Targeting the Gut Microbiome for Inflammation and Pain Management in Orthopedic Conditions.

The human gut microbiome can be altered with probiotics, prebiotics, synbiotics, and anti-inflammatory foods and spices as part of an evidence-based strategy that targets inflammation and pain in common orthopedic conditions. Implementing these strategies avoids adverse effects associated with nonsteroidal anti-inflammatory drugs and minimizes the potential for opioid use. This review focuses exclusively on human trials studying the effects of gut microbiome alterations to address pain and inflammatory markers in common orthopedic conditions: osteoarthritis, rheumatoid arthritis, fractures/osteoporosis, and bone pain associated with chemotherapy. Individualized supplementation strategies can be further explored with the information in this review. [Orthopedics. 2022;45(5):e226-e234.].

A Soft Robotic Sleeve for Compression Therapy of the Lower Limb.

'We present the development of a soft robotic-inspired device for lower limb compression therapy with application in the treatment of lymphedema. This device integrates the control capabilities of pneumatic devices with the wearability and low cost of compression garments. The design consists of a three-layered soft robotic sleeve that ensures safe skin contact, controls compression, and secures the device to the patient limb. The expandable component is made of interconnected pockets of various heights, which passively create a graduated compression profile along the lower limb. The system is inflated by a pump and a microcontroller-actuated valve, with force sensors embedded in the sleeve that monitor the pressure applied to the limb. Testing on healthy individualsq demonstrated the ability to reach clinically relevant target pressures (30, 40, 50 mmHg) and establish a distal-to-proximal descending pressure gradient of approximately 40 mmHg. Device function was shown to be robust against variations in subject anatomy.Clinical Relevance- This system provides controllable, graduated, compression therapy to lymphedema patients in an economical, portable, and customizable package.

Characterizing the recovery trajectories of knee range of motion for one year after total knee replacement.

Design: Retrospective analysis of routinely collected clinical data. Objective: This study modeled the recovery in knee flexion and extension range of motion (ROM) over 1 year after total knee replacement (TKR). Background: Recovery after TKR has been characterized for self-reported pain and functional status. Literature describing target knee ROM at different follow-up periods after TKR is scarce. Methods: Data were extracted for patients who had undergone TKR at a tertiary care hospital at 2, 8, 12, 26, and 52 weeks after TKR. A linear mixed-effects growth model was constructed that investigated the following covariates age, sex, pre-TKR range, body mass index, duration of symptoms, and their interaction with weeks post TKR. Results: Of the 559 patients included (age 64.8 ± 8.5 years), 370 were women and 189 were men. Knee ROM showed the greatest change during the first 12 weeks after TKR, plateauing by 26 weeks. For an average patient, knee flexion increased from approximately 100º 2 weeks post TKR to 117º 52 weeks post TKR. Knee extension increased from approximately 3º knee flexion 2 weeks post TKR to 1º flexion 52 weeks post TKR. Conclusions: The results showed that the maximum gains in knee ROM should be expected within the first 12 weeks with small changes occurring up to 26 weeks after TKR. In addition, age and presurgery knee ROM are associated with the gains in knee ROM and should be factored into the estimation of expected knee ROM at a given follow-up interval after TKR.

Hoverboard injuries in children and adolescents: results of a multicenter study.

With the increasing popularity of hoverboards in recent years, multiple centers have noted associated orthopaedic injuries of riders. We report the results of a multi-center study regarding hoverboard injuries in children and adolescents. who presented with extremity fractures while riding hoverboards to 12 paediatric orthopaedic centers during a 2-month period were included in the study. Circumstances of the injury, location, severity, associated injuries, and the required treatment were recorded and analysed using descriptive analysis to report the most common injuries. Between-group differences in injury location were examined using chi-squared statistics among (1) children versus adolescents and (2) males versus females. Seventy-eight patients (M/F ratio: 1.8) with average age of 11 ± 2.4 years were included in the study. Of the 78 documented injuries, upper extremity fractures were the most common (84.6%) and the most frequent fracture location overall was at the distal radius and ulna (52.6%), while ankle fractures comprised most of the lower extremity fractures (66.6%). Majority of the distal radius fractures (58.3%) and ankle fractures (62.5%) were treated with immobilization only. Seventeen displaced distal radius fractures and three displaced ankle fractures were treated with closed reduction in the majority of cases (94.1% versus 66.7%, respectively). The distal radius and ulna are the most common fracture location. Use of appropriate protective gear such as wrist guards, as well as adult supervision, may help mitigate the injuries associated with the use of this device; however, further studies are necessary to demonstrate the real effectiveness of these preventions.

Novel 3D Hybrid Nanofiber Aerogels Coupled with BMP-2 Peptides for Cranial Bone Regeneration.

An ideal synthetic bone graft is a combination of the porous and nanofibrous structure presented by natural bone tissue as well as osteoinductive biochemical factors such as bone morphogenetic protein 2 (BMP-2). In this work, ultralight 3D hybrid nanofiber aerogels composed of electrospun PLGA-collagen-gelatin and Sr-Cu codoped bioactive glass fibers with incorporation of heptaglutamate E7 domain specific BMP-2 peptides have been developed and evaluated for their potential in cranial bone defect healing. The nanofiber aerogels are surgically implanted into 8 mm × 1 mm (diameter × thickness) critical-sized defects created in rat calvariae. A sustained release of E7-BMP-2 peptide from the degradable hybrid aerogels significantly enhances bone healing and defect closure over 8 weeks in comparison to unfilled defects. Histomorphometry and X-ray microcomputed tomography (µ-CT) analysis reveal greater bone volume and bone formation area in case of the E7-BMP-2 peptide loaded hybrid nanofiber aerogels. Further, histopathology data divulged a near complete nanofiber aerogel degradation along with enhanced vascularization of the regenerated tissue. Together, this study for the first time demonstrates the fabrication of 3D hybrid nanofiber aerogels from 2D electrospun fibers and their loading with therapeutic osteoinductive BMP-2 mimicking peptide for cranial bone tissue regeneration.

Nanofiber-based sutures induce endogenous antimicrobial peptide.

AIM: The aim of this study was to develop nanofiber-based sutures capable of inducing endogenous antimicrobial peptide production. METHODS: We used co-axial electrospinning deposition and rolling to fabricate sutures containing pam3CSK4 peptide and 25-hydroxyvitamin D3 (25D3). RESULTS: The diameters and mechanical properties of the sutures were adjustable to meet the criteria of United States Pharmacopeia designation. 25D3 exhibited a sustained release from nanofiber sutures over 4 weeks. Pam3CSK4 peptide also showed an initial burst followed by a sustained release over 4 weeks. The co-delivery of 25D3 and pam3CSK4 peptide enhanced cathelicidin antimicrobial peptide production from U937 cells and keratinocytes compared with 25D3 delivery alone. In addition, the 25D3/pam3CSK4 peptide co-loaded nanofiber sutures did not significantly influence proliferation of keratinocytes, fibroblasts, or the monocytic cell lines U937 and HL-60. CONCLUSION: The use of 25D3/pam3CSK4 peptide co-loaded nanofiber sutures could potentially induce endogenous antimicrobial peptide production and reduce surgical site infections.

Binary Doping of Strontium and Copper Enhancing Osteogenesis and Angiogenesis of Bioactive Glass Nanofibers while Suppressing Osteoclast Activity.

Electrospun bioactive glass fibers show great potential as scaffolds for bone tissue engineering due to their architectural biomimicry of the bone extracellular matrix and their composition capable of providing soluble bioactive cues for bone regeneration and remodeling. Trace elements can be doped to further promote osteogenesis and angiogenesis during bone regeneration. Cationic substitution of strontium for calcium in bioactive glass positively enhances osteoblast phenotype, while suppressing osteoclast activity. Further, the addition of copper spontaneously improves the vascularization during neobone formation. The objective of this study was to fabricate and characterize electrospun bioactive glass fibers doped with strontium and copper and evaluate their potential for bone repair/regeneration in vitro. Different ratios of strontium and copper were doped in electrospun bioactive glass fibers. The released strontium and copper from doped fibers could reach effective concentrations within 40 h and last for 4 weeks. These bioactive glass fibers demonstrate their bioactivity by promoting osteoblastic and endothelial cell activity and inhibiting the formation of osteoclasts or bone resorbing cells. Additionally, in vitro cell culture of different cell types in the presence of extraction solutions of the electrospun bioactive glass fibers showed that the dopants achieved their individual goals without causing significant cytotoxicity. Altogether, this novel class of bioactive glass fibers holds great promise for bone regeneration.

Twisting electrospun nanofiber fine strips into functional sutures for sustained co-delivery of gentamicin and silver.

Surgical site infections (SSIs) represent the most common nosocomial infection among surgical patients. In order to prevent SSIs in a sustained manner and lessen side effects, we developed a twisting method for generation of nanofiber-based sutures capable of simultaneous delivery of silver and gentamicin. The prepared sutures are composed of core-sheath nanofibers with gentamicin/pluronic F127 in the core and silver/PCL in the sheath produced by co-axial electrospinning. The diameters of obtained sutures range from ~80 µm to ~1.2 mm. The in vitro release profiles of silver and gentamicin exhibit an initial burst followed by a sustained release over 5 weeks. The co-encapsulated sutures were able to kill bacteria much more effectively than gentamicin or silver alone loaded nanofiber sutures, without showing obvious impact on proliferation and migration of dermal fibroblasts and keratinocytes. The gentamicin and silver co-loaded PCL nanofiber sutures may hold great potential for prevention of SSIs.

Highly controlled coating of strontium-doped hydroxyapatite on electrospun poly(ɛ-caprolactone) fibers.

Electrospun fibers show great potential as scaffolds for bone tissue engineering due to their architectural biomimicry to the extracellular matrix (ECM). Cation substitution of strontium for calcium in hydroxyapatite (HAp) positively influences the mechanism of bone remodeling including enhancing bone regeneration and reducing bone resorption. The objective of this study was to attach strontium-doped HAp (SrHAp) to electrospun poly(ɛ-caprolactone) (PCL) fibers for creation of novel composite scaffolds that can not only mimic the architecture and composition of ECM but also affect bone remodeling favorably. We demonstrated for the first time the highly controlled SrHAp coatings on electrospun PCL fibers. We showed the reproducible manufacturing of composite fiber scaffolds with controllable thickness, composition, and morphology of SrHAp coatings. We further showed that the released strontium and calcium cations from coatings could reach effective concentrations within 1 day and endure more than 28 days. Additionally, the Young's modulus of the SrHAp-coated PCL fibers was up to around six times higher than that of raw fibers dependent on the coating thickness and composition. Together, this novel class of composite fiber scaffolds may hold great promise for bone regeneration. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 753-763, 2017.

Patient-Controlled Fentanyl Iontophoretic Transdermal System Improved Postoperative Mobility Compared to Intravenous Patient-Controlled Analgesia Morphine: A Pooled Analysis of Randomized, Controlled Trials.

BACKGROUND: Postoperative pain management protocols that use patient-controlled analgesia (PCA) can hinder mobility due to attached machinery and tubing. Immobility in the postoperative setting can increase complications, length of stay (LOS), and costs. Early and enhanced mobilization can reduce the cost of care while improving patient outcomes. A needle-free, compact, patient-activated, and portable fentanyl iontophoretic transdermal system (fentanyl ITS, IONSYS; The Medicines Company, Parsippany NJ) has been shown to provide comparable efficacy and tolerability to intravenous (IV) PCA morphine that promotes improved mobility. METHODS: This pooled analysis of 1,882 patients across three randomized, controlled trials compared fentanyl ITS to IV PCA morphine for postoperative pain management. Outcomes of patient mobility were assessed by a validated Patient Ease of Care Questionnaire that was given to patients, patients' nurses, and physical therapists involved in patient care. Safety was assessed via spontaneously reported treatment-emergent adverse events (TEAE). RESULTS: Fentanyl ITS significantly improved overall patient mobility, each mobility subscore (P < 0.0001) across all demographics (male/female; elderly/non-elderly; normal BMI/overweight/obese/morbidly obese) and surgery types, and was consistent across nurses and physical therapists mobility assessments. TEAEs were generally similar between the two groups. However, more patients reported an opioid-related TEAE with morphine IV PCA than with fentanyl IV PCA (P = 0.003). CONCLUSION: Due to improved mobility with fentanyl ITS, complications are expected to be less frequent than with IV PCA and epidural PCA. Incorporation of this strategy into postoperative pain management protocols may reduce LOS and total hospital costs.

An Anatomical Study on the Safe Placement of Orthopedic Hardware for Syndesmosis Fixation.

Articular cartilage and bony contact at the distal tibiofibular cartilage contact zone (TFCCZ) is variable. The appropriate placement of syndesmotic hardware would benefit from a more accurate characterization of the proximal extent of the TFCCZ allowing surgeons to place hardware that simultaneously improves biomechanical stability and decreases the risk of iatrogenic cartilage damage. In addition, Ilizarov wire fixation through the distal fibula and tibia can pass through the syndesmosis recess. Anatomically defining the proximal extent of this recess can help decrease the risk of inadvertent capsular penetration. This study anatomically defines the TFCCZ and syndesmosis recess establishing a safe and biomechanically advantageous distance from the plafond for orthopedic fixation. This study measured the height of the TFCCZ and the syndesmotic recess in 3158 anatomical and cadaveric specimens. A TFCCZ was present in 59% of the Robert J. Terry Anatomical Collection specimens. Maximal height of the TFCCZ averaged 5.7±1.7 mm (99% confidence interval [CI], 5.6-5.8 mm) for anatomical specimens and 5.6±1.6 mm (99% CI, 4.6-6.5 mm) for cadaveric dissections. The maximum TFCCZ height was 11.71 mm. Maximal height of the syndesmotic recess averaged 12.8±2.1 mm for anatomical specimens and 13.7±2.7 mm for cadaveric specimens. The "3 cm rule" appears to be appropriate for fine wire fixation accounting for capsular distension that can be associated with injuries but not applicable for syndesmotic fixation. There is a less than 0.1% chance of encountering the TFCCZ cartilage at 10.9 mm above the plafond and a less than 0.01% chance at 12 mm above the plafond. [Orthopedics. 2017; 40(2):e329-e333.].

Improving Rural Bone Health and Minimizing Fracture Risk in West Virginia: Validation of the World Health Organization FRAX Assessment Tool as a Phone Survey for Osteoporosis Detection.

West Virginia ranks second nationally in population ≥ 65 years old placing our state at greater risk for osteoporosis and fracture. The gold standard for detecting osteoporosis is dual X-ray absorptiometry (DXA), yet over half of West Virginia's counties do not have this machine. Due to access barriers, a validated phone-administered fracture prediction tool would be beneficial for osteoporosis screening. The World Health Organization's FRAX fracture prediction tool was administered as a phone survey to 45 patients; these results were compared to DXA bone mineral density determination. Results confirmed that the FRAX phone survey is as reliable as DXA in detecting osteoporosis or clinically significant osteopenia: 92% positive predictive value, 100% negative predictive value, 100% sensitivity and 91% specificity when compared to the gold standard. These promising results allow for the development of telephone-based protocols to improve osteoporosis detection, referral and treatment especially in areas with health care access barriers.

Hip Pain in the Pre-Arthritic Patient: A Guide for the Primary Care Physician.

Adolescents and young adults (less than 30 years of age) with pre-arthritic hip pain constitute a diagnostic dilemma for the primary care physician. The most common underlying diagnoses range from benign muscle strains/joint sprains to stress reactions, insufficiency fractures, and tears involving the articular cartilage/labrum in the setting of femoroacetabular impingement, a hip shape abnormality that is present in up to 90% of this age group. Undetected or left untreated these seemingly innocuous disorders can result in significant loss of function and, in some cases, irreversible joint damage. Despite sharing common predisposing factors, many of the above diagnoses can be identified with a focused history and physical examination. Conservative management may be safely initiated without advanced imaging, reserving orthopaedic consultation for refractory cases or more serious diagnoses. The presented focused hip clinical examination has 98% sensitivity in localizing intra-articular hip pathology and will be helpful to direct appropriate referrals. This article will serve as a guide for primary care physicians undertaking the difficult task of evaluating and treating a young patient with hip pain.

Primary Care Fall Risk Assessment for Elderly West Virginians.

West Virginia is ranked second nationally for the percent of its population 65 years of age. The elderly are especially susceptible to falls with fall risk increasing as age increases. Because falls are the number one cause of injury-related morbidity and mortality in the West Virginia elderly, evaluation of fall risk is a critical component of the patient evaluation in the primary care setting. We therefore highlight fall risk assessments that require no specialized equipment or training and can easily be completed at an established office visit. High quality clinical practice guidelines supported by the American Geriatric Society recommend yearly fall risk evaluation in the elderly. Those seniors at greatest risk of falls will benefit from the standardized therapy protocols outlined and referral to a balance treatment center. Patients with low-to-moderate fall risk attributed to muscle weakness or fatigue should be prescribed lower extremity strengthening exercises, such as kitchen counter exercises, to improve strength and balance.

Primary Care Management of Plantar Fasciitis.

Plantar fasciitis (PF) is present in 10% of the population and is the most common cause of plantar heel pain. PF is painful, can alter daily activities and presents as a sharp pain localized to the plantar foot and medial heel. The underlying etiology involves microtrauma to the plantar fascia, specifically at its insertion point on the calcaneus. Successful management of plantar fasciitis is typically achieved with the conservative therapy approaches discussed.

Smartphone Mobile Applications to Enhance Diagnosis of Skin Cancer: A Guide for the Rural Practitioner.

Primary care physicians occupy a vital position to impact many devastating conditions, especially those dependent upon early diagnosis, such as skin cancer. Skin cancer is the most common cancer in the United States and despite improvements in skin cancer therapy, patients with a delay in diagnosis and advanced disease continue to have a grave prognosis. Due to a variety of barriers, advanced stages of skin cancer are more prominent in rural populations. In order to improve early diagnosis four things are paramount: increased patient participation in prevention methods, establishment of screening guidelines, increased diagnostic accuracy of malignant lesions, and easier access to dermatologists. Recent expansion in smartphone mobile application technology offers simple ways for rural practitioners to address these problems. More than 100,000 health related applications are currently available, with over 200 covering dermatology. This review will evaluate the newest and most useful of those applications offered to enhance the prevention and early diagnosis of skin cancer, particularly in the rural population.

Delayed Pseudoaneurysm of the Popliteal Artery Following ACL Reconstruction.

Arterial complications following arthroscopic anterior cruciate ligament (ACL) reconstruction of the knee are rare. Injuries to vascular structures around the knee have historically been reported more commonly, with reconstructive procedures occurring more posteriorly, such as posterior cruciate ligament (PCL) reconstruction. The authors present a report of sequelae following a postoperative popliteal artery spasm in an 18-year-old female soccer player who underwent ACL reconstruction using an ipsilateral autologous hamstring graft along with a medial meniscal repair and developed immediate spasm of the popliteal artery responding to sustained balloon angioplasty. Seven weeks postoperatively, she developed foot paresthesias and was noted to have a 3.5×3.1×1.3-cm pseudoaneurysm of her popliteal artery. She underwent popliteal artery bypass with reverse saphenous vein autograft and had an uneventful recovery. This case highlights the importance of prolonged follow-up and maintaining a high degree of suspicion for further arterial complications, even after routine arthroscopic knee procedures. In addition to maintaining close and extended follow-up, the authors agree with other authors' suggestions that urgent computed tomography angiogram be obtained to evaluate the vascular tree in a patient presenting with a cold, pulseless extremity after routine arthroscopic knee procedures. In this particular case, angiography of the uninvolved side also proved useful in identifying the patient's aberrant vascular anatomy and may be useful in patients with bilateral aberrant vascular anatomy to better facilitate interpretation of the injured side. To the author's knowledge, this is the first case of popliteal artery spasm initially responding to sustained angioplasty with the delayed development of a pseudoaneurysm.

Electrospun nanofiber scaffolds with gradations in fiber organization.

The goal of this protocol is to report a simple method for generating nanofiber scaffolds with gradations in fiber organization and test their possible applications in controlling cell morphology/orientation. Nanofiber organization is controlled with a new fabrication apparatus that enables the gradual decrease of fiber organization in a scaffold. Changing the alignment of fibers is achieved through decreasing deposition time of random electrospun fibers on a uniaxially aligned fiber mat. By covering the collector with a moving barrier/mask, along the same axis as fiber deposition, the organizational structure is easily controlled. For tissue engineering purposes, adipose-derived stem cells can be seeded to these scaffolds. Stem cells undergo morphological changes as a result of their position on the varied organizational structure, and can potentially differentiate into different cell types depending on their locations. Additionally, the graded organization of fibers enhances the biomimicry of nanofiber scaffolds so they more closely resemble the natural orientations of collagen nanofibers at tendon-to-bone insertion site compared to traditional scaffolds. Through nanoencapsulation, the gradated fibers also afford the possibility to construct chemical gradients in fiber scaffolds, and thereby further strengthen their potential applications in fast screening of cell-materials interaction and interfacial tissue regeneration. This technique enables the production of continuous gradient scaffolds, but it also can potentially produce fibers in discrete steps by controlling the movement of the moving barrier/mask in a discrete fashion.

Local Sustained Delivery of 25-Hydroxyvitamin D3 for Production of Antimicrobial Peptides.

PURPOSE: This study seeks to develop fiber membranes for local sustained delivery of 25-hydroxyvitamin D3 to induce the expression and secretion of LL-37 at or near the surgical site, which provides a novel therapeutic approach to minimize the risk of infections. METHODS: 25-hydroxyvitamin D3 loaded poly(L-lactide) (PLA) and poly(ε-caprolactone) (PCL) fibers were produced by electrospinning. The morphology of obtained fibers was characterized using atomic force microscope (AFM) and scanning electron microscope (SEM). 25-hydroxyvitamin D3 releasing kinetics were quantified by enzyme-linked immunosorbent assay (ELISA) kit. The expression of cathelicidin (hCAP 18) and LL-37 was analyzed by immunofluorescence staining and ELISA kit. The antibacterial activity test was conducted by incubating pseudomonas aeruginosa in a monocytes' lysis solution. RESULTS: AFM images suggest that the surface of PCL fibers is smooth, however, the surface of PLA fibers is relatively rough, in particular, after encapsulation of 25-hydroxyvitamin D3. The duration of 25-hydroxyvitamin D3 release can last more than 4 weeks for all the tested samples. Plasma treatment can promote the release rate of 25-hydroxyvitamin D3. Human keratinocytes and monocytes express significantly higher levels of hCAP18/LL-37 after incubation with plasma treated and 25-hydroxyvitamin D3 loaded PCL fibers than the cells incubated with around ten times amount of free drug. After incubation with this fiber formulation for 5 days LL-37 in the lysis solutions of U937 cells can effectively kill the bacteria. CONCLUSIONS: Plasma treated and 25-hydroxyvitamin D3 loaded PCL fibers induce significantly higher levels of antimicrobial peptide production in human keratinocytes and monocytes without producing cytotoxicity.