheet resistance of the conductive lattice structures can reach as low as 340 Ohms per sq for ∼82% optical transmission. The 3D lattice structures furnished large volumetric current densities of 1.39 mA cm-3 which is about 2.4 times higher than a flat glass substrate (0.58 mA cm-3) at 1.23 V and 1.5 G illumination. Further, the 3D lattice structures showed no significant loss in performance due to a change in the angle of illumination, whereas the performance of the flat glass substrate was significantly affected. This work opens a new paradigm for more effective capture of solar radiation that will increase the solar to energy conversion efficiency.

Efficient Ternary Mn-Based Spinel Oxide with Multiple Active Sites for Oxygen Evolution Reaction Discovered via High-Throughput Screening Methods.

The discovery of more efficient and stable catalysts for oxygen evolution reaction (OER) is vital in improving the efficiency of renewable energy generation devices. Given the large numbers of possible binary and ternary metal oxide OER catalysts, high-throughput methods are necessary to accelerate the rate of discovery. Herein, Mn-based spinel oxide, Fe10 Co40 Mn50 O, is identified for the first time using high-throughput methods demonstrating remarkable catalytic activity (overpotential of 310 mV on fluorine-doped tin oxide (FTO) substrate and 237 mV on Ni foam at 10 mA cm-2 ). Using a combination of soft X-ray absorption spectroscopy and electrochemical measurements, the high catalytic activity is attributed to 1) the formation of multiple active sites in different geometric sites, tetrahedral and octahedral sites; and 2) the formation of active oxyhydroxide phase due to the strong interaction of Co2+ and Fe3+ . Structural and surface characterizations after OER show preservation of Fe10 Co40 Mn50 O surface structure highlighting its durability against irreversible redox damage on the catalytic surface. This work demonstrates the use of a high-throughput approach for the rapid identification of a new catalyst, provides a deeper understanding of catalyst design, and addresses the urgent need for a better and stable catalyst to target greener fuel.

Epidemiology and estimated economic impact of musculoskeletal injuries in polytrauma patients in a level one trauma centre in Singapore.

Introduction: Musculoskeletal injuries are the most common reason for surgical intervention in polytrauma patients. Methods: This is a retrospective cohort study of 560 polytrauma patients (injury severity score [ISS] >17) who suffered musculoskeletal injuries (ISS >2) from 2011 to 2015 in National University Hospital, Singapore. Results: 560 patients (444 [79.3%] male and 116 [20.7%] female) were identified. The mean age was 44 (range 3-90) years, with 45.4% aged 21-40 years. 39.3% of the patients were foreign migrant workers. Motorcyclists were involved in 63% of road traffic accidents. The mean length of hospital stay was 18.8 (range 0-273) days and the mean duration of intensive care unit (ICU) stay was 5.7 (range 0-253) days. Patient mortality rate was 19.8%. A Glasgow Coma Scale (GCS) score <12 and need for blood transfusion were predictive of patient mortality (p < 0.05); lower limb injuries, road traffic accidents, GCS score <8 and need for transfusion were predictive of extended hospital stay (p < 0.05); and reduced GCS score, need for blood transfusion and upper limb musculoskeletal injuries were predictive of extended ICU stay. Inpatient costs were significantly higher for foreign workers and greatly exceeded the minimum insurance coverage currently required. Conclusion: Musculoskeletal injuries in polytrauma remain a significant cause of morbidity and mortality, and occur predominantly in economically productive male patients injured in road traffic accidents and falls from height. Increasing insurance coverage for foreign workers in high-risk jobs should be evaluated.

The Utility of 'Minimal Access and Separation Surgery' in the Management of Metastatic Spine Disease.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: To compare outcomes of percutaneous pedicle screw fixation (PPSF) to open posterior stabilization (OPS) in spinal instability patients and minimal access separation surgery (MASS) to open posterior stabilization and decompression (OPSD) in metastatic spinal cord compression (MSCC) patients. METHODS: We analysed patients who underwent surgery for thoracolumbar metastatic spine disease (MSD) from Jan 2011 to Oct 2017. Patients were divided into minimally invasive spine surgery (MISS) and open spine surgery (OSS) groups. Spinal instability patients were treated with PPSF/OPS with pedicle screws. MSCC patients were treated with MASS/OPSD. Outcomes measured included intraoperative blood loss, operative time, duration of hospital stay and ASIA-score improvement. Time to initiate radiotherapy and perioperative surgical/non-surgical complications was recorded. Propensity scoring adjustment analysis was utilised to address heterogenicity of histological tumour subtypes. RESULTS: Of 200 eligible patients, 61 underwent MISS and 139 underwent OSS for MSD. There was no significant difference in baseline characteristics between MISS and OSS groups. In the MISS group, 28 (45.9%) patients were treated for spinal instability and 33 (54.1%) patients were treated for MSCC. In the OSS group, 15 (10.8%) patients were treated for spinal instability alone and 124 (89.2%) were treated for MSCC. Patients who underwent PPSF had significantly lower blood loss (95 mL vs 564 mL; P < .001) and surgical complication rates(P < .05) with shorter length of stay approaching significance (6 vs 19 days; P = .100) when compared to the OPS group. Patients who underwent MASS had significantly lower blood loss (602 mL vs 1008 mL) and shorter length of stay (10 vs 18 days; P = .098) vs the OPSD group. CONCLUSION: This study demonstrates the benefits of PPSF and MASS over OPS and OPSD for the treatment of MSD with spinal instability and MSCC, respectively.

Freestanding and Scalable Force-Softness Bimodal Sensor Arrays for Haptic Body-Feature Identification.

Tactile technologies that can identify human body features are valuable in clinical diagnosis and human-machine interactions. Previously, cutting-edge tactile platforms have been able to identify structured non-living objects; however, identification of human body features remains challenging mainly because of the irregular contour and heterogeneous spatial distribution of softness. Here, freestanding and scalable tactile platforms of force-softness bimodal sensor arrays are developed, enabling tactile gloves to identify body features using machine-learning methods. The bimodal sensors are engineered by adding a protrusion on a piezoresistive pressure sensor, endowing the resistance signals with combined information of pressure and the softness of samples. The simple design enables 112 bimodal sensors to be integrated into a thin, conformal, and stretchable tactile glove, allowing the tactile information to be digitalized while hand skills are performed on the human body. The tactile glove shows high accuracy (98%) in identifying four body features of a real person, and four organ models (healthy and pathological) inside an abdominal simulator, demonstrating identification of body features of the bimodal tactile platforms and showing their potential use in future healthcare and robotics.

Surgical Management of Missed Pediatric Monteggia Fractures: A Systematic Review and Meta-Analysis.

OBJECTIVES: To review surgical management and outcomes of missed pediatric Monteggia fractures. DATA SOURCES: A systematic review was conducted using PubMed, Medical Literature Analysis and Retrieval System Online (MEDLINE), Cumulative Index to Nursing and Allied Health Literature (CINAHL), and the Cochrane Library from inception through March 2, 2020. The keywords were "Monteggia fracture," "missed Monteggia," "neglected Monteggia," "chronic Monteggia," and "chronic radial head dislocation." STUDY SELECTION: All original human studies on missed pediatric Monteggia fractures were included. Congenital Monteggia fractures and isolated radial head dislocations were excluded. DATA EXTRACTION: The revised Methodological Index for Nonrandomised Studies tool was used to assess the quality of studies. DATA SYNTHESIS: Each patient's data were retrieved individually. The χ2 test and Fisher exact test were used to analyze the difference in outcomes for different surgical managements. Multivariate analysis was performed for variables that were significant on univariate analysis. CONCLUSIONS: Thirty studies with 600 patients were included. Proximal ulnar osteotomies (P = 0.016) and the absence of transcapitellar pinning (P = 0.001) were the most significant predictors for eventual reduction of radial head. Other surgical management variables were not significant predictors. These include open or closed reduction approach of radial head reduction; presence or absence of ulnar osteotomy; presence or absence of lengthening, angular correction, overcorrection, or bone grafting of ulnar osteotomy; type of fixation for ulnar osteotomy; presence or absence of radial osteotomy; presence or absence of annular ligament repair or reconstruction; and repair or reconstruction of annular ligament. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Association between pet ownership and physical activity and mental health during the COVID-19 "circuit breaker" in Singapore.

INTRODUCTION: The negative impact of the coronavirus disease 2019 (COVID-19) pandemic on mental health and physical activity is well reported. While prior studies showed a positive influence of pet ownership on physical activity and mental health, the interactions between the pandemic and pet ownership are not well studied. OBJECTIVE: To determine the association between pet ownership, physical activity levels and mental health during the COVID-19 pandemic. MATERIALS AND METHODS: A cross-sectional study was conducted from May 19 to July 13, 2020 among Singapore residents aged 21 to 64 years through a previously published questionnaire. Inverse probability treatment weighting was used to develop mixed-effects models for outcome comparisons. We recorded participant data on pet ownership, duration and intensity of physical activity, and RAND 36-item Health Survey mental health domains during the COVID-19 pandemic. RESULTS: The questionnaire was completed by 431 pet owners and 103 non-pet owners. A greater proportion of pet owners were female, non-married, employed and owned pets in the past. Pet owners reported 31.8 (95% CI 13.6 to 50; p = .001) more minutes per week of mild-intensity physical activity compared to non-pet owners. No statistically significant differences were found for moderate- and vigorous-intensity physical activity. Pet owners had better emotional well-being (ꞵ = 9.66, 95% CI 4.97 to 14.4; p < .001), energy (ꞵ = 8.29, 95% CI 3.46 to 13.1; p = .001) and social functioning (ꞵ = 11.2, 95% CI 5.03 to 17.4; p < .001) scores than non-pet owners. However, no statistically significant difference was observed for general health scores. Pet owner physical activity levels, general health, emotional well-being and energy scores correlated positively with pet attachment scores. CONCLUSION: Pet ownership was associated with greater physical activity levels and better mental health, particularly in main caregivers with higher pet attachment scores. These findings suggest that pet ownership is beneficial to physical and mental well-being during periods of social isolation amidst a global pandemic.

Listeria exploits IFITM3 to suppress antibacterial activity in phagocytes.

The type I interferon (IFN) signaling pathway has important functions in resistance to viral infection, with the downstream induction of interferon stimulated genes (ISG) protecting the host from virus entry, replication and spread. Listeria monocytogenes (Lm), a facultative intracellular foodborne pathogen, can exploit the type I IFN response as part of their pathogenic strategy, but the molecular mechanisms involved remain unclear. Here we show that type I IFN suppresses the antibacterial activity of phagocytes to promote systemic Lm infection. Mechanistically, type I IFN suppresses phagosome maturation and proteolysis of Lm virulence factors ActA and LLO, thereby promoting phagosome escape and cell-to-cell spread; the antiviral protein, IFN-induced transmembrane protein 3 (IFITM3), is required for this type I IFN-mediated alteration. Ifitm3-/- mice are resistant to systemic infection by Lm, displaying decreased bacterial spread in tissues, and increased immune cell recruitment and pro-inflammatory cytokine signaling. Together, our findings show how an antiviral mechanism in phagocytes can be exploited by bacterial pathogens, and implicate IFITM3 as a potential antimicrobial therapeutic target.

Readmission-Free Survival Analysis in Metastatic Spine Tumour Surgical Patients: A Novel Concept.

BACKGROUND: Outcomes commonly used to ascertain success of metastatic spine tumour surgery (MSTS) are 30-day complications/mortality and overall/disease-free survival. We believe a new, effective outcome indicator after MSTS would be the absence of unplanned hospital readmission (UHR) after index discharge. We introduce the concept of readmission-free survival (ReAFS), defined as 'the time duration between hospital discharge after index operation and first UHR or death'. The aim of this study is to identify factors influencing ReAFS in MSTS patients. PATIENTS AND METHODS: We retrospectively analysed 266 consecutive patients who underwent MSTS between 2005 and 2016. Demographics, oncological characteristics, procedural, preoperative and postoperative details were collected. ReAFS of patients within 2 years or until death was reviewed. Perioperative factors predictive of reduced ReAFS were evaluated using multivariate regression analysis. RESULTS: Of 266 patients, 230 met criteria for analysis. A total of 201 had UHR, whilst 1 in 8 (29/230) had no UHR. Multivariate analysis revealed that haemoglobin ≥ 12 g/dL, ECOG score of ≤ 2, primary prostate, breast and haematological cancers, comorbidities ≤ 3, absence of preoperative radiotherapy and shorter postoperative length of stay significantly prolonged the time to first UHR. CONCLUSIONS: Readmission-free survival is a novel concept in MSTS, which relies on patients' general condition, appropriateness of interventional procedures and underlying disease burden. Additionally, it may indicate the successful combination of a multi-disciplinary treatment approach. This information will allow oncologists and surgeons to identify patients who may benefit from increased surveillance following discharge to increase ReAFS. We envisage that ReAFS is a concept that can be extended to other surgical oncological fields.

Analysis of unplanned hospital readmissions up to 2-years after metastatic spine tumour surgery.

PURPOSE: The aim of this study was to investigate rates, causes, and risk factors of unplanned hospital readmissions (UHR) within 30 days, 90 days, 1 year and 2 years after metastatic spine tumour surgery (MSTS) to augment multi-disciplinary treatment planning and improve patient education. METHODS: We retrospectively reviewed 272-patients who underwent MSTS between 2005 and 2016. Hospital records were utilised to obtain demographics, oncological, procedural details, and postoperative outcomes. All UHR within 2 years were reviewed. Primary outcomes were rates, causes, and risk factors of UHR. Risk factors for UHR were evaluated utilising multivariate logistic regression analysis. RESULTS: Thirty-day, 90 day, 1 year, and 2 year UHR-rates after MSTS were 17.2%, 31.1%, 46.2%, and 52.7%, respectively. Lung cancer primaries had the highest UHR-events (24.7%) whilst renal/thyroid displayed the least (6.6%). Disease-related causes (16.2%) were the most common reason for readmissions across all timeframes, followed by respiratory (13.7%) and progression of metastatic spine disease (12.7%). Urological conditions accounted for majority of readmissions within 30-days; disease-related causes, symptomatic spinal metastases, and respiratory conditions represented the most common causes at 30-90 days, 90 days-1 year, and 1-2 years, respectively. An ECOG >1 (p = 0.057), CCI >7 (p = 0.01), and primary lung tumour (p = 0.02) significantly increased UHR-risk on multivariate analysis. CONCLUSION: Seventy-four percent of patients had at least one UHR within 2 years of MSTS and majority were secondary to disease-related causes. Majority of first UHR occurred between 30 and 90 days post-surgery. Local disease progression and overall disease progression account for the highest UHR-events at 90 days-1 year and 1-2 year timeframes, respectively. We define UHR in specific timeframes, thus enabling better surveillance and reducing unnecessary morbidity.

Results of a colorectal enhanced recovery after surgery (ERAS) programme and a qualitative analysis of healthcare workers' perspectives.

BACKGROUND: Enhanced recovery after surgery (ERAS) is a structured programme using a multimodal, evidence-based approach to improve post-operative outcomes. Successful implementation of ERAS can be challenging. We aimed to evaluate our initial experience with colorectal ERAS and explore the perspectives of specialist doctors and nurses. METHODS: From 1 June 2017 to 31 December 2017, all patients who underwent elective colorectal resection and met the ERAS inclusion criteria at the Department of Colorectal Surgery, Singapore General Hospital, were included in the study. Short-term outcomes were compared between patients with >70% compliance to key ERAS components versus those with ≤70% compliance. Department staff were surveyed via questionnaire in July 2019. RESULTS: Three hundred and fifteen patients were included in study. >70% ERAS compliance rate was achieved in 84 patients (26.7%). A higher compliance rate resulted in a significantly shorter length of stay of 6 (IQR 5-8) days vs. 7 (IQR 6-9.5) days (p = 0.025) and lower readmission rate of 3.6% (n = 3) vs. 4.8% (n = 11) (p = 0.042), as well as a trend towards reduced complication rate of 15.4% (n = 13) vs. 22.0% (n = 51) and earlier return to gastrointestinal function. There was a 100% questionnaire response amongst all 12 colorectal surgeons and 5 colorectal resident nurse practitioners. CONCLUSION: Increased adherence to the components of ERAS results in better early outcomes and may have long-term benefits on survival. Effective communication and professional support for the ERAS multi-disciplinary team, as well as understanding healthcare workers' concerns and addressing long-standing practices, is essential for successful implementation of the programme.

Definitive Surgery Is Safe in Borderline Patients Who Respond to Resuscitation.

OBJECTIVES: We hypothesize that in adequately resuscitated borderline polytrauma patients with long bone fractures (femur and tibia) or pelvic fractures, early (within 4 days) definitive stabilization (EDS) can be performed without an increase in postoperative ventilation and postoperative complications. DESIGN: Retrospective cohort study. SETTING: Level 1 trauma center. PATIENTS: In total, 103 patients were included in this study; of whom, 18 (17.5%) were female and 85 (82.5%) were male. These patients were borderline trauma patients who had the following parameters before definitive surgery, normal coagulation profile, lactate of <2.5 mmol/L, pH of ≥7.25, and base excess of ≥5.5. INTERVENTION: These patients were treated according to Early Total Care, definitive surgery on day of admission, or Damage Control Orthopaedics principles, temporizing external fixation followed by definitive surgery at a later date. Timing of definitive surgical fixation was recorded as EDS or late definitive surgical fixation (>4 days). MAIN OUTCOME MEASURES: Primary outcome measured was the duration of ventilation more than 3 days post definitive surgery and presence of postoperative complications. RESULTS: Thirty-five patients (34.0%) received Early Total Care, whereas 68 (66.0%) patients were treated with Damage Control Orthopaedics. In total, 51 (49.5%) of all patients had late definitive surgery, whereas 52 patients (50.5%) had EDS. On logistic regression, the following factors were found to be predictive of higher rates of postoperative ventilation ≥ 3 days, units of blood transfused, and time to definitive surgery > 4 days. Increased age, head abbreviated injury score of 3 or more and time to definitive surgery were found to be associated with an increased risk of postoperative complications. CONCLUSIONS: Borderline polytrauma patients with no severe soft tissue injuries, such as chest or head injuries, may be treated with EDS if adequately resuscitated with no increase in need for postoperative ventilation and complications. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.