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To define optimal thromboprophylaxis strategy after stent implantation in superior or total cavopulmonary connections.
Stent thrombosis is a rare complication of intravascular stenting, with a perceived higher risk in single-ventricle patients.
All patients who underwent stent implantation within superior or total cavopulmonary connections (caval vein, innominate vein, Fontan, or branch pulmonary arteries) were included. Cohort was divided into aspirin therapy alone versus advanced anticoagulation, including warfarin, enoxaparin, heparin, or clopidogrel. Primary endpoint was in-stent or downstream thrombus, and secondary endpoints included bleeding complications.
A total of 58 patients with single-ventricle circulation underwent 72 stent implantations. Of them 14 stents (19%) were implanted post-superior cavopulmonary connection and 58 (81%) post-total cavopulmonary connection. Indications for stenting included vessel/conduit stenosis (67%), external compression (18%), and thrombotic occlusion (15%). Advanced anticoagulation was prescribed for 32 (44%) patients and aspirin for 40 (56%) patients. Median follow up was 1.1 (25th–75th percentile, 0.5–2.6) years. Echocardiograms were available in 71 patients (99%), and advanced imaging in 44 patients (61%). Thrombosis was present in two patients on advanced anticoagulation (6.3%) and none noted in patients on aspirin (p = 0.187). Both patients with in-stent thrombus underwent initial stenting due to occlusive left pulmonary artery thrombus acutely post-superior cavopulmonary connection. There were seven (22%) significant bleeding complications for advanced anticoagulation and none for aspirin (p < 0.001).
Antithrombotic strategy does not appear to affect rates of in-stent thrombus in single-ventricle circulations. Aspirin alone may be sufficient for most patients undergoing stent implantation, while pre-existing thrombus may warrant advanced anticoagulation.
OBJECTIVES/SPECIFIC AIMS: Pancreatic ductal adenocarcinoma (PDA) has a dismal 5-year survival rate of 9%, making this disease one of the deadliest human malignancies (https://seer.cancer.gov/). Primary barriers to the treatment of pancreatic cancer include extensive stromal interactions and sustained immune suppression. Aberrant Hedgehog (HH) pathway activity is a hallmark of pancreatic tumorigenesis. Tumor-derived HH ligands signal in a paracrine fashion to the surrounding stroma to influence tumor growth. Expression of HH ligands increases during PDA progression, and previous work has shown that genetic deletion of Sonic HH (Shh) from the epithelium of mice with pancreatic tumors results in increased Indian HH (Ihh) expression. This research aims to investigate the translational impact of changes in immune infiltration following deletion of IHH in a preclinical mouse model of pancreatic cancer. METHODS/STUDY POPULATION: Ihh was deleted in tumor cells lines (IhhKO) derived from a genetically engineered mouse model of pancreatic cancer (LSL-KrasG12D/+;LSL-TrpR270H;P48-Cre), using CRISPR/Cas-9 gene editing to assess the role of Ihh in the tumor microenvironment. The level of HH signaling was determined using tumor cell co-cultures with Gli1lacZ fibroblasts (derived from mice with a lacZ reporter allele knocked into the Gli1 locus), in which Beta Galactosidase activity serves as a readout for HH signaling. WT and IhhKO tumor cells were orthotopically transplanted into the pancreas of syngeneic C57BL/6 mice. Human pancreas samples were obtained from surgical resection of pancreatic adenocarcinoma, or fine needle biopsy procedure (FNB). Immune profiling of mouse and human pancreatic tumors was performed using Cytometry Time-of-Flight analysis (CyTOF), and tumor composition was analyzed by single-cell RNA sequencing (scRNA seq). In vitro cultures with pancreatic fibroblasts treated with either WT or IhhKO tumor cell conditioned media (CM) were cultured with bone-marrow derived macrophages to assess tumor crosstalk. RESULTS/ANTICIPATED RESULTS: Tumor cells lacking Ihh were generated through CRISPR/Cas-9 deletion, and this was confirmed by qRT-PCR. Co-culture of IhhKO tumor cells with Gli1lacZ fibroblasts results in decreased Gli1 expression both in vitro and in vivo. Immune profiling revealed that tumors lacking Ihh have significantly fewer tumor associated macrophages (CD11b+/F4/80+/CD206+), resulting in decreased presence of immunosuppressive factors such as arginase 1 and PDL1. Immune phenotyping of human pancreatic tissues revealed similar populations of immunosuppressive myeloid cells present in tumors. In vitro co-cultures demonstrated that, in the presence of bone-marrow derived macrophages, immunosuppressive IL-6 production was reduced in pancreatic fibroblasts cultured with IhhKO-CM, as compared to fibroblasts cultured with WT-CM, providing mechanistic insight into the in vivo phenotype observed. Further, scRNA seq analysis suggests that modulation of HH signaling in the tumor microenvironment alters chemokine and immunomodulatory signaling pathways driven by fibroblasts in the pancreatic tumor microenvironment. DISCUSSION/SIGNIFICANCE OF IMPACT: HH signaling in pancreatic fibroblasts contributes to the establishment of an immune suppressive environment in pancreatic cancer. Combining methods to target HH signaling and immune checkpoint therapy has translational potential in treating pancreatic cancer patients.
Shunt-related adverse events are frequent in infants after modified Blalock–Taussig despite use of acetylsalicylic acid prophylaxis. A higher incidence of acetylsalicylic acid-resistance and sub-therapeutic acetylsalicylic acid levels has been reported in infants. We evaluated whether using high-dose acetylsalicylic acid can decrease shunt-related adverse events in infants after modified Blalock–Taussig.
In this single-centre retrospective cohort study, we included infants ⩽1-year-old who underwent modified Blalock–Taussig placement and received acetylsalicylic acid in the ICU. We defined acetylsalicylic acid treatment groups as standard dose (⩽7 mg/kg/day) and high dose (⩾8 mg/kg/day) based on the initiating dose.
There were 34 infants in each group. Both groups were similar in age, gender, cardiac defect type, ICU length of stay, and time interval to second stage or definitive repair. Shunt interventions (18 versus 32%, p=0.16), shunt thrombosis (14 versus 17%, p=0.74), and mortality (9 versus 12%, p=0.65) were not significantly different between groups. On multiple logistic regression analysis, single-ventricle morphology (odds ratio 5.2, 95% confidence interval of 1.2–23, p=0.03) and post-operative red blood cells transfusion ⩾24 hours [odds ratio 15, confidence interval of (3–71), p<0.01] were associated with shunt-related adverse events. High-dose acetylsalicylic acid treatment [odds ratio 2.6, confidence interval of (0.7–10), p=0.16] was not associated with decrease in these events.
High-dose acetylsalicylic acid may not be sufficient in reducing shunt-related adverse events in infants after modified Blalock–Taussig. Post-operative red blood cells transfusion may be a modifiable risk factor for these events. A randomised trial is needed to determine appropriate acetylsalicylic acid dosing in infants with modified Blalock–Taussig.
Transcatheter right ventricle decompression in neonates with pulmonary atresia and intact ventricular septum is technically challenging, with risk of cardiac perforation and death. Further, despite successful right ventricle decompression, re-intervention on the pulmonary valve is common. The association between technical factors during right ventricle decompression and the risks of complications and re-intervention are not well described.
This is a multicentre retrospective study among the participating centres of the Congenital Catheterization Research Collaborative. Between 2005 and 2015, all neonates with pulmonary atresia and intact ventricular septum and attempted transcatheter right ventricle decompression were included. Technical factors evaluated included the use and characteristics of radiofrequency energy, maximal balloon-to-pulmonary valve annulus ratio, infundibular diameter, and right ventricle systolic pressure pre- and post-valvuloplasty (BPV). The primary end point was cardiac perforation or death; the secondary end point was re-intervention.
A total of 99 neonates underwent transcatheter right ventricle decompression at a median of 3 days (IQR 2–5) of age, including 63 patients by radiofrequency and 32 by wire perforation of the pulmonary valve. There were 32 complications including 10 (10.5%) cardiac perforations, of which two resulted in death. Cardiac perforation was associated with the use of radiofrequency (p=0.047), longer radiofrequency duration (3.5 versus 2.0 seconds, p=0.02), and higher maximal radiofrequency energy (7.5 versus 5.0 J, p<0.01) but not with patient weight (p=0.09), pulmonary valve diameter (p=0.23), or infundibular diameter (p=0.57). Re-intervention was performed in 36 patients and was associated with higher post-intervention right ventricle pressure (median 60 versus 50 mmHg, p=0.041) and residual valve gradient (median 15 versus 10 mmHg, p=0.046), but not with balloon-to-pulmonary valve annulus ratio, atmospheric pressure used during BPV, or the presence of a residual balloon waist during BPV. Re-intervention was not associated with any right ventricle anatomic characteristics, including pulmonary valve diameter.
Technical factors surrounding transcatheter right ventricle decompression in pulmonary atresia and intact ventricular septum influence the risk of procedural complications but not the risk of future re-intervention. Cardiac perforation is associated with the use of radiofrequency energy, as well as radiofrequency application characteristics. Re-intervention after right ventricle decompression for pulmonary atresia and intact ventricular septum is common and relates to haemodynamic measures surrounding initial BPV.
We report the discovery in the Greenland ice sheet of a discrete layer of free nanodiamonds (NDs) in very high abundances, implying most likely either an unprecedented influx of extraterrestrial (ET) material or a cosmic impact event that occurred after the last glacial episode. From that layer, we extracted n-diamonds and hexagonal diamonds (lonsdaleite), an accepted ET impact indicator, at abundances of up to about 5×106 times background levels in adjacent younger and older ice. The NDs in the concentrated layer are rounded, suggesting they most likely formed during a cosmic impact through some process similar to carbon-vapor deposition or high-explosive detonation. This morphology has not been reported previously in cosmic material, but has been observed in terrestrial impact material. This is the first highly enriched, discrete layer of NDs observed in glacial ice anywhere, and its presence indicates that ice caps are important archives of ET events of varying magnitudes. Using a preliminary ice chronology based on oxygen isotopes and dust stratigraphy, the ND-rich layer appears to be coeval with ND abundance peaks reported at numerous North American sites in a sedimentary layer, the Younger Dryas boundary layer (YDB), dating to 12.9 ± 0.1 ka. However, more investigation is needed to confirm this association.
OBJECTIVES/SPECIFIC AIMS: To create a searchable public registry of all Quality Improvement (QI) projects. To incentivize the medical professionals at UF Health to initiate quality improvement projects by reducing startup burden and providing a path to publishing results. To reduce the review effort performed by the internal review board on projects that are quality improvement Versus research. To foster publication of completed quality improvement projects. To assist the UF Health Sebastian Ferrero Office of Clinical Quality & Patient Safety in managing quality improvement across the hospital system. METHODS/STUDY POPULATION: This project used a variant of the spiral software development model and principles from the ADDIE instructional design process for the creation of a registry that is web based. To understand the current registration process and management of quality projects in the UF Health system a needs assessment was performed with the UF Health Sebastian Ferrero Office of Clinical Quality & Patient Safety to gather project requirements. Biweekly meetings were held between the Quality Improvement office and the Clinical and Translational Science – Informatics and Technology teams during the entire project. Our primary goal was to collect just enough information to answer the basic questions of who is doing which QI project, what department are they from, what are the most basic details about the type of project and who is involved. We also wanted to create incentive in the user group to try to find an existing project to join or to commit the details of their proposed new project to a data registry for others to find to reduce the amount of duplicate QI projects. We created a series of design templates for further customization and feature discovery. We then proceed with the development of the registry using a Python web development framework called Django, which is a technology that powers Pinterest and the Washington Post Web sites. The application is broken down into 2 main components (i) data input, where information is collected from clinical staff, Nurses, Pharmacists, Residents, and Doctors on what quality improvement projects they intend to complete and (ii) project registry, where completed or “registered” projects can be viewed and searched publicly. The registry consists of a quality investigator profile that lists contact information, expertise, and areas of interest. A dashboard allows for the creation and review of quality improvement projects. A search function enables certain quality project details to be publicly accessible to encourage collaboration. We developed the Registry Matching Algorithm which is based on the Jaccard similarity coefficient that uses quality project features to find similar quality projects. The algorithm allows for quality investigators to find existing or previous quality improvement projects to encourage collaboration and to reduce repeat projects. We also developed the QIPR Approver Algorithm that guides the investigator through a series of questions that allows an appropriate quality project to get approved to start without the need for human intervention. RESULTS/ANTICIPATED RESULTS: A product of this project is an open source software package that is freely available on GitHub for distribution to other health systems under the Apache 2.0 open source license. Adoption of the Quality Improvement Project Registry and promotion of it to the intended audience are important factors for the success of this registry. Thanks goes to the UW-Madison and their QI/Program Evaluation Self-Certification Tool (https://uwmadison.co1.qualtrics.com/SE/?SID=SV_3lVeNuKe8FhKc73) used as example and inspiration for this project. DISCUSSION/SIGNIFICANCE OF IMPACT: This registry was created to help understand the impact of improved management of quality projects in a hospital system. The ultimate result will be to reduce time to approve quality improvement projects, increase collaboration across the UF Health Hospital system, reduce redundancy of quality improvement projects and translate more projects into publications.
To evaluate differences in interstage growth of pulmonary arteries between use of polytetrafluoroethylene and femoral vein homograft as Sano shunt during stage-I Norwood palliation.
A retrospective review of all patients who survived to the second stage following Norwood–Sano operation at two institutions was performed. Either polytetrafluoroethylene or the valved segment of femoral vein homograft was used for construction of the Sano shunt. The size of pulmonary arteries was compared at pre-Glenn catheterisation.
A total of 48 neonates with the diagnosis of hypoplastic left heart syndrome or its variants comprised the study population. Femoral vein homograft of 5–6 mm diameter was used in 14 and polytetrafluoroethylene graft of 5 mm was used in 34 patients. The two groups were comparable in terms of preoperative demographics and age at time of pre-Glenn catheterisation (3.9±0.7 versus 3.4±0.8 months, p=0.06). Patients who received femoral vein homograft demonstrated a significantly higher pre-Glenn Nakata index [264 (130–460) versus 165 (108–234) mm2/m2, p=0.004]. The individual branch pulmonary arteries were significantly larger in the femoral vein group (right, 7.8±3.6 versus 5.0±1.2, p=0.014; left, 7.2±2.1 versus 5.6±1.9, p=0.02). There were no differences in cardiac index, Qp:Qs, ventricular end-diastolic pressure or systemic oxygen saturations.
Utilisation of a valved segment of femoral vein homograft as right ventricle to pulmonary artery conduit during Norwood–Sano operation confers better interstage growth of the pulmonary arteries. Further studies are needed to evaluate the impact of femoral vein homograft on single ventricle function.
After the Portuguese discovered the Cape Verde Islands in AD 1456 they divided its main island, Santiago, into two governing captaincies. The founding settlement in the south-west, Cidade Velha, soon became the Islands’ capital and a thriving trade centre; in contrast, that in the east, Alcatrazes, only lasted as an official seat from 1484–1516 and is held to have ‘failed’ (see Richter 2015).
Estuaries were important sites of deposition throughout most of the Pennsylvanian in the Midcontinent. Modern estuaries typically occur within flooded river valleys where marine and fresh waters mix. Characteristic estuarine circulation results in locally high rates of deposition of muddy sediment that can lead to good preservation of fossils. Several Pennsylvanian conservat-Lagerstätten are best interpreted as having formed within ancient estuaries. Three types of estuarine deposits have been identified. Type 1 estuarine systems are large-scale transgressive systems that start with fluvial sands overlying an erosional surface. This is overlain successively by middle-estuarine laminated mudstone, and finally marine mudstone and shale. Well-preserved fossils occur in laminated mudstones and siltstones. This sequence may include within in it type 3 estuarine Lagerstätten. An example is the Douglas Group (Missourian, Kansas).
Type 2 estuarine Lagerstätten consist of thin estuarine deposits confined to narrow paleochannels. This includes the Garnett (Missourian, Kansas) and Hamilton (Virgilian, Kansas) deposits, both of which contain articulated vertebrates and well-preserved plants. Both channels are filled with mixed siliciclastic and carbonate sediments. Fine grained facies from which the best fossils are recovered in both contain evidence of tidal deposition, although tidal rhythmicity is best developed in the Hamilton channel. Plant assemblages in both are dominated by the conifer Walchia, probably indicating a relatively dry climate.
Type 3 estuarine Lagerstätten consist of thick gray-shale wedges that overlie coals. The best-known example is the Francis Creek Shale (Desmoinesian, Illinois). A relatively wet climate is indicated by abundant fern and seed-fern foliage. Laminations in shale facies commonly show well-developed tidal rhythmicity. A typical stratigraphic succession starts with laminated shale overlying coal. This grades upwards into flaser and lenticular bedding to ripple and then large-scale cross-bedded sandstone. Upright trees rooted in the coal indicate rapid burial. Well-preserved fossils are recovered from early-diagenetic siderite concretions from the laminated shale.
Preservation of fossils is best in laminated mudstones deposited in middle-estuarine environments where conditions are ideal for good preservation. In all cases so far studied the zones of best preservation are well laminated and have sparse (if any) burrows and sessile benthic fossils. Most of the well-preserved organisms are terrestrial, nektonic, or at least mobile. Brackish and fluctuating salinities restricted scavenging and burrowing organisms that may scatter skeletons. High turbidity and deposition rate may have further discouraged many organisms. Matching bedding rhythmicity with tidal cycles allows calculation of depositional rates of 1 cm or more of compacted sediment per 2-week neap-spring tidal cycle. This is consistent with the high rates of deposition known from modern tidal environments. High depositional rates assured that any organism that fell to the sea floor was buried in a few hours to a few days. Once buried anoxic conditions established around decaying carcasses may have led to early mineralization.
Numerous advances in surgical techniques and understanding of single-ventricle physiology have resulted in improved survival. We sought to determine the influence of various demographic, perioperative, and patient-specific factors on the survival of single-ventricle patients following stage 1 palliation at our institution.
We conducted a retrospective study of all single-ventricle patients who had undergone staged palliation at our institution over an 8-year period. Data were collected from the Society of Thoracic Surgeons Congenital Heart Surgery database and from patient charts. Information on age, weight at stage 1 palliation, prematurity, genetic abnormalities, non-cardiac anomalies, ventricular dominance, and type of palliation was collected. Information on mortality and unplanned reinterventions was also collected.
A total of 72 patients underwent stage 1 palliation over an 8-year period. There were 12 deaths before and one death after stage 2 palliation. There was no hospital mortality following Glenn or Fontan procedures. On univariate analysis, low weight at the time of stage 1 palliation and prematurity were found to be risk factors for mortality following stage 1 palliation. However, multivariable Cox regression analysis revealed weight at stage 1 palliation to be a strong predictor of mortality. The type of stage 1 palliation did not have any influence on the outcome. No difference in survival was noted following the Glenn procedure.
Low weight has a deleterious impact on survival following stage 1 palliation. This is mitigated by stage 2 palliation. The type of stage 1 palliation itself has no bearing on the outcome.
School belonging, at both a school and university level, has been well documented as a predictor of academic and psychosocial success. The construct has been examined by scholars in a variety of different professional disciplines (e.g., education, psychology, sociology) and continues to be consistently researched. Although significant contributions have been made in the field, there are still additional areas of investigation needed, as well as interventions that need to be designed and explored. The current article was designed to review the theoretical foundations of belonging, conceptualise school belonging with respect to how it is presented in the literature, discuss the key variables related to school belonging, present a summary of the predictors of school belonging, discuss school belonging in a university setting, and posit future directions for research.
Recent commentary has suggested that performance management (PM) is fundamentally “broken,” with negative feelings from managers and employees toward the process at an all-time high (Pulakos, Hanson, Arad, & Moye, 2015; Pulakos & O'Leary, 2011). In response, some high-profile organizations have decided to eliminate performance ratings altogether as a solution to the growing disenchantment. Adler et al. (2016) offer arguments both in support of and against eliminating performance ratings in organizations. Although both sides of the debate in the focal article make some strong arguments both for and against utilizing performance ratings in organizations, we believe there continue to be misunderstandings, mischaracterizations, and misinformation with respect to some of the measurement issues in PM. We offer the following commentary not to persuade readers to adopt one particular side over another but as a call to critically reconsider and reevaluate some of the assumptions underlying measurement issues in PM and to dispel some of the pervasive beliefs throughout the performance rating literature.
During August and September 2012, Sino-Japanese conflict over the Diaoyu/Senkaku Islands escalated. Alongside street demonstrations in China, there was an outpouring of public sentiment on China's leading micro-blog, Sina Weibo (微波). Using human and computer-assisted content analysis, we exploit original Weibo data to measure how public sentiment in China fluctuated over the dispute, and ask two questions. First, how cohesive and volatile were online nationalist sentiments? Second, we measure government censorship of Weibo in order to ask which sentiments did authorities allow to be expressed, and when? We first find that many of the micro-bloggers' harshest invective was directed not at Japan but at their own government. Second, while censorship remained high across topics for most of the dispute, it plummeted on 18 August – the same day as bloggers' anger at Beijing peaked. These observations suggest three theoretical explanations: two are instrumental-strategic (“audience costs” and “safety valve”) and one is ideational (elite identification with protesters).