Publications by authors named "Brendan Lilley"

Skeletal fractures are traumatic injuries that are widely accepted as requiring acute treatment to avoid long-term disability and dysfunction. There are a number of soft-tissue injuries or non-traditional fractures, frequently treated by sports medicine surgeons, which additionally require treatment in an expedited fashion in order to optimize healing and function. Sports medicine injuries of the lower extremity requiring acute treatment include, but are not limited to, irreducible shoulder dislocations, acute traumatic rotator cuff tears, posterior sternoclavicular joint dislocations, high grade acromioclavicular joint dislocations, pectoralis major tendon ruptures, distal biceps tendon ruptures, and triceps tendon ruptures.

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Skeletal fractures are traumatic injuries that are widely accepted as requiring acute treatment to avoid long-term disability and dysfunction. There are a number of soft-tissue injuries or non-traditional fractures, frequently treated by sports medicine surgeons, which additionally require treatment in an expedited fashion in order to optimize healing and function. Sports medicine injuries of the lower extremity requiring acute treatment include, but are not limited to, multiligamentous knee injuries, proximal hamstring ruptures, quadriceps tendon ruptures, patellar sleeve avulsions, patellar tendon ruptures, tibial spine avulsions, posterior cruciate ligament avulsions, bucket handle meniscus tears, and achilles tendon ruptures.

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Background: Glenohumeral osteophytes (OPs) can adversely influence postoperative range of motion (ROM) following shoulder arthroplasty due to mechanical impingement. Though commercial three-dimensional preoperative planning software (3D PPS) is available to simulate ROM before and after OP resection, little is known about the magnitude of effect OPs and their subsequent removal have on simulated glenohumeral ROM.

Methods: Included patients were 1) indicated for reverse total shoulder arthroplasty (rTSA) using 3D PPS and 2) presented with glenoid and/or humeral head OPs on preoperative two-dimensional computed tomography (2D-CT) imaging.

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Anterior cruciate ligament (ACL) injuries rarely occur as an isolated event and often include associated meniscal, subchondral bone, and collateral ligament injuries. Concomitant pathology frequently complicates primary and revision ACL reconstruction and must be addressed to ensure comprehensive diagnosis and treatment. In this Technical Note, we describe our method for treatment of complex knee instability following multiple failed ACL reconstruction using a multiligament reconstruction technique with an osteochondral allograft transplantation to the lateral femoral condyle.

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Background: Fractures are a common pediatric injury. The coronavirus disease 2019 (COVID-19) pandemic resulted in significant changes in daily life that could impact the incidence of pediatric fractures. The purpose of this study was to compare the incidence of pediatric fractures in the United States during the COVID-19 pandemic to previous seasonally adjusted fracture incidence rates using the National Electronic Injury Surveillance System (NEISS) database and the American Community Survey (ACS).

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Phosphatidic acid is a key signaling molecule heavily implicated in exocytosis due to its protein-binding partners and propensity to induce negative membrane curvature. One phosphatidic acid-producing enzyme, phospholipase D (PLD), has also been implicated in neurotransmission. Unfortunately, due to the unreliability of reagents, there has been confusion in the literature regarding the expression of PLD isoforms in the mammalian brain which has hampered our understanding of their functional roles in neurons.

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Traditionally, total shoulder arthroplasty is performed using a deltopectoral approach through which the glenohumeral joint is accessed by mobilization of the subscapularis. Despite several variations on the subscapularis management techniques, postoperative complications, including subscapularis deficiency and lower functional outcomes, remain an area for improvement. The purpose of this Technical Note is to describe in detail our technique for management of the subscapularis in the setting of a stemless humeral implant through which the repair is planned and almost entirely performed at the beginning of the case, prior to the subscapularis peel.

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Background: Three-dimensional (3D) preoperative planning software for reverse total shoulder arthroplasty (rTSA) has been implemented in recent years in order to increase accuracy, improve efficiency, and add value to the outcome. A comprehensive literature review is required to determine the utility of preoperative 3D planning software in guiding orthopedic surgeons for implant placement in rTSA. We hypothesize that implementation of 3D preoperative planning software in the setting of rTSA leads to high concordance with minimal deviation from the preoperative plan.

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Background And Hypothesis: The impact of preoperative fatty infiltration of specific rotator cuff muscles on the outcomes of reverse total shoulder arthroplasty (rTSA) has not been well defined. Preoperative fatty infiltration of the shoulder musculature will negatively affect rTSA outcomes.

Methods: A comprehensive literature review was conducted as per the Preferred Reporting Items for Systematic Reviews and Meta-analyses using PubMed, Embase, OVID Medline, Scopus, Cinahl, Web of Science, and Cochrane databases for original, English-language studies evaluating effect of fatty infiltration of shoulder musculature on rTSA outcomes published from January 1, 2000 to present.

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Alveolar and endothelial injury may be differentially associated with coronavirus disease (COVID-19) severity over time. To describe alveolar and endothelial injury dynamics and associations with COVID-19 severity, cardiorenovascular injury, and outcomes. This single-center observational study enrolled patients with COVID-19 requiring respiratory support at emergency department presentation.

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The introduction of vaccines has inspired hope in the battle against SARS-CoV-2. However, the emergence of viral variants, in the absence of potent antivirals, has left the world struggling with the uncertain nature of this disease. Antibodies currently represent the strongest correlate of immunity against SARS-CoV-2, thus we profiled the earliest humoral signatures in a large cohort of acutely ill (survivors and nonsurvivors) and mild or asymptomatic individuals with COVID-19.

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BACKGROUNDSARS-CoV-2 plasma viremia has been associated with severe disease and death in COVID-19 in small-scale cohort studies. The mechanisms behind this association remain elusive.METHODSWe evaluated the relationship between SARS-CoV-2 viremia, disease outcome, and inflammatory and proteomic profiles in a cohort of COVID-19 emergency department participants.

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Retinitis pigmentosa (RP) and associated inherited retinal diseases (IRDs) are caused by rod photoreceptor degeneration, necessitating therapeutics promoting rod photoreceptor survival. To address this, we tested compounds for neuroprotective effects in multiple zebrafish and mouse RP models, reasoning drugs effective across species and/or independent of disease mutation may translate better clinically. We first performed a large-scale phenotypic drug screen for compounds promoting rod cell survival in a larval zebrafish model of inducible RP.

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Mechanisms underlying severe coronavirus disease 2019 (COVID-19) disease remain poorly understood. We analyze several thousand plasma proteins longitudinally in 306 COVID-19 patients and 78 symptomatic controls, uncovering immune and non-immune proteins linked to COVID-19. Deconvolution of our plasma proteome data using published scRNA-seq datasets reveals contributions from circulating immune and tissue cells.

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Article Synopsis
  • A randomized trial was conducted at 34 US hospitals to assess the effectiveness of hydroxychloroquine for treating hospitalized adults with COVID-19, enrolling 479 patients from April to June 2020 and stopping early due to futility.
  • Participants were divided into two groups, receiving either hydroxychloroquine or a placebo, with primary outcomes measured 14 days post-randomization using a 7-category scale.
  • Results showed that despite a diverse patient sample, hydroxychloroquine did not demonstrate improved clinical outcomes compared to the placebo, leading to a conclusion of its ineffectiveness for this patient population.
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Article Synopsis
  • The accessory optic system (AOS) plays a key role in stabilizing visual images by detecting retinal image slip and communicating this to the brain.
  • Researchers studied two specific Cre lines that target different components of AOS circuits related to vertical motion: one line focuses on a subtype of retinal cells that respond to downward motion, while the other targets neurons in the medial terminal nucleus.
  • The protein semaphorin 6A (Sema6A) is essential for forming connections between these neurons and other parts of the AOS, indicating its importance in the overall development of these visual circuits.
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Age-related decreases in neural function result in part from alterations in synapses. To identify molecular defects that lead to such changes, we focused on the outer retina, in which synapses are markedly altered in old rodents and humans. We found that the serine/threonine kinase LKB1 and one of its substrates, AMPK, regulate this process.

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Axons develop in a series of steps, beginning with specification, outgrowth, and arborization, and terminating with formation and maturation of presynaptic specializations. We found previously that the SAD-A and SAD-B kinases are required for axon specification and arborization in subsets of mouse neurons. Here, we show that following these steps, SAD kinases become localized to synaptic sites and are required within presynaptic cells for structural and functional maturation of synapses in both peripheral and central nervous systems.

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Liver kinase b1 (Lkb1) protein kinase activity regulates cell growth and cell polarity. Here, we show Lkb1 is essential for maintaining a balance between mitotic and postmitotic cell fates in development of the mammalian skeleton. In this process, Lkb1 activity controls the progression of mitotic chondrocytes to a mature, postmitotic hypertrophic fate.

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The mammalian target of rapamycin (mTOR) plays an important role in controlling islet β-cell function. However, the underlying molecular mechanisms remain poorly elucidated. Synapses of amphids defective kinase-A (SAD-A) is a 5' adenosine monophosphate-activated protein kinase-related protein kinase that is exclusively expressed in pancreas and brain.

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Extrinsic cues activate intrinsic signaling mechanisms to pattern neuronal shape and connectivity. We showed previously that three cytoplasmic Ser/Thr kinases, LKB1, SAD-A, and SAD-B, control early axon-dendrite polarization in forebrain neurons. Here, we assess their role in other neuronal types.

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Type 2 diabetes is characterized by defective glucose-stimulated insulin secretion (GSIS) from pancreatic β cells, which can be restored by glucagon-like peptide 1 (GLP-1), an incretin hormone commonly used for the treatment of type 2 diabetes. However, molecular mechanisms by which GLP-1 affects glucose responsiveness in islet β cells remain poorly understood. Here we investigated a role of SAD-A, an AMP-activated protein kinase (AMPK)-related kinase, in regulating GSIS in mice with conditional SAD-A deletion.

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Protein quality control is a balance between chaperone-assisted folding and removal of misfolded proteins from the endoplasmic reticulum (ER). Cell-based assays have been used to identify key players of the dislocation machinery, including members of the Derlin family. We generated conditional knockout mice to examine the in vivo role of Derlin-2, a component that nucleates cellular dislocation machinery.

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Background: Neurons assemble into a functional network through a sequence of developmental processes including neuronal polarization and synapse formation. In Caenorhabditis elegans, the serine/threonine SAD-1 kinase is essential for proper neuronal polarity and synaptic organization. To determine if SAD-1 activity regulates the establishment or maintenance of these neuronal structures, we examined its temporal requirements using a chemical-genetic method that allows for selective and reversible inactivation of its kinase activity in vivo.

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The polarization of axon and dendrites underlies the ability of neurons to integrate and transmit information in the brain. We show here that the serine/threonine kinase LKB1, previously implicated in the establishment of epithelial polarity and control of cell growth, is required for axon specification during neuronal polarization in the mammalian cerebral cortex. LKB1 polarizing activity requires its association with the pseudokinase Stradalpha and phosphorylation by kinases such as PKA and p90RSK, which transduce neurite outgrowth-promoting cues.

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