Verteporfin attenuates trauma-induced heterotopic ossification of Achilles tendon by inhibiting osteogenesis and angiogenesis involving YAP/ß-catenin signaling.

Heterotopic ossification occurs as a pathological ossification condition characterized by ectopic bone formation within soft tissues following trauma. Vascularization has long been established to fuel skeletal ossification during tissue development and regeneration. However, the feasibility of vascularization as a target of heterotopic ossification prevention remained to be further clarified. Here, we aimed to identify whether verteporfin as a widely used FDA-approved anti-vascularization drug could effectively inhibit trauma-induced heterotopic ossification formation. In the current study, we found that verteporfin not only dose dependently inhibited the angiogenic activity of human umbilical vein endothelial cells (HUVECs) but also the osteogenic differentiation of tendon stem cells (TDSCs). Moreover, YAP/ß-catenin signaling axis was downregulated by the verteporfin. Application of lithium chloride, an agonist of ß-catenin, recovered TDSCs osteogenesis and HUVECs angiogenesis that was inhibited by verteporfin. In vivo, verteporfin attenuated heterotopic ossification formation by decelerating osteogenesis and the vessels densely associated with osteoprogenitors formation, which could also be readily reversed by lithium chloride, as revealed by histological analysis and Micro-CT scan in a murine burn/tenotomy model. Collectively, this study confirmed the therapeutic effect of verteporfin on angiogenesis and osteogenesis in trauma-induced heterotopic ossification. Our study sheds light on the anti-vascularization strategy with verteporfin as a candidate treatment for heterotopic ossification prevention.

STING contributes to trauma-induced heterotopic ossification through NLRP3-dependent macrophage pyroptosis.

Trauma-induced heterotopic ossification (HO) is featured by aberrant bone formation at extra-skeletal site. STING is a master adaptor protein linking cellular damage to immune responses, while its role in HO remains elusive. A murine burn/tenotomy model was used to mimic trauma-induced HO in vivo. We demonstrated elevated STING expression in macrophages in inflammatory stage after burn/tenotomy, and STING inhibition significantly alleviated HO formation. Activated NLRP3-dependent macrophage pyroptosis was also found in inflammatory stage after burn/tenotomy. Either STING or NLRP3 suppression reduced mature HO by weakening macrophage pyroptotic inflammation, while protective effects of STING were abolished by NLRP3 overexpression. Further, in vitro, we also found a prominent STING level in pyroptotic BMDMs. STING suppression relieved macrophage pyroptotic inflammation, while abolished by NLRP3 overexpression. Our results reveal that STING poses regulatory effects on trauma-induced HO formation, via modulating NLRP3-dependent macrophage pyroptosis. Targeting STING-NLRP3 axis represents an attractive approach for trauma-induced HO prevention.

Human osteoprogenitor cells obtained from traumatic heterotopic ossification samples showed enhanced osteogenic differentiation potential and ERK/hedgehog signaling than that from normal bone.

Traumatic heterotopic ossification (HO) refers to the abnormal ectopic osteogenesis following trauma, causing limb dysfunction and seriously lowering the life quality of patients. Aberrant osteogenic behavior of progenitor cells that ectopically accumulated within the soft tissues are believed to be responsible for HO formation. However, the detailed mechanism still remained to be clarified. Here in this study, we successfully isolated osteoprogenitors from human heterotopic ossification tissues (HO-ops) and identified their stemness and multi-directional differentiation potential. Using alkaline phosphatase staining together with alizarin red staining, we confirmed that the HO-ops in the heterotopic ossified tissues gained greater osteogenic potential than the normal human bone marrow mesenchymal stem cells (HBMSCs). RT-qPCR also indicated that HO-ops obtained more gene transcriptions of critical osteogenic determinators than HBMSCs. In addition, through Western blot, we proved that ERK signaling pathway and hedgehog signaling pathway were significantly activated in the HO-ops. When U0126 and cyclopamine were used to inhibit ERK signaling and hedgehog signaling respectively, the osteogenic potential of HO-ops decreased significantly. The hedgehog signaling and ERK signaling also showed cross-talk in HO-ops during osteogenic differentiation in HO-ops during osteogenic differentiation. The elevated ERK signaling and hedgehog signaling were further confirmed in the human traumatic HO sample sections by immunohistochemical staining. In sum, our results showed that the activation of ERK and hedgehog signaling pathway jointly enhanced the osteogenic potential of HO-ops to induce the formation of traumatic HO, which provides novel insights into the molecular basis of HO formation and offers promising targets for future therapeutic strategy.

Application of a novel osteotomy instrumentation as a substitute tool in total hip arthroplasty.

BACKGROUND: Mechanical failure, power shortage, and inadvertent contamination of the oscillating saw occasionally occurs in actualizing femoral neck osteotomy during total hip arthroplasty (THA); however, no appropriate alternative solution is currently available. This study aimed to introduce a novel osteotomy instrumentation (fretsaw, jig, cable passer hook) as a substitute tool while the oscillating saw was unavailable during THA. METHODS: This study included 40 patients (40 hips) who underwent femoral neck osteotomy during primary THA using the new osteotomy instrumentation (n = 20) and the oscillating saw (n = 20). Clinical data and intraoperative findings of all patients were evaluated. RESULTS: The mean osteotomy time was 22.3 ± 3.1 s (range, 17-30 s) and 29.4 ± 3.7 s (range, 25-39 s) in the oscillating saw group and in the new osteotomy instrumentation group, respectively (P < 0.001). The Harris Hip Score (HHS) improved in both groups; the mean HSS was 82.3 ± 2.5 and 83.3 ± 3.5 in the oscillating saw group and new osteotomy instrumentation group at 6 months after surgery, respectively (P = 0.297). CONCLUSIONS: The original osteotomy instrumentation can be an ideal substitute tool for femoral neck osteotomy in THA, especially when the oscillating saw is unavailable or malfunctioning.

Long-term outcomes of open arthrolysis combined with radial head arthroplasty for post-traumatic elbow stiffness: results are durable over 8 years.

BACKGROUND: Post-trauma elbow stiffness (PTES) is a common complication after elbow trauma that causes severe upper limb disability. Open elbow arthrolysis (OEA) with radial head arthroplasty (RHA) is an effective method to treat PTES with rotation limitation, or persistent pain/instability after radial head resection. However, no long-term results have been reported for this technique. This study aimed to show the clinical and radiographic outcomes of OEA with RHA over 8 years and compare its efficacy at 3 years (short-term). METHODS: Patients with PTES treated by OEA with RHA between September 2010 and December 2012 were retrospectively reviewed. Seventeen patients were followed up over 8 years (range, 100-106 months). A bipolar prosthesis of RHA was performed during OEA. Preoperative, 3-year, and 8-year elbow and forearm motion, upper limb function, radiographic outcomes, and complications were recorded. RESULTS: Clinically important improvements in elbow motion and forearm rotation were obtained, from 34° and 58° preoperatively, to 109° and 135° at 3 years, which were maintained over 8 years, to 113° (P = .262) and 134° (P = .489). The Mayo Elbow Performance Index had clinically important increases from the preoperative level of 58 to 94 points at 3 years, and was maintained over 8 years (95 points, P = .422), with 100% reporting excellent to good outcomes. Pain and nerve symptoms were also improved. Complications consisted of new-onset ulnar nerve symptoms in 1 patient, nonclinically significant heterotopic ossification recurrence in 3, humeroulnar arthritis exacerbation in 4, and periprosthetic lucency in 8. CONCLUSIONS: OEA with RHA yielded satisfactory short-term outcomes for PTES at 3 years, with substantial improvements in elbow mobility and function, and the results were durable over the long term (8 years).

What are the prevalence of and factors independently associated with depression and anxiety among patients with posttraumatic elbow stiffness? A cross-sectional, multicenter study.

BACKGROUND: Joint stiffness is a common complication after articular-related trauma in the elbow, resulting in significant limb disability, psychological stress, and a negative impact on daily life. No previous study has reported the impact of post-traumatic elbow stiffness (PTES) on psychological health. This study aims to (1) investigate the depression and anxiety levels and (2) identify factors independently associated with depression and anxiety symptoms in patients with PTES. METHODS: A total of 108 patients with PTES presenting to 4 collaborative municipal hospitals were consecutively enrolled from September to December 2020. Sociodemographic and clinical characteristics were collected through questionnaires and medical records. The Depression Anxiety Stress Scale-21 was used to assess depression and anxiety status. Ordinal logistic regression analysis was performed to identify factors independently associated with depression and anxiety symptoms. RESULTS: The detection rates of mild-to-moderate depression and anxiety are 40.7% and 27.8%, and severe-to-extremely severe levels are 23.1% and 25.9%, respectively. Regression results show that factors independently associated with depression include elbow flexion (odds ratio [OR]per 1° loss = 1.021, 95% confidence interval [CI]: 1.001-1.041, P = .035), elbow pain on movement (ORper 1 point increase = 1.236, 95% CI: 1.029-1.484, P = .023), family relationship (ORless close/very close = 10.059, 95% CI: 2.170-46.633, P = .003), and self-care ability (ORunable/able = 3.858, 95% CI: 1.244-11.961, P = .019). Factors independently associated with anxiety are elbow flexion (ORper 1° loss = 1.031, 95% CI: 1.009-1.052, P = .005), elbow pain on movement (ORper 1 point increase = 1.212, 95% CI: 1.003-1.465, P = .047), and clinically significant heterotopic ossification around elbow (ORyes/no = 2.344, 95% CI: 1.048-5.243, P = .038). CONCLUSION: Patients with PTES exhibit significant depression and anxiety symptoms. Several sociodemographic and clinical characteristics are independently associated with depression and anxiety levels. Identifying and addressing these factors may be of particular benefit during PTES management. Future research might address whether depression and anxiety affect the outcome after stiff elbow surgery.

Precision Wormlike Nanoadjuvant Governs Potency of Vaccination.

It remains unclear how the precise length of one-dimensional nanovehicles influences the characters of vaccination. Here, a unimolecular nanovehicle with tailored size and aspect ratio (AR) is applied to deliver CpG oligodeoxynucleotide, a Toll-like receptor (TLR) 9 agonist, as an adjuvant of recombinant hepatitis B virus surface antigen (rHBsAg), for treating chronic hepatitis B (CHB). Cationic nanovehicles with fixed width (ca. 45 nm) but varied length (46 nm-180 nm), AR from 1 to 4, are prepared through controlled polymerization and are loaded with CpG by electrostatic interaction. We reveal that the nanoadjuvant with AR = 2 shows the highest retention in proximal lymph nodes. Importantly, it is more easily internalized into antigen-presenting cells and accumulates in the late endosome, where TLR9 is located. Such a nanoadjuvant exhibits the strongest immune response with rHBsAg to clear the hepatitis B virus in the CHB mouse model, showing that the AR of nanovehicles governs the efficiency of vaccination.

Processing-Structure-Properties Relationships of Glycerol-Plasticized Silk Films.

Silk possesses excellent mechanical properties and biocompatibility due to its unique protein sequences and hierarchical structures. Thus, it has been widely used as a biomaterial in a broad spectrum of biomedical applications. In this study, an in-depth investigation of glycerol-plasticized silk films was carried out to understand the processing-structure-properties relationships. A series of glycerol-plasticized silk films with glycerol contents in the range of 0 to 30% (w/w) were prepared. The molecular structures and organizations of silk proteins and the interactions between glycerol and proteins were studied using FTIR, XRD, and DSC. At a low glycerol content (<12%), DSC revealed that the glass transition temperature and thermally induced crystallization temperature decreased as the glycerol content increased, implying that glycerol mainly interacts with silk proteins through hydrogen bonding. As the glycerol content further increased, the chain mobility of the silk proteins was promoted, leading to the formation of ß-sheet structures, water insolubility, and increased crystallinity. In addition, the stretchability and toughness of the films were significantly enhanced. The role of glycerol as a plasticizer in regulating the silk protein structures and determining the properties of the films was thoroughly discussed.

How effective is periarticular multimodal drug injection in open elbow arthrolysis? A prospective double-blind randomized controlled trial.

BACKGROUND: Evidence on the efficacy and safety of periarticular multimodal drug injection (PMDI) in open elbow arthrolysis (OEA) is limited. This study aimed to investigate differences in postoperative pain, blood loss, and range of motion (ROM) between PMDI vs. no injection among patients undergoing OEA, and the presence of PMDI-related complications. METHODS: This prospective, double-blind randomized controlled trial included 59 patients who underwent OEA. Patients randomly received PMDI (ropivacaine, epinephrine, ketoprofen) before wound closure or no injection. The primary outcomes were elbow pain over the first postoperative week at rest and during motion, measured using the visual analog scale (VAS). VAS scores were compared to attain the 20-mm threshold values for a minimum clinically important difference. Parecoxib consumption on OEA night and postoperative days (PODs) 1-3 and total consumption during the first postoperative week were recorded. Blood loss was recorded every 24 hours until POD 3. ROM during rehabilitation was measured daily from day 1 to day 7 after surgery, as well as at 3-month follow-up. Medication-related side effects were recorded prospectively. RESULTS: The mean VAS score showed clinically important differences between PMDI and control groups at rest on OEA night (mean difference [MD], 25 mm; P < .001) and first 3 PODs with motion (POD 1: MD, 28 mm, P < .001; POD 2: MD, 21 mm, P < .001; POD 3: MD, 21 mm, P < .001) but not in other postoperative assessments. Parecoxib consumption was lower in the PMDI group on OEA night and PODs 1-3. Total parecoxib consumption during the first postoperative week was lower in the PMDI group vs. the control group (MD, 148 mg; P < .001). Blood drainage was less in the PMDI group vs. the control group on POD 1 (MD, 38 mL; P = .016) but not on POD 2 (P = .950), POD 3 (P = .259), or total (P = .184). The PMDI group exhibited significantly better ROM during the first 4 PODs than the control group, whereas there was no difference at 3-month follow-up. No medication-related side effects were noted in the PMDI group. CONCLUSION: PMDI effectively relieves pain and reduces analgesic consumption for OEA patients, without an apparent increase in risks.

Intravenous tranexamic acid reduce postoperative drainage and pain after open elbow arthrolysis: a randomized controlled trial.

BACKGROUND: Open elbow arthrolysis (OEA), which has become an established treatment for post-traumatic elbow stiffness (PTES), requires complete release of contracture tissue and wide excision of ectopic bone, which results in extensive bleeding. The aim of the present study is to evaluate the efficacy of intravenous tranexamic acid (TXA) on postoperative drainage, calculated blood loss, and early clinical outcomes in patients undergoing OEA. METHODS: A double-blind, randomized, placebo-controlled trial including 96 patients undergoing OEA was undertaken. Patients received intravenously either 100 mL saline (placebo group, n = 48), or 100 mL saline plus 1 g TXA (TXA group, n = 48) before skin incision. The primary outcome was the drainage volume on postoperative days (PODs) 1-3. Secondary outcomes included the calculated blood loss, elbow pain score measured by visual analog scale (VAS), elbow function valued by Mayo Elbow Performance Score (MEPS), and rate of complications after OEA. RESULTS: Mean total postoperative drainage volume (TXA group: 182 mL vs. placebo group: 214 mL, P = .003) and mean calculated total blood loss (TXA group: 582 mL vs. placebo group: 657 mL, P = .004) were significantly lower in the TXA group. No transfusions were necessary in either group. Mean VAS pain scores in elbow motion showed marked differences between both groups on POD 1 (TXA: 5 vs. placebo: 6, P = .003) and POD 2 (TXA: 4 vs. placebo: 5, P = .023) but not in other postoperative time points. No differences were detected in complications, such as pin-related infection, hematoma, new or exacerbation of ulnar nerve symptoms, and recurrent heterotopic ossification. At the 6-month follow-up, no statistical differences were found between the 2 groups with respect to the elbow functions including range of motion, VAS score, and MEPS. CONCLUSION: Intravenous administration of TXA significantly decreased the postoperative drainage volume and the total estimated blood loss and alleviated the elbow pain with motion during early postoperative days in patients undergoing OEA.

Midterm Outcomes After Open Arthrolysis for Posttraumatic Elbow Stiffness in Children and Adolescents.

BACKGROUND: Open arthrolysis is used for treating elbow stiffness in adults. This study evaluated the midterm outcomes after open arthrolysis in children and adolescents with posttraumatic elbow stiffness. METHODS: Data of 31 children and adolescents with posttraumatic elbow stiffness following open arthrolysis with or without hinged external fixation from 2010 to 2014 were retrospectively analyzed. Their mean age was 15 (range: 6 to 19) years. At baseline and the follow-up (>4 y), we evaluated the outcomes (range of motion and Mayo Elbow Performance Index) and postoperative complications (pain, ulnar nerve symptoms, infections, and instability) and analyzed the association between outcomes and clinical variables. RESULTS: The Mayo Elbow Performance Index improved from 67.9 (range: 35 to 95 points) to 93.7 points (range: 65 to 100 points; P<0.001). The elbow active flexion/extension arc increased significantly from 49 degrees (range: 0 to 120 degrees) to 108 degrees (range: 0 to 120 degrees; P<0.001), with a mean flexion of 123 degrees (range: 70 to 140 degrees; P<0.001) and mean extension of 15 degrees (range: 0 to 85 degrees; P<0.001) postoperatively. The increasing age at surgery was associated with improved elbow motions (P=0.004). Patients with increased preoperative serum alkaline phosphatase level demonstrated decreased arc of motion (P=0.015). Patients with extra-articular fractures had better outcomes than the other patients. At the final follow-up, 8 patients experienced recurrent contracture in the flexion arc with heterotopic ossification. Two patients had postoperative pain, 1 elbow instability, and 1 ulnar neuropathy. CONCLUSIONS: Most patients showed satisfactory functional outcomes after arthrolysis, indicating that open release with or without hinged external fixation is an effective and maintained technique for children and adolescents with posttraumatic elbow stiffness. The age at surgery, preoperative alkaline phosphatase level, and injury type should be considered to achieve good outcomes. LEVEL OF EVIDENCE: Therapeutic level III.

A new pathologic classification for elbow stiffness based on our experience in 216 patients.

BACKGROUND: Elbow stiffness commonly causes functional impairment and upper-limb disability. This study aimed to develop a new pathologic classification to further understand and standardize elbow arthrolysis from a new perspective, as well as to determine clinical outcomes. METHODS: Extension-flexion dysfunction was classified into 4 types: EFI, tethers alone; EFII, tethers with blocks; EFIII, articular malformation; and EFIV, bony ankylosis. Forearm rotation dysfunction was classified into 3 types: FRI, contracture alone; FRII, radial head malunion or nonunion; and FRIII, proximal radioulnar bony ankylosis. A total of 216 patients with elbow stiffness were prospectively included and categorized preoperatively. All surgical procedures were performed by the same chief surgeon; different types underwent specific procedures. Patient data, elbow motion, and functional scores were analyzed. RESULTS: Mean range of motion (ROM) increased from 40° preoperatively to 118° at final follow-up; 88% of patients regained ROM of 100° or greater. The forearm rotation arc (FRA) with forearm rotation dysfunction increased from a preoperative mean of 76° to 128°; 82% of patients regained an FRA of 100° or greater. The mean Mayo Elbow Performance Index (MEPI) increased from 63 to 91 points; the proportion of patients with good or excellent results was 95%. EFI patients had the best ROM (129°) and MEPI (93 points) and EFIV patients achieved the most-changed ROM (116°), whereas EFIII patients had the worst ROM (104°) and MEPI (84 points) and the least-changed ROM (64°). The FRA was best in FRI patients (142°), followed by FRII patients (118°), and worst in FRIII patients (82°); in contrast, the changed FRA was greatest in FRIII patients (82°), followed by FRII patients (64°), and least in FRI patients (37°). CONCLUSION: This study suggests that the proposed pathologic classification provides a new perspective on the understanding and standardization of elbow arthrolysis, providing satisfactory clinical outcomes.

Effect of hyperuricemia on functional outcomes and complications in patients with elbow stiffness after open arthrolysis combined with hinged external fixation: a retrospective study.

BACKGROUND: Hyperuricemia is considered a risk factor for increased postoperative complications and adverse functional outcomes in a variety of orthopedic surgeries. The purpose of this retrospective study was to investigate the clinical efficacy of patients with different uric acid levels after elbow arthrolysis. METHODS: The study included 131 patients with post-traumatic elbow stiffness who underwent arthrolysis between March 2014 and March 2016. All patients were divided into 4 groups based on the preoperative serum level of uric acid (UA). The quartile method was used for grouping patients, including 33 in Q1 (UA <293 µmol/L), 34 in Q2 (293-348 µmol/L), 32 in Q3 (348-441 µmol/L), and 32 in Q4 (441-710 µmol/L). At baseline and each time point of follow-up, functional performance, Mayo Elbow Performance Score, visual analog scale for pain, and complications were evaluated. RESULTS: Preoperative data were not significantly different among the 4 groups (Q1, Q2, Q3, and Q4). At the final follow-up, the following data showed significant differences among the 4 groups: extension (P = .031), flexion (P = .008), range of motion (P = .003), Mayo Elbow Performance Score (P = .011), and visual analog scale (P = .032). Interestingly, patients in the Q4 group had the poorest clinical outcomes. However, no significant differences were found among the 4 groups in new onset or exacerbation of nerve symptoms (P = .919), reduced muscle strength (P = .536), instability (P = .567), or infection (P = .374) at the last follow-up. CONCLUSION: This study confirms that in patients with post-traumatic elbow stiffness, abnormal serum uric acid metabolism was a risk factor for poor performance and postoperative pain after arthrolysis. Therefore, detecting the preoperative serum uric acid levels of the patients would be helpful for evaluating the postoperative outcomes.

Tadpole-like Unimolecular Nanomotor with Sub-100 nm Size Swims in a Tumor Microenvironment Model.

Inspired by the natural motors capable of performing multiple tasks in complex living environments, synthetic nanomotors emerge as a potential vehicle for revolutionizing biomedical processes. Yet current motors suffer from decreased and even completely hindered motion in a complex physiological environment, shadowing the future of this booming field. To address this problem, a unimolecular nanomotor based on molecular bottlebrush (MBB) of sub-100 nm size is reported. This motor is constructed precisely via controlled radical polymerization and click chemistry and propelled with biocompatible catalase. Such a molecular nanomotor possesses tadpole-like asymmetry and is able to overcome Brownian motion, and demonstrates strong directional propulsion (linear and coiled cyclic trajectories) in a viscous tumor microenvironment gel model at an ultralow hydrogen peroxide level of 2 mM (0.006%). In addition, the molecular nanomotor exhibits superior stability in serum containing cell medium and good biocompatibility in blood. Such molecular bottlebrush based nanomotors may represent a unique platform for overcoming the tissue penetration barrier.

What Range of Motion and Functional Results Can Be Expected After Open Arthrolysis with Hinged External Fixation For Severe Posttraumatic Elbow Stiffness?

BACKGROUND: The elbow is more susceptible to loss of motion after trauma than any other joint. Open arthrolysis often is performed for posttraumatic elbow stiffness if the stiffness does not improve with nonsurgical treatment, but the midterm results of this procedure and factors that may limit recovery have not been widely studied. QUESTIONS/PURPOSES: We reviewed patients who had undergone open arthrolysis with hinged external fixator for severe posttraumatic elbow stiffness (ROM ≤ 60°) with a minimum of 5 years followup to (1) analyze ROM gains; (2) assess functional improvement with the Mayo Elbow Performance Index (MEPI) and DASH, quality of life with the SF-36, pain with VAS, and ulnar nerve function with the Amadio rating scale and Dellon classification; and (3) identify complications and risk factors that might hinder mid-term elbow motion recovery after this procedure. METHODS: Between March 2011 and December 2012, we generally offered patients with elbow stiffness an open arthrolysis procedure when function did not improve with 6 months of nonoperative therapy, and no contraindications such as immature heterotopic ossification or complete destruction of articular cartilage were present. During that time, 161 patients underwent open arthrolysis for posttraumatic elbow stiffness at our institution; 49 of them satisfied the study inclusion criteria (adults with elbow ROM ≤ 60° as a result of trauma) and exclusion criteria (stiffness caused by burns or central nervous system injuries, causative trauma associated with nonunion or malunion of the elbow, severe articular damage that would have necessitated joint arthroplasty, or prior elbow release). In general, a combined medial-lateral approach to the elbow was performed to address the soft tissue tethers and any blocks to elbow motion, and a hinged external fixator was applied for 6 weeks to maintain elbow stability and improve the efficacy of postoperative rehabilitation. These patients were evaluated retrospectively at a mean followup period of 69 months (range, 62-83 months), and demographics, disease characteristics, arthrolysis details, pre- and postoutcome measures as noted, and complications were recorded via an electronic database. Multivariate regression analysis was performed to identify factors associated with ROM recovery. RESULTS: At final followup, total ROM increased from a preoperative mean of 27 ± 20° to a postoperative mean of 131 ± 11° (mean difference, 104°; 95% CI, 98°-111°; p < 0.001), and 98% (48 of 49) of patients achieved a functional ROM of 30° to 130°. Improvements were also found in functional scores (MEPI: 54 ± 12 to 95 ± 7, mean difference, 41 points; DASH: 48 ± 17 to 8 ± 8, mean difference, 40 points; both p < 0.001), life quality (physical SF-36: 46 ± 11 to 81 ± 12, mean difference, 35 points; mental SF-36: 43 ± 14 to 80 ± 9, mean difference, 37 points; both p < .001), pain (VAS: 2.5 ± 2.4 to 0.4 ± 0.8; mean difference, 2.0 points; p < 0.001), and ulnar nerve function (Amadio score: 7.8 ± 1.9 to 8.4 ± 0.8; mean difference, 0.6 points; p = 0.004). A total of 18% (nine of 49 patients) developed complications, including new-onset or exacerbated nerve symptoms (four patients), recurrent heterotopic ossification (two patients), and pin-related infections (three patients). No patients underwent subsequent surgery for any of the above complications. Lastly, the medium-term ROM was divided into ROM ≤ 120° (n = 9) and ROM > 120° (n = 40). After controlling for potential confounding variables such as duration of stiffness and tobacco use, we found that tobacco use was the only independent risk factor examined (odds ratio, 9; 95% CI, 2-47; p = 0.009) associated with recovery of ROM. CONCLUSIONS: Satisfactory medium-term results were found for open arthrolysis with hinged external fixation with our protocol in patients who had severe posttraumatic elbow stiffness. Appropriate and sufficient releases of tethered soft tissues and correction of any blocks that affect elbow motion intraoperatively, a dedicated team approach, and an aggressive and systematic postoperative rehabilitation program are the core steps for this procedure. Additionally, the importance of preoperative discontinuation of tobacco use should be emphasized. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Determining the effective timing of an open arthrolysis for post-traumatic elbow stiffness: a retrospective cohort study.

BACKGROUND: Following trauma, the elbow is the most susceptible to restricted motion among all joints. Open arthrolysis is often performed for post-traumatic elbow stiffness if that stiffness does not improve with non-operative management. However, the optimal timing for performing an open arthrolysis remains controversial. The purpose of this study was to compare the outcome (elbow motion and function) and the rate of complications among patients who had undergone early, median and late release procedures to establish an optimal time interval following the injury, after which, an effective open arthrolysis can be performed. METHODS: In this retrospective cohort study, we included total 133 patients, who had undergone open arthrolysis for post-traumatic elbow stiffness. The subjects were divided into 3 groups, with 31 patients in the early release group (arthrolysis performed at 6-10 months after injury), 78 patients in the median release group (at 11-20 months), and 24 patients in the late release group (at > 20 months). The release procedure in all patients was performed by the same surgeon, using the same technique. The general data, functional performance, and complications, if any, were retrospectively documented for all patients and statistically analysed. RESULTS: The demographic data and disease characteristics of all patients were comparable at baseline. Postoperatively, no significant differences were found among the three groups with respect to the range of motion (p = 0.067), Mayo Elbow Performance Score (p = 0.350) and its ratings (p = 0.329), visual analog scale score for pain (p = 0.227), Dellon classification for ulnar nerve symptoms (p = 0.497), and each discrete complication (all p values > 0.05). CONCLUSIONS: At the final follow-up, our results showed no significant difference in the postoperative elbow motion capacities, functional scores and the rates of complications among patients who had undergone an early, median, and late release. Therefore, we have recommended that an early arthrolysis would be preferable due to its multiple advantages, and the conventionally observed interval of > 1 year after the injury, could be shortened. LEVEL OF EVIDENCE: Level III; Retrospective Cohort Design; Therapeutic Study.

Development and validation of a new elbow-specific scoring system for patients with elbow stiffness: the Shanghai Elbow Dysfunction Score.

BACKGROUND: Clinical scoring systems are increasingly important and popular for the evaluation of orthopedic patients. Elbow stiffness commonly causes functional impairment and upper-limb disability. The purpose of this study was to develop and validate a new elbow-specific assessment score to evaluate joint function in patients with elbow stiffness. METHODS: The new system, the Shanghai Elbow Dysfunction Score (SHEDS), was developed in 3 portions: elbow motion capacities, elbow-related symptoms, and patient satisfaction level. A total of 73 patients with elbow stiffness were prospectively included. Intraclass correlation coefficients and Cronbach α values were calculated for test-retest reliability and internal consistency, respectively. Construct validity was assessed by correlating the SHEDS with previously validated scoring systems. Effect sizes (ES) and standardized response means (SRMs) were calculated for responsiveness. RESULTS: Positive reliability with an intraclass correlation coefficient of 0.83 and adequate homogeneity with a Cronbach α value of 0.74 were found for the SHEDS. Good to excellent validity using Spearman correlation coefficients (SCCs) were determined for the total (0.51-0.82), motion (0.65-0.89), and symptom (0.35-0.53) scores. Responsiveness was large for the total ES, 3.48; SRM, 2.96), motion (ES, 2.54; SRM, 2.08), and symptom (ES, 1.26; SRM, 1.14) scores. There were no ceiling or floor effects. Significant positive correlations were found between patient satisfaction levels and the final scores (SCC, 0.62), as well as the score changes of the SHEDS (SCC, 0.42). CONCLUSION: Our results suggest that the newly developed SHEDS is an excellent, comprehensive, valid scoring system to evaluate joint function in patients with elbow stiffness.

Tobacco use predicts poorer clinical outcomes and higher post-operative complication rates after open elbow arthrolysis.

INTRODUCTION: Tobacco use is a worldwide public health problem, and has been found to be a predisposing factor for adverse functional outcomes and increased postoperative complication rates after various orthopedic operations. The purpose of this study was to determine the potential impact of tobacco use on open arthrolysis for post-traumatic elbow stiffness. MATERIALS AND METHODS: A database search identified 145 patients with open arthrolysis performed for post-traumatic elbow stiffness; these were divided into three groups: current tobacco users (37), former users (28), and nonusers (80). All surgeries were performed using the same technique by the same doctor. General patient data, functional performance, and complications were documented and analyzed. RESULTS: Demographic data and disease characteristics were comparable at baseline. Postoperatively, significant differences were found among the three groups in terms of range of motion (P < 0.001), Mayo Elbow Performance Score (P = 0.006), visual analog scale score for pain (P = 0.015), Dellon classification for ulnar nerve symptoms (P = 0.013), and total complication rates (P < 0.001). The current tobacco users group had the poorest clinical outcomes and highest complication rates, while no significant differences were found between former users and nonusers. CONCLUSIONS: Current tobacco users reported increased risk of poorer clinical outcomes and higher postoperative complication rates after open arthrolysis. Former users were found to have outcomes similar to those of nonusers. This study underlines the importance of discontinuing tobacco use for patients with post-traumatic elbow stiffness who are considering open arthrolysis. LEVEL OF EVIDENCE: Level III; Retrospective Cohort Design; Therapeutic Study.

Validation of the Liverpool Elbow Score for evaluation of elbow stiffness.

BACKGROUND: The Liverpool Elbow Score (LES) has been widely used to assess the outcomes of total elbow replacement in various conditions. However, there have been no published validation studies on LES for patients with stiff elbows undergoing arthrolysis. The purpose of this study was to find out whether LES could be equally applied to evaluate joint function in patients with elbow stiffness. METHODS: A total of 63 patients with elbow stiffness were included in this retrospective validation study. The LES combines a nine-item patient-answered questionnaire (PAQ) and a six-item clinical assessment score (CAS), and can also be divided to evaluate two different parameters: elbow motion capacity (EMC) and elbow-related symptoms (ERS). Construct validity was assessed by correlating LES with previously validated scoring systems, and Spearman correlation coefficients (SCCs) were calculated. Effect size (ES) and standardized response mean (SRM) were calculated to determine responsiveness. RESULTS: There were no ceiling or floor effects in the target population. Good-to-excellent validity was determined based on total score (0.45-0.89), PAQ (0.42-0.88), CAS (0.35-0.60), EMC (0.46-0.86), and ERS (0.36-0.59). High responsiveness (ES/SRM) was observed in total score (2.80/2.24), PAQ (2.34/1.78), CAS (2.90/2.34), EMC (2.92/2.35), and ERS (0.55/0.52). CONCLUSION: Our results suggest that the LES is a valid elbow-specific scoring system that can be used to evaluate joint function in patients with elbow stiffness, though some items included had some weakness either.

Impact of different glucose metabolism status on clinical outcomes of open arthrolysis for post-traumatic elbow stiffness.

BACKGROUND: Diabetes and prediabetes are worldwide public health problems and are considered predisposing factors for adverse functional outcomes after various orthopedic operations. The purpose of this retrospective study was to determine the impact of glucose metabolism status on functional outcomes and complications after open arthrolysis for post-traumatic elbow stiffness. METHODS: The study included 152 patients with post-traumatic elbow stiffness undergoing arthrolysis, including 120 in the normoglycemic group, 21 in the impaired glucose regulation group, and 11 in the diabetes mellitus group. General patient data, functional performance, and complications were documented and analyzed. RESULTS: Demographic data and disease characteristics were comparable at baseline. Postoperatively, significant differences were found in range of motion and the Mayo Elbow Performance Score: the diabetes mellitus group had the poorest clinical outcomes. However, there were no significant differences in forearm rotation, visual analog scale pain scores, and complication rates. CONCLUSION: Patients with post-traumatic elbow stiffness and abnormal glucose metabolism were at increased risk of poorer outcomes after open arthrolysis, and patients with diabetes mellitus had the poorest performance. This study underlines the importance of glycemic control in patients with abnormal glucose metabolism before open arthrolysis.