Precision needle-punch tumor enrichment from paraffin blocks improves the detection of clinically actionable genomic alterations and biomarkers.

Background: While many molecular assays can detect mutations at low tumor purity and variant allele frequencies, complex biomarkers such as tumor mutational burden (TMB), microsatellite instability (MSI), and genomic loss of heterozygosity (gLOH) require higher tumor purity for accurate measurement. Scalable, quality-controlled, tissue-conserving methods to increase tumor nuclei percentage (TN%) from tumor specimens are needed for complex biomarkers and hence necessary to maximize patient matching to approved therapies or clinical trial enrollment. We evaluated the clinical utility and performance of precision needle-punch enrichment (NPE) compared with traditional razor blade macroenrichment of tumor specimens on molecular testing success.

Potential pathogenic germline variant reporting from tumor comprehensive genomic profiling complements classic approaches to germline testing.

Existing guidance regarding clinically informed germline testing for patients with cancer is effective for evaluation of classic hereditary cancer syndromes and established gene/cancer type associations. However, current screening methods may miss patients with rare, reduced penetrance, or otherwise occult hereditary risk. Secondary finding of suspected germline variants that may confer inherited cancer risk via tumor comprehensive genomic profiling (CGP) has the potential to help address these limitations.

Variation in Reported Learning Outcomes and Measurement Instruments in Hip Arthroscopy Simulation Training: A Systematic Review.

Purpose: To systematically review the current literature on the effectiveness of hip arthroscopy simulation training and to determine the consistency of reporting and validation of simulation used in hip arthroscopy.

Methods: Three databases (PubMed, EMBase, and CINAHL) were screened using PRISMA guidelines in January 2022 for published literature on virtual simulation in hip arthroscopy. Studies reporting on the use of hip arthroscopy simulation training in orthopedic surgical trainees were included and assessed for quality and risk of bias using MINORS criteria.

Programmatic Precision Oncology Decision Support for Patients With Gastrointestinal Cancer.

Purpose: With the growing number of available targeted therapeutics and molecular biomarkers, the optimal care of patients with cancer now depends on a comprehensive understanding of the rapidly evolving landscape of precision oncology, which can be challenging for oncologists to navigate alone.

Methods: We developed and implemented a precision oncology decision support system, GI TARGET, (Gastrointestinal Treatment Assistance Regarding Genomic Evaluation of Tumors) within the Gastrointestinal Cancer Center at the Dana-Farber Cancer Institute. With a multidisciplinary team, we systematically reviewed tumor molecular profiling for GI tumors and provided molecularly informed clinical recommendations, which included identifying appropriate clinical trials aided by the computational matching platform MatchMiner, suggesting targeted therapy options on or off the US Food and Drug Administration-approved label, and consideration of additional or orthogonal molecular testing.

MatchMiner: an open-source platform for cancer precision medicine.

Widespread, comprehensive sequencing of patient tumors has facilitated the usage of precision medicine (PM) drugs to target specific genomic alterations. Therapeutic clinical trials are necessary to test new PM drugs to advance precision medicine, however, the abundance of patient sequencing data coupled with complex clinical trial eligibility has made it challenging to match patients to PM trials. To facilitate enrollment onto PM trials, we developed MatchMiner, an open-source platform to computationally match genomically profiled cancer patients to PM trials.

Systematic review of prevalence, risk factors, and management of instability following reverse shoulder arthroplasty.

Background: Since its approval for use, reverse shoulder arthroplasty (RSA) has become the primary treatment for cuff tear arthropathy, with indications expanding more recently to include revision fracture, osteoarthritis with significant glenoid bone loss, tumor, and chronic instability. Instability is a well-described postoperative complication, occurring in 1to 31% of relatively small cohorts and case series. Given the relative infrequency of instability, there remains a need for a comprehensive review of instability with a focus on risk factors and management.

Biological augmentation of meniscal repair: a systematic review.

Purpose: Orthopedic literature remains divided on the utility of biologic augmentation to optimize outcomes after isolated meniscal repair. The aim of this systematic review is to analyze the clinical outcomes and re-operation rates of biologically augmented meniscal repairs.

Methods: PubMed, CINAHL, Cochrane, and EMBASE databases were queried in October 2020 for published literature on isolated meniscal repair with biological augmentation.

Terrible triad of the elbow and associated variants: a systematic review.

Background: The terrible triad of the elbow (TTE) is a complex injury consisting of simultaneous elbow dislocation or subluxation, radial head fracture, and coronoid fracture. During the initial assessment of a TTE, the typical severity of presenting pain, swelling, and limited range of motion may limit the ability to perform a thorough physical examination and thus divert a clinician's attention away from additional injuries to the ipsilateral upper extremity. Therefore, the purpose of this study was to review the literature for reported cases of concomitant ipsilateral upper extremity injuries associated with a TTE and discuss various strategies to increase clinician awareness to avoid underdiagnosis and missed diagnoses.

Extracellular Domain In-Frame Deletions Are Therapeutically Targetable Genomic Alterations That Function as Oncogenic Drivers in Cholangiocarcinoma.

We conducted next-generation DNA sequencing on 335 biliary tract cancers and characterized the genomic landscape by anatomic site within the biliary tree. In addition to frequent fusions among patients with intrahepatic cholangiocarcinoma (IHCC), we identified extracellular domain in-frame deletions (EID) in 5 of 178 (2.8%) patients with IHCC, including two patients with p.

Rehabilitation variability after rotator cuff repair.

Background: There has been increasing recognition of the importance for standardized postoperative rehabilitation protocols. Despite published guidelines in 2016 by the American Society of Shoulder and Elbow Therapists (ASSET), optimal postoperative rehabilitation after rotator cuff repair (RCR) remains an area of active academic debate. The goals of this study were (1) to assess the variability of RCR rehabilitation protocols published online, (2) to study the congruence between online RCR rehabilitation protocols and the ASSET consensus statement, and (3) to identify differences in online RCR rehabilitation protocols from before and after 2016.

Molecular Characterization and Therapeutic Targeting of Colorectal Cancers Harboring Receptor Tyrosine Kinase Fusions.

Purpose: Receptor tyrosine kinase fusions in colorectal cancers are rare, but potentially therapeutically relevant. We describe clinical, molecular, and pathologic attributes of RTK fusion-associated colorectal cancer.

Experimental Design: We identified all cases with RTK fusions in patients with colorectal cancer seen at Dana-Farber Cancer Institute (Boston, MA) who underwent OncoPanel testing between 2013 and 2018.

Paget-Schroetter syndrome in athletes: a comprehensive and systematic review.

Background: Paget-Schroetter syndrome (PSS) is a rare condition of axillosubclavian vein thrombosis often seen in athletes with a history of repetitive external rotation and abduction of the shoulder. The purpose of this review was to analyze the literature and characterize PSS in the athletic population, including risk of PSS by sport. We also provide a comprehensive review of PSS to inform clinicians on the pathophysiology, detection, and management of the condition.

Monoallelic and biallelic CREB3L1 variant causes mild and severe osteogenesis imperfecta, respectively.

PurposeOsteogenesis imperfecta (OI) is a heritable skeletal dysplasia. Dominant pathogenic variants in COL1A1 and COL1A2 explain the majority of OI cases. At least 15 additional genes have been identified, but those still do not account for all OI phenotypes that present.

A structural equation model looking at student's participatory behavior and their success in Calculus I.

Background: Government projections in the USA indicate that the country will need a million more science, technology, engineering, and mathematics (STEM) graduates above and beyond those already projected by the year 2022. Of crucial importance to the STEM pipeline is success in Calculus I, without which continuation in a STEM major is not possible. The STEM community at large, and mathematics instructors specifically, need to understand factors that influence and promote success in order to mitigate the alarming attrition trend.

Endothelial and circulating C19MC microRNAs are biomarkers of infantile hemangioma.

Infantile hemangioma (IH) is the most common vascular tumor of infancy, and it uniquely regresses in response to oral propranolol. MicroRNAs (miRNAs) have emerged as key regulators of vascular development and are dysregulated in many disease processes, but the role of miRNAs in IH growth has not been investigated. We report expression of C19MC, a primate-specific megacluster of miRNAs expressed in placenta with rare expression in postnatal tissues, in glucose transporter 1-expressing (GLUT-1-expressing) IH endothelial cells and in the plasma of children with IH.

Methylation status of the chromosome arm 19q MicroRNA cluster in sporadic and androgenetic-Biparental mosaicism-associated hepatic mesenchymal hamartoma.

The C19MC gene on chromosome band 19q13.4 encodes a cluster of 46 microRNAs; those microRNAs are normally only expressed from the paternal allele and in the placenta. Placental expression correlates with selective demethylation of the paternal C19MC promoter, in contrast to methylation of both maternal and paternal alleles in nonplacental tissues.

Nursing students practice primary fire prevention.

Unlabelled: The purpose of this project was to evaluate a standardized, interactive, home fire safety program for elementary school students.

Background: Senior baccalaureate nursing students in their pediatric clinical rotation taught burn prevention techniques using Hazard House, a model house filled with common household fire hazards (Hazard House, 2006, Ref. 1).

CTC1 Mutations in a patient with dyskeratosis congenita.

Dyskeratosis congenita (DC) is a rare inherited bone marrow failure syndrome caused by mutations in seven genes involved in telomere biology, with approximately 50% of cases remaining genetically uncharacterized. We report a patient with classic DC carrying a compound heterozygous mutation in the CTC1 (conserved telomere maintenance component 1) gene, which has recently implicated in the pleiotropic syndrome Coats plus. This report confirms a molecular link between DC and Coats plus and expands the genotype-phenotype complexity observed in telomere-related genetic disorders.

Porphyrins are not present in feline ocular tissues or corneal sequestra.

Objective: To determine if feline lacrimal glands, glands of the third eyelid, corneas, and corneal sequestra contain porphyrins, which could be responsible for the brown/amber discoloration of corneal sequestra and tears in affected cats.

Procedures: Samples of grossly normal cornea, lacrimal gland, gland of the third eyelid, and sequestra obtained via keratectomy were collected. Porphyrin concentrations of the homogenate were determined by spectrofluorometry with protoporphyrin IX and coproporphyrin III dihydrochloride used as standards.

Shope fibroma virus keratitis and spontaneous cataracts in a domestic rabbit.

A 7-year-old domestic rabbit presented for an enlarging ventral perilimbal mass OS. Keratectomy was performed to remove the mass. A diagnosis of Shope fibroma virus keratitis was confirmed based on signalment, clinical signs, histologic evaluation and virus isolation.

Evaluation of canine serum for the presence of antiretinal autoantibodies in sudden acquired retinal degeneration syndrome.

Objective: To determine the presence of serum antiretinal antibodies in sudden acquired retinal degeneration syndrome (SARDS) affected dogs and the size of the antigen to which these antibodies bind via the use of enzyme-linked immunosorbent assay (ELISA) and Western blot immunoassays.

Animals Studied: Serum was collected from 13 dogs affected by SARDS and five dogs with normal ocular examinations.

Procedures: All serum samples were subjected to ELISA with saline-soluble canine retinal tissue and Western blot analyses with SDS solubilized normal canine retinal tissue as the antigen.