Galaxy Training: A powerful framework for teaching!

There is an ongoing explosion of scientific datasets being generated, brought on by recent technological advances in many areas of the natural sciences. As a result, the life sciences have become increasingly computational in nature, and bioinformatics has taken on a central role in research studies. However, basic computational skills, data analysis, and stewardship are still rarely taught in life science educational programs, resulting in a skills gap in many of the researchers tasked with analysing these big datasets. In order to address this skills gap and empower researchers to perform their own data analyses, the Galaxy Training Network (GTN) has previously developed the Galaxy Training Platform (https://training.galaxyproject.org), an open access, community-driven framework for the collection of FAIR (Findable, Accessible, Interoperable, Reusable) training materials for data analysis utilizing the user-friendly Galaxy framework as its primary data analysis platform. Since its inception, this training platform has thrived, with the number of tutorials and contributors growing rapidly, and the range of topics extending beyond life sciences to include topics such as climatology, cheminformatics, and machine learning. While initially aimed at supporting researchers directly, the GTN framework has proven to be an invaluable resource for educators as well. We have focused our efforts in recent years on adding increased support for this growing community of instructors. New features have been added to facilitate the use of the materials in a classroom setting, simplifying the contribution flow for new materials, and have added a set of train-the-trainer lessons. Here, we present the latest developments in the GTN project, aimed at facilitating the use of the Galaxy Training materials by educators, and its usage in different learning environments.

Utilization of older deceased donors for pediatric liver transplant may negatively impact long-term survival.

BACKGROUND: Multiple adult studies have investigated the role of older donors (ODs) in expanding the donor pool. However, the impact of donor age on pediatric liver transplantation (LT) has not been fully elucidated. METHODS: UNOS database was used to identify pediatric (≤18 years) LTs performed in the United States during 2002-22. Donors ≥40 years at donation were classified as older donors (ODs). Propensity analysis was performed with 1:1 matching for potentially confounding variables. RESULTS: A total of 10,024 pediatric liver transplantation (PLT) patients met inclusion criteria; 669 received liver grafts from ODs. Candidates receiving OD liver grafts were more likely to be transplanted for acute liver failure, have higher Model End-Stage Liver Disease/Pediatric End-Stage Liver Disease (MELD/PELD) scores at LT, listed as Status 1/1A at LT, and be in the intensive care unit (ICU) at time of LT (all p < 0.001). Kaplan-Meier (KM) analyses showed that recipients of OD grafts had worse patient and graft survival (p < 0.001) compared to recipients of younger donor (YD) grafts. KM analyses performed on candidates matched for acuity at LT revealed inferior patient and graft survival in recipients of deceased donor grafts (p < 0.001), but not living donor grafts (p > 0.1) from ODs. Cox regression analysis demonstrated that living donor LT, diagnosis of biliary atresia and first liver transplant were favorable predictors of recipient outcomes, whereas ICU stay before LT and transplantation during 2002-12 were unfavorable. CONCLUSION: Livers from ODs were used for candidates with higher acuity. Pediatric recipients of livers from ODs had worse outcome compared to YDs; however, living donor LT from ODs had the least negative impact on recipient outcomes.

Normothermic Machine Perfusion of Donor Livers for Transplantation in the United States: A Randomized Controlled Trial.

OBJECTIVE: To compare conventional low-temperature storage of transplant donor livers [static cold storage (SCS)] with storage of the organs at physiological body temperature [normothermic machine perfusion (NMP)]. BACKGROUND: The high success rate of liver transplantation is constrained by the shortage of transplantable organs (eg, waiting list mortality >20% in many centers). NMP maintains the liver in a functioning state to improve preservation quality and enable testing of the organ before transplantation. This is of greatest potential value with organs from brain-dead donor organs (DBD) with risk factors (age and comorbidities), and those from donors declared dead by cardiovascular criteria (donation after circulatory death). METHODS: Three hundred eighty-three donor organs were randomized by 15 US liver transplant centers to undergo NMP (n = 192) or SCS (n = 191). Two hundred sixty-six donor livers proceeded to transplantation (NMP: n = 136; SCS: n = 130). The primary endpoint of the study was "early allograft dysfunction" (EAD), a marker of early posttransplant liver injury and function. RESULTS: The difference in the incidence of EAD did not achieve significance, with 20.6% (NMP) versus 23.7% (SCS). Using exploratory, "as-treated" rather than "intent-to-treat," subgroup analyses, there was a greater effect size in donation after circulatory death donor livers (22.8% NMP vs 44.6% SCS) and in organs in the highest risk quartile by donor risk (19.2% NMP vs 33.3% SCS). The incidence of acute cardiovascular decompensation at organ reperfusion, "postreperfusion syndrome," as a secondary outcome was reduced in the NMP arm (5.9% vs 14.6%). CONCLUSIONS: NMP did not lower EAD, perhaps related to the inclusion of lower-risk liver donors, as higher-risk donor livers seemed to benefit more. The technology is safe in standard organ recovery and seems to have the greatest benefit for marginal donors.

Sclerosing Epithelioid Fibrosarcoma of the Liver in a Pediatric Patient.

Sclerosing epithelioid fibrosarcoma (SEF) is a rare but aggressive sarcoma. We report the first case of hepatic SEF in pediatric patient, which is also the second case in literature. A 17-year-old previously healthy female presented with a liver mass measuring 13.7 cm in greatest dimension and mild elevation of liver enzymes and cancer antigen 19-9. Needle biopsy revealed multiple cores of liver parenchyma mostly replaced by densely hyalinized fibrotic tissue and areas of small-to-medium sized epithelioid cells with eosinophilic and clear cytoplasm. Immunohistochemistry (IHC) demonstrated diffuse strong cytoplasmic staining of MUC4, suggesting a working diagnosis of sclerosing epithelioid fibrosarcoma (SEF)/low-grade fibromyxoid sarcoma (LGFMS). Liver explant demonstrated a well-circumscribed, nodular mass with firm, gray-white cut surface, and similar histopathology as seen in needle biopsy with no convincing evidence suggesting LGFMS. Sequencing panel revealed EWSR1::CREB3L1 gene fusion and confirmed the diagnosis of SEF. Post-operative cancer antigen 19-9 normalized 3 months after transplant; follow-up 3 and 6 months post-transplant imaging at that time showed no concern for disease recurrence.

Interfacing Seurat with the R tidy universe.

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.

A Single-Center Study on the Outcomes of Target Limb Revascularization in Femoropopliteal Lesions Treated With Drug Coated Balloons and Bare Metal Stents.

PURPOSE: Multiple randomized controlled trials have shown that both drug coated balloons (DCBs) and bare metal stents (BMSs) significantly reduce restenosis in femoropopliteal lesions compared with plain balloon angioplasty. However, few studies have directly compared DCB and BMS treatments. Therefore, the goal of our study was to determine if the rate of target lesion revascularization (TLR) differs between DCB and BMS treatment at our center. MATERIALS AND METHODS: We performed a retrospective chart review of femoropopliteal interventions at a single center from 2009 to 2017. The intervention, patient and lesion characteristics, and TLR events were recorded. Exclusion criteria were loss of follow-up, death, bail-out stenting, and amputation within 60 days of treatment. Freedom from TLR was analyzed over a 3 year period with Kaplan-Meier survival curves. Cox hazard ratios were calculated to account for patient and lesion characteristics. RESULTS: A total of 322 lesions (234 patients) treated with DCBs and 225 lesions (194 patients) treated with BMSs were included in this study. There were significant differences in baseline patient and lesion characteristics between groups-a greater proportion of women, patients with dyslipidemia, and lesions with popliteal involvement were treated with DCBs. There was no difference in the freedom from TLR between DCBs and BMSs. Accounting for patient and lesion characteristics, there was still no difference between DCBs and BMSs on the hazard of TLR. While our analysis did not detect a difference in the rate of TLR, there was a significant difference in the type of TLR. Compared with DCBs, a greater proportion of lesions initially treated with BMSs were retreated via surgical bypass rather than endovascular intervention, suggesting that lesions treated with DCBs may be more amenable to future endovascular intervention. CONCLUSION: Our retrospective analysis showed no difference in the rate of TLR between lesions treated with DCBs and BMSs. However, DCBs were more often used in complicated lesions involving popliteal arteries and may also allow for easier endovascular reintervention.

Characterization of Biomarkers of Hemostasis and Bleeding-Related Outcomes in Children With Cirrhosis.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Characteristics, risk factors, and outcomes of neutropenia after liver or kidney transplantation in children.

BACKGROUND: While prior adult studies have shown that approximately 20%-38% of subjects undergoing solid-organ transplant develop neutropenia, similar analyses in pediatric subjects are scarce. METHODS: We conducted a retrospective chart review of liver transplant (LT) and kidney transplant (KT) recipients at our center during the period 2008-2018. All of the KT and none of the LT subjects during this time period had induction with either anti-thymocyte globulin (ATG) or basiliximab at time of transplant. Neutropenia was defined as absolute neutrophil count (ANC) value ≤1000/mm3 . RESULTS: One hundred subjects with LT and 82 subjects with KT were included. The incidence of neutropenia within the first year of transplant in KT was higher compared to LT (54.8% vs 39%, p = .01). The median number of hospitalizations (p = .001) and infectious complications (p = .04) was significantly higher only in the KT subjects who developed neutropenia (compared to those who did not). Multivariate analysis identified factors associated with severity of liver disease at transplant, namely h/o upper gastrointestinal bleeding (p = .02), weight deficit (p = .01), and pre-LT ANC (p = .01), along with high or moderate risk cytomegalovirus status (p = .05) as predictors of neutropenia in LT subjects. Female gender (p = .03) predicted neutropenia, while BK virus infection was protective for neutropenia (p = .04) in KT subjects. CONCLUSIONS: The incidence of and morbidity associated with neutropenia within 1 year post-transplant is higher in KT subjects compared to LT subjects. The likely reason for this is the use of induction therapy (ATG, basiliximab) at the time of transplant in KT subjects.

Outcomes Analyses of Pediatric Acute Liver Failure Subjects Listed for Liver Transplantation.

BACKGROUND: We characterized recent outcomes in US pediatric acute liver failure (PALF) subjects listed for liver transplantation (LT) using the Scientific Registry of Transplant Recipients (SRTR) database. METHODS: Pediatric subjects listed for LT from 2002 to 2015 were assigned to the "PALF" group based on status 1/1A listing, INR >2, no hepatic artery thrombosis, and no primary graft nonfunction (N = 397). Subjects were assigned to the "non-PALF" group if listed with any status other than 1/1A (N = 4509). RESULTS: The PALF group had more infants <3 months of age and males at listing for LT compared to the non-PALF group. Two-thirds of PALF subjects had an indeterminate etiology. LT waitlist survival was significantly worse in the PALF group compared to the non-PALF group. Likelihood of removal from the LT waitlist for being "too sick" was higher, while that of removal for "spontaneous recovery" was lower in PALF subjects. Post-LT short-term (30 days) and long-term (60 months) outcomes were also significantly worse in PALF versus non-PALF subjects. PALF subjects who underwent living-donor-liver-transplant (LDLT) had similar LT waitlist times and post-LT survival compared to those undergoing deceased-donor-liver-transplant (DDLT). Over the study period, we observed a decreased number of liver transplants, and increase in LT waitlist- and short-term post-LT-survival in PALF subjects. CONCLUSION: LT waitlist and post-LT outcomes are worse in PALF subjects compared to non-PALF subjects. PALF subjects who undergo LDLT have similar waitlist times and post-LT outcomes compared to those undergoing DDLT.

Improved outcomes with minimally invasive pancreaticoduodenectomy in patients with dilated pancreatic ducts: a prospective study.

BACKGROUND: Little is known about what factors predict better outcomes for patients who undergo minimally invasive pancreaticoduodenectomy (MIPD) versus open pancreaticoduodenectomy (OPD). We hypothesized that patients with dilated pancreatic ducts have improved postoperative outcomes with MIPD compared to OPD. METHODS: All patients undergoing pancreaticoduodenectomy were prospectively followed over a time period of 47 months, and perioperative and pathologic covariates and outcomes were compared. Ideal outcome after PD was defined as follows: (1) no complications, (2) postoperative length of stay < 7 days, and (3) negative (R0) margins on pathology. Patients with dilated pancreatic ducts (≥ 3 mm) who underwent MIPD were 1:3 propensity score-matched to patients with dilated ducts who underwent OPD and outcomes compared. Likewise, patients with non-dilated pancreatic ducts (< 3 mm) who underwent MIPD were 1:3 propensity score-matched to patients with non-dilated ducts who underwent OPD and outcomes were compared. RESULTS: 371 patients underwent PD-74 (19.9%) MIPD and 297 (80.1%) underwent OPD. Overall, patients who underwent MIPD had significantly less intraoperative blood loss. After 1:3 propensity score matching, patients with dilated pancreatic ducts who underwent MIPD (n = 45) had significantly lower overall complication and 90-day readmission rates compared to matched OPD patients (n = 135) with dilated ducts. Patients with dilated duct who underwent MIPD were more likely to have an ideal outcome than patients with OPD (29 vs 15%, p = 0.035). There were no significant differences in postoperative outcomes among propensity score-matched patients with non-dilated pancreatic ducts who underwent MIPD (n = 29) compared to matched patients undergoing OPD (n = 87) with non-dilated ducts. CONCLUSIONS: MIPD is safe with comparable perioperative outcomes to OPD. Patients with pancreatic ducts ≥ 3 mm appear to derive the most benefit from MIPD in terms of fewer complications, lower readmission rates, and higher likelihood of ideal outcome.

Outcomes following formation of a dedicated pediatric liver transplant anesthesia team.

BACKGROUND: Given the complex nature of liver transplant surgery, adult centers typically use a dedicated liver transplant anesthesia team, which has improved patient outcomes. AIMS: Our goal was to determine whether a dedicated pediatric liver transplant anesthesia team was associated with improved patient outcomes. METHODS: This retrospective cohort study analyzed patients who underwent liver transplantation from April 2013 to September 2020 at St. Louis Children's Hospital. The general group (April 2013-December 2016) was compared with the liver group (January 2017-September 2020). Outcomes measured included cases per anesthesiologist, early extubation, ventilator days, fluid and blood administration, postoperative events, and intensive care unit and hospital length of stay (LOS). RESULTS: Patients in both groups had similar demographics. The average number of cases/anesthesiologist/year was 2.9 times higher in the liver group (mean (SD) general 0.7 (0.5), liver 2.0 (0.6), and difference in mean [95% CI] 1.3 [0.8, 1.8]). The rate of extubation in the operating room was higher for patients in the liver group (general 56%, liver 80%, and difference in proportion [95% CI] 24.7 [7.0, 42.4]), while the number of ventilator days was lower (mean (SD) general 2.1 (4.4), liver 1.1 (3.6), and difference in proportion [95%CI] -0.9 [-2.6, 0.7]). Colloid administration was higher in the liver group (mean (SD) general 23.9 (14.5) ml/kg, liver 48.4 (37.7) ml/kg, and difference in mean [95% CI] 24.6 [12.7, 36.4]), while fresh frozen plasma administration was lower in the liver group (mean (SD) general 15.3 (23.9) ml/kg, liver 6.2 (14) ml/kg, and difference in mean [95% CI] -9.0 [-16.8, -1.3]). There were no significant differences between the groups in postoperative events including blood product transfusions, vasopressor use, and thromboses, or in the intensive care unit and hospital LOS. CONCLUSIONS: The liver group was associated with increased early extubations, decreased ventilator days, and decreased fresh frozen plasma use.

Contemporary Imaging of the Surgically Placed Hepatic Arterial Infusion Chemotherapy Pump.

Hepatic arterial infusion (HAI) of chemotherapy is a locoregional treatment strategy for hepatic malignancy involving placement of a surgically implanted pump or percutaneous port-catheter device into a branch of the hepatic artery. HAI has been used for metastatic colorectal cancer for decades but has recently attracted new attention because of its potential impact on survival, when combined with systemic therapy, in patients presenting with unresectable hepatic disease. Although various HAI device-related complications have been described, little attention has been given to their appearance on imaging. Radiologists are uniquely positioned to identify these complications given that patients receiving HAI therapy typically undergo frequent imaging and may have complications that are delayed or clinically unsuspected. Therefore, this article reviews the multimodality imaging considerations of surgically implanted HAI devices. The role of imaging in routine perioperative assessment, including the normal postoperative appearance of the device, is described. The imaging findings of potential complications, including pump pocket complications, catheter or arterial complications, and toxic or ischemic complications, are presented, with a focus on CT. Familiarity with the device and its complications will aid radiologists in playing an important role in the treatment of patients undergoing HAI therapy.

Random forest analysis identifies change in serum creatinine and listing status as the most predictive variables of an outcome for young children on liver transplant waitlist.

Young children listed for liver transplant have high waitlist mortality (WL), which is not fully predicted by the PELD score. SRTR database was queried for children < 2 years listed for initial LT during 2002-17 (n = 4973). Subjects were divided into three outcome groups: bad (death or removal for too sick to transplant), good (spontaneous improvement), and transplant. Demographic, clinical, listing history, and laboratory variables at the time of listing (baseline variables), and changes in variables between listing and prior to outcome (trajectory variables) were analyzed using random forest (RF) analysis. 81.5% candidates underwent LT, and 12.3% had bad outcome. RF model including both baseline and trajectory variables improved prediction compared to model using baseline variables alone. RF analyses identified change in serum creatinine and listing status as the most predictive variables. 80% of subjects listed with a PELD score at time of listing and outcome underwent LT, while ~70% of subjects in both bad and good outcome groups were listed with either Status 1 (A or B) prior to an outcome, regardless of initial listing status. Increase in creatinine on LT waitlist was predictive of bad outcome. Longer time spent on WL was predictive of good outcome. Subjects with biliary atresia, liver tumors, and metabolic disease had LT rate >85%, while >20% of subjects with acute liver failure had a bad outcome. Change in creatinine, listing status, need for RRT, time spent on LT waitlist, and diagnoses were the most predictive variables.

The RNA workbench 2.0: next generation RNA data analysis.

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.

Feasibility and safety of non-operative management of portal vein aneurysms: a thirty-five year experience.

BACKGROUND: Portal vein aneurysms (PVAs) are rare, though clinically challenging with post-operative mortality approaching 20% and no evidence-based treatment guidelines. We aim to describe our experience with PVAs and recommend optimum management strategies. METHODS: Demographics and clinical details of patients with PVAs admitted to our institution from 1984 to 2019 were reviewed. Clinical presentation, management and outcomes were analysed. RESULTS: PVAs were identified in 18 patients (median age 56 years, range 20-101 years; 13 female); 10 were incidental and 8 diagnosed during abdominal pain work-up. Median aneurysm diameter at diagnosis was 3.4 cm (1.8-5.5 cm), remaining unchanged at 3.5 cm (1.9-4.8 cm) during a 3.2-year follow-up (4 months-31 years). Aneurysm sites were the main portal vein (n = 12), porto-splenic-junction (n = 3), splenic-SMV-junction (n = 2) and right portal vein (n = 1). Thrombosis occurred in 4 patients; 3 developed clinically insignificant cavernous transformation. Two patients underwent surgery for abdominal pain. Postoperatively, one developed PV thrombosis and PVA recurrence occurred in the second. No aneurysm ruptures or mortalities occurred during follow-up. CONCLUSION: PVAs follow a clinically indolent course with structural stability and minimal complications over time. Non-operative management is feasible for most patients. Abdominal pain, large size or thrombosis don't appear to confer additional risks and should not, in isolation, merit surgical intervention.

Germline whole exome sequencing of a family with appendiceal mucinous tumours presenting with pseudomyxoma peritonei.

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. 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: Fifteen novel variants in 15 genes were shared by the father and daughter, including a nonsense mutation in REEP5. 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 AMTs or 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.

Atypical ductal hyperplasia is a multipotent precursor of breast carcinoma.

The current model for breast cancer progression proposes independent 'low grade (LG)-like' and 'high grade (HG)-like' pathways but lacks a known precursor to HG cancer. We applied low-coverage whole-genome sequencing to atypical ductal hyperplasia (ADH) with and without carcinoma to shed light on breast cancer progression. Fourteen out of twenty isolated ADH cases harboured at least one copy number alteration (CNA), but had fewer aberrations than LG or HG ductal carcinoma in situ (DCIS). ADH carried more HG-like CNA than LG DCIS (e.g. 8q gain). Correspondingly, 64% (7/11) of ADH cases with synchronous HG carcinoma were clonally related, similar to LG carcinoma (67%, 6/9). This study represents a significant shift in our understanding of breast cancer progression, with ADH as a common precursor lesion to the independent 'low grade-like' and 'high grade-like' pathways. These data suggest that ADH can be a precursor of HG breast cancer and that LG and HG carcinomas can evolve from a similar ancestor lesion. We propose that although LG DCIS may be committed to a LG molecular pathway, ADH may remain multipotent, progressing to either LG or HG carcinoma. This multipotent nature suggests that some ADH cases could be more clinically significant than LG DCIS, requiring biomarkers for personalising management. Copyright © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Organ procurement center allows for daytime liver transplantation with less resource utilization: May address burnout, pipeline, and safety for field of transplantation.

Abdominal organ transplantation faces several challenges: burnout, limited pipeline of future surgeons, changes in liver allocation potentially impacting organ procurement travel, and travel safety. The organ procurement center (OPC) model may be one way to mitigate these issues. Liver transplants from 2009 to 2016 were reviewed. There were 755 liver transplants performed with 525 OPC and 230 in-hospital procurements. The majority of transplants (87.4%) were started during daytime hours (5 am-7 pm). Transplants with any portion occurring after-hours were more likely to have procurements in-hospital (P < .001). Daytime cases (n = 400) had more OPC procured livers and hepatitis C recipients and were less likely to have a donation after circulatory death donor (all P < .05). In adjusted analyses, daytime cases were independently associated with extubation in the operating room and less postoperative transfusion. There were no significant differences in short- or long-term postoperative outcomes. For exported livers, 54.3% were procured by a local team, saving 137 flights (151 559 miles). The OPC resulted in optimally timed liver transplants and decreased resource utilization with no negative impact on patient outcomes. It allows for ease in exporting organs procured by local surgeons, and potentially addresses provider burnout, the transplant surgery pipeline, and surgeon travel.