Feasibility and Usability of Augmented Reality Technology in the Orthopaedic Operating Room.

PURPOSE OF REVIEW: Augmented reality (AR) has gained popularity in various sectors, including gaming, entertainment, and healthcare. The desire for improved surgical navigation within orthopaedic surgery has led to the evaluation of the feasibility and usability of AR in the operating room (OR). However, the safe and effective use of AR technology in the OR necessitates a proper understanding of its capabilities and limitations. This review aims to describe the fundamental elements of AR, highlight limitations for use within the field of orthopaedic surgery, and discuss potential areas for development. RECENT FINDINGS: To date, studies have demonstrated evidence that AR technology can be used to enhance navigation and performance in orthopaedic procedures. General hardware and software limitations of the technology include the registration process, ergonomics, and battery life. Other limitations are related to the human response factors such as inattentional blindness, which may lead to the inability to see complications within the surgical field. Furthermore, the prolonged use of AR can cause eye strain and headache due to phenomena such as the vergence-convergence conflict. AR technology may prove to be a better alternative to current orthopaedic surgery navigation systems. However, the current limitations should be mitigated to further improve the feasibility and usability of AR in the OR setting. It is important for both non-clinicians and clinicians to work in conjunction to guide the development of future iterations of AR technology and its implementation into the OR workflow.

Racial and Ethnic Disparities in the Management of Diabetic Feet.

PURPOSE OF REVIEW: Diabetes mellitus is a chronic medical condition affecting many individuals worldwide and leads to billions of dollars spent within the healthcare system for its treatment and complications. Complications from diabetes include diabetic foot conditions that can have a devasting impact on quality of life. Diabetic foot ulcers and amputations occur in minority individuals at an increased rate compared to Caucasian individuals. This review provides an update examining the racial and ethnic disparities in the management of diabetic foot conditions and the differences in rates of amputation. RECENT FINDINGS: Current research continues to show a disparity as it relates to diabetic foot management. There are novel treatment options for diabetic foot ulcers that are currently being explored. However, there continues to be a lack in racial diversity in new treatment studies conducted in the USA. Individuals from racial and ethnic minority groups have diabetes at higher rates compared to Caucasian individuals, and are also more likely to develop diabetic foot ulcers and receive amputations. Over the last few years, more efforts have been made to improve health disparities. However, there needs to be an improvement in increasing racial diversity when investigating new therapies for diabetic foot ulcers.

Characterization of the structure, vascularity, and stem/progenitor cell populations in porcine Achilles tendon (PAT).

This study aimed to characterize porcine Achilles tendon (PAT) in terms of its structural components, vascularity, and resident tendon cells. We found that PAT is composed of a paratenon sheath, a core of fascicles, and an endotenon/interfascicular matrix (IFM) that encases the fascicle bundles. We analyzed each of these three tendon components structurally using tissue sections and by isolating cells from each component and analyzing in vitro. Many blood vessel-like tissues were present in the paratenon and IFM but not in fascicles, and the vessels in the paratenon and IFM appeared to be inter-connected. Cells isolated from the paratenon and IFM displayed characteristics of vascular stem/progenitor cells expressing the markers CD105, CD31, with α-smooth muscle actin (α-SMA) localized surrounding blood vessels. The isolated cells from paratenon and IFM also harbored abundant stem/progenitor cells as evidenced by their ability to form colonies and express stem cell markers including CD73 and CD146. Furthermore, we demonstrate that both paratenon and IFM-isolated cells were capable of undergoing multi-differentiation. In addition, both paratenon and IFM cells expressed elastin, osteocalcin, tubulin polymerization promoting protein (TPPP), and collagen IV, whereas fascicle cells expressed none of these markers, except collagen I. The neurotransmitter substance P (SP) was also found in the paratenon and IFM-localized surrounding blood vessels. The findings of this study will help us to better understand the vascular and cellular mechanisms of tendon homeostasis, injury, healing, and regeneration.

Biologic therapies for foot and ankle injuries.

Introduction: The use of orthobiologics as supplemental treatment for foot and ankle pathologies have increased in the past decades. They have been used to improve the healing of bone and soft tissue injuries. There have been several studies that examined the use of biologics for knee and hip pathologies but the foot and ankle construct has unique features that must be considered.Areas covered: The biologics for foot and ankle injuries that are covered in this review are platelet-rich plasma (PRP), stem cells, growth factors, hyaluronic acid, bone grafts, bone substitutes, and scaffolds. These modalities are used in the treatment of pathologies related to tendon and soft tissue as well as cartilage.Expert opinion: The utilization of biological adjuncts for improved repair and regeneration of ankle injuries represents a promising future in our efforts to address difficult clinical problems. The application of concentrated bone marrow and PRP each represents the most widely studied and commonly used injection therapies with early clinical studies demonstrating promising results, research is also being done using other potential therapies such as stem cells and growth factors; further investigation and outcome data are still needed.

Trends in prevalence, mortality, and morbidity associated with high systolic blood pressure in Brazil from 1990 to 2017: estimates from the "Global Burden of Disease 2017" (GBD 2017) study.

BACKGROUND: Hypertension remains the leading risk factor for cardiovascular disease (CVD) worldwide, and its impact in Brazil should be assessed in order to better address the issue. We aimed to describe trends in prevalence and burden of disease attributable to high systolic blood pressure (HSBP) among Brazilians ≥ 25 years old according to sex and federal units (FU) using the Global Burden of Disease (GBD) 2017 estimates. METHODS: We used the comparative risk assessment developed for the GBD study to estimate trends in attributable deaths and disability-adjusted life-years (DALY), by sex, and FU for HSBP from 1990 to 2017. This study included 14 HSBP-outcome pairs. HSBP was defined as ≥ 140 mmHg for prevalence estimates, and a theoretical minimum risk exposure level (TMREL) of 110-115 mmHg was considered for disease burden. We estimated the portion of deaths and DALYs attributed to HSBP. We also explored the drivers of trends in HSBP burden, as well as the correlation between disease burden and sociodemographic development index (SDI). RESULTS: In Brazil, the prevalence of HSBP is 18.9% (95% uncertainty intervals [UI] 18.5-19.3%), with an annual 0.4% increase rate, while age-standardized death rates attributable to HSBP decreased from 189.2 (95%UI 168.5-209.2) deaths to 104.8 (95%UI 94.9-114.4) deaths per 100,000 from 1990 to 2017. In spite of that, the total number of deaths attributable to HSBP increased 53.4% and HSBP raised from 3rd to 1st position, as the leading risk factor for deaths during the period. Regarding total DALYs, HSBP raised from 4th in 1990 to 2nd cause in 2017. The main driver of change of HSBP burden is population aging. Across FUs, the reduction in the age-standardized death rates attributable to HSBP correlated with higher SDI. CONCLUSIONS: While HSBP prevalence shows an increasing trend, age-standardized death and DALY rates are decreasing in Brazil, probably as results of successful public policies for CVD secondary prevention and control, but suboptimal control of its determinants. Reduction was more significant in FUs with higher SDI, suggesting that the effect of health policies was heterogeneous. Moreover, HSBP has become the main risk factor for death in Brazil, mainly due to population aging.

High pulsatility flow stimulates smooth muscle cell hypertrophy and contractile protein expression.

Proximal arterial stiffening is an important predictor of events in systemic and pulmonary hypertension, partly through its contribution to downstream vascular abnormalities. However, much remains undetermined regarding the mechanisms involved in the vascular changes induced by arterial stiffening. We therefore addressed the hypothesis that high pulsatility flow, caused by proximal arterial stiffening, induces downstream pulmonary artery endothelial cell (EC) dysfunction that in turn leads to phenotypic change of smooth muscle cells (SMCs). To test the hypothesis, we employed a model pulmonary circulation in which upstream compliance regulates the pulsatility of flow waves imposed onto a downstream vascular mimetic coculture composed of pulmonary ECs and SMCs. The effects of high pulsatility flow on SMCs were determined both in the presence and absence of ECs. In the presence of ECs, high pulsatility flow increased SMC size and expression of the contractile proteins, smooth muscle α-actin (SMA) and smooth muscle myosin heavy chain (SM-MHC), without affecting proliferation. In the absence of ECs, high pulsatility flow decreased SMC expression of SMA and SM-MHC, without affecting SMC size or proliferation. To identify the molecular signals involved in the EC-mediated SMC responses, mRNA and/or protein expression of vasoconstrictors [angiotensin-converting enzyme (ACE) and endothelin (ET)-1], vasodilator (eNOS), and growth factor (TGF-ß1) in EC were examined. Results showed high pulsatility flow decreased eNOS and increased ACE, ET-1, and TGF-ß1 expression. ACE inhibition with ramiprilat, ET-1 receptor inhibition with bosentan, and treatment with the vasodilator bradykinin prevented flow-induced, EC-dependent SMC changes. In conclusion, high pulsatility flow stimulated SMC hypertrophy and contractile protein expression by altering EC production of vasoactive mediators and cytokines, supporting the idea of a coupling between proximal vascular stiffening, flow pulsatility, and downstream vascular function.

Mechanics and function of the pulmonary vasculature: implications for pulmonary vascular disease and right ventricular function.

he relationship between cardiac function and the afterload against which the heart muscle must work to circulate blood throughout the pulmonary circulation is defined by a complex interaction between many coupled system parameters. These parameters range broadly and incorporate system effects originating primarily from three distinct locations: input power from the heart, hydraulic impedance from the large conduit pulmonary arteries, and hydraulic resistance from the more distal microcirculation. These organ systems are not independent, but rather, form a coupled system in which a change to any individual parameter affects all other system parameters. The result is a highly nonlinear system which requires not only detailed study of each specific component and the effect of disease on their specific function, but also requires study of the interconnected relationship between the microcirculation, the conduit arteries, and the heart in response to age and disease. Here, we investigate systems-level changes associated with pulmonary hypertensive disease progression in an effort to better understand this coupled relationship.

Mechanics and Function of the Pulmonary Vasculature: Implications for Pulmonary Vascular Disease and Right Ventricular Function.

The relationship between cardiac function and the afterload against which the heart muscle must work to circulate blood throughout the pulmonary circulation is defined by a complex interaction between many coupled system parameters. These parameters range broadly and incorporate system effects originating primarily from three distinct locations: input power from the heart, hydraulic impedance from the large conduit pulmonary arteries, and hydraulic resistance from the more distal microcirculation. These organ systems are not independent, but rather, form a coupled system in which a change to any individual parameter affects all other system parameters. The result is a highly nonlinear system which requires not only detailed study of each specific component and the effect of disease on their specific function, but also requires study of the interconnected relationship between the microcirculation, the conduit arteries, and the heart in response to age and disease. Here, we investigate systems-level changes associated with pulmonary hypertensive disease progression in an effort to better understand this coupled relationship.

NAD(P)H:quinone oxidoreductase 1-compromised human bone marrow endothelial cells exhibit decreased adhesion molecule expression and CD34+ hematopoietic cell adhesion.

NAD(P)H:quinone oxidoreductase 1 (NQO1) deficiency resulting from a homozygous NQO1*2 polymorphism has been associated with an increased risk of benzene-induced myeloid toxicity and a variety of de novo and therapy-induced leukemias. Endothelial cells in human bone marrow form one of the two known hematopoietic stem cell microenvironments and are one of the major cell types that express NQO1 in bone marrow. We have used a transformed human bone marrow endothelial cell (TrHBMEC) line to study the potential impact of a lack of NQO1 activity on adhesion molecule [endothelial leukocyte adhesion molecule 1 (E-selectin), vascular cell adhesion molecule (VCAM)-1, and intercellular adhesion molecule (ICAM)-1] expression and functional adhesion to bone marrow progenitor cells. We used both 5-methoxy-1,2-dimethyl-3-[(4-nitrophenoxy)methyl]indole-4,7-dione (ES936), a mechanism-based inhibitor of NQO1, and anti-NQO1 small interfering RNA to abrogate NQO1 activity. Real-time reverse transcription-polymerase chain reaction data demonstrated a significant inhibition of tumor necrosis factor (TNF)alpha-induced E-selectin mRNA levels after ES936 pretreatment. Immunoblot assays demonstrated a significant reduction in TNFalpha-stimulated E-selectin, VCAM-1, and ICAM-1 proteins after inhibition or knockdown of NQO1. The mechanisms underlying this effect remain undefined, but modulation of nuclear factor-kappaB (p65), c-Jun, and activating transcription factor 2, transcriptional regulators of adhesion molecules, were observed after inhibition or knockdown of NQO1. Decreased level of E-selectin, VCAM-1, and ICAM-1 also resulted in a functional deficit in adhesion. A parallel plate flow chamber study demonstrated a marked reduction in CD34(+) cell (KG1a) adhesion to NQO1-deficient TrHBMECs relative to controls. The reduced adhesive ability of TrHBMECs may affect the function of the vascular stem cell niche and also may contribute to the increased susceptibility of polymorphic individuals lacking NQO1 to leukemias and hematotoxicants such as benzene.

High pulsatility flow induces adhesion molecule and cytokine mRNA expression in distal pulmonary artery endothelial cells.

BACKGROUND: Arterial stiffening or reduced compliance of proximal pulmonary vessels has been shown to be an important predictor of outcomes in patients with pulmonary hypertension. Though current evidence indicates that arterial stiffening modulates flow pulsatility in downstream vessels and is likely related to microvascular damage in organs without extensive distributing arteries, the cellular mechanisms underlying this relationship in the pulmonary circulation are unexplored. Thus, this study was designed to examine the responses of the microvascular pulmonary endothelium to changes in flow pulsatility. METHODS: A flow system was developed to reproduce arterial-like pulse flow waves with the capability of modulating flow pulsatility through regulation of upstream compliance. Pulmonary microvascular endothelial cells (PMVECs) were exposed to steady flow and pulse flow waves of varied pulsatility with varied hemodynamic energy (low: pulsatility index or PI = 1.0; medium: PI = 1.7; high: PI = 2.6) at flow frequency of 1 or 2 Hz for different durations (1 and 6 h). The mean flow rates in all the conditions were kept the same with shear stress at 14 dynes/cm(2). Gene expression was evaluated by analyzing mRNA levels of adhesion molecules (ICAM-1, E-selectin), chemokine (MCP-1) and growth factor/receptor (VEGF, Flt-1) in PMVECs. Functional changes were observed with monocyte adhesion assay. RESULTS: 1) Compared to either steady flow or low pulsatility flow, increased flow pulsatility for 1 h induced significant increases in mRNA levels of ICAM-1, E-selectin and MCP-1. 2) Sustained high pulsatility flow perfusion induced increases in ICAM, E-selectin, MCP-1, VEGF and its receptor Flt-1 expression. 3) Flow pulsatility effects on PMVECs were frequency-dependent with greater responses at 2 Hz and likely associated with the hemodynamic energy level. 4) Pulse flow waves with high flow pulsatility at 2 Hz induced leukocyte adhesion and recruitment to PMVECs. CONCLUSION: Increased upstream pulmonary arterial stiffness increases flow pulsatility in distal arteries and induces inflammatory gene expression, leukocyte adhesion and cell proliferation in the downstream PMVECs.

Development and evaluation of microdevices for studying anisotropic biaxial cyclic stretch on cells.

Mechanical effects on cells have received more and more attention in the studies of tissue engineering, cellular pathogenesis, and biomedical device design. Anisotropic biaxial cyclic stress, reminiscent of the in vivo cellular mechanical environment, may promise significant implications for biotechnology and human health. We have designed, fabricated and characterized a microdevice that imparts a variety of anisotropic biaxial cyclic strain gradients upon cells. The device is composed of an elastic membrane with microgroove patterns designed to associate cell orientation axes with biaxial strain vectors on the membrane and a Flexcell stretcher with timely controlled vacuum pressure. The stretcher generates strain profile of anisotropic biaxial microgradients on the membrane. Cell axes determined by the microgrooves are associated with the membrane strain profile to impose proper biaxial strains on cells. Using vascular smooth muscle cells as a cell model, we demonstrated that the strain anisotropy index of a cell was likely one of the determinant mechanical factors in cell structural and functional adaptations. The nuclear shape and cytoskeleton structure of smooth muscle cells were influenced by mechanical loading, but were not significantly affected by the strain anisotropy. However, cell proliferation has profound responses to strain anisotropy.