An Exome Capture-Based RNA-Sequencing Assay for Genome-Wide Identification and Prioritization of Clinically Important Fusions in Pediatric Tumors.

This study reports the development of an exome capture-based RNA-sequencing assay to detect recurring and novel fusions in hematologic, solid, and central nervous system tumors. The assay used Twist Comprehensive Exome capture with either fresh or formalin-fixed samples and a bioinformatic platform that provides fusion detection, prioritization, and downstream curation. A minimum of 50 million uniquely mapped reads, a consensus read alignment/fusion calling approach using four callers (Arriba, FusionCatcher, STAR-Fusion, and Dragen), and custom software were used to integrate, annotate, and rank the candidate fusion calls.

Survival outcomes and surgical morbidity based on surgical approach to pulmonary metastasectomy in pediatric, adolescent and young adult patients with osteosarcoma.

Background: Thoracotomy is considered the standard surgical approach for the management of pulmonary metastases in osteosarcoma (OST). Several studies have identified the advantages of a thoracoscopic approach, however, the clinical significance of thoracotomy compared to thoracoscopy is yet to be evaluated in a randomized trial.

Aims: The primary aim was to determine the survival outcomes in OST patients based on surgical approach for pulmonary metastasectomy (PM) and secondary aim was to assess the post-operative morbidities of OST PM through various surgical approaches.

VEGF Secretion Drives Bone Formation in Classical MAP2K1+ Melorheostosis.

Patients with classical melorheostosis exhibit exuberant bone overgrowth in the appendicular skeleton, resulting in pain and deformity with no known treatment. Most patients have somatic, mosaic mutations in MAP2K1 (encoding the MEK1 protein) in osteoblasts and overlying skin. As with most rare bone diseases, lack of affected tissue has limited the opportunity to understand how the mutation results in excess bone formation.

Combined low-pass whole genome and targeted sequencing in liquid biopsies for pediatric solid tumors.

We designed a liquid biopsy (LB) platform employing low-pass whole genome sequencing (LP-WGS) and targeted sequencing of cell-free (cf) DNA from plasma to detect genome-wide copy number alterations (CNAs) and gene fusions in pediatric solid tumors. A total of 143 plasma samples were analyzed from 19 controls and 73 patients, including 44 bone or soft-tissue sarcomas and 12 renal, 10 germ cell, five hepatic, and two thyroid tumors. cfDNA was isolated from plasma collected at diagnosis, during and after therapy, and/or at relapse.

Role of Intraoperative Neurophysiological Monitoring in Preventing Stroke After Cardiac Surgery.

Background: Perioperative stroke after cardiac surgical procedures carries significant morbidity. Dual intraoperative neurophysiological monitoring with electroencephalography (EEG) and somatosensory-evoked potentials detects cerebral hypoperfusion and predicts postoperative stroke in noncardiac procedures. We further evaluated preoperative risk factors and intraoperative neuromonitoring ability to predict postoperative stroke after cardiac operations.

Paradoxical Effects of Endoplasmic Reticulum Aminopeptidase 1 Deficiency on HLA-B27 and Its Role as an Epistatic Modifier in Experimental Spondyloarthritis.

Objective: We undertook this study to examine the functional basis for epistasis between endoplasmic reticulum aminopeptidase 1 (ERAP1) and HLA-B27 in experimental spondyloarthritis (SpA).

Methods: ERAP1-knockout rats were created using genome editing and bred with HLA-B27/human β -microglobulin-transgenic (HLA-B27-Tg) rats and HLA-B7-Tg rats. The effects of ERAP1 deficiency on HLA allotypes were determined using immunoprecipitation and immunoblotting, flow cytometry, allogeneic T cell proliferation assays, and gene expression analyses.

Sex-based outcomes after surgery for acute type A aortic dissection.

Background: While prior data have suggested worse outcomes in women after acute type A aortic dissection (ATAAD) repair when compared to men, results have been inconsistent across studies over time. This study sought to evaluate the impact of sex on short- and long-term outcomes after ATAAD repair.

Methods: This was a retrospective study utilizing an institutional database of ATAAD repairs from 2007 to 2021.

Effect of untreated carotid artery stenosis at the time of isolated coronary artery bypass grafting.

Background: Severe carotid artery stenosis (sCAS) is frequently discovered at the time of evaluation for coronary arterial revascularization. However, there has been controversy regarding the optimal management of sCAS. This study evaluated the potential effects of untreated sCAS at time of coronary artery bypass grafting (CABG) in contemporary practice.

Central versus peripheral cannulation for acute type A aortic dissection.

Objective: This study sought to evaluate the impact of central aortic versus peripheral cannulation on outcomes after acute type A aortic dissection repair.

Methods: This was an observational study using an institutional database of acute type A aortic dissection repairs from 2007 to 2021. Patients were stratified according to central, subclavian, or femoral cannulation.

Outcomes of emergency surgery for acute type A aortic dissection complicated by malperfusion syndrome.

Objective: The study objective was to determine the impact of malperfusion syndrome on in-hospital mortality and midterm survival after emergency aortic arch reconstruction for acute type A aortic dissection.

Methods: This was an observational study of aortic surgeries from 2010 to 2018. All patients with acute type A aortic dissection undergoing open aortic arch reconstruction were included.

Preservation versus replacement of the aortic root for acute type A aortic dissection.

Objective: To determine the impact of aortic root preservation versus aortic root replacement (ARR) after acute type A aortic dissection (ATAAD) repair.

Methods: In this observational study of consecutive aortic surgeries between 2007 and 2021, patients with ATAAD were identified via a prospectively maintained institutional database and were stratified by root preservation versus ARR (including valve-sparing and complete ARR). Kaplan-Meier survival estimation and multivariable Cox regression analysis were performed.

The impact of prolonged mechanical ventilation after acute type A aortic dissection repair.

Objective: Patients with type A aortic dissection have increased resource use. The objective of this study was to describe the relationship between prolonged mechanical ventilation and longitudinal survival in patients undergoing type A aortic dissection repair.

Methods: We conducted a retrospective analysis of patients with type A aortic dissection undergoing repair from 2010 to 2018; Kaplan-Meier function and adjusted Cox regression analysis were used to compare in-hospital mortality and longitudinal survival accounting for time on mechanical ventilatory support.

The Role of Pharmacotherapeutic Agents in Children with Desmoid Tumors.

Desmoid tumors (DT) are rare fibroblastic, soft-tissue tumors that do not metastasize but can aggressively infiltrate tissues causing significant chronic discomfort and/or functional impairment. In the pediatric population, the incidence of DT is greatest during infancy and adolescence but can occur at any age. Dysregulated β-catenin, most commonly resulting from mutations in either CTNNB1 or germline APC (adenomatous polyposis coli) drives DT.

Cerebral protection using deep hypothermic circulatory arrest versus retrograde cerebral perfusion for aortic hemiarch reconstruction.

Background: With evolutions in technique, recent data encourage the use of cerebral perfusion during aortic arch repair. However, a randomized data have demonstrated higher rates of neurologic injury according to MRI lesions using antegrade cerebral perfusion during hemiarch reconstruction.

Methods: This was a retrospective review of two institutional aortic center databases to identify adult patients who underwent aortic hemiarch reconstruction for elective aortic aneurysm or acute type A aortic dissection.

Coronary Artery Bypass With Multiarterial Grafting vs Percutaneous Coronary Intervention.

Background: Data comparing patients who undergo multiarterial grafting during coronary artery bypass grafting (CABG) vs percutaneous coronary intervention (PCI) in patients with multivessel coronary disease are scarce. This study addresses the relevance of using multiple arterial conduits vs PCI for appropriate patients.

Methods: This retrospective study included all patients with coronary artery disease who underwent CABG with multiple arterial conduits or PCI.

Impact of Aortic Root Enlargement on Patients Undergoing Aortic Valve Replacement.

Background: Aortic root enlargement (ARE) can be an important adjunct for aortic valve replacement (AVR). This study compared outcomes of AVR with or without ARE.

Methods: This was an observational study using an institutional database of AVRs from 2010 to 2020 comparing patients who underwent isolated AVR vs AVR with ARE (AVR+ARE).

Impact of Transcatheter Aortic Valve Implantation on Severe Gastrointestinal Bleeding in Patients With Aortic Stenosis.

To investigate the effectiveness of transcatheter aortic valve implantation (TAVI) for resolving gastrointestinal bleeding (GIB) in patients with severe GIB and severe aortic stenosis. This was an observational study of consecutive TAVI procedures from 2011 to 2018, identified through a prospectively maintained institutional database. Patients with severe GIB defined as abnormal hemoglobin/hematocrit and overt bleeding or positive fecal occult blood test.

Misdiagnosis of Thoracic Aortic Emergencies Occurs Frequently Among Transfers to Aortic Referral Centers: An Analysis of Over 3700 Patients.

Background Acute aortic syndromes may be prone to misdiagnosis by nonreferral aortic centers with less diagnostic experience. We evaluated regional variability in these misdiagnosis trends among patients transferred to different regional quaternary care centers with presumed acute aortic syndromes. Methods and Results Two institutional aortic center databases were retrospectively reviewed for emergency transfers in patients diagnosed with acute aortic dissection, intramural hematoma, penetrating aortic ulcer, thoracic aortic aneurysm, or aortic pseudoaneurysm between 2008 and 2020.

The long-term impact of acute renal failure after aortic arch replacement for acute type A aortic dissection.

Objective: To determine the long-term impact of developing acute renal failure (ARF) on survival after open aortic arch reconstruction for acute type A aortic dissection (ATAAD).

Methods: This was an observational study of consecutive aortic surgeries from 2007 to 2021. Patients with ATAAD were identified via a prospectively maintained institutional database and were stratified by the presence or absence of postoperative ARF (by RIFLE criteria).

Long-term outcomes of patients undergoing mechanical versus bioprosthetic aortic root replacement.

Background: We evaluated the impact of valve type (mechanical vs. bioprosthetic) on survival after aortic root replacement (ARR).

Methods: In a propensity-matched analysis, we evaluated consecutive operations from 2010 to 2018.