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We aimed to evaluate differences in laboratory tests, bleeding, transfusions, and thrombosis between (1) children without and with cirrhosis and (2) children and adults with cirrhosis, and to correlate thromboelastography (TEG) parameters with biomarkers of hemostasis, bleeding, and transfusions in children and adults with cirrhosis.This single-center, retrospective study included 20 children without cirrhosis, 40 children with cirrhosis, and 40 adults with cirrhosis who underwent a liver transplant (LT). We collected demographic data, preoperative laboratory values, and intraoperative TEG parameters. Biomarkers of hemostasis just prior to the start of LT surgery were analyzed including international normalized ratio (INR), platelet, fibrinogen level, R time, K time, alpha angle (α), and maximum amplitude (MA). We also collected outcome data including blood loss, transfusion requirements, and thrombosis.A significantly higher proportion of children with cirrhosis had abnormal PT ( P = 0.001), platelet ( P = 0.001), K time ( P = 0.02), and MA ( P = 0.05) compared to children without cirrhosis. The incidences of thrombosis, bleeding events, blood loss or PRBC transfusion were not significantly different between these 2 groups. A significantly higher proportion of adults with cirrhosis had abnormal R time ( P = 0.01) and alpha angle ( P = 0.01) than children with cirrhosis.Children with cirrhosis had defects in fibrinogen and platelets compared to children without cirrhosis at time of LT; however, these abnormalities did not translate into higher rates of bleeding in the former. Adults with cirrhosis had more defects in clotting factors compared to children with cirrhosis.

Science, technology, engineering, mathematics, and medicine (STEMM) fields change rapidly and are increasingly interdisciplinary. Commonly, STEMM practitioners use short-format training (SFT) such as workshops and short courses for upskilling and reskilling, but unaddressed challenges limit SFT’s effectiveness and inclusiveness. Prior work, including the NSF 2026 Reinventing Scientific Talent proposal, called for addressing SFT challenges, and a diverse international group of experts in education, accessibility, and life sciences came together to do so. This paper describes the phenomenography and content analyses that produced a set of 14 actionable recommendations to systematically strengthen SFT. Recommendations were derived from findings in the educational sciences and the experiences of several of the largest life science SFT programs. Recommendations cover the breadth of SFT contexts and stakeholder groups and include actions for instructors (e.g., make equity and inclusion an ethical obligation), programs (e.g., centralize infrastructure for assessment and evaluation), as well as organizations and funders (e.g., professionalize training SFT instructors; deploy SFT to counter inequity). Recommendations are aligned into a purpose-built framework— “The Bicycle Principles”—that prioritizes evidenced-based teaching, inclusiveness, and equity, as well as the ability to scale, share, and sustain SFT. We also describe how the Bicycle Principles and recommendations are consistent with educational change theories and can overcome systemic barriers to delivering consistently effective, inclusive, and career-spanning SFT.SIGNIFICANCE STATEMENTSTEMM practitioners need sustained and customized professional development to keep up with innovations. Short-format training (SFT) such as workshops and short-courses are relied upon widely but have unaddressed limitations. This project generated principles and recommendations to make SFT consistently effective, inclusive, and career-spanning. Optimizing SFT could broaden participation in STEMM by preparing practitioners more equitably with transformative skills. Better SFT would also serve members of the STEMM workforce who have several decades of productivity ahead, but who may not benefit from education reforms that predominantly focus on undergraduate STEMM. The Bicycle Principles and accompanying recommendations apply to any SFT instruction and may be especially useful in rapidly evolving and multidisciplinary fields such as artificial intelligence, genomics, and precision medicine.

Motivation Seurat is one of the most popular software suites for the analysis of single-cell RNA sequencing data. Considering the popularity of the tidyverse ecosystem, which offers a large set of data display, query, manipulation, integration and visualization utilities, a great opportunity exists to interface the Seurat object with the tidyverse. This interface gives the large data science community of tidyverse users the possibility to operate with familiar grammar. Results To provide Seurat with a tidyverse-oriented interface without compromising efficiency, we developed tidyseurat, a lightweight adapter to the tidyverse. Tidyseurat displays cell information as a tibble abstraction, allowing intuitively interfacing Seurat with dplyr, tidyr, ggplot2 and plotly packages powering efficient data manipulation, integration and visualization. Iterative analyses on data subsets are enabled by interfacing with the popular nest-map framework. Availability and implementation The software is freely available at cran.r-project.org/web/packages/tidyseurat and github.com/stemangiola/tidyseurat. Supplementary information Supplementary data are available at Bioinformatics online.

There are multiple geographical crime prediction techniques to use and comparing different prediction techniques therefore becomes important. In the current study we compared the accuracy (Predictive Accuracy Index) and precision (Recapture Rate Index) of simply counting crimes: Simple Count with Kernel Density Estimation in the prediction of where people are reported to commit violent crimes (assault and robbery) and property crimes (residential burglary, property damage, theft, vehicle theft and arson), geographically. These predictions were done using a different number of years into the future and based on a different number of years combined to do the crime prediction, in a large Swedish municipality. The Simple Count technique performed quite well in comparison to simple Kernel Density Estimation no matter what crime was being predicted, making us conclude that it may not be necessary to use the more complex method of Kernel Density Estimation to predict where people are reported to commit crime geographically.

Recently, efforts have been made toward the harmonization of transcriptomic data structures and workflows using the concept of data tidiness, to facilitate modularisation. We present tidybulk, a modular framework for bulk transcriptional analyses that introduces a tidy transcriptomic data structure paradigm and analysis grammar. Tidybulk covers a wide variety of analysis procedures and integrates a large ecosystem of publicly available analysis algorithms under a common framework. Tidybulk decreases coding burden, facilitates reproducibility, increases efficiency for expert users, lowers the learning curve for inexperienced users, and bridges transcriptional data analysis with the tidyverse. Tidybulk is available at R/Bioconductor bioconductor.org/packages/tidybulk.

Hepatoblastoma (HB) is a rare childhood malignancy with hepatic resection (HR) or liver transplantation (LT) providing the best chance of cure. In this study, we analyze the National Cancer Database lacks (NCDB) to compare outcomes following HR and LT for HB. Review of the US experience with surgical (HR and LT) management of pediatric (

Surgical resection of colorectal liver metastases is associated with greater survival compared with non-surgical treatment, and a meaningful possibility of cure. However, the majority of patients are not eligible for resection and may require other non-surgical interventions, such as liver-directed therapies, to be converted to surgical eligibility. Given the number of available therapies, a general framework is needed that outlines the specific roles of chemotherapy, surgery, and locoregional treatments [including selective internal radiation therapy (SIRT) with Y-90 microspheres]. Using a data-driven, modified Delphi process, an expert panel of surgical oncologists, transplant surgeons, and hepatopancreatobiliary (HPB) surgeons convened to create a comprehensive, evidence-based treatment algorithm that includes appropriate treatment options for patients stratified by their eligibility for surgical treatment. The group coined a novel, more inclusive phrase for targeted locoregional tumor treatment (a blanket term for resection, ablation, and other emerging locoregional treatments): local parenchymal tumor destruction therapy. The expert panel proposed new nomenclature for 3 distinct disease categories of liver-dominant metastatic colorectal cancer that is consistent with other tumor types: (I) surgically treatable (resectable); (II) surgically untreatable (borderline resectable); (III) advanced surgically untreatable (unresectable) disease. Patients may present at any point in the algorithm and move between categories depending on their response to therapy. The broad intent of therapy is to transition patients toward individualized treatments where possible, given the survival advantage that resection offers in the context of a comprehensive treatment plan. This article reviews what is known about the role of SIRT with Y-90 as neoadjuvant, definitive, or palliative therapy in these different clinical situations and provides insight into when treatment with SIRT with Y-90 may be appropriate and useful, organized into distinct treatment algorithm steps.

As the demand for organ transplantation increases, utilization of liver allografts of donation after cardiac death (DCD) is becoming increasingly necessary. Although the clinical outcomes of DCD allografts have been well described, the histologic features are not well characterized. Liver biopsies (n = 131) from age-matched DCD (n = 60) and donation after brain death (DBD; n = 71) recipients with hepatitis C virus were compared. Histologic features were studied in a blinded fashion, subgrouped into time 0, 0-6 months, and6 months. In time 0 biopsies, more DCD cases had zone 3 (43.8 vs 29%) and bridging necrosis (19 vs 0%), albeit not statistically significant. At 0-6 months, more DCD cases had portal edema (p = 0.01). Pericholangitis (30.4% vs 18.8%) and acute cholestasis (21.7% vs 12.5%) were more common in DCD, but not statistically significant. At6 months, pericholangitis (19% vs 4.5%) persisted in DCD, although not statistically significant. Overall, both groups had similar bile duct injury, portal inflammation, and fibrosis. Postoperative biliary complications were more common in DCD (19% vs 0%). Three-year and 10-year graft survival and patient outcomes were similar in both cohorts. Biliary alterations were more prevalent in the 0-6 month time period DCD biopsies, reflecting increased vulnerability of this group to biliary complications in the early post-orthotopic liver transplant (OLT) period. This finding may suggest poor graft perfusion despite comparable cold ischemia times. However, these features improved and DCD recipients have similar graft and overall survival compared to DBD recipients, indicating that carefully selected DCD liver allografts are a viable option for transplantation.

Cholangiocarcinoma is an aggressive malignancy of the extrahepatic bile ducts. Hilar lesions are most common. Patients present with obstructive jaundice and intrahepatic bile duct dilation. Cross-sectional imaging reveals local, regional, and distant extent of disease, with direct cholangiography providing tissue for diagnosis. The consensus of a multidisciplinary committee dictates treatment. Resection of the extrahepatic bile duct and ipsilateral hepatic lobe with or without vascular resection and transplantation after neoadjuvant protocol are options for curative treatment. The goal of surgery is to remove the tumor with negative margins. Patients with inoperable tumors or metastatic disease are best served with palliative chemoradiotherapy.

RNA has become one of the major research topics in molecular biology. As a central player in key processes regulating gene expression, RNA is in the focus of many efforts to decipher the pathways that govern the transition of genetic information to a fully functional cell. As more and more researchers join this endeavour, there is a rapidly growing demand for comprehensive collections of tools that cover the diverse layers of RNA-related research. However, increasing amounts of data, from diverse types of experiments, addressing different aspects of biological questions need to be consolidated and integrated into a single framework. Only then is it possible to connect findings from e.g. RNA-Seq experiments and methods for e.g. target predictions. To address these needs, we present the RNA Workbench 2.0 , an updated online resource for RNA related analysis. With the RNA Workbench we created a comprehensive set of analysis tools and workflows that enables researchers to analyze their data without the need for sophisticated command-line skills. This update takes the established framework to the next level, providing not only a containerized infrastructure for analysis, but also a ready-to-use platform for hands-on training, analysis, data exploration, and visualization. The new framework is available at https://rna.usegalaxy.eu , and login is free and open to all users. The containerized version can be found at https://github.com/bgruening/galaxy-rna-workbench.

A complete RNA-Seq analysis involves the use of several different tools, with substantial software and computational requirements. The Galaxy platform simplifies the execution of such bioinformatics analyses by embedding the needed tools in its web interface, while also providing reproducibility. Here, we describe how to perform a reference-based RNA-Seq analysis using Galaxy, from data upload to visualization and functional enrichment analysis of differentially expressed genes.

A complete RNA-Seq analysis involves the use of several different tools, with substantial software and computational requirements. The Galaxy platform simplifies the execution of such bioinformatics analyses by embedding the needed tools in its web interface, while also providing reproducibility. Here, we describe how to perform a reference-based RNA-Seq analysis using Galaxy, from data upload to visualization and functional enrichment analysis of differentially expressed genes.

Background Spatial technologies that query the location of cells in tissues such as multiplex immunohistochemistry and spatial transcriptomics are gaining popularity and are likely to become commonplace. The resulting data often includes the X, Y coordinates of millions of cells, cell phenotypes and marker or gene expression levels. In cancer, the spatial location of lymphocytes has been linked to prognosis and response to immunotherapy. While these advances have been exciting for the field, the methods currently being used are still coarse, making us severely underpowered in our ability to extract quantifiable information. Appropriate quantitative tools are desperately needed to refine and uncover novel biologically and clinically meaningful insights from the spatial distribution of cells of the tumor immune microenvironment. Methods We compiled over 60 prostate cancer and melanoma FFPE tumor sections and performed Opal multiplex immunohistochemistry for a diversity of T-cell and other immune markers, including CD3, CD4, CD8, FOXP3 and PDL1, as well as a prostate cancer (AMACR) or melanoma (SOX10) marker and DAPI. Following spectral imaging on the Vectra Polaris, we performed cell and tissue segmentation and phenotyping with the inForm or HALO image analysis software. The detected X, Y coordinates of cells and marker intensities were used for subsequent method development. Results We developed SPIAT (Spatial Image Analysis of Tissues)1, an R package with a suite of data processing, quality control, visualization, data handling and data analysis tools for spatial data. SPIAT includes our novel algorithms for the identification of cell clusters, tumor margins and cell gradients, the calculation of neighborhood proportions and algorithms for the prediction of cell phenotypes. By interfacing with packages used in ecology, geographic data analysis and spatial statistics, we have begun to robustly address fundamental questions in the analysis of cell spatial data, such as metrics to measure mixing between cell types, the identification of tumor borders and statistical approaches to compare samples. Conclusions SPIAT is compatible with multiplex immunohistochemistry, spatial transcriptomics and data generated from other spatial platforms, and continues to be actively developed. We expect SPIAT to become a user-friendly and speedy go-to package for the spatial analysis of cells in tissues, as well as promote the use of quantitative metrics in the spatial analysis of the tumor immune microenvironment. Reference Tianpei Yang, Volkan Ozcoban, Anu Pasam, Nikolce Kocovski, Angela Pizzolla, Yu-Kuan Huang, Greg Bass, Simon P. Keam, Paul J. Neeson, Shahneen K. Sandhu, David L. Goode, Anna S. Trigos. SPIAT: An R package for the Spatial Image Analysis of Cells in Tissues. BioRxiv doi: https://doi.org/10.1101/2020.05.28.122614

BackgroundThe vast ecosystem of single-cell RNA-sequencing tools has until recently been plagued by an excess of diverging analysis strategies, inconsistent file formats, and compatibility issues between different software suites. The uptake of 10x Genomics datasets has begun to calm this diversity, and the bioinformatics community leans once more towards the large computing requirements and the statistically driven methods needed to process and understand these ever-growing datasets.ResultsHere we outline several Galaxy workflows and learning resources for single-cell RNA-sequencing, with the aim of providing a comprehensive analysis environment paired with a thorough user learning experience that bridges the knowledge gap between the computational methods and the underlying cell biology. The Galaxy reproducible bioinformatics framework provides tools, workflows, and trainings that not only enable users to perform 1-click 10x preprocessing but also empower them to demultiplex raw sequencing from custom tagged and full-length sequencing protocols. The downstream analysis supports a range of high-quality interoperable suites separated into common stages of analysis: inspection, filtering, normalization, confounder removal, and clustering. The teaching resources cover concepts from computer science to cell biology. Access to all resources is provided at the singlecell.usegalaxy.eu portal.ConclusionsThe reproducible and training-oriented Galaxy framework provides a sustainable high-performance computing environment for users to run flexible analyses on both 10x and alternative platforms. The tutorials from the Galaxy Training Network along with the frequent training workshops hosted by the Galaxy community provide a means for users to learn, publish, and teach single-cell RNA-sequencing analysis.

BackgroundThe vast ecosystem of single-cell RNA-seq tools has until recently been plagued by an excess of diverging analysis strategies, inconsistent file formats, and compatibility issues between different software suites. The uptake of 10x Genomics datasets has begun to calm this diversity, and the bioinformatics community leans once more towards the large computing requirements and the statistically-driven methods needed to process and understand these ever-growing datasets.ResultsHere we outline several Galaxy workflows and learning resources for scRNA-seq, with the aim of providing a comprehensive analysis environment paired with a thorough user learning experience that bridges the knowledge gap between the computational methods and the underlying cell biology. The Galaxy reproducible bioinformatics framework provides tools, workflows and trainings that not only enable users to perform one-click 10x preprocessing, but also empowers them to demultiplex raw sequencing from custom tagged and full-length sequencing protocols. The downstream analysis supports a wide range of high-quality interoperable suites separated into common stages of analysis: inspection, filtering, normalization, confounder removal and clustering. The teaching resources cover an assortment of different concepts from computer science to cell biology. Access to all resources is provided at the singlecell.usegalaxy.eu portal.ConclusionsThe reproducible and training-oriented Galaxy framework provides a sustainable HPC environment for users to run flexible analyses on both 10x and alternative platforms. The tutorials from the Galaxy Training Network along with the frequent training workshops hosted by the Galaxy Community provide a means for users to learn, publish and teach scRNA-seq analysis.Key PointsSingle-cell RNA-seq has stabilised towards 10x Genomics datasets.Galaxy provides rich and reproducible scRNA-seq workflows with a wide range of robust tools.The Galaxy Training Network provides tutorials for the processing of both 10x and non-10x datasets.

Hepatoblastoma (HB) is a rare childhood malignancy with hepatic resection (HR) or liver transplantation (LT) providing the best chance of cure. In this study, we analyze the National Cancer Database lacks (NCDB) to compare outcomes following HR and LT for HB.Review of the US experience with surgical (HR and LT) management of pediatric ( 18 years) HB over the last decade (2004-2014) using data extracted from the NCDB.A total of 628 children underwent surgical treatment for HB during the study period: HR in 525 (83.6%) and LT in 103 (16.4%). The two groups were comparable for age, sex, race, tumor size, and metastatic disease at initial diagnosis. LT group had significantly higher number of patients with bilobar disease (40 vs 21%; p 0.001), longer median time from diagnosis to surgery (120 vs 78 days; p 0.001), and longer post-operative length of stay (LOS) (14 vs 6 days; p 0.001). There were no differences in rates of 30-day readmission and 30- or 90-day mortality between groups. Both groups had comparable 5-year overall survival (OS) (84.1% HR vs 80.0% LT; p = 0.4). Univariate analysis identified metastatic disease at initial presentation (HR 2.56, CI 1.51-4.35) and age ≥ 4 years (HR 2.68, CI 1.5-4.7) as risk factors for worse overall 5-yr OS, while administration of adjuvant chemotherapy was associated with improved 5-yr OS (92.3% with chemo vs 85.4% without chemo; HR 0.51, CI 0.31-0.84).The outcome of HB has improved compared with historical controls. Age at presentation, metastatic disease, and post-operative chemotherapy impact outcomes.

The coronavirus disease 2019 (COVID-19) pandemic is a rapidly changing circumstance with dramatic policy changes and universal efforts to deal with the initial crisis and minimize its consequences. To identify changes to organ donation and transplantation during this time, an anonymous web-based survey was distributed to 19 select organ procurement organizations (OPOs) throughout the United States comparing 90-day activity during March-May 2020 and March-May 2019. Seventeen OPOs responded to the survey (response rate of 89.5%). Organ authorization decreased by 11% during the current pandemic (n = 1379 vs n = 1552, P = .0001). Organ recovery for transplantation fell by 17% (P = .0001) with a further 18% decrease in the number of organs transplanted (P = .0001). Donor cause of death demonstrated a 4.5% decline in trauma but a 35% increase in substance abuse cases during the COVID-19 period. All OPOs reported significant modifications in response to the pandemic, limiting the onsite presence of staff and transitioning to telephonic approaches for donor family correspondence. Organ donation during the current climate has seen significant changes and the long-term implications of such shifts remain unclear. These trends during the COVID-19 era warrant further investigation to address unmet needs, plan for a proportionate response to the virus and mitigate the collateral impact.

Single-cell RNA-Seq (scRNA-Seq) data analysis requires expertise in command-line tools, programming languages and scaling on compute infrastructure. As scRNA-Seq becomes widespread, computational pipelines need to be more accessible, simpler and scalable. We introduce an interactive analysis environment for scRNA-Seq, based on Galaxy, with ~70 functions from major single-cell analysis tools, which can be run on compute clusters, cloud providers or single machines, to bring compute to the data in scRNA-Seq.

CDK12 and CDK13 regulate POLII elongation rate and processivity and influence the selection of transcription termination sites., The RNA polymerase II (POLII)–driven transcription cycle is tightly regulated at distinct checkpoints by cyclin-dependent kinases (CDKs) and their cognate cyclins. The molecular events underpinning transcriptional elongation, processivity, and the CDK-cyclin pair(s) involved remain poorly understood. Using CRISPR-Cas9 homology-directed repair, we generated analog-sensitive kinase variants of CDK12 and CDK13 to probe their individual and shared biological and molecular roles. Single inhibition of CDK12 or CDK13 induced transcriptional responses associated with cellular growth signaling pathways and/or DNA damage, with minimal effects on cell viability. In contrast, dual kinase inhibition potently induced cell death, which was associated with extensive genome-wide transcriptional changes including widespread use of alternative 3′ polyadenylation sites. At the molecular level, dual kinase inhibition resulted in the loss of POLII CTD phosphorylation and greatly reduced POLII elongation rates and processivity. These data define substantial redundancy between CDK12 and CDK13 and identify both as fundamental regulators of global POLII processivity and transcription elongation.

Incisional hernias (IH) develop in up to 40% of liver transplant (LT) recipients and can contribute to considerable morbidity.A single center retrospective review of a prospectively maintained LT database was conducted to identify all patients diagnosed with IH after LT during a 13-year study period (2003-2015). Analyzed data included patient demographics, LT details, incidence and timing of IH, risk factors, management strategies and long-term outcomes.During the 13-year study period, IH was diagnosed in 16.7% (163/976) of LT recipients after a median of 19.6 months (range 6.7-49.5 months) from transplant surgery. Identified risk factors for developing IH included male gender (p 0.001) while acute cellular rejection (ACR) was found to be negatively associated with the risk of developing IH (p = 0.014). Acute incarceration/strangulation was seen in 4 patients with IH while the remaining (n = 159) presented with non-emergent symptoms. Surgical repair was undertaken in 70/163 (43%) IH patients after medical optimization when possible (open repair 83%, mesh use 90%). IH recurrence rate was 14.3% (10/70) with comparable rates in no-mesh and with-mesh repairs (42.9% vs. 11.3%; p = 0.057) and open (15.8%) and laparoscopic (9.1%) approaches (p = 0.68).IH is a late complication following LT and male gender is a consistent predictive marker. Acute presentation is infrequent and elective repair can be planned in most patients allowing for risk factor optimization to ensure promising long-term outcomes.

Background: Combined hepatocellular-cholangiocarcinoma tumors (cHCC-CCA) are a heterogeneous group of rare malignancies that have no established optimal treatment. Patients and Methods: We identified patients with cHCC-CCA treated at a tertiary center and retrospectively examined their histology, interventions, and outcomes. We calculated disease control rate (DCR), disease progression, overall survival, and progression-free survival (PFS) between treatment subgroups. Results: A total of 123 patients were evaluable. Interventions included resection, locoregional therapy, transplant, chemotherapy, and targeted agents. Ultimately, 68 patients received systemic treatment-57 with gemcitabine plus either 5-fluoropyrimidine (5-FU) or a platinum combination. Disease progression was more common in the gemcitabine/5-FU group versus gemcitabine/platinum (P=.028), whereas DCR favored gemcitabine/platinum (78.4% vs 38.5%; P=.0143). Median PFS from time of initial diagnosis favored the gemcitabine/platinum group, but the difference did not reach statistical significance. Targeted agents had minimal to no effect on survival metrics. Conclusions: Gemcitabine/platinum seems to be a superior regimen for patients with cHCC-CCA who require systemic treatment. Further studies are needed to clarify the regimen's efficacy and applicability in patient subgroups.

Background Increasing use of Living Donor Kidney Transplantation (LDKT) would decrease the discrepancy between patients awaiting transplantation and organ availability. Minimally invasive surgical approaches attempt to improve outcomes and foster living donation. This report compares outcomes of open minimal incision nephrectomy (Mini N) and a hand assisted laparoscopic nephrectomy (HALN). Methods This is a retrospective analysis of a prospectively maintained clinical database of LDKT using HALN or Mini N at a single institution between July 2007 and December 2015. Donor and recipient demographics, relevant pre-, intra- and post-operative factors, outcomes such as patient and graft survival rates, and complications were evaluated. Results Four hundred and fifty-four adult LDKT (243 Mini N, 211 HALN) were performed during the study period. Recipient and donor demographics were comparable except for higher BMI (p = 0.027) in HALN donors. One-, 3- and 5-year patient and graft survival rates were comparable. Six HALN donors experienced infectious wound complications or superficial skin dehiscence; none did in the Mini N group (p = 0.009). Eight HALN donors and one Mini N donor required an incisional hernia repair (p = 0.014). Recipients had similar warm ischemia times (33 v. 35 min, p = 0.491), but recipient surgeons of HALN nephrectomies subjectively noted higher anastomotic difficulty (10.4% v. 4.5%, p = 0.0183). Other parameters were similar between groups. Conclusion Both Mini N and HALN provide similar long term recipient and donor outcomes. Offering techniques such as Mini N and HALN for living donor kidney procurement facilitates the opportunity to provide living donors safer and better tolerated nephrectomy procedures.

Background The increasing affordability of DNA sequencing has allowed it to be widely deployed in pathology laboratories. However, this has exposed many issues with the analysis and reporting of variants for clinical diagnostic use. Implementing a high-throughput sequencing (NGS) clinical reporting system requires a diverse combination of capabilities, statistical methods to identify variants, global variant databases, a validated bioinformatics pipeline, an auditable laboratory workflow, reproducible clinical assays and quality control monitoring throughout. These capabilities must be packaged in software that integrates the disparate components into a useable system. Results To meet these needs, we developed a web-based application, PathOS, which takes variant data from a patient sample through to a clinical report. PathOS has been used operationally in the Peter MacCallum Cancer Centre for two years for the analysis, curation and reporting of genetic tests for cancer patients, as well as the curation of large-scale research studies. PathOS has also been deployed in cloud environments allowing multiple institutions to use separate, secure and customisable instances of the system. Increasingly, the bottleneck of variant curation is limiting the adoption of clinical sequencing for molecular diagnostics. PathOS is focused on providing clinical variant curators and pathology laboratories with a decision support system needed for personalised medicine. While the genesis of PathOS has been within cancer molecular diagnostics, the system is applicable to NGS clinical reporting generally. Conclusions The widespread availability of genomic sequencers has highlighted the limited availability of software to support clinical decision-making in molecular pathology. PathOS is a system that has been developed and refined in a hospital laboratory context to meet the needs of clinical diagnostics. The software is available as a set of Docker images and source code at https://github.com/PapenfussLab/PathOS. Electronic supplementary material The online version of this article (doi:10.1186/s13073-017-0427-z) contains supplementary material, which is available to authorized users.

The American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) Surgical Risk Calculator was developed to help counsel patients regarding estimated postoperative risk for a variety of surgical complications. This retrospective single institutional study examined the calculator's ability to accurately predict complications and length of hospital stay (LOS) in patients who had undergone a Pancreaticoduodenectomy (PD) at our institution.165 patients at Washington University School of Medicine who underwent a PD from 8/2011 to 7/2013 were included. Surgical complication risk as determined by the ACS-NSQIP Surgical Risk Calculator were compared to actual 30 day complications. PD complications not accounted for by the calculator were compared to those without PD-specific complications.Overall predicted LOS was significantly shorter than actual duration of hospitalization (median 8.5 vs. 8.0 days; p 0.001). 38% patients (n = 62) with Whipple-specific complication demonstrated a significant increase in LOS (8.0 vs. 12.2 days; p 0.0001).A large proportion of complications experienced after PD are pancreas-specific, accounting for the difference in predicted vs. actual LOS and providing rationale for future development of PD specific risk models.

Background In general surgery residency, hepatobiliary training varies significantly across the world. The aim of this study was to establish an international consensus among hepatobiliary surgeons on components of a hepatobiliary curriculum for general surgery residents. Methods A three-round modified Delphi technique was employed. Fifty-two hepatobiliary surgeons involved in general surgery training programs were invited. An initial questionnaire was developed by a group of experts in hepatobiliary and educational research after a systematic literature review. It comprised 90 statements about knowledge, technical skills, attitudes, and postoperative care. Panelists could add or alter items. The survey was delivered electronically and the panel was instructed to score the items based on 5-point Likert scale. Consensus was reached when at least 80% of panelists agreed on a statement with Cronbach's alpha value >0.8. Results Forty-one (79%) experts have participated. Sixteen panelists are based in Asia, 14 in Europe, and 11 in the Americas. Eighty percent of all proposed skills (81/101) were considered fundamental including knowledge (39/43), technical skills (16/32), attitude (15/15), and postoperative care (11/11). Conclusion An international consensus was achieved on components of a hepatobiliary curriculum. Acquiring broad knowledge is fundamental during residency. Advanced liver resection techniques require specialized hepatobiliary training.

Background Familial cases of appendiceal mucinous tumours (AMTs) are extremely rare and the underlying genetic aetiology uncertain. We identified potential predisposing germline genetic variants in a father and daughter with AMTs presenting with pseudomyxoma peritonei (PMP) and correlated these with regions of loss of heterozygosity (LOH) in the tumours. Materials and Methods Through germline whole exome sequencing, we identified novel heterozygous loss-of-function (LoF) (i.e. nonsense, frameshift and essential splice site mutations) and missense variants shared between father and daughter, and validated all LoF variants, and missense variants with a Combined Annotation Dependent Depletion (CADD) scaled score of ≥10. Genome-wide copy number analysis was performed on tumour tissue from both individuals to identify regions of LOH. Results Seventeen novel variants in 17 genes were shared by the father and daughter: a nonsense mutation in REEP5 , an essential splice site mutation in THOP1 , and 15 missense variants. None of these germline variants were located in tumour regions of LOH shared by the father and daughter. Four genes ( EXOG , RANBP2, RANBP6 and TNFRSF1B ) harboured missense variants that fell in a region of LOH in the tumour from the father only, but none showed somatic loss of the wild type allele in the tumour. The REEP5 gene was sequenced in 23 individuals with presumed sporadic PMP; no LoF or rare missense germline variants were identified. Conclusion Germline exome sequencing of a father and daughter with AMTs identified novel candidate predisposing genes. Further studies are required to clarify the role of these genes in familial AMTs.

Objective There are 16 accredited hepatopancreatobiliary (HPB) fellowships in North America. The purpose of this study is to portray the expectations of the incoming HPB fellows about their training and its implication on their career. Design A 29-questions survey was sent out to all HPB fellows starting in August 2017. The survey was divided in 3 sections depicting background, in-training and postfellowship expectations. Descriptive statistics were generated for aggregate survey responses. Setting This study was performed through an online questionnaire that was sent to the participants via e-mail. The answers were processed in our offices in Methodist Richardson Medical Center, in Richardson, Texas which is a private tertiary medical center part of the Methodist Health System. Participants Participants were all incoming HPB Fellows (In HPB fellowship programs accredited by the Fellowship Council) starting their fellowship in August 2017. Results We had a 94% response rate. Forty-six percent of fellows anticipate doing about 150 to 250 HPB cases during the fellowship, and all 15 fellows anticipate having at least 1 publication during fellowship. Despite that >90% of fellows believe that minimally invasive surgery (MIS) approaches will be more frequently utilized in HPB surgery, only 3/15 anticipate being able to apply MIS techniques and only 54% will be robotically trained. Interestingly the majority of fellows believe that the attending should be performing the case the first few months. Conclusion The trainees believe that case volume is the most important factor for choosing a fellowship and for adequate training. Most of the fellows anticipate doing adequate number of cases but only the minority feels they will be adequately trained in MIS-robotic techniques.

Background Hepatobiliary contrast enhanced MRI is known to be the most sensitive imaging modality for detection of colorectal hepatic metastasis. To date no study has investigated the rate of disappearing lesions with gadoxetic acid MR (Eovist/Primovist), or characterized the pathologic response of lesions which disappear on gadoxetic acid MR. Methods Retrospective review of hepatic resections for colorectal metastases between 01/2008 and 01/2014 was performed to evaluated the rate of disappearance of lesions on gadoxetic acid MR and the rate of complete pathologic response in the lesions that disappear. “Disappearing lesions” were lesions on baseline imaging that were not identifiable on pre-operative Eovist MRI. Complete pathologic response was defined as no viable tumor on pathology or by lack of recurrence within 1 year. Results In 23 patients, 200 colorectal metastases were identified on baseline imaging. On pre-operative Eovist MR 77 of the 200 lesions (38.5%) were “disappearing” lesions. At surgical pathology or 1 year follow-up imaging, 42 of 77 lesions (55%) demonstrated viable tumor (21) or recurrence (21). Thirty of 77 lesions (39%) were nonviable at pathology (10) or without evidence of recurrence at 1 year (20). 5 lesions were indeterminate. Discussion Despite disappearance on Eovist MR imaging (the most sensitive available imaging modality), 38.5% of all colorectal metastases disappeared and of those, 55% were viable.