Quantitative 1H Magnetic Resonance Imaging on Normal and Pathologic Rat Bones by Solid-State 1H ZTE Sequence with Water and Fat Suppression.

BACKGROUND: Osteoporosis (OP) and osteomalacia (OM) are metabolic bone diseases characterized by mineral and matrix density changes. Quantitative bone matrix density differentiates OM from OP. MRI is a noninvasive and nonionizing imaging technique that can measure bone matrix density quantitatively in ex vivo and in vivo. PURPOSE: To demonstrate water + fat suppressed 1H MRI to compute bone matrix density in ex vivo rat femurs in the preclinical model. STUDY TYPE: Prospective. ANIMAL MODEL: Fifteen skeletally mature female Sprague-Dawley rats, five per group (normal, ovariectomized (OVX), partially nephrectomized/vitamin D (Vit-D) deficient), 250-275 g, ∼15 weeks old. FIELD STRENGTH/SEQUENCE: 7T, zero echo time sequence with water + fat (VAPOR) suppression capability, µCT imaging, and gravimetric measurements. ASSESSMENT: Cortical and trabecular bone segments from normal and disease models were scanned in the same coil along with a dual calibration phantom for quantitative assessment of bone matrix density. STATISTICAL TESTS: ANOVA and linear regression were used for data analysis, with P-values <0.05 statistically significant. RESULTS: The MRI-derived three-density PEG pellet densities have a strong linear relationship with physical density measures (r2 = 0.99). The Vit-D group had the lowest bone matrix density for cortical bone (0.47 ± 0.16 g cm-3), whereas the OVX had the lowest bone matrix density for trabecular bone (0.26 ± 0.04 g cm-3). Gravimetry results confirmed these MRI-based observations for Vit-D cortical (0.51 ± 0.07 g cm-3) and OVX trabecular (0.26 ± 0.03 g cm-3) bone groups. DATA CONCLUSION: Rat femur images were obtained using a modified pulse sequence and a custom-designed double-tuned (1H/31P) transmit-receive solenoid-coil on a 7T preclinical MRI scanner. Phantom experiments confirmed a strong linear relation between MRI-derived and physical density measures and quantitative bone matrix densities in rat femurs from normal, OVX, and Vit-D deficient/partially nephrectomized animals were computed. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

Antibiotic prophylaxis following low-velocity gunshot fractures: an updated review.

PURPOSE: Low-velocity gunshot fractures (LVGFs) are a common type of gunshot-induced trauma with the potential for complications such as infection and osteomyelitis. The effectiveness of antibiotic therapy in LVGFs remains uncertain, leading to ongoing debate about the appropriate treatment. In this review, we evaluate recent updates on the current understanding of antibiotic therapy in LVGFs, how previous studies have investigated the use of antibiotics in LVGFs, and the current state of institutional policies and protocols for treating LVGFs with antibiotics. METHODS: We conducted a review of PubMed, Embase, and Web of Science databases to identify studies that investigated the use of antibiotics in LVGFs after the last review in 2013. Due to the lack of quantitative clinical trial studies, we employed a narrative synthesis approach to analyze and present the findings from the included primary studies. We categorized the outcomes based on the anatomical location of the LVGFs. RESULTS: After evaluating 67 publications with the necessary qualifications out of 578 abstracts, 17 articles were included. The sample size of the studies ranged from 22 to 252 patients. The antibiotics used in the studies varied, and the follow-up period ranged from three months to ten years. The included studies investigated the use of antibiotics in treating LVGFs at various anatomic locations, including the humerus, forearm, hand and wrist, hip, femur, tibia, and foot and ankle. CONCLUSION: Our study provides updated evidence for the use of antibiotics in LVGFs and highlights the need for further research to establish evidence-based guidelines. We also highlight the lack of institutional policies for treating LVGFs and the heterogeneity in treatments among institutions with established protocols. A single-dose antibiotic approach could be cost-effective for patients with non-operatively treated LVGFs. We suggest that a national or international registry for gunshot injuries, antibiotics, and infections could serve as a valuable resource for collecting and analyzing data related to these important healthcare issues.

Clinic follow-up of orthopaedic trauma patients during and after the post-surgical global period: a retrospective cohort study.

BACKGROUND: Insurance status is important as medical expenses may decrease the likelihood of follow-up after musculoskeletal trauma, especially for low-income populations. However, it is unknown what insurance factors are associated with follow-up care. In this study, we assessed the association between insurance plan benefits, the end of the post-surgical global period, and follow-up after musculoskeletal injury. METHODS: This is a retrospective cohort study of 394 patients with isolated extremity fractures who were treated at three level-I trauma centers over four months in 2018. Paired t-tests were utilized to assess the likelihood of follow-up in relation to the 90-day post-surgical global period. Regression analysis was used to assess factors associated with the likelihood of follow-up. Supervised machine learning algorithms were used to develop predictive models of follow-up after the post-surgical global period. RESULTS: Our final analysis included 328 patients. Likelihood of follow-up did not significantly change while within the post-surgical global period. When comparing follow-up within and outside of the post-surgical global period, there was a 20.1% decrease in follow-up between the 6-weeks and 6-month time points (68.3% versus 48.2%, respectively; p < 0.0001). Medicaid insurance compared to Medicare (OR 0.27, 95% confidence interval (CI) = [0.09, 0.84], p = 0.02) was a predictor of decreased likelihood of follow-up at 6-months post-operatively. CONCLUSIONS: Our study demonstrates a statistically significant decrease in follow-up for orthopaedic trauma patients after the post-surgical global period, particularly for patients with Medicaid or Private insurance.

Management of arthrofibrosis in neuromuscular disorders: a review.

Arthrofibrosis, or rigid contracture of major articular joints, is a significant morbidity of many neurodegenerative disorders. The pathogenesis depends on the mechanism and severity of the precipitating neuromuscular disorder. Most neuromuscular disorders, whether spastic or hypotonic, culminate in decreased joint range of motion. Limited range of motion precipitates a cascade of pathophysiological changes in the muscle-tendon unit, the joint capsule, and the articular cartilage. Resulting joint contractures limit functional mobility, posing both physical and psychosocial burdens to patients, economic burdens on the healthcare system, and lost productivity to society. This article reviews the pathophysiology of arthrofibrosis in the setting of neuromuscular disorders. We describe current non-surgical and surgical interventions for treating arthrofibrosis of commonly affected joints. In addition, we preview several promising modalities under development to ameliorate arthrofibrosis non-surgically and discuss limitations in the field of arthrofibrosis secondary to neuromuscular disorders.

Intraarticular injection of relaxin-2 alleviates shoulder arthrofibrosis.

Arthrofibrosis is a prevalent condition affecting greater than 5% of the general population and leads to a painful decrease in joint range of motion (ROM) and loss of independence due to pathologic accumulation of periarticular scar tissue. Current treatment options are limited in effectiveness and do not address the underlying cause of the condition: accumulation of fibrotic collagenous tissue. Herein, the naturally occurring peptide hormone relaxin-2 is administered for the treatment of adhesive capsulitis (frozen shoulder) and to restore glenohumeral ROM in shoulder arthrofibrosis. Recombinant human relaxin-2 down-regulates type I collagen and α smooth muscle actin production and increases intracellular cAMP concentration in human fibroblast-like synoviocytes, consistent with a mechanism of extracellular matrix degradation and remodeling. Pharmacokinetic profiling of a bolus administration into the glenohumeral joint space reveals the brief systemic and intraarticular (IA) half-lives of relaxin-2: 0.96 h and 0.62 h, respectively. Furthermore, using an established, immobilization murine model of shoulder arthrofibrosis, multiple IA injections of human relaxin-2 significantly improve ROM, returning it to baseline measurements collected before limb immobilization. This is in contrast to single IA (sIA) or multiple i.v. (mIV) injections of relaxin-2 with which the ROM remains constrained. The histological hallmarks of contracture (e.g., fibrotic adhesions and reduced joint space) are absent in the animals treated with multiple IA injections of relaxin-2 compared with the untreated control and the sIA- and mIV-treated animals. As these findings show, local delivery of relaxin-2 is an innovative treatment of shoulder arthrofibrosis.

Modifiable lifestyle factors associated with fragility hip fracture: a systematic review and meta-analysis.

INTRODUCTION: Among the various hip fracture predictors explored to date, modifiable risk factors warrant special consideration, since they present promising targets for preventative measures. This systematic review and meta-analysis aims to assess various modifiable risk factors. MATERIAL AND METHODS: We searched four online databases in September 2017. We included studies that reported on modifiable lifestyle risk factors for sustaining fragility hip fractures. The quality of the included studies was assessed using the Newcastle-Ottawa Scale (NOS). The inclusion criteria consisted of (1) adult patients with osteoporotic hip fracture, (2) original study, (3) availability of full text articles in English, and (4) report of a modifiable lifestyle risk factor. RESULTS: Thirty-five studies, containing 1,508,366 subjects in total, were included in this study. The modifiable risk factors that were significantly associated with an increased risk of hip fracture were the following: weight < 58 kg (128 lbs) (pooled OR 4.01, 95% CI 1.62-9.90), underweight body mass index (BMI) (< 18.5) (pooled OR 2.83, 95% CI 1.82-4.39), consumption of ≥ 3 cups of coffee daily (pooled OR 2.27, 95% CI 1.04-4.97), inactivity (pooled OR 2.14, 95% CI 1.21-3.77), weight loss (pooled OR 1.88, 95% CI 1.32-2.68), consumption of ≥ 27 g (approx. > 2 standard drinks) alcohol per day (pooled OR 1.54, 95% CI 1.12-2.13), and being a current smoker (pooled OR 1.50, 95% CI 1.22-1.85). Conversely, two factors were significantly associated with a decreased risk of hip fracture: obese BMI (> 30) (pooled OR 0.58, 95% CI 0.34-0.99) and habitual tea drinking (pooled OR 0.72, 95% CI 0.66-0.80). CONCLUSION: Modifiable factors may be utilized clinically to provide more effective lifestyle interventions for at risk populations. We found that low weight and underweight BMI carried the highest risk, followed by high coffee consumption, inactivity, weight loss, and high daily alcohol consumption.

What Factors Predict Adverse Discharge Disposition in Patients Older Than 60 Years Undergoing Lower-extremity Surgery? The Adverse Discharge in Older Patients after Lower-extremity Surgery (ADELES) Risk Score.

BACKGROUND: Adverse discharge disposition, which is discharge to a long-term nursing home or skilled nursing facility is frequent and devastating in older patients after lower-extremity orthopaedic surgery. Predicting individual patient risk allows for preventive interventions to address modifiable risk factors and helps managing expectations. Despite a variety of risk prediction tools for perioperative morbidity in older patients, there is no tool available to predict successful recovery of a patient's ability to live independently in this highly vulnerable population. QUESTIONS/PURPOSES: In this study, we asked: (1) What factors predict adverse discharge disposition in patients older than 60 years after lower-extremity surgery? (2) Can a prediction instrument incorporating these factors be applied to another patient population with reasonable accuracy? (3) How does the instrument compare with other predictions scores that account for frailty, comorbidities, or procedural risk alone? METHODS: In this retrospective study at two competing New England university hospitals and Level 1 trauma centers with 673 and 1017 beds, respectively; 83% (19,961 of 24,095) of patients 60 years or older undergoing lower-extremity orthopaedic surgery were included. In all, 5% (1316 of 24,095) patients not living at home and 12% (2797 of 24,095) patients with missing data were excluded. All patients were living at home before surgery. The mean age was 72 ± 9 years, 60% (11,981 of 19,961) patients were female, 21% (4155 of 19,961) underwent fracture care, and 34% (6882 of 19,961) underwent elective joint replacements. Candidate predictors were tested in a multivariable logistic regression model for adverse discharge disposition in a development cohort of all 14,123 patients from the first hospital, and then included in a prediction instrument that was validated in all 5838 patients from the second hospital by calculating the area under the receiver operating characteristics curve (ROC-AUC).Thirty-eight percent (5360 of 14,262) of patients in the development cohort and 37% (2184 of 5910) of patients in the validation cohort had adverse discharge disposition. Score performance in predicting adverse discharge disposition was then compared with prediction scores considering frailty (modified Frailty Index-5 or mFI-5), comorbidities (Charlson Comorbidity Index or CCI), and procedural risks (Procedural Severity Scores for Morbidity and Mortality or PSS). RESULTS: After controlling for potential confounders like BMI, cardiac, renal and pulmonary disease, we found that the most prominent factors were age older than 90 years (10 points), hip or knee surgery (7 or 8 points), fracture management (6 points), dementia (5 points), unmarried status (3 points), federally provided insurance (2 points), and low estimated household income based on ZIP code (1 point). Higher score values indicate a higher risk of adverse discharge disposition. The score comprised 19 variables, including socioeconomic characteristics, surgical management, and comorbidities with a cutoff value of ≥ 23 points. Score performance yielded an ROC-AUC of 0.85 (95% confidence interval 0.84 to 0.85) in the development and 0.72 (95% CI 0.71 to 0.73) in the independent validation cohort, indicating excellent and good discriminative ability. Performance of the instrument in predicting adverse discharge in the validation cohort was superior to the mFI-5, CCI, and PSS (ROC-AUC 0.72 versus 0.58, 0.57, and 0.57, respectively). CONCLUSION: The Adverse Discharge in Older Patients after Lower Extremity Surgery (ADELES) score predicts adverse discharge disposition after lower-extremity surgery, reflecting loss of the ability to live independently. Its discriminative ability is better than instruments that consider frailty, comorbidities, or procedural risk alone. The ADELES score identifies modifiable risk factors, including general anesthesia and prolonged preoperative hospitalization, and should be used to streamline patient and family expectation management and improve shared decision making. Future studies need to evaluate the score in community hospitals and in institutions with different rates of adverse discharge disposition and lower income. A non-commercial calculator can be accessed at www.adeles-score.org. LEVEL OF EVIDENCE: Level III, diagnostic study.

The effect of surgeon-controlled variables on construct stiffness in lateral locked plating of distal femoral fractures.

BACKGROUND: Nonunion following treatment of supracondylar femur fractures with lateral locked plates (LLP) has been reported to be as high as 21 %. Implant related and surgeon-controlled variables have been postulated to contribute to nonunion by modulating fracture-fixation construct stiffness. The purpose of this study is to evaluate the effect of surgeon-controlled factors on stiffness when treating supracondylar femur fractures with LLPs: 1. Does plate length affect construct stiffness given the same plate material, fracture working length and type of screws? 2. Does screw type (bicortical locking versus bicortical nonlocking or unicortical locking) and number of screws affect construct stiffness given the same material, fracture working length, and plate length? 3. Does fracture working length affect construct stiffness given the same plate material, length and type of screws? 4. Does plate material (titanium versus stainless steel) affect construct stiffness given the same fracture working length, plate length, type and number of screws? METHODS: Mechanical study of simulated supracondylar femur fractures treated with LLPs of varying lengths, screw types, fractureworking lenghts, and plate/screw material. Overall construct stiffness was evaluated using an Instron hydraulic testing apparatus. RESULTS: Stiffness was 15 % higher comparing 13-hole to the 5-hole plates (995 N/mm849N vs. /mm, p = 0.003). The use of bicortical nonlocking screws decreased overall construct stiffness by 18 % compared to bicortical locking screws (808 N/mm vs. 995 N/mm, p = 0.0001). The type of screw (unicortical locking vs. bicortical locking) and the number of screws in the diaphysis (3 vs. 10) did not appear to significantly influence construct stiffness (p = 0.76, p = 0.24). Similarly, fracture working length (5.4 cm vs. 9.4 cm, p = 0.24), and implant type (titanium vs. stainless steel, p = 0.12) did also not appear to effect stiffness. DISCUSSION: Using shorter plates and using bicortical nonlocking screws (vs. bicortical locking screws) reduced overall construct stiffness. Using more screws, using unicortical locking screws, increasing fracture working length and varying plate material (titanium vs. stainless steel) does not appear to significantly alter construct stiffness. Surgeons can adjust plate length and screw types to affect overall fracture-fixation construct stiffness; however, the optimal stiffness to promote healing remains unknown.

Computational modeling of human bone fracture healing affected by different conditions of initial healing stage.

BACKGROUND: Bone healing process includes four phases: inflammatory response, soft callus formation, hard callus development, and remodeling. Mechanobiological models have been used to investigate the role of various mechanical and biological factors on bone healing. However, the effects of initial healing phase, which includes the inflammatory stage, the granulation tissue formation, and the initial callus formation during the first few days post-fracture, are generally neglected in such studies. METHODS: In this study, we developed a finite-element-based model to simulate different levels of diffusion coefficient for mesenchymal stem cell (MSC) migration, Young's modulus of granulation tissue, callus thickness and interfragmentary gap size to understand the modulatory effects of these initial phase parameters on bone healing. RESULTS: The results quantified how faster MSC migration, stiffer granulation tissue, thicker callus, and smaller interfragmentary gap enhanced healing to some extent. However, after a certain threshold, a state of saturation was reached for MSC migration rate, granulation tissue stiffness, and callus thickness. Therefore, a parametric study was performed to verify that the callus formed at the initial phase, in agreement with experimental observations, has an ideal range of geometry and material properties to have the most efficient healing time. CONCLUSIONS: Findings from this paper quantified the effects of the initial healing phase on healing outcome to better understand the biological and mechanobiological mechanisms and their utilization in the design and optimization of treatment strategies. It is also demonstrated through a simulation that for fractures, where bone segments are in close proximity, callus development is not required. This finding is consistent with the concepts of primary and secondary bone healing.

Effect of sarcopenia on clinical and surgical outcome in elderly patients with proximal femur fractures.

PURPOSE: To investigate the relationship between sarcopenia with short-term surgical outcome in elderly patients with proximal femur fractures. METHODS AND MATERIALS: Following Institutional Review Board approval, a database of patients receiving a pelvis CT scan for acute trauma between January 2000-August 2016 was screened for an isolated proximal femur fracture. Patients were excluded if they were: < 50 years old, had conditions predisposing to sarcopenia (renal failure, congestive heart failure, muscular dystrophies), had undergone no surgical treatment, had other major traumatic injuries, or had a pathologic femur fracture. The paraspinal muscle density (PSD) at the L4 level was measured in Hounsfield units. The skeletal muscle index (SMI) was measured as the total skeletal muscle area at L4 divided by patient height.2 PSD and SMI were tested for association with surgical outcome measures: length of hospital stay, perioperative mortality, medical complications, in-hospital blood transfusion volume, and 90-day readmission rate, using multiple variable regression analysis. Pearson correlation of PSD and SMI was performed. RESULTS: Controlling for age, gender, body mass index (BMI), and fracture type, low PSD and SMI were both independently associated with longer length of hospitalization (p = 0.008 and p = 0.032, respectively). Low PSD was associated with a higher amount of blood transfusion volume during the perioperative period (p = 0.004). Pearson correlation revealed moderate positive correlation between the SMI and PSD (r = 0.579, p < 0.001). CONCLUSION: In proximal femur fractures, elderly patients with sarcopenia are more likely to have prolonged hospitalization following surgery and require more blood transfusion volume during the perioperative period.

Risk of Injury to Neurovascular Structures During Open Cerclage Wiring of the Femur: A Cadaveric Study.

The objective of this study was to examine the risk to the sciatic nerve and femoral artery during open passage of cerclage wires and to evaluate the safest techniques. After a standard lateral approach, cerclage passes along the femur were made in cadaveric specimens. Distance to the sciatic nerve and femoral artery was recorded. Careful technique resulted in an increase in distance to the sciatic nerve and femoral artery. There was an increase in the distance to the femoral artery with passes in an anterior to posterior direction. There was decreased distance to structures proximally and distally. There was a trend toward increased safety with smaller passers. Open cerclage wiring of the femur is safest if proper technique is used, care is taken at the proximal and distal ends of the femur, passes are made in an anterior to posterior direction, and the smallest cerclage passer that can be passed is utilized.

Recent Advances in Dendritic Macromonomers for Hydrogel Formation and Their Medical Applications.

Hydrogels represent one of the most important classes of biomaterials and are of interest for various medical applications including wound repair, tissue engineering, and drug release. Hydrogels possess tunable mechanical properties, biocompatibility, nontoxicity, and similarity to natural soft tissues. The need for hydrogels with specific properties, based on the design requirements of the in vitro, in vivo, or clinical application, motivates researchers to develop new synthetic approaches and cross-linking methodologies to form novel hydrogels with unique properties. The use of dendritic macromonomers represents one elegant strategy for the formation of hydrogels with specific properties. Specifically, the uniformity of dendrimers combined with the control of their size, architecture, density, and surface groups make them promising cross-linkers for hydrogel formation. Over the last two decades, a large variety of dendritic-based hydrogels are reported for their potential use in the clinic. This review describes the state of the art with these different dendritic hydrogel formulations including their design requirements, the synthetic routes, the measurement and determination of their properties, the evaluation of their in vitro and in vivo performances, and future perspectives.

On-Demand Dissolution of a Dendritic Hydrogel-based Dressing for Second-Degree Burn Wounds through Thiol-Thioester Exchange Reaction.

An adhesive yet easily removable burn wound dressing represents a breakthrough in second-degree burn wound care. Current second-degree burn wound dressings absorb wound exudate, reduce bacterial infections, and maintain a moist environment for healing, but are surgically or mechanically debrided from the wound, causing additional trauma to the newly formed tissues. We have developed an on-demand dissolvable dendritic thioester hydrogel burn dressing for second-degree burn care. The hydrogel is composed of a lysine-based dendron and a PEG-based crosslinker, which are synthesized in high yields. The hydrogel burn dressing covers the wound and acts as a barrier to bacterial infection in an in vivo second-degree burn wound model. A unique feature of the hydrogel is its capability to be dissolved on-demand, via a thiol-thioester exchange reaction, allowing for a facile burn dressing removal.

Mortality and Revision Surgery Are Increased in Patients With Parkinson's Disease and Fractures of the Femoral Neck.

BACKGROUND: Patients with Parkinson's disease are at increased risk for falls and associated hip fractures as a result of tremor, bradykinesia, rigidity, and postural instability. The available literature is limited and conflicting regarding the optimal surgical treatment and risk for postoperative complications and mortality in this unique patient population. QUESTIONS/PURPOSES: We asked: (1) Is there a difference in mortality after surgical treatment of hip fractures in patients with Parkinson's disease compared with similar patients with hip fractures without Parkinson's disease? (2) Does Parkinson's disease lead to a higher rate of reoperation after operative treatment of femoral neck fractures? (3) Does Parkinson's disease lead to a higher rate of dislocation after hemiarthroplasty for displaced femoral neck fractures, and (4) does the operative approach affect dislocation rates? METHODS: In this case-controlled study, we retrospectively reviewed 141 patients with a diagnosis of Parkinson's disease and a fracture of the femoral neck. Each patient with Parkinson's disease was matched with two control patients (n = 282) without Parkinson's disease stratified by age, sex, American Society of Anesthesiologists classification, and fracture type (nondisplaced/displaced). Clinical outcomes included mortality after surgical intervention, rate of reoperation, dislocation events after hemiarthroplasty, and the rate of failure after internal fixation for nondisplaced fractures. RESULTS: The median survival time of the patients with Parkinson's disease after fracture was 31 months (95% CI, 25-37 months) compared with 45 months (95% CI, 39-50 months) in our control group (p = 0.007). The rate of reoperation for displaced and nondisplaced fractures was higher in the Parkinson's disease group compared with the control group (11% versus 4%; p = 0.005). Failure of fixation for patients treated with internal fixation of nondisplaced femoral neck fractures was significantly higher in the Parkinson's disease group compared with our control group (22% versus 5%; p = 0.01). Dislocation rates after hemiarthroplasty were significantly higher in the Parkinson's disease group compared with the control group (8% versus 1%; p = 0.003). Patients treated with a hemiarthroplasty through an anterolateral approach had a significantly lower dislocation rate compared with those treated with a posterior approach (2% versus 15%; p = 0.002). CONCLUSIONS: Parkinson's disease is an independent predictor of mortality after femoral neck fracture and is associated with an increased rate of dislocation, revision surgery, and failure of internal fixation. Although patients with Parkinson's disease with a nondisplaced or valgus impacted femoral neck fracture may be treated with internal fixation, they are at significantly higher risk of failure of fixation compared with patients without Parkinson's disease. Use of a hemiarthroplasty through an anterolateral approach may reduce the likelihood of requiring a revision operation. LEVEL OF EVIDENCE: Level III, therapeutic study.

The efficacy of a lysine-based dendritic hydrogel does not differ from those of commercially available tissue sealants and adhesives: an ex vivo study.

BACKGROUND: Hemostatic agents, tissue adhesives and sealants may contribute to a reduction in hemorrhage-associated morbidity and mortality. Towards this end, we have recently developed a lysine-based dendritic hydrogel (PEG-LysNH2) that can potentially be used in the management of severe trauma and/or intraoperative bleeding. As a first step in demonstrating the potential utility of this approach, our objective was to ascertain the ability of the PEG-LysNH2 to adhere to and seal injured tissues, as well as to maintain the seal under physiological conditions. METHODS: The efficacy of the PEG-LysNH2 in sealing injured tissues was evaluated using an ex-vivo pressure testing system. A 2.5 mm incision was made on intact ex-vivo tissues and then sealed with the PEG-LysNH2. Application of the PEG-LysNH2 was followed by 1) step-wise pressure increase to a maximum of 250 mmHg and 2) fluctuating pressures, between 100-180 mmHg with a rate of 3 Hz, over a 24-hour period. The performance of the PEG-LysNH2 was compared to those of commercially available sealants and adhesives. RESULTS: During gradual pressure increase, mean pressures at 30 seconds (P30) ranged between 206.36 - 220.17 mmHg for the sealants, and they were greater than control and suture groups (p < 0.01 and p = 0.013, respectively). Additionally, all products held under fluctuating pressures: mean pressures ranged between 135.20 - 160.09 mmHg, and there were no differences observed between groups (p = 0.96). CONCLUSIONS: The efficacy of the PEG-LysNH2 was significantly superior to conventional injury repair methods (sutures) and did not differ from those of commercially available products when sealing small incisions.

In vivo kinetic evaluation of an adhesive capsulitis model in rats.

BACKGROUND AND HYPOTHESIS: We hypothesized that extra-articular, internal fixation of the shoulder in rats would result in a subsequent decrease in rotational range of motion (ROM) and an increase in joint stiffness. We further hypothesized that residual kinematic changes would still be present at 8 weeks after immobilization. Extra-articular, internal fixation of the shoulder has been used to induce adhesive capsulitis in rats; however, the effects on in vivo kinematics have not been assessed. METHODS: Baseline measurements of rotational torque and ROM were acquired (n = 10 rats), and the left forelimb of each animal was immobilized with sutures passed between the scapula and the humeral shaft. After 8 weeks, the sutures were removed, and changes in kinematics and kinetics were longitudinally quantified in the follow-up period. Changes in stiffness, defined as the area under the angle-torque curve, were also quantified. RESULTS: Immediately after suture removal, there was a 63% decrease in total ROM compared with baseline (51° ± 10° vs. 136° ± 0°; P < .001). Similarly, total torque was found to increase 13.4 N.mm compared with baseline (22.6 ± 5.9 N.mm vs. 9.2 ± 2.6 N.mm; P = .002). Residual total ROM restrictions and an increased torque in internal rotation were still evident at 8 weeks of follow-up (113° ± 8° vs. 137° ± 0°, P < .001 and 3.5 ± 0.4 N.mm vs. 2.7 ± 0.7 N.mm, P = .036). Stiffness also increased after suture removal and at 8 weeks of follow-up compared with baseline. CONCLUSION: This animal model of adhesive capsulitis rendered lasting effects on in vivo kinematics of the shoulder.

An Automated Vertebrae Localization, Segmentation, and Osteoporotic Compression Fracture Detection Pipeline for Computed Tomographic Imaging.

Osteoporosis is the most common chronic metabolic bone disease worldwide. Vertebral compression fracture (VCF) is the most common type of osteoporotic fracture. Approximately 700,000 osteoporotic VCFs are diagnosed annually in the USA alone, resulting in an annual economic burden of ~$13.8B. With an aging population, the rate of osteoporotic VCFs and their associated burdens are expected to rise. Those burdens include pain, functional impairment, and increased medical expenditure. Therefore, it is of utmost importance to develop an analytical tool to aid in the identification of VCFs. Computed Tomography (CT) imaging is commonly used to detect occult injuries. Unlike the existing VCF detection approaches based on CT, the standard clinical criteria for determining VCF relies on the shape of vertebrae, such as loss of vertebral body height. We developed a novel automated vertebrae localization, segmentation, and osteoporotic VCF detection pipeline for CT scans using state-of-the-art deep learning models to bridge this gap. To do so, we employed a publicly available dataset of spine CT scans with 325 scans annotated for segmentation, 126 of which also graded for VCF (81 with VCFs and 45 without VCFs). Our approach attained 96% sensitivity and 81% specificity in detecting VCF at the vertebral-level, and 100% accuracy at the subject-level, outperforming deep learning counterparts tested for VCF detection without segmentation. Crucially, we showed that adding predicted vertebrae segments as inputs significantly improved VCF detection at both vertebral and subject levels by up to 14% Sensitivity and 20% Specificity (p-value = 0.028).

Relaxin as a treatment for musculoskeletal fibrosis: What we know and future directions.

Fibrotic changes in musculoskeletal diseases arise from the abnormal buildup of fibrotic tissue around the joints, leading to limited mobility, compromised joint function, and diminished quality of life. Relaxin (RLX) attenuates fibrosis by accelerating collagen degradation and inhibiting excessive extracellular matrix (ECM) production. Further, RLX disrupts myofibroblast activation by modulating the TGF-ß/Smads signaling pathways, which reduces connective tissue fibrosis. However, the mechanisms and effects of RLX in musculoskeletal pathologies are emerging as increasing research focuses on relaxin's impact on skin, ligaments, tendons, cartilage, joint capsules, connective tissues, and muscles. This review delineates the actions of relaxin within the musculoskeletal system and the challenges to its clinical application. Relaxin shows significant potential in both in vivo and in vitro studies for broadly managing musculoskeletal fibrosis; however, challenges such as short biological half-life and sex-specific responses may pose hurdles for clinical use.

Detection and Localization of Spine Disorders from Plain Radiography.

Spine disorders can cause severe functional limitations, including back pain, decreased pulmonary function, and increased mortality risk. Plain radiography is the first-line imaging modality to diagnose suspected spine disorders. Nevertheless, radiographical appearance is not always sufficient due to highly variable patient and imaging parameters, which can lead to misdiagnosis or delayed diagnosis. Employing an accurate automated detection model can alleviate the workload of clinical experts, thereby reducing human errors, facilitating earlier detection, and improving diagnostic accuracy. To this end, deep learning-based computer-aided diagnosis (CAD) tools have significantly outperformed the accuracy of traditional CAD software. Motivated by these observations, we proposed a deep learning-based approach for end-to-end detection and localization of spine disorders from plain radiographs. In doing so, we took the first steps in employing state-of-the-art transformer networks to differentiate images of multiple spine disorders from healthy counterparts and localize the identified disorders, focusing on vertebral compression fractures (VCF) and spondylolisthesis due to their high prevalence and potential severity. The VCF dataset comprised 337 images, with VCFs collected from 138 subjects and 624 normal images collected from 337 subjects. The spondylolisthesis dataset comprised 413 images, with spondylolisthesis collected from 336 subjects and 782 normal images collected from 413 subjects. Transformer-based models exhibited 0.97 Area Under the Receiver Operating Characteristic Curve (AUC) in VCF detection and 0.95 AUC in spondylolisthesis detection. Further, transformers demonstrated significant performance improvements against existing end-to-end approaches by 4-14% AUC (p-values < 10-13) for VCF detection and by 14-20% AUC (p-values < 10-9) for spondylolisthesis detection.