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Children with complex congenital heart defects often show delays and deficits in cognitive, language, motor, and social-emotional functioning. As such, the American Academy of Pediatrics and the American Heart Associated recommend ongoing monitoring and support of development. In conjunction with the formal therapeutic supports frequently recommended for young children with CHD, caregivers are instrumental in providing an enriching environment to enhance development in the hospital, at home, and in early childhood settings. In this article, we review the common developmental sequelae associated with CHD, underlying causes, and ways in which parents, family members, and professional caregivers can support development for children with CHD from birth to three years old. [ABSTRACT FROM AUTHOR]

Background: The 2021 Future of Nursing Report 2020-2030: Charting a Path to Achieve Health Equity recognizes increasing racial and ethnic diversity in nursing as an imperative to achieving health equity. Practice Initiatives: Over a 3-year period, nursing and human resource leaders at Boston Children's Hospital, a tertiary care, 454-bed pediatric academic medical center in Massachusetts, developed, implemented, and evaluated specific strategies to increase racial and ethnic diversity in recruitment and hiring of the nursing workforce. These specific strategies focused on cultivating partnerships, building relationships with candidates, and supporting transition into practice. Results: Significant increases in racial and ethnic diversity recruitment and hiring were achieved over the 3-year period. In 2019, strategies yielded a 6% overall increase in total registered nurse diversity hiring with an 18% increase in new graduate diversity hires over 2018. In total, 16.2% of registered nurse hires for 2019 were racially and ethnically diverse. Subsequent years yielded similar success in the recruitment of diverse registered nurses. Clinical Implications: With the projected growth of racial and ethnic minority populations, nursing and health care leaders must prioritize intentional strategic diversity recruitment and retention actions to address this imperative to advance health equity through the creation of a racially and ethnically diverse nursing workforce. Nurse and human resource leaders at Boston Children's Hospital, a tertiary care, 454-bed pediatric academic medical center, developed, implemented, and evaluated strategies to increase racial and ethnic diversity in recruitment and hiring of the nursing workforce. Significant increases in racial and ethnic diversity recruitment and hiring were achieved. These strategies can be helpful for nurses and other health care leaders to advance health equity through the creation of a racially and ethnically diverse nursing workforce. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to identify risk factors for recurrence after pancreatic resection for intraductal papillary mucinous neoplasm (IPMN). Summary Background Data: Long-term follow-up data on recurrence after surgical resection for IPMN are currently lacking. Previous studies have presented mixed results on the role of margin status in risk of recurrence after surgical resection. Methods: A total of 126 patients that underwent resection for noninvasive IPMN were followed for a median of 9.5 years. Dedicated pathological and radiological reviews were performed to correlate clinical and pathological features (including detailed pathological features of the parenchymal margin) with recurrence after surgical resection. In addition, in a subset of 32 patients with positive margins, we determined the relationship between the margin and original IPMN using driver gene mutations identified by next-generation sequencing. Results: Family history of pancreatic cancer and high-grade IPMN was identified as risk factors for recurrence in both uni- and multivariate analysis (adjusted hazard ratio 3.05 and 1.88, respectively). Although positive margin was not significantly associated with recurrence in our cohort, the size and grade of the dysplastic focus at the margin were significantly correlated with recurrence in margin-positive patients. Genetic analyses showed that the neoplastic epithelium at the margin was independent from the original IPMN in at least 9 of 32 cases (28%). The majority of recurrences (74%) occurred after 3 years, and a significant minority (32%) occurred after 5 years. Conclusion: Sustained postoperative surveillance for all patients is indicated, particularly those with risk factors such has family history and high-grade dysplasia. [ABSTRACT FROM AUTHOR]

Supplemental digital content is available in the text. OBJECTIVE: To provide an organization-wide, systematic approach to creating and sustaining healthy work environments (HWEs) through frontline interprofessional staff education and coaching engagement. BACKGROUND: HWE has been an overarching concept in the organization's nursing professional practice model since 2014; however, few practice settings routinely translated survey findings to improve the work environment's health via local interprofessional direct care team members. METHODS: The program used a participatory approach where HWE champions committed to participate in centralized professional development activities and local quality improvement initiatives to bolster the health of area work environments. RESULTS: Fifty-one champions representing 44 practice settings participated in the professional development program. Mean HWE scores for all standards increased from year 1 to 2, with 15 practice settings seeing categorical improvement. Meaningful recognition and true collaboration were the standards most often targeted for improvement. CONCLUSION: The HWE champion role appears to be a promising strategy for engaging frontline interprofessional staff in the assessment and implementation of initiatives to improve the health of work environments. [ABSTRACT FROM AUTHOR]

The Greater Boston Nursing Collective, a consortium composed of university nursing deans and chief nursing officers within academic medical centers and specialty hospitals in Boston, Massachusetts, was formed in 2014. Since the group's inception, our mission has been to create and reinforce whole-person/whole-system healing environments to improve the health of all communities. Through our collaboration in navigating the dual epidemics of COVID-19 and structural racism within our respective organizations, and across the United States and the world, we share experiences and lessons learned. Our common mission is clearer than ever: to create safe and joyful work environments, to protect the dignity of those we are privileged to serve, and to generate policies to advance health equity to rectify societal forces that have shaped this dual epidemic. We are humbled by the many who persist despite limited rest and respite, and whose stories, innovations, and leadership we are honored to witness and share. They have defined our generation, just as nurses in earlier crises have done: leading through service to others as our purpose and privilege. [ABSTRACT FROM AUTHOR]

The treatment of advanced renal cell carcinoma has changed dramatically since 2005 with the approval of 12 regimens including oral, intravenous, and combination strategies. These approvals have changed the treatment paradigm for these patients and developed new challenges and a critical role for oncology nurses to ensure that the treatment plan and adverse events are managed effectively. The majority of these regimens include an oral anticancer drug, which requires patients and their caregivers to understand the medication, the potential adverse events, the importance of medicine adherence, and the importance of early and ongoing education with the oncology team to maximize clinical outcomes. The evolution of the role of the nurse in meeting this need and its critical contribution to the comprehensive care of the kidney cancer patient will be reviewed. [ABSTRACT FROM AUTHOR]

This final installment presents an overview of the series and calls for NPs to become more educated in disaster response planning, more involved in disaster response research, and better trained to lead in disaster response. [ABSTRACT FROM AUTHOR]

The fourth article in the Disaster Series presents the various duties that NPs may assume in a disaster. NPs possess advanced clinical knowledge and skills that position them to play key roles in all phases of a disaster. [ABSTRACT FROM AUTHOR]

Objectives: Previous retrospective studies demonstrated that circulating tumor cells (CTCs) subtypes correlate with overall survival in patients with pancreatic ductal adenocarcinoma (PDAC). Herein, we report results of a prospective observational study on CTCs dynamics to assess their clinical significance. Methods: The CLUSTER study is a prospective longitudinal study on PDAC CTCs dynamics (NCT02974764). Multiple peripheral blood samples were collected from 200 consecutively enrolled patients with presumed PDAC diagnosis. CTCs were isolated and characterized by immunofluorescence. Results: Two major CTCs subtypes were identified in PDAC patients: epithelial CTCs (eCTCs) and epithelial/mesenchymal CTCs (mCTCs). Patients who received neoadjuvant chemotherapy had significantly lower total CTCs (tCTCs, P = 0.007), eCTCs (P = 0.007), and mCTCs (P = 0.034), compared with untreated patients eligible for upfront resection. Surgical resection of the primary tumor resulted in significant reduction, but not disappearance, of CTCs burden across all cell subtypes (P < 0.001). In multivariable logistic regression analysis, preoperative numbers of all CTCs subpopulations were the only predictors of early recurrence within 12 months from surgery in both chemo-naive and post-neoadjuvant patients (odds ratio 5.9 to 11.0). Alterations in CTCs were also observed longitudinally, before disease recurrence. A risk assessment score based on the difference of tCTCs increase accurately identified disease recurrence within the next 2 months, with an accuracy of 75% and 84% for chemo-naive and post-neoadjuvant patients, respectively. Conclusion: We report novel findings regarding CTCs from a large prospective cohort of PDAC patients. CTCs dynamics reflect progression of disease and response to treatment, providing important information on clinical outcomes, not available by current tumor markers and imaging. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the correlation between neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) values, and the presence of invasive carcinoma in patients with intraductal papillary mucinous neoplasm (IPMN). Background: NLR and (PLR) are inflammatory markers that have been associated with overall survival in patients with invasive malignancies, including pancreatic cancer. Methods: We retrospectively reviewed 272 patients who underwent surgical resection for histologically confirmed IPMN from January 1997 to July 2015. NLR and PLR were calculated and coevaluated with additional demographic, clinical, and imaging data for possible correlation with IPMN-associated carcinoma in the form of a predictive nomogram. Results: NLR and PLR were significantly elevated in patients with IPMN-associated invasive carcinoma (P < 0.001). In the multivariate analysis, NLR value higher than 4 (P < 0.001), IPMN cyst of size more than 3 cm (P < 0.001), presence of enhanced solid component (P = 0.014), main pancreatic duct dilatation of more than 5mm (P < 0.001), and jaundice (P < 0.001) were statistically significant variables. The developed statistical model has a c-index of 0.895. Implementation of the statistically significant variables in a predictive nomogram provided a reliable point system for estimating the presence of IPMN-associated invasive carcinoma. Conclusions: NLR is an independent predictive marker for the presence of IPMN-associated invasive carcinoma. Further prospective studies are needed to assess the predictive ability of NLR and how it can be applied in the clinical setting. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to characterize patterns of local progression following resection for pancreatic intraductal papillary mucinous neoplasms (IPMN) using targeted next-generation sequencing (NGS). Background: Progression of neoplastic disease in the remnant pancreas following resection of IPMN may include development of a new IPMN or ductal adenocarcinoma (PDAC). However, it is not clear whether this progression represents recurrence of the same neoplasm or an independent second neoplasm. Methods: Targeted-NGS on genes commonly mutated in IPMN and PDAC was performed on tumors from (1) 13 patients who developed disease progression in the remnant pancreas following resection of IPMN; and (2) 10 patients who underwent a resection for PDAC and had a concomitant IPMN. Mutations in the tumors were compared in order to determine the relationship between neoplasms. In parallel, clinical and pathological characteristics of 260 patients who underwent resection of noninvasive IPMN were reviewed to identify risk factors associated with local progression. Results: We identified 3 mechanisms underlying local progression in the remnant pancreas: (1) residual microscopic disease at the resection margin, (2) intraparenchymal spread of neoplastic cells, leading to an anatomically separate but genetically related recurrence, and (3) multifocal disease with genetically distinct lesions. Analysis of the 260 patients with noninvasive IPMNs showed that family history of pancreatic cancer (P = 0.027) and highgrade dysplasia (HGD) (P = 0.003) were independent risk factors for the development of an IPMN with HGD or an invasive carcinoma in the remnant pancreas. Conclusions: Using NGS, we identify distinct mechanisms for development of metachronous or synchronous neoplasms in patients with IPMN. Patients with a primary IPMN with HGD or with positive family history are at an increased risk to develop subsequent high-risk neoplasms in the remnant pancreas. [ABSTRACT FROM AUTHOR]

Cancer is fundamentally a genetic disease caused by the accumulation of somatic mutations in oncogenes and tumor suppressor genes. In the last decade, rapid advances in sequencing and bioinformatic technology led to an explosion in sequencing studies of cancer genomes, greatly expanding our knowledge of the genetic changes underlying a variety of tumor types. Several of these studies of cancer genomes have focused on pancreatic neoplasms, and cancers from the pancreas are some of the best characterized tumors at the genetic level. Pancreatic neoplasms encompass a wide array of clinical diseases, from benign cysts to deadly cancers, and the genetic alterations underlying neoplasms of the pancreas are similarly diverse. This new knowledge of pancreatic cancer genomes has deepened our understanding of tumorigenesis in the pancreas and has opened several promising new avenues for novel diagnostics and therapeutics. [ABSTRACT FROM AUTHOR]

Discusses ways to protect patients receiving drugs called vesicants or antineoplastic agents, which are most likely to damage and irritate tissue, from the dangers of extravasation. Factors putting a patient at risk for extravasation; Choosing an administration site to minimize risks; Preparation of the patient; Delivery methods on administering vesicants; Cannula selection; Drug sequencing.

Objectives: This study proposes and evaluates a deep learning method to detect pancreatic neoplasms and to identify main pancreatic duct (MPD) dilatation on portal venous computed tomography scans., Materials and Methods: A total of 2890 portal venous computed tomography scans from 9 institutions were acquired, among which 2185 had a pancreatic neoplasm and 705 were healthy controls. Each scan was reviewed by one in a group of 9 radiologists. Physicians contoured the pancreas, pancreatic lesions if present, and the MPD if visible. They also assessed tumor type and MPD dilatation. Data were split into a training and independent testing set of 2134 and 756 cases, respectively.A method to detect pancreatic lesions and MPD dilatation was built in 3 steps. First, a segmentation network was trained in a 5-fold cross-validation manner. Second, outputs of this network were postprocessed to extract imaging features: a normalized lesion risk, the predicted lesion diameter, and the MPD diameter in the head, body, and tail of the pancreas. Third, 2 logistic regression models were calibrated to predict lesion presence and MPD dilatation, respectively. Performance was assessed on the independent test cohort using receiver operating characteristic analysis. The method was also evaluated on subgroups defined based on lesion types and characteristics., Results: The area under the curve of the model detecting lesion presence in a patient was 0.98 (95% confidence interval [CI], 0.97-0.99). A sensitivity of 0.94 (469 of 493; 95% CI, 0.92-0.97) was reported. Similar values were obtained in patients with small (less than 2 cm) and isodense lesions with a sensitivity of 0.94 (115 of 123; 95% CI, 0.87-0.98) and 0.95 (53 of 56, 95% CI, 0.87-1.0), respectively. The model sensitivity was also comparable across lesion types with values of 0.94 (95% CI, 0.91-0.97), 1.0 (95% CI, 0.98-1.0), 0.96 (95% CI, 0.97-1.0) for pancreatic ductal adenocarcinoma, neuroendocrine tumor, and intraductal papillary neoplasm, respectively. Regarding MPD dilatation detection, the model had an area under the curve of 0.97 (95% CI, 0.96-0.98)., Conclusions: The proposed approach showed high quantitative performance to identify patients with pancreatic neoplasms and to detect MPD dilatation on an independent test cohort. Performance was robust across subgroups of patients with different lesion characteristics and types. Results confirmed the interest to combine a direct lesion detection approach with secondary features such as the MPD diameter, thus indicating a promising avenue for the detection of pancreatic cancer at early stages., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: The aim of this study was to investigate the key molecular alterations in small primary pancreatic neuroendocrine tumors (PanNETs) associated with the development of liver metastases., Background: Well-differentiated PanNETs with small size are typically indolent; however, a limited subset metastasize to the liver., Methods: A total of 87 small primary PanNETs (<3 cm), including 32 metastatic cases and 55 nonmetastatic cases after a 5-year follow-up, were immunolabeled for DAXX/ATRX and analyzed for alternative lengthening of telomeres (ALT) by Fluorescence In Situ Hybridization. A subset of these cases, 24 that metastasized and 24 that did not metastasize, were assessed by targeted next-generation sequencing and whole-genome copy number variation., Results: In the entire cohort, high Ki-67 (OR 1.369; 95% CI 1.121-1.673; P = 0.002), N-stage (OR 4.568; 95% CI 1.458-14.312; P = 0.009), and ALT-positivity (OR 3.486; 95% CI 1.093-11.115; P = 0.035) were independently associated with liver metastases. In the subset assessed by next-generation sequencing and copy number variation analysis, 3 molecular subtypes with differing risks of liver metastases were identified. Group 1 (n = 15; 73% metastasized) was characterized by recurrent chromosomal gains, CN-LOH, DAXX mutations, and ALT-positivity. Group 2 (n = 19; 42% metastasized, including 5 G1 tumors) was characterized by limited copy number alterations and mutations. Group 3 (n = 14; 35% metastasized) were defined by chromosome 11 loss., Conclusions: We identified genomic patterns of small PanNETs associated with a different risk for liver metastases. Molecular alterations, such as DAXX mutations, chromosomal gains, and ALT, are associated with an increased risk of metastasis in small PanNETs. Therefore, targeted sequencing and/or ALT analysis may help in the clinical decisions for these small PanNETs.

Although pathologic lesions in the pancreas are 3-dimensional (3D) complex structures, we currently use thin 2D hematoxylin and eosin stained slides to study and diagnose pancreatic pathology. Two technologies, tissue clearing and advanced microscopy, have recently converged, and when used together they open the remarkable world of 3D anatomy and pathology to pathologists. Advances in tissue clearing and antibody penetration now make even dense fibrotic tissues amenable to clearing, and light sheet and confocal microscopies allow labeled cells deep within these cleared tissues to be visualized. Clearing techniques can be categorized as solvent-based or aqueous-based techniques, but both clearing methods consist of 4 fundamental steps, including pretreatment of specimens, permeabilization and/or removal of lipid, immunolabeling with antibody penetration, and clearing by refractive index matching. Specialized microscopes, including the light sheet microscope, the 2-photon microscope, and the confocal microscope, can then be used to visualize and evaluate the 3D histology. Both endocrine and exocrine pancreas pathology can then be visualized. The application of labeling and clearing to surgically resected human pancreatic parenchyma can provide detailed visualization of the complexities of normal pancreatic anatomy. It also can be used to characterize the 3D architecture of disease processes ranging from precursor lesions, such as pancreatic intraepithelial neoplasia lesions and intraductal papillary mucinous neoplasms, to infiltrating pancreatic ductal adenocarcinomas. The evaluation of 3D histopathology, including pathology of the pancreatic lesions, will provide new insights into lesions that previously were seen, and thought of, only in 2 dimensions.

Pancreatic cancer is an aggressive disease with a dismal prognosis in dire need of novel diagnostic and therapeutic approaches. The past decade has witnessed an explosion of data on the genetic alterations that occur in pancreatic cancer, as comprehensive next-generation sequencing analyses have been performed on samples from large cohorts of patients. These studies have defined the genomic landscape of this disease and identified novel candidates whose mutations contribute to pancreatic tumorigenesis. They have also clarified the genetic alterations that underlie multistep tumorigenesis in precursor lesions and provided insights into clonal evolution in pancreatic neoplasia. In addition to these important insights into pancreatic cancer biology, these large scale genomic studies have also provided a foundation for the development of novel early detection strategies and targeted therapies. In this review, we discuss the results of these comprehensive sequencing studies of pancreatic neoplasms, with a particular focus on how their results will impact the clinical care of patients with pancreatic cancer.

Objective: We assessed circulating tumor cells (CTCs) with epithelial and mesenchymal phenotypes as a potential prognostic biomarker for patients with pancreatic adenocarcinoma (PDAC)., Background: PDAC is the fourth leading cause of cancer death in the United States. There is an urgent need to develop biomarkers that predict patient prognosis and allow for better treatment stratification., Methods: Peripheral and portal blood samples were obtained from 50 patients with PDAC before surgical resection and filtered using the Isolation by Size of Epithelial Tumor cells method. CTCs were identified by immunofluorescence using commercially available antibodies to cytokeratin, vimentin, and CD45., Results: Thirty-nine patients (78%) had epithelial CTCs that expressed cytokeratin but not CD45. Twenty-six (67%) of the 39 patients had CTCs which also expressed vimentin, a mesenchymal marker. No patients had cytokeratin-negative and vimentin-positive CTCs. The presence of cytokeratin-positive CTCs (P < 0.01), but not mesenchymal-like CTCs (P = 0.39), was associated with poorer survival. The presence of cytokeratin-positive CTCs remained a significant independent predictor of survival by multivariable analysis after accounting for other prognostic factors (P < 0.01). The detection of CTCs expressing both vimentin and cytokeratin was predictive of recurrence (P = 0.01). Among patients with cancer recurrence, those with vimentin-positive and cytokeratin-expressing CTCs had decreased median time to recurrence compared with patients without CTCs (P = 0.02)., Conclusions: CTCs are an exciting potential strategy for understanding the biology of metastases, and provide prognostic utility for PDAC patients. CTCs exist as heterogeneous populations, and assessment should include phenotypic identification tailored to characterize cells based on epithelial and mesenchymal markers., Competing Interests: The author reports no conflicts of interest.

Axitinib is a novel, oral, multitargeted tyrosine kinase inhibitor, which inhibits vascular endothelial growth factor receptors 1, 2, and 3 at subnanomolar concentrations in vitro. In the phase III clinical trial in patients with metastatic renal cell carcinoma, axitinib showed a high objective response rate, and significantly prolonged progression-free survival compared with sorafenib. Thus, it is the first drug that has proven the concept of sequencing tyrosine kinase inhibitors in second-line treatment in a phase III prospective randomized trial. Although generally well tolerated and associated with a low incidence of grade 3 or 4 toxicities, axitinib shows a distinct pattern of adverse events that require monitoring and management. The most common adverse events observed with axitinib include diarrhea, hypertension, fatigue, nausea, and vomiting. This article summarizes the most important adverse events observed and proposes recommendations for their monitoring, prevention, and treatment. The recommendations are based on the existing literature and discussion by an expert group of international physicians and nurses specialized in oncologic treatment of metastatic renal cell carcinoma, which gathered in July 2011 in London, UK. Proactive assessment and management of adverse events during axitinib therapy can minimize treatment interruptions and ensure optimal effect of treatment.