Early Physical Therapist Interventions for Patients With COVID-19 in the Acute Care Hospital: A Case Report Series.

The aim of this case series was to describe the experience of Swiss physical therapists in the treatment of patients with COVID-19 during their acute care hospital stay and to discuss challenges and potential strategies in the clinical management of these patients. We report 11 cases of patients with COVID-19 from 5 Swiss hospitals that illustrate the various indications for physical therapy, clinical challenges, potential treatment methods, and short-term response to treatment. Physical therapists actively treated patients with COVID-19 on wards and in the intensive care unit. Interventions ranged from patient education, to prone positioning, to early mobilization and respiratory therapy. Patients were often unstable with quick exacerbation of symptoms and a slow and fluctuant recovery. Additionally, many patients who were critically ill developed severe weakness, postextubation dysphagia, weaning failure, or presented with anxiety or delirium. In this setting, physical therapy was challenging and required specialized and individualized therapeutic strategies. Most patients adopted the proposed treatment strategies, and lung function and physical strength improved over time. Physical therapists clearly have a role in the COVID-19 pandemic. Based on our experience in Switzerland, we recommend that physical therapists routinely screen and assess patients for respiratory symptoms and exercise tolerance on acute wards. Treatment of patients who are critically ill should start as soon as possible to limit further sequelae. More research is needed for awake prone positioning and early breathing exercises as well as post-COVID rehabilitation. To date, there are few data on the physical therapist management of patients with COVID-19. This article is among the first to describe the role of physical therapists in the complex pandemic environment and to describe the potential treatment strategies for countering the various challenges in the treatment of these patients

Full‐field strain of regenerated bone tissue in a femoral fracture model

The mechanical behavior of regenerated bone tissue during fracture healing is key in determining its ability to withstand physiological loads. However, the strain distribution in the newly formed tissue and how this influences the way a fracture heals it is still unclear. X-ray Computed Tomography (XCT) has been extensively used to assess the progress of mineralized tissues in regeneration and when combined with in situ mechanics and digital volume correlation (DVC) has been proven a powerful tool to understand the mechanical behavior and full-field three-dimensional (3D) strain distribution in bone. The purpose of this study is therefore to use in situ XCT mechanics and DVC to investigate the strain distribution and load-bearing capacity in a regenerating fracture in the diaphyseal bone, using a rodent femoral fracture model stabilized by external fixation. Rat femurs with 1 mm and 2 mm osteotomy gaps were tested under in situ XCT step-wise compression in the apparent elastic region. High strain was present in the newly formed bone (εp1 and εp3 reaching 29000 με and -43000 με, respectively), with a wide variation and inhomogeneity of the 3D strain distribution in the regenerating tissues of the fracture gap, which is directly related to the presence of unmineralized tissue observed in histological images. The outcomes of this study will contribute in understanding natural regenerative ability of bone and its mechanical behavior under loading

Scaffold Translation: Barriers Between Concept and Clinic

Translation of scaffold-based bone tissue engineering (BTE) therapies to clinical use remains, bluntly, a failure. This dearth of translated tissue engineering therapies (including scaffolds) remains despite 25 years of research, research funding totaling hundreds of millions of dollars, over 12,000 papers on BTE and over 2000 papers on BTE scaffolds alone in the past 10 years (PubMed search). Enabling scaffold translation requires first an understanding of the challenges, and second, addressing the complete range of these challenges. There are the obvious technical challenges of designing, manufacturing, and functionalizing scaffolds to fill the Form, Fixation, Function, and Formation needs of bone defect repair. However, these technical solutions should be targeted to specific clinical indications (e.g., mandibular defects, spine fusion, long bone defects, etc.). Further, technical solutions should also address business challenges, including the need to obtain regulatory approval, meet specific market needs, and obtain private investment to develop products, again for specific clinical indications. Finally, these business and technical challenges present a much different model than the typical research paradigm, presenting the field with philosophical challenges in terms of publishing and funding priorities that should be addressed as well. In this article, we review in detail the technical, business, and philosophical barriers of translating scaffolds from Concept to Clinic. We argue that envisioning and engineering scaffolds as modular systems with a sliding scale of complexity offers the best path to addressing these translational challenges.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90495/1/ten-2Eteb-2E2011-2E0251.pd

Identification of the allosteric P2X7 receptor antagonist [11C]SMW139 as a PET tracer of microglial activation

The P2X7 receptor plays a significant role in microglial activation, and as a potential drug target, the P2X7 receptor is also an interesting target in positron emission tomography. The current study aimed at the development and evaluation of a potent tracer targeting the P2X7 receptor, to which end four adamantanyl benzamide analogues with high affinity for the human P2X7 receptor were labelled with carbon-11. All four analogues could be obtained in excellent radiochemical yield and high radiochemical purity and molar activity, and all analogues entered the rat brain. [11C]SMW139 showed the highest metabolic stability in rat plasma, and showed high binding to the hP2X7 receptor in vivo in a hP2X7 receptor overexpressing rat model. Although no significant difference in binding of [11C]SMW139 was observed between post mortem brain tissue of Alzheimer's disease patients and that of healthy controls in in vitro autoradiography experiments, [11C]SMW139 could be a promising tracer for P2X7 receptor imaging using positron emission tomography, due to high receptor binding in vivo in the hP2X7 receptor overexpressing rat model. However, further investigation of both P2X7 receptor expression and binding of [11C]SMW139 in other neurological diseases involving microglial activation is warranted

Mechanical analysis of the bone to plate interface of the LC-DCP and of the PC-FIX on human femora.

The scope of this analysis was to evaluate the mechanical behaviour of newly developed plates at the junction between plate and bone (friction between plate and bone) for the limited contact dynamic compression plate (LC-DCP) and the point contact fixator (PC-Fix) under simulated physiological load and using the tension band principle on the human femur. The intact human cadaveric femora were plated on the lateral aspect according to the tension band principle (AO) and subjected to a load which simulated careful physiological load in single stance. Five strain gauges were glued around the bones, parallel to the bone axis, at five levels, whereby three of them had to be covered by a bone plate and the two others were just outside the plate location. The cross-sectional geometry had been obtained at these levels using computed tomography. One side was plated using the conventional compression plate LC-DCP and the contralateral side using the internal fixator PC-Fix. The LC-DCP was affixed using screws tightened at different torque values and the PC-Fix at a standard torque value. Motion (slippage) between the plate and the bone was indicated by a hysteresis of the strain reading during loading and unloading. Slippage was more important for the LC-DCP than for the PC-Fix, particularly at the proximal end of the plate and when the screws were insufficiently tightened on the LC-DCP. As expected, better stability was obtained with the PC-Fix

In silico biology of bone modelling and remodelling: regeneration.

Bone regeneration is the process whereby bone is able to (scarlessly) repair itself from trauma, such as fractures or implant placement. Despite extensive experimental research, many of the mechanisms involved still remain to be elucidated. Over the last decade, many mathematical models have been established to investigate the regeneration process in silico. The first models considered only the influence of the mechanical environment as a regulator of the healing process. These models were followed by the development of bioregulatory models where mechanics was neglected and regeneration was regulated only by biological stimuli such as growth factors. The most recent mathematical models couple the influences of both biological and mechanical stimuli. Examples are given to illustrate the added value of mathematical regeneration research, specifically in the in silico design of treatment strategies for non-unions. Drawbacks of the current continuum-type models, together with possible solutions in extending the models towards other time and length scales are discussed. Finally, the demands for dedicated and more quantitative experimental research are presented