Mind the gap: why we need to consider teenage and young adult cancers across the research pipeline.

Historically, teenage and young adult (TYA) cancers have been understudied, with research largely focussing on paediatric or older adult (OA) indications. With increasing TYA cancer incidence rates internationally, now is the time to focus on teenagers and young adults across the research pipeline to improve not only outcomes but also the quality of life for this underserved group.

MiR-130b modulates the invasive, migratory, and metastatic behavior of leiomyosarcoma.

Leiomyosarcoma (LMS) is an aggressive, often poorly differentiated cancer of the smooth muscle (SM) lineage for which the molecular drivers of transformation and progression are poorly understood. In microRNA (miRNA) profiling studies, miR-130b was previously found to be upregulated in LMS vs. normal SM, and down-regulated during the differentiation of mesenchymal stem cells (MSCs) into SM, suggesting a role in LMS tumor progression.

Regulates the Proliferation Capacity of Bone-Marrow Derived Mesenchymal Stem Cells.

TSC1 is a tumor suppressor that inhibits cell growth via negative regulation of the mammalian target of rapamycin complex (mTORC1). mutations are associated with Tuberous Sclerosis Complex (TSC), characterized by multiple benign tumors of mesenchymal and epithelial origin. TSC1 modulates self-renewal and differentiation in hematopoietic stem cells; however, its effects on mesenchymal stem cells (MSCs) are unknown.

Special Feature: Countering Vaccine Misinformation.

Evidence consistently shows that vaccines are safe, effective, and cost-efficient. Yet preventable outbreaks of infectious diseases are occurring in the United States, leading to a strong public response and intense scrutiny of the antivaccine movement and its persistent spread of misinformation. Social media has been a major platform for such misinformation, and recent examinations have found that nurses are not exempt from engaging in antivaccine discourse.

SHH pathway inhibition is protumourigenic in adamantinomatous craniopharyngioma.

Pharmacological inhibition of the sonic hedgehog (SHH) pathway can be beneficial against certain cancers but detrimental in others. Adamantinomatous craniopharyngioma (ACP) is a relevant pituitary tumour, affecting children and adults, that is associated with high morbidity and increased mortality in long-term follow-up. We have previously demonstrated overactivation of the SHH pathway in both human and mouse ACP.

Microvascular abnormalities secondary to radiation therapy in neovascular age-related macular degeneration: findings from the INTREPID clinical trial.

Purpose: To report the incidence and features of retinal microvascular abnormalities (MVAs) occurring secondary to stereotactic radiotherapy (SRT) in a randomised double-masked sham-controlled clinical trial at 21 European sites.

Methods: Two hundred and thirty participants with neovascular age-related macular degeneration (AMD) treated with at least three intravitreal antivascular endothelial growth factor (anti-VEGF) injections prior to enrolment, and demonstrating a continuing need for re-treatment.

Interventions: 16 Gy, 24 Gy or sham SRT.

Metastatic group 3 medulloblastoma is driven by PRUNE1 targeting NME1-TGF-β-OTX2-SNAIL via PTEN inhibition.

Genetic modifications during development of paediatric groups 3 and 4 medulloblastoma are responsible for their highly metastatic properties and poor patient survival rates. PRUNE1 is highly expressed in metastatic medulloblastoma group 3, which is characterized by TGF-β signalling activation, c-MYC amplification, and OTX2 expression. We describe the process of activation of the PRUNE1 signalling pathway that includes its binding to NME1, TGF-β activation, OTX2 upregulation, SNAIL (SNAI1) upregulation, and PTEN inhibition.

Pilot Study to Determine Safety and Efficacy of Paclitaxel Infusion in De Novo Peripheral Lesions Using the Atrium ClearWay Balloon.

Objective: To evaluate the safety and efficacy of a one-time infusion of paclitaxel through an Atrium ClearWay balloon in infra inguinal de novo peripheral lesions.

Methods: This is a single-center prospective study looking at treatment of 50 limbs. Treatment includes standard infra inguinal endovascular revascularization followed by a pre-prescribed infusion of paclitaxel.

Enhancing Accessibility for Students With Decoding Difficulties on Large-Scale Reading Assessments.

This study reports findings from studies examining potential read-aloud accommodations on standardized reading comprehension assessments for students with decoding difficulties. Three types of accommodations were evaluated: question stems and answer options read aloud; question stems, answer options, and proper nouns read aloud; and full read-aloud. Drawing from a sample of 207 fourth-grade students with and without decoding difficulties, we used 3-level hierarchical linear modeling to assess whether there were significant differences between students with and without decoding difficulties in the effect of each accommodation relative to no accommodation.

Preclinical transgenic and patient-derived xenograft models recapitulate the radiological features of human adamantinomatous craniopharyngioma.

To assess the clinical relevance of transgenic and patient-derived xenograft models of adamantinomatous craniopharyngioma (ACP) using serial magnetic resonance imaging (MRI) and high resolution post-mortem microcomputed tomography (μ-CT), with correlation with histology and human ACP imaging. The growth patterns and radiological features of tumors arising in Hesx1 ;Ctnnb1 transgenic mice, and of patient-derived ACP xenografts implanted in the cerebral cortex, were monitored longitudinally in vivo with anatomical and functional MRI, and by ex vivo μ-CT at study end. Pathological correlates with hematoxylin and eosin stained sections were investigated.

Immunoassays for the quantification of ALK and phosphorylated ALK support the evaluation of on-target ALK inhibitors in neuroblastoma.

Targeted inhibition of anaplastic lymphoma kinase (ALK) is a successful approach for the treatment of many ALK-aberrant malignancies; however, the presence of resistant mutations necessitates both the development of more potent compounds and pharmacodynamic methods with which to determine their efficacy. We describe immunoassays designed to quantitate phosphorylation of ALK, and their use in preclinical models of neuroblastoma, a pediatric malignancy in which gain-of-function ALK mutations predict a poor overall outcome to conventional treatment. Validation of the immunoassays is presented using a panel of neuroblastoma cell lines and evidence of on-target ALK inhibition provided by treatment of a genetically engineered murine model of neuroblastoma with two clinical ALK inhibitors, crizotinib and ceritinib, highlighting the superior efficacy of ceritinib.

The ALK inhibitor PF-06463922 is effective as a single agent in neuroblastoma driven by expression of ALK and MYCN.

The first-in-class inhibitor of ALK, c-MET and ROS1, crizotinib (Xalkori), has shown remarkable clinical efficacy in treatment of ALK-positive non-small cell lung cancer. However, in neuroblastoma, activating mutations in the ALK kinase domain are typically refractory to crizotinib treatment, highlighting the need for more potent inhibitors. The next-generation ALK inhibitor PF-06463922 is predicted to exhibit increased affinity for ALK mutants prevalent in neuroblastoma.

Osteoporosis: A Review.

Osteoporosis is a silent disease which can significantly increase an individual's risk of fracture. Fractures can be physically debilitating and consequently cause a financial burden on the patient, so it is key to treat osteoporosis before a fracture occurs. Osteoporosis is defined based on the patient's bone mineral density (BMD) as compared to a young adult's BMD using standard deviations (SD).

Examination of near-wall hemodynamic parameters in the renal bridging stent of various stent graft configurations for repairing visceral branched aortic aneurysms.

Objective: This study examined the flow behavior of four stent graft configurations for endovascular repair of complex aneurysms of the descending aorta.

Methods: Computational fluid dynamics models with transient boundary conditions and rigid wall simplifying assumptions were developed and used with four distinct geometries to compare various near-wall hemodynamic parameters.

Results: Graphic plots for time-averaged wall shear stress, oscillating shear index, and relative residence time were presented and compared among the four stent graft configurations of interest.

Tackling Crizotinib Resistance: The Pathway from Drug Discovery to the Pediatric Clinic.

Neuroblastoma is a childhood malignancy that has not yet benefitted from the rapid progress in the development of small-molecule therapeutics for cancer. An opportunity to take advantage of pharmaceutical innovation in this area arose when the identification of ALK fusion proteins in non-small cell lung cancer (NSCLC) occurred in parallel to the discovery of point mutations of ALK in neuroblastomas. ALK is now known to be a marker of poor outcome in neuroblastoma, and therefore, urgent development of specific ALK inhibitors to treat this devastating disease is a necessity.

Timing of optimal surgical intervention for neonates with necrotizing enterocolitis.

Up to half of all patients with necrotizing enterocolitis require acute surgical treatment. Determining when to operate on these patients can be challenging. Utilizing a combination of clinical and metabolic indicators, we sought to identify the optimal timing of surgical intervention.

Limited miR-17-92 overexpression drives hematologic malignancies.

The overexpression of microRNA cluster miR-17-92 has been implicated in development of solid tumors and hematological malignancies. The role of miR-17-92 in lymphomagenesis has been extensively investigated; however, because of the developmental defects caused by miR-17-92 dysregulation, its ability to drive tumorigenesis has remained undetermined until recently. Here we demonstrate that overexpression of miR-17-92 in a limited number of hematopoietic cells is sufficient to cause B cell malignancies.

The kinase ALK stimulates the kinase ERK5 to promote the expression of the oncogene MYCN in neuroblastoma.

Anaplastic lymphoma kinase (ALK) is an important molecular target in neuroblastoma. Although tyrosine kinase inhibitors abrogating ALK activity are currently in clinical use for the treatment of ALK-positive (ALK(+)) disease, monotherapy with ALK tyrosine kinase inhibitors may not be an adequate solution for ALK(+) neuroblastoma patients. Increased expression of the gene encoding the transcription factor MYCN is common in neuroblastomas and correlates with poor prognosis.

Stereotactic radiotherapy for neovascular age-related macular degeneration: year 2 results of the INTREPID study.

Purpose: To determine the safety and efficacy of low-voltage, external-beam, stereotactic radiotherapy (SRT) for patients with neovascular age-related macular degeneration (AMD).

Design: Randomized, double-masked, sham-controlled, multicenter, clinical trial.

Participants: A total of 230 participants with neovascular AMD who received ≥ 3 ranibizumab or bevacizumab injections within the preceding year and requiring treatment at enrollment.

Blood transfusion in patients treated with surgery for necrotizing enterocolitis.

Background: Necrotizing enterocolitis (NEC) is a common surgical emergency in premature infants and has high morbidity and mortality. Intraoperative treatment with fluid and transfusions may be difficult.

Objectives: We evaluated risk factors for patients who needed transfusion with packed red blood cells during surgery for necrotizing enterocolitis with bowel resection.

A novel endovascular debranching technique using physician-assembled endografts for repair of thoracoabdominal aneurysms.

Objective: The objective of this study was to demonstrate a technique that uses physician-assembled endografts to make use of the benefits of parallel grafts while also providing for circumferential seal and fixation in repair of thoracoabdominal aneurysms in inoperable patients.

Methods: A single-center all-comers retrospective analysis of 14 patients was performed that looked at the early outcomes of patients treated for thoracoabdominal aneurysms. Three Crawford type II, four type III, four type IV, and three type V thoracoabdominal aneurysms were treated.

Enteral nutrition and total parenteral nutrition components in the course of total parenteral nutrition-associated cholestasis in neonatal necrotizing enterocolitis.

Background: Newborns with necrotizing enterocolitis (NEC) are at high risk for the development of total parenteral nutritional-associated cholestasis (TPNAC). Patients with NEC were evaluated to determine risk factors for development of TPNAC and predictors of resolution. We hypothesized that there are additional factors relating to the timing of enteral nutrition or TPN components that effect development and persistence of TPNAC in patients with NEC that may be altered to decrease the chance of progression to liver failure.

Timing of ostomy reversal in neonates with necrotizing enterocolitis.

Introduction: Most neonates with necrotizing enterocolitis (NEC) requiring laparotomy have bowel resection and intestinal diversion. At present, there is no consensus regarding the best time for enterostomy reversal. Our aim is to determine if there is any difference in outcomes of infants whose enterostomy was reversed early versus late.