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Embedded pragmatic clinical trials (ePCTs) and quality improvement (QI) activities often occur simultaneously within healthcare systems (HCSs). Embedded PCTs within HCSs are conducted to test interventions and provide evidence that may impact public health, health system operations, and quality of care. They are larger and more broadly generalizable than QI initiatives, and may generate what is considered high-quality evidence for potential use in care and clinical practice guidelines. QI initiatives often co-occur with ePCTs and address the same high-impact health questions, and this co-occurrence may dilute or confound the ability to detect change as a result of the ePCT intervention. During the design, pilot, and conduct phases of the large-scale NIH Collaboratory Demonstration ePCTs, many QI initiatives occurred at the same time within the HCSs. Although the challenges varied across the projects, some common, generalizable strategies and solutions emerged, and we share these as case studies. KEY LESSONS: Study teams often need to monitor, adapt, and respond to QI during design and the course of the trial. Routine collaboration between ePCT researchers and health systems stakeholders throughout the trial can help ensure research and QI are optimally aligned to support high-quality patient-centered care., (Copyright © 2020. Published by Elsevier Inc.)

Background: The arteriovenous fistula (AVF) is central to haemodialysis treatment, but up to half of surgically created AVF fail to mature. Chronic kidney disease often leads to mineral metabolism disturbances that may interfere with AVF maturation through adverse vascular effects. This study tested associations between mineral metabolism markers and vein histology at AVF creation and unassisted and overall clinical AVF maturation., Methods: Concentrations of fibroblast growth factor 23, parathyroid hormone, calcium, phosphate, and vitamin D metabolites: 1,25(OH) 2 D, 24,25(OH) 2 D, 25(OH)D, and bioavailable 25(OH)D were measured in pre-operative serum samples from 562 of 602 participants in the Haemodialysis Fistula Maturation Study, a multicentre, prospective cohort study of patients undergoing surgical creation of an autologous upper extremity AVF. Unassisted and overall AVF maturation were ascertained for 540 and 527 participants, respectively, within nine months of surgery or four weeks of dialysis initiation. Study personnel obtained vein segments adjacent to the portion of the vein used for anastomosis, which were processed, embedded, and stained for measurement of neointimal hyperplasia, calcification, and collagen deposition in the medial wall., Results: Participants in this substudy were 71% male, 43% black, and had a mean age of 55 years. Failure to achieve AVF maturation without assistance occurred in 288 (53%) participants for whom this outcome was determined. In demographic and further adjusted models, mineral metabolism markers were not significantly associated with vein histology characteristics, unassisted AVF maturation failure, or overall maturation failure, other than a biologically unexplained association of higher 24,25(OH) 2 D with overall failure. This exception aside, associations were non-significant for continuous and categorical analyses and relevant subgroups., Conclusions: Serum concentrations of measured mineral metabolites were not substantially associated with major histological characteristics of veins in patients undergoing AVF creation surgery, or with AVF maturation failure, suggesting that efforts to improve AVF maturation rates should increase attention to other processes such as vein mechanics, anatomy, and cellular metabolism among end stage renal disease patients., (Copyright © 2019 European Society for Vascular Surgery. All rights reserved.)

Background: The survival benefit from simultaneous liver-kidney transplantation (SLK) over liver transplant alone (LTA) in recipients with moderate renal dysfunction is not well understood. Moreover, the impact of deceased donor organ quality in SLK transplant survival has not been well described in the literature., Methods: The Scientific Registry of Transplant Recipients was studied for adult recipients receiving LTA (N=2,700) or SLK (N=1,361) transplantation with moderate renal insufficiency between 2003 and 2013. The study cohort was stratified into four groups based on serum creatinine (Scr< 2 mg/dL versus Scr≥ 2 mg/dL) and dialysis status at listing and at transplant. The patients with end-stage renal disease and requiring acute dialysis more than three months before transplantation were excluded. A propensity score (PS)-matching was performed in each stratified groups to factor out imbalances between the SLK and LTA regarding covariates distribution and to reduce measured confounding. Donor quality was assessed with liver-donor risk index (L-DRI). The primary outcome of interest was post-transplant mortality., Results: On multivariable PS-matched Cox proportional hazard models, SLK led to decrease in post-transplant mortality compared to LTA across all four groups, but only reached statistical significance (HR 0.77; 95% CI, 0.62-0.96) in the recipients not exposed to dialysis and Scr≥ 2 mg/dL at transplant (mortality incidence rate per patient-year 5.7% in SLK vs. 7.6% in LTA, p=0.005). The decrease in mortality was observed among SLK recipients with better quality donors (L-DRI<1.5)., Conclusions: Exposure to pre-transplantation dialysis and donor quality affected overall survival among SLK recipients., Competing Interests: Authors describe no conflict of interest relevant to the manuscript.

A retrospective cohort multicenter study was conducted to analyze the risk factors for tumor recurrence after liver transplantation (LT) in cirrhotic patients found to have an intrahepatic cholangiocarcinoma (iCCA) on pathology examination. We also aimed to ascertain whether there existed a subgroup of patients with single tumors ≤2 cm ("very early") in which results after LT can be acceptable. Twenty-nine patients comprised the study group, eight of whom had a "very early" iCCA (four of them incidentals). The risk of tumor recurrence was significantly associated with larger tumor size as well as larger tumor volume, microscopic vascular invasion and poor degree of differentiation. None of the patients in the "very early" iCCA subgroup presented tumor recurrence compared to 36.4% of those with single tumors >2 cm or multinodular tumors, p = 0.02. The 1-, 3- and 5-year actuarial survival of those in the "very early" iCCA subgroup was 100%, 73% and 73%, respectively. The present is the first multicenter attempt to ascertain the risk factors for tumor recurrence in cirrhotic patients found to have an iCCA on pathology examination. Cirrhotic patients with iCCA ≤2 cm achieved excellent 5-year survival, and validation of these findings by other groups may change the current exclusion of such patients from transplant programs., (© Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Paramutation involves trans-interactions between alleles or homologous sequences that establish distinct gene expression states that are heritable for generations. It was first described in maize by Alexander Brink in the 1950s, with his studies of the red1 (r1) locus. Since that time, paramutation-like phenomena have been reported in other maize genes, other plants, fungi, and animals. Paramutation can occur between endogenous genes, two transgenes or an endogenous gene, and transgene. Recent results indicate that paramutation involves RNA-mediated heritable chromatin changes and a number of genes implicated in RNAi pathways. However, not all aspects of paramutation can be explained by known mechanisms of RNAi-mediated transcriptional silencing., (2010 Elsevier Ltd. All rights reserved.)

Purpose: To compare healing rates of distal radius fractures in patients on bisphosphonate therapy at the time of injury to rates in those not on bisphosphonate therapy., Methods: A total of 196 consecutive patients treated for distal radius fractures were included in this study. Patients currently on bisphosphonate therapy at the time of injury (bisphosphonate group, n = 43) were compared to the remaining patient group (control group, n = 153). Demographic information was recorded from the patients' medical records, and radiographs were reviewed to determine fracture healing. Patients were further stratified according to age, gender, fracture complexity, type of treatment, and comorbidities. Univariate and multivariate regression were used to identify factors associated with time to radiographic fracture union., Results: The mean time to union was 55 (+/-17) days in the bisphosphonate group versus 49 (+/-14) days in the control group. Bisphosphonate use and surgical treatment were associated with a longer time to radiographic union. Bisphosphonate use was associated with increased healing times when individually controlling for age, gender, fracture complexity, or comorbidities. Bisphosphonate use was also associated with longer time to healing after adjusting for age, gender, and treatment type. Surgical fracture fixation was associated with a longer time to healing after adjusting for bisphosphonate use., Conclusions: Current bisphosphonate use and surgical treatment were both associated with longer times to radiographic union of distal radius fractures. However, the small differences in healing times (<1 week) are not considered clinically relevant. Although further studies are needed to better define the effects of bisphosphonate therapy on fracture healing, our results suggest that bisphosphonate therapy can be continued after distal radius fractures without notable deleterious effects., Type of Study/level of Evidence: Therapeutic III.

Pseudoaneurysms represent a well-recognized vascular complication of renal transplantation, but true aneurysms involving the donor renal artery have not been described. We report a patient who had a de novo aneurysm of the donor renal artery 6 years after receiving a cadaveric renal transplant from a child. The aneurysm was repaired successfully, and allograft function was preserved. Histologic evidence confirmed that the lesion was a true aneurysm. Given the potential for graft loss associated with complications of unrepaired aneurysms, we believe that the presence of a true aneurysm in a donor renal artery represents an indication for repair.

Chronic rejection is the most important cause for returning to dialysis after failure of a renal transplant. The term chronic allograft nephropathy refers to the progressive decline of renal function seen in some renal transplant recipients in association with alloantigen-dependent and alloantigen-independent factors. This review examines the role of factors related to allorecognition, injury, nephron dosing, and donor and recipient characteristics in the development of chronic allograft nephropathy. The clinical associations to chronic allograft nephropathy are presented in the context of pathogenetic mechanisms of renal damage and disease progression. As there is no therapy available at this time for established chronic allograft nephropathy, possible areas of intervention for the prevention of chronic rejection are discussed.

Aim: 13C-urea breath test is one of the best methods for the diagnosis of Helicobacter pylori infection. Although a citric acid solution is generally used prior to urea intake, the superiority of this strategy has not been sufficiently demonstrated. Thus, our aim was to compare 13C-urea breath test with and without citric acid solution, to evaluate whether 13C-urea breath test can also achieve favourable results when the test meal is omitted., Methods: 13C-urea breath test with and without citric acid were compared prospectively in 53 subjects without prior Helicobacter pylori eradication therapy prescription. Basal samples and at 15', 30', and 45' after taking 100 mg of 13C-urea were obtained. The gold standard for Helicobacter pylori diagnosis was the 13C-urea breath test result with citric acid at 30', and "Delta Over Baseline" values >5 at that time were considered positive., Results: The prevalence of Helicobacter pylori infection was 68%. Mean Delta Over Baseline values with citric acid at 15', 30' and 45' were: 29.6+/-39, 30.8+/-37 and 24.6+/-27; whereas respective values without citric acid were lower: 14.9+/-22, 12.2+/-17 and 10D+/-13 (p

Allograft rejection can be caused by numerous factors such as damage to the donor kidney during surgical removal or implantation, injury sustained during the transport process between the donor and recipient, and suboptimal allograft perfusion during the intra- and post-operative period. In cadaveric allografts, damage can occur during cold storage, during the transit stage between donor and recipient, and hemodynamic instability due to the initial damage that caused its removal from the donor (such as brain death or trauma). We hypothesize that rejection requires recognition of this injury in addition to recognition of alloantigens. If indeed injury proves to be one factor in acute rejection episodes, then therapeutic efforts can be made to reduce injury during the transplantation process.