Simplified Mechanical Tests Can Simulate Physiological Mechanics of a Fixation Construct for Periprosthetic Femoral Fractures

2021 ◽  
Vol 144 (3) ◽  
Author(s):  
Xiang Chen ◽  
Casey A. Myers ◽  
Chadd W. Clary ◽  
Ryan J. DeWall ◽  
Bryan Fritz ◽  
...  

Abstract Plate fractures after fixation of a Vancouver Type B1 periprosthetic femoral fracture (PFF) are difficult to treat and could lead to severe disability. However, due to the lack of direct measurement of in vivo performance of the PFF fixation construct, it is unknown whether current standard mechanical tests or previous experimental and computational studies have appropriately reproduced the in vivo mechanics of the plate. To provide a basis for the evaluation and development of appropriate mechanical tests for assessment of plate fracture risk, this study applied loads of common activities of daily living (ADLs) to implanted femur finite element (FE) models with PFF fixation constructs with an existing or a healed PFF. Based on FE simulated plate mechanics, the standard four-point-bend test adequately matched the stress state and the resultant bending moment in the plate as compared with femur models with an existing PFF. In addition, the newly developed constrained three-point-bend tests were able to reproduce plate stresses in models with a healed PFF. Furthermore, a combined bending and compression cadaveric test was appropriate for risk assessment including both plate fracture and screw loosening after the complete healing of PFF. The result of this study provides the means for combined experimental and computational preclinical evaluation of PFF fixation constructs.

2021 ◽  
Vol 20 (3) ◽  
pp. 156-160
Author(s):  
CARLOS RODRIGO DE MELLO ROESLER ◽  
RÔMULO PEDROZA PINHEIRO ◽  
ANDRÉ LUÍS ALMEIDA PIZZOLATTI ◽  
VALERIA ROMERO ◽  
HELTON LUIZ APARECIDO DEFINO

ABSTRACT Objective Evaluate and compare the mechanical resistance and the fatigue behavior associated with the use of three different modalities of vertebral fixation system rod connectors through in vitro pre-clinical mechanical tests developed specifically for this application (linear, lateral with square connector and lateral with oblique connector). Methods Cobalt chromium rods 5.5 mm in diameter were used and coupled with three types of connectors: a) side rod with oblique connector, b) side rod with square connector, and c) rod and linear connectors. Quasi-static mechanical four-point bending and fatigue tests were performed. The variables measured were (I) the bending moment at the yield limit, (II) the displacement at the yield limit, (III) the rigidity of the system in flexion and (IV) the number of cycles until system failure. Results The linear system presented the greatest force and the greatest moment at the yield limit, as well as the greatest stiffness equivalent to bending. All specimens with square and oblique connectors endured 2.5 million cycles in the minimum and maximum conditions of applied moment. The specimens with linear connector endured 2.5 million cycles with fractions of 40.14% of the bending moment at the yield limit, but failed with levels of 60.17% and 80.27%. Conclusions Systems with linear connectors showed greater mechanical resistance when compared to systems with square and oblique connectors. All systems supported cyclic loads that mimic in vivo demands. Level of evidence V; In vitro research.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Dilakshan Srikanthan ◽  
Michael S. Taccone ◽  
Randy Van Ommeren ◽  
Joji Ishida ◽  
Stacey L. Krumholtz ◽  
...  

AbstractDiffuse intrinsic pontine glioma (DIPG) is a lethal pediatric brain tumor and the leading cause of brain tumor–related death in children. As several clinical trials over the past few decades have led to no significant improvements in outcome, the current standard of care remains fractionated focal radiation. Due to the recent increase in stereotactic biopsies, tumor tissue availabilities have enabled our advancement of the genomic and molecular characterization of this lethal cancer. Several groups have identified key histone gene mutations, genetic drivers, and methylation changes in DIPG, providing us with new insights into DIPG tumorigenesis. Subsequently, there has been increased development of in vitro and in vivo models of DIPG which have the capacity to unveil novel therapies and strategies for drug delivery. This review outlines the clinical characteristics, genetic landscape, models, and current treatments and hopes to shed light on novel therapeutic avenues and challenges that remain.


2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii19-ii19
Author(s):  
Anca Mihalas ◽  
Heather Feldman ◽  
Anoop Patel ◽  
Patrick Paddison

Abstract Current standard of care therapy for glioblastoma (GBM) includes cytoreduction followed by ablative therapies that target rapidly dividing cell types. However, the presence of quiescent-like/G0 states, therefore, represents a natural reservoir of tumor cells that are resistant to current treatments. Quiescence or G0 phase is a reversible state of “stasis” cells enter in response to developmental or environmental cues. To gain insight into how glioblastoma cells might regulate G0-like states, we performed a genome-wide CRISPR-Cas9 screen in patient-derived GBM stem-like cells (GSCs) harboring a G0-reporter to identify genes that when inhibited trap GSCs in G0-like states. Among the top screen hits were members of the Tip60/KAT5 histone acetyltransferase complex, which targets both histones (e.g., H4) and non-histone proteins for acetylation. NuA4 functions as a transcriptional activator, whose activities are coordinated with MYC in certain contexts, and also participates in DNA double-strand break repair by facilitating chromatin opening. However, currently little is known about the roles for NuA4 complex in GBM biology. Through modeling KAT5 function in GSC in vitro cultures and in vivo tumors, we find that KAT5 inhibition causes cells to arrest in a G0-like state with high p27 levels, G1-phase DNA content, low protein synthesis rates, low rRNA rates, lower metabolic rate, suppression of cell cycle gene expression, and low histone H4 acetylation. Interestingly, partial inhibition of KAT5 activity slows highly aggressive tumor growth, while increasing p27hi H4-aclow populations. Remarkably, we that low grade gliomas have significantly higher H4-aclow subpopulations and generally lower H4-ac levels than aggressive grade IV tumors. Taken together, our results suggest that NuA4/KAT5 activity may play a key role in quiescence ingress/egress in glioma and that targeting its activity in high grade tumors may effectively “down grade” them, thus, increase patient survival.


2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Andreas Wartak ◽  
John G. Garber ◽  
Qian Yuan ◽  
Wayne G. Shreffler ◽  
Paul E. Hesterberg ◽  
...  

AbstractHistopathologic analysis of biopsy specimens obtained via white light endoscopy (WLE) is the gold standard for the diagnosis of several mucosal diseases in the upper gastrointestinal (GI) tract. However, this standard of care entails a series of critical shortcomings such as missing depth information, high costs, time inefficiency, low-resolution imaging in vivo, high sampling variability, missing intrinsic tissue-specific contrast, and anesthesia related risk. In the quest for a diagnostic technology to replace the current standard of care, in vivo optical endomicroscopy has emerged as a promising alternative. This paper tells the story of a cluster of optical microscopy-based modalities invented, further developed, or first-validated in the laboratory of Dr. Guillermo J. Tearney (Tearney Lab) at the Wellman Center for Photomedicine of Massachusetts General Hospital over the past two decades, that combined lead to a novel method for diagnosis of eosinophilic esophagitis (EoE). Rather than being a comprehensive literature review, this paper aims to describe the translational journey towards a disease specific diagnostic and research tool for this increasingly recognized yet poorly understood immune-mediated disorder of the esophagus.


Author(s):  
Jérôme Chambert ◽  
Thomas Lihoreau ◽  
Sylvain Joly ◽  
Brice Chatelain ◽  
Patrick Sandoz ◽  
...  

2021 ◽  
Vol 887 ◽  
pp. 116-122
Author(s):  
A.A. Bryansky ◽  
O.V. Bashkov ◽  
Daria P. Malysheva ◽  
Denis B. Solovev

The paper presents the results of the study of registered acoustic emission (AE) parameters during static deformation and damaging of polymer composite materials (PCM). Mechanical tests were done by a static tension and a static three-point bend, accompanied by an acoustic emission method. The assessment of the loading rate effect on defects formation processes was done by additional static tension test at rate equal half of recommended by the standard and static three-point bend test at rate ten times lower than that calculated by the standard. Clustering by frequency components of the recorded AE signals with a self-organizing Kohonen map was performed. The characteristics of the types of PCM structure damage by the centroids of the obtained clusters are given. Based on the clusters accumulation during mechanical tests, the stages of damage formation for static tension and static three-point bend, the loading rate effect on the process of damage formation are described.


2008 ◽  
Vol 54 (2) ◽  
pp. 264-272 ◽  
Author(s):  
John W McMurdy ◽  
Gregory D Jay ◽  
Selim Suner ◽  
Gregory Crawford

Abstract Background: Anemia is an underdiagnosed, significant public health concern afflicting >2 billion people worldwide. The detrimental effects of tissue oxygen deficiency on the cardiovascular system and concurrent appearance of anemia with numerous high-risk disorders highlight the importance of clinical screening. Currently there is no universally accepted, clinically applicable, noninvasive hemoglobin/hematocrit screening tool. The need for such a device has prompted an investigation into a breadth of techniques. Methods: A synopsis of the literature and current directions of research in noninvasive total hemoglobin measurement was collected. Contributions highlighted in this review are limited to those studies conducted with a clinical aspect, and most include in vivo patient studies. Results: The review of potential techniques presented here includes optoacoustic spectroscopy, spectrophotometric imaging, diffuse reflectance spectroscopy, transcutaneous illumination, electrical admittance plethysmography, and photoplethysmography. The technological performance, relative benefits of each approach, potential instrumentation design considerations, and future directions are discussed in each subcategory. Conclusions: Many techniques reviewed here have shown excellent accuracy, sensitivity, and specificity in measuring hemoglobin/hematocrit, thus in the near future a new clinically viable tool for noninvasive hemoglobin/hematocrit monitoring will likely be widely used for patient care. Limiting factors in clinical adoption will likely involve technology integration into the current standard of care in each field routinely dealing with anemia.


1997 ◽  
Vol 31 (4) ◽  
pp. 445-456 ◽  
Author(s):  
Susan M Abdel-Rahman ◽  
Milap C Nahata

Objective To review the pharmacology, pharmacokinetics, efficacy, adverse effects, drug interactions, and dosage guidelines of terbinafine. Available comparative data of terbinafine and other antimycotic agents are described for understanding the potential role of terbinafine in patient care. Data Sources A MEDLINE search restricted to English language during 1966–1996 and extensive review of journals was conducted to prepare this article. MeSH headings included allylamines, terbinafine, SF 86–327, dermatophytosis, dermatomycosis. Data Extraction The data on pharmacokinetics, adverse effects, and drug interactions were obtained from open-label and controlled studies and case reports. Controlled single- or double-blind studies were evaluated to describe the efficacy of terbinafine in the treatment of various fungal infections. Data Synthesis Terbinafine is the first oral antimycotic in the allylamines class: a fungicidal agent that inhibits ergosterol synthesis at the stage of squalene epoxidation. Terbinafine demonstrates excellent in vitro activity against the majority of dermatophyte species including Trichophyton rubrum, Trichophyton mentagrophytes, and Epidermophyton floccosum; less activity is seen against Dematiaceae and the filamentous fungi. It is least active against the pathogenic yeast and this correlates with the relatively poor efficacy against these organisms in vivo. High concentrations of terbinafine are achieved in keratinous tissues, the site of superficial infections, and these concentrations are maintained for up to 3 months. The clinical efficacy of terbinafine against a number of dermatophyte infections exceeds that of the current standard of therapy, griseofulvin. The efficacy of terbinafine may be as good or better than that of the azole antifungals. Additional studies are required to confirm these observations. Terbinafine demonstrates a good safety profile, and relatively few drug interactions have been identified. Conclusions Terbinafine is more effective than the gold standard, griseofulvin, in the treatment of tinea pedis and tinea unguinum, with considerably shorter treatment duration in the latter. It has been proven as effective as griseofulvin in the treatment of tinea capitis, tinea corporis, and tinea cruris. Terbinafine does not appear to offer any advantage in the treatment of nondermatophyte infections; its utility in the treatment of systemic infections has yet to be established. Depending on individual institutional costs, terbinafine may be a front-line drug for some superficial infections responding poorly to the current standard of therapy.


2019 ◽  
Author(s):  
Nicholas J Hanne ◽  
Elizabeth D Easter ◽  
Sandra Stangeland-Molo ◽  
Jacqueline H Cole

AbstractIn biomedical and preclinical research, the current standard method for measuring blood perfusion inside murine bone, radiolabeled microspheres, is a terminal procedure that cannot be used to monitor longitudinal perfusion changes. Laser Doppler flowmetry (LDF) can quantify perfusion within the proximal tibial metaphysis of mice in vivo but requires a surgical procedure to place the measurement probe directly onto the bone surface. Sustained inflammation for over a month following this technique was previously reported, and previous studies have used LDF as an endpoint-only procedure. We developed a modified, minimally invasive LDF procedure to measure intraosseous perfusion in the murine tibia without stimulating local or systemic inflammation or inducing gait abnormalities. This modified technique can be used to measure perfusion weekly for up to at least a month. Unlike previous endpoint-only techniques, this modified LDF procedure can be performed weekly to monitor serial changes to intraosseous perfusion in the murine tibiaThe modified LDF technique utilizes a smaller, more localized incision to minimize invasiveness and speed recovery


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