SummaryBackgroundSurgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world.MethodsThis international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231.FindingsBetween Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p<0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p<0·001).InterpretationCountries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication.FundingDFID-MRC-Wellcome Trust Joint Global Health Trial Development Grant,...

BackgroundLittle is known about the roles of myeloid cell subsets in kidney injury and in the limited ability of the organ to repair itself. Characterizing these cells based only on surface markers using flow cytometry might not provide a full phenotypic picture. Defining these cells at the single-cell, transcriptomic level could reveal myeloid heterogeneity in the progression and regression of kidney disease.MethodsIntegrated droplet– and plate-based single-cell RNA sequencing were used in the murine, reversible, unilateral ureteric obstruction model to dissect the transcriptomic landscape at the single-cell level during renal injury and the resolution of fibrosis. Paired blood exchange tracked the fate of monocytes recruited to the injured kidney.ResultsA single-cell atlas of the kidney generated using transcriptomics revealed marked changes in the proportion and gene expression of renal cell types during injury and repair. Conventional flow cytometry markers would not have identified the 12 myeloid cell subsets. Monocytes recruited to the kidney early after injury rapidly adopt a proinflammatory, profibrotic phenotype that expresses Arg1, before transitioning to become Ccr2+ macrophages that accumulate in late injury. Conversely, a novel Mmp12+ macrophage subset acts during repair.ConclusionsComplementary technologies identified novel myeloid subtypes, based on transcriptomics in single cells, that represent therapeutic targets to inhibit progression or promote regression of kidney disease.

Objective: Long noncoding RNAs (lncRNAs) are an emergent class of molecules with diverse functional roles, widely expressed in human physiology and disease. Although some lncRNAs have been identified in cardiovascular disease, their potential as novel targets in the prevention of atherosclerosis is unknown. We set out to discover important lncRNAs in unstable plaque and gain insight into their functional relevance. Approach and Results: Analysis of RNA sequencing previously performed on stable and unstable atherosclerotic plaque identified a panel of 47 differentially regulated lncRNAs. We focused on LINC01272, a lncRNA upregulated in unstable plaque previously detected in inflammatory bowel disease, which we termed PELATON (plaque enriched lncRNA in atherosclerotic and inflammatory bowel macrophage regulation). Here, we demonstrate that PELATON is highly monocyte- and macrophage-specific across vascular cell types, and almost entirely nuclear by cellular fractionation (90%–98%). In situ hybridization confirmed enrichment of PELATON in areas of plaque inflammation, colocalizing with macrophages around the shoulders and necrotic core of human plaque sections. Consistent with its nuclear localization, and despite containing a predicted open reading frame, PELATON did not demonstrate any protein-coding potential in vitro. Functionally, knockdown of PELATON significantly reduced phagocytosis, lipid uptake and reactive oxygen species production in high-content analysis, with a significant reduction in phagocytosis independently validated. Furthermore, CD36, a key mediator of phagocytic oxLDL (oxidized low-density lipoprotein) uptake was significantly reduced with PELATON knockdown. Conclusions: PELATON is a nuclear expressed, monocyte- and macrophage-specific lncRNA, upregulated in unstable atherosclerotic plaque. Knockdown of PELATON affects cellular functions associated with plaque progression.

BackgroundWith the advent of smartphones together with their downloadable applications (apps), there is increasing opportunities for doctors, including orthopaedic sports surgeons, to integrate such technology into clinical practice. However, the clinical reliability of these medical apps remains questionable. We reviewed available apps themed specifically towards Orthopaedic Sports Medicine and related conditions and assessed the level of medical professional involvement in their design and content, along with a review of these apps.MethodThe most popular smartphone app stores (Android, Apple, Blackberry, Windows, Samsung, Nokia) were searched for Orthopaedic Sports medicine themed apps, using the search terms; Orthopaedic Sports Medicine, Orthopaedics, Sports medicine, Knee Injury, Shoulder Injury, Anterior Cruciate Ligament Tear, Medial Collateral Ligament Tear, Rotator Cuff Tear, Meniscal Tear, Tennis Elbow. All English language apps related to orthopaedic sports medicine were included.ResultsA total of 76 individual Orthopaedic Sports Medicine themed apps were identified. According to app store classifications, there were 45 (59 %) medical themed apps, 28 (37 %) health and fitness themed apps, 1 (1 %) business app, 1 (1 %) reference app and 1 (1 %) sports app. Forty-nine (64 %) apps were available for download free of charge. For those that charged access, the prices ranged from £0.69 to £69.99. Only 51 % of sports medicine apps had customer satisfaction ratings and 39 % had named medical professional involvement in their development or content.ConclusionsWe found the majority of Orthopaedic Sports Medicine apps had no named medical professional involvement, raising concerns over their content and evidence-base. We recommend increased regulation of such apps to improve the accountability of app content.

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The use of artificial intelligence and machine learning (ML) has revolutionized our daily lives and will soon be instrumental in healthcare delivery. The rise of ML is due to multiple factors: increasing access to massive datasets, exponential increases in processing power, and key algorithmic developments which allow ML models to tackle increasingly challenging questions. Progressively more transplantation research is exploring the potential utility of ML models throughout the patient journey, although this has not yet widely transitioned into the clinical domain. In this review, we explore common approaches used in ML in solid organ clinical transplantation and consider opportunities for ML to help clinicians and patients. We discuss ways in which ML can aid leverage of large complex datasets, generate cutting-edge prediction models, perform clinical image analysis, discover novel markers in molecular data, and fuse datasets to generate novel insights in modern transplantation practice. We focus on key areas in transplantation where ML is driving progress, explore the future potential roles of ML, and discuss the challenges and limitations of these powerful tools.

Background. The management of choledocholithiasis has evolved from open common bile duct exploration (OCBDE) to therapeutic endoscopic retrograde cholangiopancreatography (ERCP) to laparoscopic common bile duct exploration (LCBDE). Each entails a degree of difficulty. Aim. To review 5-year results of bile duct exploration in an UGI unit. Methods. Common bile duct explorations (CBDEs) performed between January 2008 and January 2013 were identified from a prospectively collected clinical audit system and results reviewed retrospectively. Results. 216 CBDEs were performed, 119 (55%) as an emergency and 52 (24%) following failed ERCP. Open CBDE (OCBDE) was performed primarily in 34/216 (16%) patients and attempted laparoscopically in 182 (84%). Fifty nine (32%) Laparoscopic CBDEs (LCBDEs) were converted to OCBDE. Of the remaining 123 LCBDEs, 51 (41%) primary choledochotomies and 72 (59%) primary transcystic CBDEs (TC-CBDEs) were performed. Forty nine (68%) TC-CBDEs were considered successful and 23 (32%) failed. Fifteen failed TC-CBDEs were converted to a successful laparoscopic choledochotomy. Ductal clearance was achieved in 187/216 (87%) patients and retained stones were identified in 20/123 (16%) LCBDEs. Complications occurred in 52/216 (24%) patients. There were 8/216 (4%) bile leaks requiring further intervention. Postoperative ERCP was carried out in 32/216 (15%) patients and 9/216 (4%) required relaparoscopy/laparotomy. No patient died. Conclusions. Successful management of choledocholithiasis requires a breadth of laparoscopic and endoscopic expertise.

Short running title: Myeloid cell heterogeneity in kidney injury and repair Corresponding authors: Bryan Conway (Bryan.Conway@ed.ac.uk), Eoin O'Sullivan (Eoin.osullivan@ed.ac.uk), Tamir Chandra (Tamir.Chandra@ed.ac.uk) Laura Denby (Laura.Denby@ed.ac.uk) Word Count = 4810 Number of figures = 8 2 AbstractThe kidney has a limited capacity to repair following injury, however, the endogenous reparative pathways are not well understood. Here we employ integrated droplet-and platebased scRNA-seq in the murine reversible unilateral ureteric obstruction model to dissect the transcriptomic landscape at the single cell level during renal injury and resolution of fibrosis.We generate a comprehensive catalogue of the changes induced during injury and repair, revealing significant myeloid cell heterogeneity, which would not have been identifiable by conventional flow cytometry. We identify new markers for the myeloid populations within the kidney as well as identification of novel subsets including an Arg1 + monocyte population specific to early injury and a Mmp12 + macrophage subset exclusive to repair. Finally, using paired blood exchange to track circulating immune cells, we confirm that monocytes are recruited to the kidney early after injury and are the source of Ccr2 + macrophages that accumulate in late injury. Our data demonstrate the utility of complementary technologies to identify novel myeloid subtypes that may represent therapeutic targets to inhibit progression or promote regression of kidney disease. Methods Animal modelsAll protocols and surgical procedures were approved by the Animal Ethics Committee, University of Edinburgh. Animal experiments were conducted in accordance with the Animals Scientific Procedures Act UK 1986, under Home Office project licenses 70/8093 and 70/8867. Reversible unilateral ureteric obstruction model (R-UUO)The R-UUO model was performed as previously described (33). Briefly, 8 week old male C57BL/6JOlaHsd mice (Enviago) underwent laparotomy and the left ureter was isolated and the distal portion was ligated twice with 6/O black braided silk suture close to the bladder. In