Computed tomography-based structural rigidity analysis can assess tumor- and treatment-induced changes in rat bones with metastatic lesions.

BACKGROUND: Breast cancer (BrCa) is a predominant malignancy, with metastasis occurring in one in eight patients, nearly half of which target the bone, leading to serious complications such as pain, fractures, and compromised mobility. Structural rigidity, crucial for bone strength, becomes compromised with osteolytic lesions, highlighting the vulnerability and increased fracture risk in affected areas. Historically, two-dimensional radiographs have been employed to predict these fracture risks; however, their limitations in capturing the three-dimensional structural and material changes in bone have raised concerns. Recent advances in CT-based Structural Rigidity Analysis (CTRA), offer a promising, more accurate non-invasive 3D approach. This study aims to assess the efficacy of CTRA in monitoring osteolytic lesions' progression and response to therapy, suggesting its potential superiority over existing methodologies in guiding treatment strategies. METHODS: Twenty-seven female nude rats underwent femoral intra-medullary inoculation with MDA-MB-231 human breast cancer cells or saline control. They were divided into Control, Cancer Control, Ibandronate, and Paclitaxel groups. Osteolytic progression was monitored weekly using biplanar radiography, quantitative computed tomography (QCT), and dual-energy X-ray absorptiometry (DEXA). CTRA was employed to predict fracture risk, normalized using the contralateral femur. Statistical analyses, including Kruskal-Wallis and ANOVA, assessed differences in outcomes among groups and over time. RESULTS: Biplanar radiographs showed treatment benefits over time; however, only certain time-specific differences between the Control and other treatment groups were discernible. Notably, observer subjectivity in X-ray scoring became evident, with significant inter-operator variations. DEXA measurements for metaphyseal Bone Mineral Content (BMC) did not exhibit notable differences between groups. Although diaphyseal BMC highlighted some variance, it did not reveal significant differences between treatments at specific time points, suggesting a limited ability for DEXA to differentiate between treatment effects. In contrast, the CTRA consistently demonstrated variations across different treatments, effectively capturing bone rigidity changes over time, and the axial- (EA), bending- (EI), and torsional rigidity (GJ) outcomes from the CTRA method successfully distinguished differences among treatments at specific time points. CONCLUSION: Traditional approaches, such as biplanar radiographs and DEXA, have exhibited inherent limitations, notably observer bias and time-specific inefficacies. Our study accentuates the capability of CTRA in capturing real-time, progressive changes in bone structure, with the potential to predict fractures more accurately and provide a more objective analysis. Ultimately, this innovative approach may bridge the existing gap in clinical guidelines, ushering in enhanced Clinical Decision Support Tool (CDST) for both surgical and non-surgical treatments.

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.

Effect of intraarticular pressure on glenohumeral kinematics during a simulated abduction motion: a cadaveric study.

BACKGROUND: The current understanding of glenohumeral joint stability is defined by active restrictions and passive stabilizers including naturally-occurring negative intraarticular pressure. Cadaveric specimens have been used to evaluate the role of intraarticular pressure on joint stability, although, while the shoulder's negative intraarticular pressure is universally acknowledged, it has been inconsistently accounted for. HYPOTHESIS: During continuous, passive humeral abduction, releasing the native intraarticular pressure increases joint translation, and restoring this pressure decreases joint translations. STUDY DESIGN: Descriptive Laboratory Study. METHODS: A validated shoulder testing system was used to passively abduct the humerus in the scapular plane and measure joint translations for seven (n = 7) cadaveric specimens. The pressure within the glenohumeral joint was measured via a 25-gauge needle during passive abduction of the arm, which was released and subsequently restored. During motion, the rotator cuff muscles were loaded using stepper motors in a force feedback loop and electromagnetic sensors were used to continuously measure the position of the humerus and scapula. Joint translation was defined according to the instant center of rotation of the glenohumeral head according to the recommendations by the International Society of Biomechanics. RESULTS: Area under the translation versus abduction angle curve suggests that releasing the pressure within the capsule results in significantly less posterior translation of the glenohumeral head as compared to intact (85-90˚, p < 0.05). Posterior and superior translations were reduced after 70˚ of abduction when the pressure within the joint was restored. CONCLUSION: With our testing system employing a smooth continuous passive motion, we were able to show that releasing intraarticular pressure does not have a major effect on the path of humeral head motion during glenohumeral abduction. However, both violating the capsule and restoring intraarticular pressure after releasing alter glenohumeral translations. Future studies should study the effect of simultaneous external rotation and abduction on the relationship between joint motion and IAP, especially in higher degrees of abduction. CLINICAL RELEVANCE: Thoroughly simulating the glenohumeral joint environment in the cadaveric setting may strengthen the conclusions that can be translated from this setting to the clinic.

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.

The Role of Interleukin-27 in Atherosclerosis: A Contemporary Review.

Atherosclerosis is a chronic inflammation characterized by an imbalance between inhibitors and stimulators of the inflammatory system that leads to the formation of atherosclerotic plaques in the vessel walls. Interleukin (IL)-27 is one of the recently discovered cytokines that have an immunomodulatory role in autoimmune and inflammatory diseases. However, the definite role of IL-27 in the pathogenesis of atherosclerosis remains unclear. Recent studies on cardiomyocytes and vascular endothelium have demonstrated mechanisms through which IL-27 could potentially modulate atherosclerosis. Upregulation of the IL-27 receptor was also observed in the atherosclerotic plaques. In addition, circulatory IL-27 levels were increased in patients with acute coronary syndrome and myocardial infarction. A regenerative, neovascularization, and cardioprotective role of IL-27 has also been implicated. Future studies are warranted to elucidate the biologic function and clinical significance of IL-27 in atherosclerosis.

Evolution of knowledge on meniscal biomechanics: a 40 year perspective.

BACKGROUND: Knowledge regarding the biomechanics of the meniscus has grown exponentially throughout the last four decades. Numerous studies have helped develop this knowledge, but these studies have varied widely in their approach to analyzing the meniscus. As one of the subcategories of mechanical phenomena Medical Subject Headings (MeSH) terms, mechanical stress was introduced in 1973. This study aims to provide an up-to-date chronological overview and highlights the evolutionary comprehension and understanding of meniscus biomechanics over the past forty years. METHODS: A literature review was conducted in April 2021 through PubMed. As a result, fifty-seven papers were chosen for this narrative review and divided into categories; Cadaveric, Finite element (FE) modeling, and Kinematic studies. RESULTS: Investigations in the 1970s and 1980s focused primarily on cadaveric biomechanics. These studies have generated the fundamental knowledge basis for the emergence of FE model studies in the 1990s. As FE model studies started to show comparable results to the gold standard cadaveric models in the 2000s, the need for understanding changes in tissue stress during various movements triggered the start of cadaveric and FE model studies on kinematics. CONCLUSION: This study focuses on a chronological examination of studies on meniscus biomechanics in order to introduce concepts, theories, methods, and developments achieved over the past 40 years and also to identify the likely direction for future research. The biomechanics of intact meniscus and various types of meniscal tears has been broadly studied. Nevertheless, the biomechanics of meniscal tears, meniscectomy, or repairs in the knee with other concurrent problems such as torn cruciate ligaments or genu-valgum or genu-varum have not been extensively studied.

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.

Successive tendon injury in an in vivo rat overload model induces early damage and acute healing responses.

Introduction: Tendinopathy is a degenerative condition resulting from tendons experiencing abnormal levels of multi-scale damage over time, impairing their ability to repair. However, the damage markers associated with the initiation of tendinopathy are poorly understood, as the disease is largely characterized by end-stage clinical phenotypes. Thus, this study aimed to evaluate the acute tendon responses to successive fatigue bouts of tendon overload using an in vivo passive ankle dorsiflexion system. Methods: Sprague Dawley female rats underwent fatigue overloading to their Achilles tendons for 1, 2, or 3 loading bouts, with two days of rest in between each bout. Mechanical, structural, and biological assays were performed on tendon samples to evaluate the innate acute healing response to overload injuries. Results: Here, we show that fatigue overloading significantly reduces in vivo functional and mechanical properties, with reductions in hysteresis, peak stress, and loading and unloading moduli. Multi-scale structural damage on cellular, fibril, and fiber levels demonstrated accumulated micro-damage that may have induced a reparative response to successive loading bouts. The acute healing response resulted in alterations in matrix turnover and early inflammatory upregulations associated with matrix remodeling and acute responses to injuries. Discussion: This work demonstrates accumulated damage and acute changes to the tendon healing response caused by successive bouts of in vivo fatigue overloads. These results provide the avenue for future investigations of long-term evaluations of tendon overload in the context of tendinopathy.

The effect of cannabinoids on single-level lumbar arthrodesis outcomes in a rat model.

BACKGROUND CONTEXT: The opioid epidemic is a public health crisis affecting spine care and pain management. Medical marijuana is a potential non-opioid analgesic yet to be studied in the surgical setting since its effects on bone healing are not fully understood. Studies have demonstrated analgesic and potentially osteoinductive properties of cannabinoids with endocannabinoid receptor expression in bone tissue. PURPOSE: We hypothesize that tetrahydrocannabinol (THC) and cannabidiol (CBD) will not decrease bone healing in spinal fusion. STUDY DESIGN: Seventy-eight adult Sprague-Dawley rats were used for this study. Utilizing allogenic bone grafts (6 donor rats), posterolateral inter-transverse lumbar fusion at the L4-L5 level was performed. The animals were equally divided into four treatment groups, each receiving 0.1 ml intraperitoneal injections weekly as follows: placebo (saline), 5 mg/kg THC, 5 mg/kg CBD, and a combination of 5 mg/kg THC and 5mg/kg CBD (Combo). METHODS: Callus tissue was harvested 2- and 8-weeks post-surgery for qPCR assessment to quantify changes in the expression of osteogenic genes. Manual palpation was done to assess the strength of the L4-L5 arthrodesis on all rats. µCT image-based callus analysis and histology were performed. One-way ANOVA followed by post hoc comparisons was performed. RESULTS: µCT demonstrated no significant differences. Treatment groups had slightly increased bone volume and density compared to control. qPCR at two weeks indicated downregulated RANKL/OPG ratios skewing towards osteogenesis in the CBD group, with the THC and CBD+THC groups demonstrating a downward trend (p>.05). ALPL, BMP4, and SOST were significantly higher in the CBD group, with CTNNB1 and RUNX2 also showing an upregulating trend. The CBD group showed elevation in Col1A1 and MMP13. Data at eight weeks showed ALPL, RUNX2, BMP4, and SOST were downregulated for all treatment groups. In the CBD+THC group, RANK, RANKL, and OPG were downregulated. OPG downregulation reached significance for the THC and CBD+THC group compared to saline. Interestingly, the RANKL/OPG ratio showed upregulation in the CBD and CBD+THC groups. RANKL showed upregulation in the CBD group. At 2 and 8 weeks, the CBD treatment group showed superior histological progression, increasing between time points. CONCLUSION: This study demonstrates that CBD and THC have no adverse effect on bone healing and the rate of spinal fusion in rats. Osteogenic factors were upregulated in the CBD-treated groups at two weeks, which indicates a potential for bone regeneration. In this group, compared to control, the RANKL/OPG ratio at the early healing phase demonstrates the inhibition of osteoclast differentiation, enhancing bone formation. Interestingly, it shows promoted osteoclast differentiation at the later healing phase, enhancing bone remodeling. This aligns with the physiological expectation of a lower ratio in the early phases and a higher ratio in the later remodeling phases. CLINICAL SIGNIFICANCE: CBD and THC showed no inhibitory effects on bone healing in a spinal fusion model. Moreover, histologic and gene expression analysis demonstrated that CBD may, in fact, enhance bone healing. Further research is needed to confirm the safe usage of THC and CBD in the post-operative setting following spinal fusions.

A Passive Ankle Dorsiflexion Testing System for an In Vivo Model of Overuse-induced Tendinopathy.

Tendinopathy is a chronic tendon condition that results in pain and loss of function and is caused by repeated overload of the tendon and limited recovery time. This protocol describes a testing system that cyclically applies mechanical loads via passive dorsiflexion to the rat Achilles tendon. The custom-written code consists of pre- and post-cyclic loading measurements to assess the effects of the loading protocol along with the feedback control-based cyclic fatigue loading regimen. We used 25 Sprague-Dawley rats for this study, with 5 rats per group receiving either 500, 1,000, 2,000, 3,600, or 7,200 cycles of fatigue loads. The percentage differences between the pre- and post-cyclic loading measurements of the hysteresis, peak stress, and loading and unloading moduli were calculated. The results demonstrate that the system can induce varying degrees of damage to the Achilles tendon based on the number of loads applied. This system offers an innovative approach to apply quantified and physiological varying degrees of cyclic loads to the Achilles tendon for an in vivo model of fatigue-induced overuse tendon injury.

While the Incidence of Venous Thromboembolism After Shoulder Arthroscopy Is Low, the Risk Factors Are a Body Mass Index Greater than 30 and Hypertension.

Purpose: This study aims to determine the overall incidence of venous thromboembolism (VTE) following shoulder arthroscopy and to define potential risk factors associated with its development that may help define guidelines for the use of thromboprophylaxis. Methods: A systematic review was performed using PubMed, Embase, Web of Science, CINAHL, and Cochrane databases per PRISMA guidelines. The search terms consisted of variations of "Venous Thromboembolism" and "Shoulder Arthroscopy." Information regarding arthroscopy indication, risk factors, outcomes, and patient demographics was recorded and analyzed, and pooled odds ratios were reported for each variable. Results: Six hundred eighty-five articles were identified in the initial search, and 35 articles reported DVT, PE, or VTE incidence following shoulder arthroscopy. Seventeen nonoverlapping articles with a unique patient population incidence rates. Four articles were then used for subgroup meta-analysis. The incidence rate of VTE was 0.24%, ranging from 0.01% to 5.7%. BMI >30 (OR = 1.46; 95% CI = [1.22, 1.74]; I2 = 0%) and hypertension (OR = 1.64; 95% CI = [1.03, 2.6]; I2 = 75%) were significant risk factors (P < .05) for developing VTE following shoulder arthroscopy. Diabetes (OR = 1.2; 95% CI = [0.97, 1.48]; I2 = 0%), insulin-dependent diabetes (OR = 5.58; 95% CI = [0.12, 260.19]; I2 = 85%), smoking (OR = 1.04; 95% CI = [0.79, 1.37]; I2 = 12%), male sex (OR = 0.95; 95% CI = [0.49, 1.85]; I2 = 86%) and age over 65 (OR = 4.3; 95% CI = [0.25, 72.83]; I2 = 85%) were not associated with higher VTE risk. Conclusion: The VTE incidence following shoulder arthroscopy is low at 0.24%. Patients with BMI >30 and hypertension are at a higher risk for VTE after shoulder arthroscopy. Level of Evidence: Level IV, systematic review and meta-analysis of Level I-IV studies.

Tuning the Biodegradation Rate of Silk Materials via Embedded Enzymes.

Conventional thinking when designing biodegradable materials and devices is to tune the intrinsic properties and morphological features of the material to regulate their degradation rate, modulating traditional factors such as molecular weight and crystallinity. Since regenerated silk protein can be directly thermoplastically molded to generate robust dense silk plastic-like materials, this approach afforded a new tool to control silk degradation by enabling the mixing of a silk-degrading protease into bulk silk material prior to thermoplastic processing. Here we demonstrate the preparation of these silk-based devices with embedded silk-degrading protease to modulate the degradation based on the internal presence of the enzyme to support silk degradation, as opposed to the traditional surface degradation for silk materials. The degradability of these silk devices with and without embedded protease XIV was assessed both in vitro and in vivo. Ultimately, this new process approach provides direct control of the degradation lifetime of the devices, empowered through internal digestion via water-activated proteases entrained and stabilized during the thermoplastic process.

Excellent accuracy of magnetic resonance imaging for diagnosis of discoid meniscus tears: A systematic review and meta-analysis.

Purpose: The discoid meniscus (DM) is distinguished by its thickened, disc-shaped formation, which extends over the tibial plateau. The likelihood of developing osteoarthritis escalates if a DM tear remains undiagnosed and untreated. While DM tears can be diagnosed through arthroscopy, the high cost, invasive nature and limited availability of this procedure highlight the need for a better diagnostic modality. This study aims to determine the accuracy of magnetic resonance imaging (MRI) in diagnosing DM tears. Methods: A systematic review was conducted to gather articles with at least 10 cases on the comparison of MRI and arthroscopy as the gold standard for DM tear diagnosis. Stata and MetaDisc were used to conduct the statistical analysis. The quality of the included studies was evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Results: Five diagnostic performance studies, derived from four original research papers involving 305 patients, were evaluated. Based on the pooled data, the sensitivity, specificity, diagnostic odds ratio, positive limit of detection and negative limit of detection were found to be 0.87 (95% confidence interval [CI], 0.82-0.91) and 0.84 (95% CI, 0.75-0.90), 32.88 (95% CI, 5.81-186.02), 5.22 (95% CI, 1.71-15.92) and 0.18 (95% CI, 0.09-0.38), respectively. A hierarchical summary receiver operating characteristic curve with an area under the curve of 0.92 was generated. Conclusion: This meta-analysis demonstrates that MRI has excellent sensitivity and specificity for diagnosing DM tears. Despite its lower accuracy compared to arthroscopy, MRI can be used in symptomatic patients as a viable alternative to arthroscopy due to its inherent advantages. Level of Evidence: Level IV.

Propylene glycol and Kolliphor as solvents for systemic delivery of cannabinoids via intraperitoneal and subcutaneous routes in preclinical studies: a comparative technical note.

BACKGROUND: Substance administration to laboratory animals necessitates careful consideration and planning in order to enhance agent distribution while reducing any harmful effects from the technique. There are numerous methods for administering cannabinoids; however, several parameters must be considered, including delivery frequency, volume of administration, vehicle, and the level of competence required for staff to use these routes properly. There is a scarcity of information about the appropriate delivery method for cannabinoids in animal research, particularly those that need the least amount of animal manipulation during the course of the investigation. This study aims to assess the feasibility and potential side effects of intraperitoneal and subcutaneous injection of CBD and THC using propylene glycol or Kolliphor in animal models. By evaluating the ease of use and histopathological side effects of these solvents, this study intends to help researchers better understand an accessible long-term delivery route of administration in animal experiments while minimizing the potential confounding effects of the delivery method on the animal. METHODS: Intraperitoneal and subcutaneous methods of systemic cannabis administration were tested in rat models. Subcutaneous delivery via needle injection and continuous osmotic pump release were evaluated using propylene glycol or Kolliphor solvents. In addition, the use of a needle injection and a propylene glycol solvent for intraperitoneal (IP) administration was investigated. Skin histopathological changes were evaluated following a trial of subcutaneous injections of cannabinoids utilizing propylene glycol solvent. DISCUSSION: Although IP delivery of cannabinoids with propylene glycol as solvent is a viable method and is preferable to oral treatment in order to reduce gastrointestinal tract degradation, it has substantial feasibility limitations. We conclude that subcutaneous delivery utilizing osmotic pumps with Kolliphor as a solvent provides viable and consistent route of administration for long-term systemic cannabinoid delivery in the preclinical context.

A Validated Three-Dimensional, Heterogenous Finite Element Model of the Rotator Cuff and The Effects of Collagen Orientation.

Continuum mechanics-based finite element models of the shoulder aim to quantify the mechanical environment of the joint to aid in clinical decision-making for rotator cuff injury and disease. These models allow for the evaluation of the internal loading of the shoulder, which cannot be measured in-vivo. This study uses human cadaveric rotator cuff samples with surface tendon strain estimates, to validate a heterogeneous finite element model of the supraspinatus-infraspinatus complex during various load configurations. The computational model was considered validated when the absolute difference in average maximum principal strain for the articular and bursal sides for each load condition estimated by the model was no greater than 3% compared to that measured in the biomechanical study. The model can predict the strains for varying infraspinatus loads allowing for the study of load sharing between these two tightly coordinated tendons. The future goal is to use the modularity of this validated model to study the initiation and propagation of rotator cuff tear and other rotator cuff pathologies to ultimately improve care for rotator cuff tear patients.

A passive ankle dorsiflexion testing system to assess mechanobiological and structural response to cyclic loading in rat Achilles tendon.

Tendinopathy is thought to be caused by repeated overload of the tendon with insufficient recovery time, leading to an inadequate healing response and incomplete recovery of preinjury material strength and function. The etiology of tendinopathy induced by mechanical load is being explored with a variety of mechanical load scenarios in small animals. This study establishes a testing system that applies passive ankle dorsiflexion to a rat hindlimb, estimates the force applied to the tendon during cyclic loading and enables the assessment of subsequent structural and biological changes. We demonstrated that the system had no drift in the applied angle, and the registered maximum angle and torque inputs and outputs were consistent between tests. We showed that cyclic loading decreased hysteresis and loading and unloading moduli with increasing cycles applied to the tendon. Histology showed gross changes to tendon structure. This work establishes a system for passively loading the rat Achilles tendon in-vivo in a physiological manner, facilitating future studies that will explore how mechanics, structure, and biology are altered by mechanical repetitive loading.

Anatomic Structures at Risk During Posterior to Anterior Percutaneous Screw Fixation of Posterior Malleolar Fractures: A Cadaveric Study.

Background. There are no established guidelines for fixation of posterior malleolus fractures (PMFs). However, fixation of PMFs appears to be increasing with growing evidence demonstrating benefits for stability, alignment, and early functional outcomes. The purpose of this study was to determine the risk to anatomic structures utilizing a percutaneous technique for posterior to anterior (PA) screw fixation of PMFs. Methods. Percutaneous PA screw placement was carried out on 10 fresh frozen cadaveric ankles followed by dissection to identify soft tissue and neurovascular structures at risk. The distance from the guidewire to each anatomic structure of interest was measured. The correlation between the mean distances from the guidewire to each structure was calculated. Results. The sural nerve was directly transected in 1/10 specimens (10%) and in contact with the wire in a second specimen (10%). There was a significant correlation between the proximity of the guidewire to the apex of Volkmann's tubercle and its proximity to the sural nerve. The flexor hallucis longus (FHL) muscle belly was perforated by the guidewire 40% of the time but was not tethered or entrapped by the screw. Conclusions. Percutaneous PA screw placement is a safe technique which can be improved with several modifications. A mini-open technique is recommended to protect the sural nerve. There may be potential for tethering of the FHL with use of a washer or large screw head. Risk to the anterior and posterior neurovascular bundles is minimal.Levels of Evidence: Level V.

Plaster of Paris: Squeeze, But Not Too Hard!

Plaster of Paris (PoP) has been the predominant treatment option for most acute and chronic orthopedic conditions. Water immersion significantly decreases the PoP bandage strength. Moreover, concerns have been raised about the possibility of breaks in PoP splints and cast failures once solid. The current study was designed to account for the increase in weight associated with increased PoP layers. The authors hypothesized that by controlling for weight variation as layers increased, they could determine the number of layers of PoP bandage that truly results in optimal mechanical properties. They assessed whether adequate plaster weight control while increasing layers could improve the mechanical properties of the splint. [Orthopedics. 2022;45(1):e57-e61.].

Minimally invasive, sustained-release relaxin-2 microparticles reverse arthrofibrosis.

Substantial advances in biotherapeutics are distinctly lacking for musculoskeletal diseases. Musculoskeletal diseases are biomechanically complex and localized, highlighting the need for novel therapies capable of addressing these issues. All frontline treatment options for arthrofibrosis, a debilitating musculoskeletal disease, fail to treat the disease etiology-the accumulation of fibrotic tissue within the joint space. For millions of patients each year, the lack of modern and effective treatment options necessitates surgery in an attempt to regain joint range of motion (ROM) and escape prolonged pain. Human relaxin-2 (RLX), an endogenous peptide hormone with antifibrotic and antifibrogenic activity, is a promising biotherapeutic candidate for musculoskeletal fibrosis. However, RLX has previously faltered through multiple clinical programs because of pharmacokinetic barriers. Here, we describe the design and in vitro characterization of a tailored drug delivery system for the sustained release of RLX. Drug-loaded, polymeric microparticles released RLX over a multiweek time frame without altering peptide structure or bioactivity. In vivo, intraarticular administration of microparticles in rats resulted in prolonged, localized concentrations of RLX with reduced systemic drug exposure. Furthermore, a single injection of RLX-loaded microparticles restored joint ROM and architecture in an atraumatic rat model of arthrofibrosis with clinically derived end points. Finally, confirmation of RLX receptor expression, RXFP1, in multiple human tissues relevant to arthrofibrosis suggests the clinical translational potential of RLX when administered in a sustained and targeted manner.

Death due to COVID-19 in a patient with diabetes, epilepsy, and gout comorbidities.

There is evidence of increased incidence, rapid progression, and poor prognosis of COVID-19 in patients with underlying comorbidities such as diabetes and epilepsy. Developing effective treatment regimens for COVID-19 patients with multiple comorbidities is crucial, as patients' past medical history is an essential contributor to possible organ injuries in COVID-19 patients. Herein, we report a confirmed case of COVID-19 patient with a history of multiple underlying diseases, including diabetes, epilepsy, and gout. The patient developed multiple organ failure and died a week after intensive care unit (ICU) admission. Multiple organ failure is the most common cause of death in COVID-19 patients.