To evaluate the current evidence for surgical sabermetrics: digital methods of assessing surgical nontechnical skills and investigate the implications for enhancing surgical performance.
Surgeons ...need high-quality, objective, and timely feedback to optimize performance and patient safety. Digital tools to assess nontechnical skills have the potential to reduce human bias and aid scalability. However, we do not fully understand which of the myriad of digital metrics of performance assessment have efficacy for surgeons.
A systematic review was conducted by searching PubMed, EMBASE, CINAHL, and PSYCINFO databases following PRISMA-ScR guidelines. MeSH terms and keywords included "Assessment," "Surgeons," and "Technology". Eligible studies included a digital assessment of nontechnical skills for surgeons, residents, and/or medical students within an operative context.
From 19,229 articles screened, 81 articles met the inclusion criteria. The studies varied in surgical specialties, settings, and outcome measurements. A total of 122 distinct objective, digital metrics were utilized. Studies digitally measured at least 1 category of surgical nontechnical skill using a single (n=54) or multiple objective measures (n=27). The majority of studies utilized simulation (n=48) over live operative settings (n=32). Surgical Sabermetrics has been demonstrated to be beneficial in measuring cognitive load (n=57), situation awareness (n=24), communication (n=3), teamwork (n=13), and leadership (n=2). No studies measured intraoperative decision-making.
The literature detailing the intersection between surgical data science and operative nontechnical skills is diverse and growing rapidly. Surgical Sabermetrics may provide a promising modifiable technique to achieve desirable outcomes for both the surgeon and the patient. This study identifies a diverse array of measurements possible with sensor devices and highlights research gaps, including the need for objective assessment of decision-making. Future studies may advance the integration of physiological sensors to provide a holistic assessment of surgical performance.
This review article focuses on current clinical outcomes with novel perfusion strategies in organ transplantation. Broadly, these approaches can be divided into in situ regional perfusion in the ...donor and ex situ machine perfusion of individual organs. In both settings, hypothermic and normothermic techniques are in clinical use. Evidence from full text articles, abstracts, and data presented at scientific meetings has been considered. Animal studies have been excluded. The review focuses on kidney, liver, pancreas, heart, and lungs. The level of evidence ranges from quasi-experimental work in human pancreas to multiple meta-analyses of Randomized Controlled Trials for hypothermic machine perfusion of kidneys. The data in this review were presented to experts in organ perfusion and preservation at the National Health Service Blood and Transplant Preservation and Perfusion Future Strategy Summit in London in October 2018. The outcomes of the meeting are discussed in the review after due consideration of the available evidence base.
The use of artificial intelligence and machine learning (ML) has revolutionised our daily lives and will soon be instrumental in healthcare delivery. The rise of ML is due to multiple ...factorsincreasing access to massive data sets, 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.
PURPOSE OF REVIEWCachexia remains an important cause of morbidity and mortality among cancer patients. The mechanisms underlying this syndrome remain unclear and are almost certainly multifactorial. ...Evidence from animal models suggests a compelling link between cachexia and inflammation, and a variety of pro-inflammatory cytokines play an integral role. This review summarizes current thinking relating to inflammation, cachexia and prognosis in cancer patients, with particular emphasis on studies relating to recent therapeutic advances.
RECENT FINDINGSPro-inflammatory cytokines induce the acute phase protein response, a key marker of systemic inflammation. Recent evidence has also implicated other tumour-derived mediators, such as proteolysis-inducing factor and parathyroid hormone-related peptide. In addition, systemic inflammation has been found in association with many malignancies, and has been correlated with weight loss, hypermetabolism, anorexia, and adverse prognosis. Treatments such as fish oil, monoclonal antibodies, and non-steroidal anti-inflammatory drugs, have all been utilized to attenuate systemic inflammation and influence weight loss. Recent clinical studies have suggested that eicosapentaenoic acid and cyclo-oxygenase 2 inhibitors promote weight gain and downregulate the acute phase protein response.
SUMMARYPro-inflammatory processes are clearly implicated in the hypermetabolism and weight loss associated with cancer-associated cachexia. In addition, the presence of systemic inflammation is now clearly linked with adverse prognosis in patients with cancer, which cannot be fully explained by the association with weight loss. Systemic inflammation remains an important area for novel therapeutic targets in combating cachexia, and eicosapentaenoic acid and cyclo-oxygenase 2 inhibitors appear to be efficacious in the armory against cachexia.
Duplicate publication can introduce significant bias into a meta-analysis if studies are inadvertently included more than once. Many studies are published in more than one journal to maximize ...readership and impact of the study findings. Inclusion of multiple publications of the same study within a meta-analysis affords inappropriate weight to the duplicated data if reports of the same study are not linked together. As studies which have positive findings are more likely to be published in multiple journals this leads to a potential overestimate of the benefits of an intervention. Recent advances in immunosuppression strategies following liver transplantation have led to many studies investigating immunosuppressive regimes including immunosuppression monotherapy. In this letter we focus on a recently published meta-analysis by Lan et al investigating studies assessing immunosuppression monotherapy for liver transplantation. The authors claim to have identified fourteen separate randomised studies investigating immunosuppression monotherapy. Seven of the references appear to relate to only three studies which have been subject to duplicate publication. Several similarities can be identified in each of the duplicate publications including similar authorship, identical immunosuppression regimes, identical dates of enrolment and citation of the original publication in the subsequent manuscripts. We discuss the evidence of the duplicate publication inclusion in the meta-analysis.
IntroductionSurgeons need high fidelity, high quality, objective, non-judgemental and quantitative feedback to measure their performance in order to optimise their performance and improve patient ...safety. This can be provided through surgical sabermetrics, defined as ‘advanced analytics of digitally recorded surgical training and operative procedures to enhance insight, support professional development and optimise clinical and safety outcomes’. The aim of this scoping review is to investigate the assessment of surgeon’s non-technical skills using sabermetrics principles, focusing on digital, automated measurements that do not require a human observer.Methods and analysisTo investigate the current methods of digital, automated measurements of surgeons’ non-technical skills, a systematic scoping review will be conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines, using databases from medicine and other fields. Covidence software is used for screening of potential studies. A data extraction tool will be developed specifically for this study to evaluate the methods of measurement. Quality assurance will be assessed using Quality Assessment Tool for Diverse Designs. Multiple reviewers will be responsible for screening of studies and data extraction.Ethics and disseminationThis is a review study, not using primary data, and therefore, ethical approval is not required. A range of methods will be employed for dissemination of the results of this study, including publication in journals and conference presentations.
Acute kidney injury is associated with a poor prognosis in acute liver failure but little is known of outcomes in patients undergoing transplantation for acute liver failure who require renal ...replacement therapy.
A retrospective analysis of the United Kingdom Transplant Registry was performed (1 January 2001-31 December 2011) with patient and graft survival determined using Kaplan-Meier methods. Cox proportional hazards models were used together with propensity-score based full matching on renal replacement therapy use.
Three-year patient and graft survival for patients receiving renal replacement therapy were 77.7% and 72.6% compared with 85.1% and 79.4% for those not requiring renal replacement therapy (P<0.001 and P = 0.009 respectively, n = 725). In a Cox proportional hazards model, renal replacement therapy was a predictor of both patient death (hazard ratio (HR) 1.59, 95% CI 1.01-2.50, P = 0.044) but not graft loss (HR 1.39, 95% CI 0.92-2.10, P = 0.114). In groups fully matched on baseline covariates, those not receiving renal replacement therapy with a serum creatinine greater than 175 μmol/L had a significantly worse risk of graft failure than those receiving renal replacement therapy.
In patients being transplanted for acute liver failure, use of renal replacement therapy is a strong predictor of patient death and graft loss. Those not receiving renal replacement therapy with an elevated serum creatinine may be at greater risk of early graft failure than those receiving renal replacement therapy. A low threshold for instituting renal replacement therapy may therefore be beneficial.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Cholangiocarcinoma (CCA) is a cancer of the hepatic bile ducts that is rarely resectable and is associated with poor prognosis. Tumour necrosis factor-like weak inducer of apoptosis (TWEAK) is known ...to signal via its receptor fibroblast growth factor-inducible 14 (Fn14) and induce cholangiocyte and myofibroblast proliferation in liver injury. We aimed to characterise its role in CCA.
The expression of the TWEAK ligand and Fn14 receptor was assessed immunohistochemically and by bulk RNA and single cell transcriptomics of human liver tissue. Spatiotemporal dynamics of pathway regulation were comprehensively analysed in rat and mouse models of thioacetamide (TAA)-mediated CCA. Flow cytometry, qPCR and proteomic analyses of CCA cell lines and conditioned medium experiments with primary macrophages were performed to evaluate the downstream functions of TWEAK/Fn14. In vivo pathway manipulation was assessed via TWEAK overexpression in NICD/AKT-induced CCA or genetic Fn14 knockout during TAA-mediated carcinogenesis.
Our data reveal TWEAK and Fn14 overexpression in multiple human CCA cohorts, and Fn14 upregulation in early TAA-induced carcinogenesis. TWEAK regulated the secretion of factors from CC-SW-1 and SNU-1079 CCA cells, inducing polarisation of proinflammatory CD206+ macrophages. Pharmacological blocking of the TWEAK downstream target chemokine monocyte chemoattractant protein 1 (MCP-1 or CCL2) significantly reduced CCA xenograft growth, while TWEAK overexpression drove cancer-associated fibroblast proliferation and collagen deposition in the tumour niche. Genetic Fn14 ablation significantly reduced inflammatory, fibrogenic and ductular responses during carcinogenic TAA-mediated injury.
These novel data provide evidence for the action of TWEAK/Fn14 on macrophage recruitment and phenotype, and cancer-associated fibroblast proliferation in CCA. Targeting TWEAK/Fn14 and its downstream signals may provide a means to inhibit CCA niche development and tumour growth.
Cholangiocarcinoma is an aggressive, chemotherapy-resistant liver cancer. Interactions between tumour cells and cells that form a supportive environment for the tumour to grow are a source of this aggressiveness and resistance to chemotherapy. Herein, we describe interactions between tumour cells and their supportive environment via a chemical messenger, TWEAK and its receptor Fn14. TWEAK/Fn14 alters the recruitment and type of immune cells in tumours, increases the growth of cancer-associated fibroblasts in the tumour environment, and is a potential target to reduce tumour formation.
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•Fn14 is upregulated on tumour cells and CAFs, and TWEAK is expressed by TAMs in human CCA.•TWEAK/Fn14 are progressively upregulated during rodent tumour development.•TWEAK/Fn14 signalling induces TAM accumulation via TWEAK-inducible MCP-1 chemotaxis which can be blocked in vivo.•TWEAK-inducible factors from tumour cells pattern macrophages to a TAM-like phenotype.•TWEAK overexpression in experimental tumour formation drives CAF proliferation, collagen deposition and increases macrophages in mice.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background
Hepatic resection for colorectal liver metastasis (CLM) with concomitant extrahepatic disease (EHD) is a controversial topic. We sought to evaluate the long-term outcome of patients ...undergoing liver resection for CLM in presence of EHD and identify factors associated with prognosis.
Methods
From 1996 to 2007, a total of 1629 patients who underwent resection of CLM were identified from an international multi-institutional database. One hundred seventy-one patients (10.4%) underwent resection of EHD. Clinicopathologic and outcome data were collected and analyzed by univariate and multivariate analyses.
Results
Median number of treated CLM was 2 (range, 1–18); most patients had solitary EHD (
n
= 114; 66.6%) a single anatomic site of EHD (
n
= 153; 89.4%). The 5-year survival for patients with EHD was 26% compared with 58% for those without EHD (
P
< 0.001). Recurrence was common (84%). Among patients with EHD, R1 margin status, multiple EHD sites, and location of EHD were associated with worse survival (all
P
< 0.05). Patients with multiple EHD sites or aortocaval lymph node metastasis had a 5-year survival of 14% and 7%, respectively. When survival was stratified by the total number of metastases treated, the presence of EHD still had a prognostic impact, but the relative impact of EHD diminished as the total number of metastases treated increased.
Conclusion
Concurrent resection of hepatic and EHD in well-selected patients may provide the possibility of long-term survival. The risk of recurrence, however, remains high, and a worse outcome is associated with both number of metastases and location of EHD.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Abstract
Background
Features of cancer cachexia adversely influence patient outcomes, yet few currently inform clinical decision-making. This study assessed the value of the cachexia index (CXI), a ...novel prognostic marker, in patients for whom neoadjuvant chemotherapy and surgery for oesophagogastric cancer is planned.
Methods
Consecutive patients newly diagnosed with locally advanced (T3–4 or at least N1) oesophagogastric cancer between 1 January 2010 and 31 December 2015 were identified through the West of Scotland and South-East Scotland Cancer Networks. CXI was calculated as (L3 skeletal muscle index) × (serum albumin)/(neutrophil lymphocyte ratio). Sex-stratified cut-off values were determined based on the area under the curve (AUC), and patients were divided into groups with low or normal CXI. Primary outcomes were disease progression during neoadjuvant chemotherapy and overall survival (at least 5 years of follow-up).
Results
Overall, 385 patients (72% men, median age 66 years) were treated with neoadjuvant chemotherapy for oesophageal (274) or gastric (111) cancer across the study interval. Although patients with a low CXI (men: CXI below 52 (AUC 0.707); women: CXI below 41 (AUC 0.759)) were older with more co-morbidity, disease characteristics were comparable to those in patients with a normal CXI. Rates of disease progression during neoadjuvant chemotherapy, leading to inoperability, were higher in patients with a low CXI (28 versus 12%; adjusted OR 3.07, 95% c.i. 1.67 to 5.64; P < 0.001). Low CXI was associated with worsened postoperative mortality (P = 0.019) and decreased overall survival (median 14.9 versus 56.9 months; adjusted HR 1.85, 1.42 to 2.42; P < 0.001).
Conclusion
CXI is associated with disease progression, worse postoperative mortality, and overall survival, and could improve prognostication and decision-making in patients with locally advanced oesophagogastric cancer.
Cachexia index represents a valuable marker of ‘host stage’, and a potential adjunct to routine tumour staging. This could improve prognostication and decision-making in patients with locally advanced oesophagogastric cancer.
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BFBNIB, FZAB, GIS, IJS, KILJ, NUK, OILJ, SBCE, SBMB, UL, UPUK
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