The Impact of On-Target Resistance Mediated by EGFR-T790M or EGFR-C797S on EGFR Exon 20 Insertion Mutation Active Tyrosine Kinase Inhibitors.

Introduction: Mechanisms of resistance to EGFR exon 20 insertion mutation active inhibitors have not been extensively studied in either robust preclinical models or patient-derived rebiopsy specimens. We sought to characterize on-target resistance mutations identified in exon 20 insertion-mutated lung cancers treated with mobocertinib or poziotinib and evaluate whether these mutations would or would not have cross-resistance to next-generation inhibitors zipalertinib, furmonertinib, and sunvozertinib.

Methods: We identified mechanisms of resistance to EGFR exon 20 insertion mutation active inhibitors and then used preclinical models of EGFR exon 20 insertion mutations (A767_V769dupASV, D770_N771insSVD, V773_C774insH) plus common EGFR mutants to probe inhibitors in the absence/presence of EGFR-T790M or EGFR-C797S.

Heritability and variance component estimation for feed and water intake behaviors of feedlot cattle.

Feed and water intake are two important aspects of cattle production that greatly impact the profitability, efficiency, and sustainability of producers. Feed and, to a lesser degree, water intake have been studied previously; however, there is little research on their associated animal behaviors and there is a lack of standardized phenotypes for these behaviors. Feed and water intakes obtained with an Insentec system (Hokofarm Group, The Netherlands) from 830 crossbred steers were used to compute five intake behaviors for both feed and water: daily sessions (DS), intake rate (IR), session size (SS), time per session (TS), and session interval (SI).

EGFR exon 19 insertion EGFR-K745_E746insIPVAIK and others with rare XPVAIK amino-acid insertions: Preclinical and clinical characterization of the favorable therapeutic window to all classes of approved EGFR kinase inhibitors.

Background: The epidermal growth factor receptor (EGFR)-K745_E746insIPVAIK and others with XPVAIK amino-acid insertions are exon 19 insertion mutations, which, at the structural modeling level, resemble EGFR tyrosine kinase inhibitor (TKI)-sensitizing mutants. An important unmet need is the characterization of therapeutic windows plus clinical outcomes of exon 19 XPVAIK amino-acid insertion mutations to available EGFR TKIs.

Methods: We used preclinical models of EGFR-K745_E746insIPVAIK and more typical EGFR mutations (exon 19 deletion, L858R, L861Q, G719S, A763_Y764insFQEA, other exon 20 insertion mutations) to probe representative 1st (erlotinib), 2nd (afatinib), 3rd generation (osimertinib), and EGFR exon 20 insertion active (mobocertinib) TKIs.

Biologic Association Annual Summit: 2020 Report.

Interest and research in biologic approaches for tissue healing are exponentially growing for a variety of musculoskeletal conditions. The recent hype concerning musculoskeletal biological therapies (including viscosupplementation, platelet-rich plasma, and cellular therapies, or "stem cells") is driven by several factors, including demand by patients promising regenerative evidence supported by substantial basic and translational work, as well as commercial endeavors that complicate the scientific and lay understanding of biological therapy outcomes. While significant improvements have been made in the field, further basic and preclinical research and well-designed randomized clinical trials are needed to better elucidate the optimal indications, processing techniques, delivery, and outcome assessment.

Harmonized outcome measures for use in degenerative lumbar spondylolisthesis patient registries and clinical practice.

Objective: The development of new treatment approaches for degenerative lumbar spondylolisthesis (DLS) has introduced many questions about comparative effectiveness and long-term outcomes. Patient registries collect robust, longitudinal data that could be combined or aggregated to form a national and potentially international research data infrastructure to address these and other research questions. However, linking data across registries is challenging because registries typically define and capture different outcome measures.

Osteoporosis: Recent Recommendations and Positions of the American Society for Bone and Mineral Research and the International Society for Clinical Densitometry.

➤: Osteoporosis is common in orthopaedic patients, not only in those sustaining fragility fractures but also in patients ≥50 years old who are having elective orthopaedic surgery.

➤: The American Society for Bone and Mineral Research (ASBMR) has developed consensus-based recommendations for secondary fracture prevention for all patients who are ≥65 years old with a hip or spine fracture.

➤: The ASBMR encourages orthopaedic surgeons to "Own the Bone," by beginning prevention of a secondary fracture during hospitalization for a fragility fracture, if practicable, and arranging follow-up for continued bone health care after discharge.

Atypical Presentation of Extramedullary Plasmacytoma.

Background: Plasmacytomas are monoclonal proliferations of plasma cells that typically affect the intramedullary axial skeleton. Imaging findings of an extramedullary plasmacytoma on radiograph and computed tomography can be nonspecific and can resemble other entities such as lymphoma, metastases, chondrosarcomas, or giant cell tumors.

Case Report: A 60-year-old female with a medical history of partial complex seizures, hypertension, diabetes, glaucoma, and hyperlipidemia presented with complaints of superficial abdominal pain associated with erythema and swelling for 3 weeks.

Mitochondrial Encephalomyopathy With Lactic Acidosis and Stroke-Like Episodes-MELAS Syndrome.

Background: Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome is a rare inherited disorder that results in waxing and waning nervous system and muscle dysfunction. MELAS syndrome may overlap with other neurologic disorders but shows distinctive imaging features.

Case Report: We present the case of a 28-year-old female with atypical stroke-like symptoms, a strong family history of stroke-like symptoms, and a relapsing-remitting course for several years.

Cannabis use in people with Parkinson's disease and Multiple Sclerosis: A web-based investigation.

Objectives: Cannabis has been used for medicinal purpose for thousands of years; however the positive and negative effects of cannabis use in Parkinson's disease (PD) and Multiple Sclerosis (MS) are mostly unknown. Our aim was to assess cannabis use in PD and MS and compare results of self-reported assessments of neurological disability between current cannabis users and non-users.

Methods: An anonymous web-based survey was hosted on the Michael J.

Persistent Sciatic Artery: A Favorable Anatomic Variant in a Setting of Trauma.

Background: Persistent sciatic artery (PSA) is a rare congenital anomaly of the circulation of the lower limb that results from the persistence of an artery that normally regresses early in embryonic development. PSA is usually an incidental finding and is exceedingly rare to find bilaterally.

Case Report: We present the case of a rare presentation of PSA that resulted in a favorable outcome for a patient who sustained a gunshot wound to his midthigh and discuss the history, embryology, anatomy, classification schema, imaging evaluation, complications, diagnosis, and management of PSA.

The Medicare Access and CHIP Reauthorization Act (MACRA) of 2015: What's New?

The Centers for Medicare and Medicaid Services (CMS) released its Final Rule on the Medicare Access and CHIP [Children's Health Insurance Program] Reauthorization Act (MACRA) in November 2016. The Rule finalizes the details of the merit-based incentive payment system (MIPS) and the alternative payment model (APM), which will now collectively be referred to as the Quality Payment Program (QPP). This article offers the orthopaedic community a summary of the alterations in healthcare policy that will affect practices nationwide.

Understanding Value-based Reimbursement Models and Trends in Orthopaedic Health Policy: An Introduction to the Medicare Access and CHIP Reauthorization Act (MACRA) of 2015.

In 2015, the US Congress passed legislation entitled the Medicare Access and CHIP [Children's Health Insurance Program] Reauthorization Act (MACRA), which led to the formation of two reimbursement paradigms: the merit-based incentive payment system (MIPS) and alternative payment models (APMs). The MACRA effectively repealed the Centers for Medicare and Medicaid Services (CMS) sustainable growth rate (SGR) formula while combining several CMS quality-reporting programs. As such, MACRA represents an unparalleled acceleration toward reimbursement models that recognize value rather than volume.

An evidence-based clinical guideline for antibiotic prophylaxis in spine surgery.

Background Context: The North American Spine Society's (NASS) Evidence-Based Clinical Guideline on Antibiotic Prophylaxis in Spine Surgery provides evidence-based recommendations to address key clinical questions regarding the efficacy and the appropriate antibiotic prophylaxis protocol to prevent surgical site infections in patients undergoing spine surgery. The guideline is intended to address these questions based on the highest quality clinical literature available on this subject as of June 2011.

Purpose: Provide an evidence-based educational tool to assist spine surgeons in preventing surgical site infections.

An evidence-based clinical guideline for the diagnosis and treatment of degenerative lumbar spinal stenosis (update).

Background Context: The evidence-based clinical guideline on the diagnosis and treatment of degenerative lumbar spinal stenosis by the North American Spine Society (NASS) provides evidence-based recommendations to address key clinical questions surrounding the diagnosis and treatment of degenerative lumbar spinal stenosis. The guideline is intended to reflect contemporary treatment concepts for symptomatic degenerative lumbar spinal stenosis as reflected in the highest quality clinical literature available on this subject as of July 2010. The goals of the guideline recommendations are to assist in delivering optimum efficacious treatment and functional recovery from this spinal disorder.

An evidence-based clinical guideline for the diagnosis and treatment of cervical radiculopathy from degenerative disorders.

Background Context: The North American Spine Society (NASS) Evidence-Based Clinical Guideline on the Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders provides evidence-based recommendations on key clinical questions concerning the diagnosis and treatment of cervical radiculopathy from degenerative disorders. The guideline addresses these questions based on the highest quality clinical literature available on this subject as of May 2009. The guideline's recommendations assist the practitioner in delivering optimum efficacious treatment of and functional recovery from this common disorder.

An evidence-based clinical guideline for the use of antithrombotic therapies in spine surgery.

Background Context: The objective of the North American Spine Society (NASS) Evidence-Based Clinical Guideline on antithrombotic therapies in spine surgery was to provide evidence-based recommendations to address key clinical questions surrounding the use of antithrombotic therapies in spine surgery. The guideline is intended to address these questions based on the highest quality clinical literature available on this subject as of February 2008. The goal of the guideline recommendations was to assist in delivering optimum, efficacious treatment with the goal of preventing thromboembolic events.

An evidence-based clinical guideline for the diagnosis and treatment of degenerative lumbar spondylolisthesis.

Background Context: The objective of the North American Spine Society (NASS) evidence-based clinical guideline on the diagnosis and treatment of degenerative lumbar spondylolisthesis is to provide evidence-based recommendations on key clinical questions concerning the diagnosis and treatment of degenerative lumbar spondylolisthesis. The guideline is intended to address these questions based on the highest quality clinical literature available on this subject as of January 2007. The goal of the guideline recommendations is to assist the practitioner in delivering optimum, efficacious treatment of and functional recovery from this common disorder.

Interventional therapies, surgery, and interdisciplinary rehabilitation for low back pain: an evidence-based clinical practice guideline from the American Pain Society.

Study Design: Clinical practice guideline.

Objective: To develop evidence-based recommendations on use of interventional diagnostic tests and therapies, surgeries, and interdisciplinary rehabilitation for low back pain of any duration, with or without leg pain.

Summary Of Background Data: Management of patients with persistent and disabling low back pain remains a clinical challenge.

Surgery for low back pain: a review of the evidence for an American Pain Society Clinical Practice Guideline.

Study Design: Systematic review.

Objective: To systematically assess benefits and harms of surgery for nonradicular back pain with common degenerative changes, radiculopathy with herniated lumbar disc, and symptomatic spinal stenosis.

Summary Of Background Data: Although back surgery rates continue to increase, there is uncertainty or controversy about utility of back surgery for various conditions.