Heterotopic bone formation in a case of clear cell renal cell carcinoma: A case report.

Renal cell carcinoma (RCC) with heterotopic formation has been reported very rarely. We report this rare entity in a 33-year-old female patient who came to the out-patient department after complaining of pain in the lumbar region of the left side for 2 years. A computed tomography scan showed a heterogeneously enhancing lesion originating from the posterior cortex of the left kidney in the upper pole. It had many chunky calcification foci and was treated with left robotic partial nephrectomy. Histo-pathological examination revealed clear cell RCC with the heterotopic bone formation with a tumor size measuring 5 × 4 × 2.5 cm; the tumor was limited to the kidney, and the tumor resection margin were free of tumor, WHO/ISUP Grade 2. The pathological stage (AJCC 8th edition PTNM) was p T1b p NX p MX. The prognostic implications regarding calcification are poorly addressed in the literature. Patients suffering from osseous metaplasia are often in their early stages of the disease and have a favorable prognosis.

Intersections of Fibrodysplasia Ossificans Progressiva and Traumatic Heterotopic Ossification.

Heterotopic ossification (HO) is a debilitating pathology where ectopic bone develops in areas of soft tissue. HO can develop as a consequence of traumatic insult or as a result of dysregulated osteogenic signaling, as in the case of the orphan disease fibrodysplasia ossificans progressiva (FOP). Traumatic HO (tHO) formation is mediated by the complex interplay of signaling between progenitor, inflammatory, and nerve cells, among others, making it a challenging process to understand. Research into the pathogenesis of genetically mediated HO (gHO) in FOP has established a pathway involving uninhibited activin-like kinase 2 receptor (ALK2) signaling that leads to downstream osteogenesis. Current methods of diagnosis and treatment lag behind pre-mature HO detection and progressive HO accumulation, resulting in irreversible decreases in range of motion and chronic pain for patients. As such, it is necessary to draw on advancements made in the study of tHO and gHO to better diagnose, comprehend, prevent, and treat both.

Arthroscopic debridement improves range of motion for heterotopic ossification after total knee replacement: a retrospective cohort study.

The presence of heterotopic ossification (HO) after primary total knee replacement (TKR) is rare and associated with limited mobility and stiffness of the knee. This study aimed to identify if the arthroscopic debridement after TKR could decrease HO and improve the function and range of motion. Thirty HO patients after TKR were retrospectively separated into 2 cohorts. 15 patients of group A accepted the arthroscopic debridement, while 15 patients of group B only had non-operative treatment, mainly including oral nonsteroidal anti-inflammatory drugs (NSAIDs) and rehabilitative treatment. Visual analog scale (VAS) scores, knee society knee scores (KSS), range of motion (knee flexion and knee extension) were obtained before treatment and at 1 month, 3 months, and 6 months after treatment. Radiography of after-treatment was also evaluated to assess the changes in HO. There were 3 males and 27 females with a mean age of 67.4 ± 0.8 years in group A and 68.2 ± 1.3 in group B. The onset time of HO was 3-6 months. The maximum size of the ossification was < 2 cm in 23 knees, 2 cm < heterotopic bone < 5 cm in 6 knees and > 5 cm in 1 knee. The size of HO decreased gradually in all knees by X-ray film at the last follow-up. There were no significant differences in VAS scores after replacement between two groups (p > 0.05). The average range of motion preoperatively in group A was - 15.2-90.6°, which postoperatively increased to - 4.2-110.0°. Meanwhile, the KSS scores and average range of motion of the group A were better than those of the group B at each follow-up time after treatment. Arthroscopic debridement can decrease HO seen from postoperative X-rays, improve the function and range of motion, as well as the pain remission between two groups are comparable. Consequently, arthroscopic resection of HO after TKR is recommended as soon as there is aggravating joint stiffness.

Heterotopic Ossification of Bilateral Hips Post-COVID-19 and Prolonged Immobilization: A Case Report.

CASE: A 43-year-old healthy man developed hip pain post-coronavirus disease 2019 (COVID-19) immobilization. Imaging confirmed bilateral bridging heterotopic ossification (HO) of the hips, Brooker Class IV. Bilateral HO caused functional arthrodesis (45° flexion: -20° internal rotation). Bilateral HO resection resulted in almost full mobility at 1-year follow-up (90° flexion; 30° internal rotation). CONCLUSION: Many cases of HO after immobilization for COVID-19 have been reported, but as far as we know, this is the first case report describing surgical intervention as an adequate treatment option for severe restricted mobility caused by HO due to COVID-19-induced prolonged immobilization. Caution and preoperative 3D planning are recommended of HO formation near neurovascular structures.

Incidence and Risk Factors of Heterotopic Ossification in the Knee After Reamed Tibial Nailing.

INTRODUCTION: Heterotopic ossification (HO) in the knee after tibial intramedullary nailing (IMN) has yet to be thoroughly investigated. Our aim was to assess frequency and associated factors for HO in the knee after tibial IMN. METHODS: This is a retrospective review at a single level 1 urban trauma center of 213 patients who underwent reamed tibial IMN. Plain radiographs were reviewed postoperatively and on final follow-up (≥6 weeks). Chart review was performed for surgical approach (suprapatellar versus infrapatellar), demographics, injury characteristics, and clinical follow-up. The primary outcome was frequency of HO. RESULTS: HO on final follow-up (mean: 41.43 weeks) was recorded in 15% cases. Postsurgical retroinfrapatellar reaming debris (odds ratio [OR], 4.73), Injury Severity Score (OR, 1.05), intensive care unit admission (OR, 2.89), chest injury (OR, 3.4), and ipsilateral retrograde femoral IMN (OR, 5.08) showed a notable association with HO development. No association was observed in HO formation between surgical approach, knee pain, or range-of-motion deficits. DISCUSSION: Radiographic evidence of HO in the knee after reamed tibial IMN is not uncommon and is associated with retained reaming debris, Injury Severity Score, chest injury, intensive care unit admission, and ipsilateral retrograde femoral nailing. No differences were noted in HO formation between approaches. HO was not associated with knee pain or range-of-motion deficits.

Heterotopic ossification, osteolysis and implant failure following cervical total disc replacement with the M6-C™ artificial disc.

INTRODUCTION: A recent study reported a 34% mid-term revision rate after M6-C™ cervical total disc replacement (CTDR) for wear-related osteolysis. Here, we aim to investigate the prevalence, risk factors, and radiographic characteristics of periprosthetic bony changes and implant failure of the M6-C™ artificial disc. METHODS: We retrospectively analysed radiographic (conventional X-ray, CT scan) and clinical outcomes (EQ-5D-5L, Neck Disability Index (NDI), and Visual Analog Scale (VAS) for neck and arm pain) data collected during routine follow-up of patients who underwent CTDR with the M6-C™ between 2011 and 2015. RESULTS: In total, 85 patients underwent CTDR with the M6-C™. Follow-up data were available for 43 patients (54% female, mean age 44 years) with 50 implants and a mean follow-up of 8.1 years (6.5-11 years). Implant failure with the presence of severe osteolysis was identified in 5 (12%) patients who were all male (p = 0.016) and implanted at the C5/6 level (p = 0.11). All failed implants required revision surgery. The overall prevalence of osteolysis was 44% (22/50 implants) and 34% (17/50 implants) for significant heterotopic ossification. Patients with high-grade osteolysis showed higher VAS arm pain (p = 0.05) and lower EQ-5D-VAS health VAS (p = 0.03). CONCLUSION: We report a lower reoperation rate for failed M6-C™ implants than previously published, but confirmed that osteolysis and heterotopic ossification are common following CTDR with the M6-C™ and may be asymptomatic. Therefore, we strongly recommend ongoing clinical and radiographic monitoring after CTDR with the M6-C™, particularly for male patients implanted at the C5/6 level.

Treatment and rehabilitation of post-traumatic elbow stiffness with heterotopic ossification.

AIM: To investigate surgical treatment, postoperative rehabilitation and prevention of heterotopic ossification (HO) in patients with post-traumatic elbow stiffness. METHODS: We performed a retrospective review of patients with post-traumatic elbow stiffness combined with HO between 2007 and 2021. This study was performed on a total of 15 patients (18 elbows) admitted to our hospital, consisting of 12 males and 3 females, with post-traumatic stiffness of the elbow combined with HO, where elbow function could not be recovered by rehabilitation and orthosis treatment. Fifteen patients were treated by surgical excision of heterotopic bones and release of elbow contracture combined with postoperative rehabilitation and orthosis-wearing. Comprehensive treatments, including radiation, oral ibuprofen medication, and manipulation techniques to improve range of motion, were used to prevent HO recurrence. The flexion-extension arc and functional score of the elbow were measured after treatment and compared with the preoperative measurements. Roentgenography was used to observe HO recurrence. RESULTS: After surgical treatment and postoperative rehabilitation, the patients' range of motion improved, and the functional score improved considerably. The postoperative flexion-extension arc and The Hospital for Special Surgery (HSS) functional score were statistically significantly higher than the preoperative values (p < 0.01). Roentgenographic examination showed no HO recurrence during the follow-up period. CONCLUSION: Surgical excision of heterotopic bones and elbow contracture release combined with postoperative rehabilitation and preventative HO measures can be an effective treatment for cases of post-traumatic elbow stiffness combined with HO, for which conservative treatment is ineffective.

[Binocular loupe assisted mini-lateral and medial incisions in lateral position for release of elbow stiffness].

Objective: To analyze the effectiveness of binocular loupe assisted mini-lateral and medial incisions in lateral position for the release of elbow stiffness. Methods: The clinical data of 16 patients with elbow stiffness treated with binocular loupe assisted mini-internal and external incisions in lateral position release between January 2021 and December 2022 were retrospectively analyzed. There were 9 males and 7 females, aged from 19 to 57 years, with a median age of 33.5 years. Etiologies included olecranon fracture in 6 cases, elbow dislocation in 4 cases, medial epicondyle fracture in 2 cases, radial head fracture in 4 cases, terrible triad of elbow joint in 2 cases, supracondylar fracture of humerus in 1 case, coronoid process fracture of ulna in 1 case, and humerus fracture in 1 case, with 5 cases presenting a combination of two etiologies. The duration of symptoms ranged from 5 to 60 months, with a median of 8 months. Preoperatively, 12 cases had concomitant ulnar nerve numbness, and 6 cases exhibited ectopic ossification. The preoperative range of motion for elbow flexion and extension was (58.63±22.30)°, the visual analogue scale (VAS) score was 4.3±1.6, and the Mayo score was 71.9±7.5. Incision lengths for both lateral and medial approaches were recorded, as well as the occurrence of complications. Clinical outcomes were evaluated using Mayo scores, VAS scores, and elbow range of motion both preoperatively and postoperatively. Results: The lateral incision lengths for all patients ranged from 3.0 to 4.8 cm, with an average of 4.1 cm. The medial incision lengths ranged from 2.4 to 4.2 cm, with an average of 3.0 cm. The follow-up duration ranged from 6 to 19 months and a mean of 9.2 months. At last follow-up, 1 patient reported moderate elbow joint pain, and 3 cases exhibited residual mild ulnar nerve numbness. The other patients had no complications such as new heterotopic ossification and ulnar nerve paralysis, which hindered the movement of elbow joint. At last follow-up, the elbow range of motion was (130.44±9.75)°, the VAS score was 1.1±1.0, and the Mayo score was 99.1±3.8, which significantly improved when compared to the preoperative ones ( t=-12.418, P<0.001; t=6.419, P<0.001; t=-13.330, P<0.001). Conclusion: The binocular loupe assisted mini-lateral and medial incisions in lateral position integrated the advantages of traditional open and arthroscopic technique, which demonstrated satisfying safety and effectivity for the release of elbow contracture, but it is not indicated for patients with posterior medial heterolateral heterotopic ossification.

Heterotopic mineralization (ossification or calcification) in aged musculoskeletal soft tissues: A new candidate marker for aging.

Aging can lead to various disorders in organisms and with the escalating impact of population aging, the incidence of age-related diseases is steadily increasing. As a major risk factor for chronic illnesses in humans, the prevention and postponement of aging have become focal points of research among numerous scientists. Aging biomarkers, which mirror molecular alterations at diverse levels in organs, tissues, and cells, can be used to monitor and evaluate biological changes associated with aging. Currently, aging biomarkers are primarily categorized into physiological traits, imaging characteristics, histological features, cellular-level alterations, and molecular-level changes that encompass the secretion of aging-related factors. However, in the context of the musculoskeletal soft tissue system, aging-related biological indicators primarily involve microscopic parameters at the cellular and molecular levels, resulting in inconvenience and uncertainty in the assessment of musculoskeletal soft tissue aging. To identify convenient and effective indicators, we conducted a comprehensive literature review to investigate the correlation between ectopic mineralization and age-related changes in the musculoskeletal soft tissue system. Here, we introduce the concept of ectopic mineralization as a macroscopic, reliable, and convenient biomarker for musculoskeletal soft tissue aging and present novel targets and strategies for the future management of age-related musculoskeletal soft tissue disorders.

Interorgan communication in neurogenic heterotopic ossification: the role of brain-derived extracellular vesicles.

Brain-derived extracellular vesicles participate in interorgan communication after traumatic brain injury by transporting pathogens to initiate secondary injury. Inflammasome-related proteins encapsulated in brain-derived extracellular vesicles can cross the blood‒brain barrier to reach distal tissues. These proteins initiate inflammatory dysfunction, such as neurogenic heterotopic ossification. This recurrent condition is highly debilitating to patients because of its relatively unknown pathogenesis and the lack of effective prophylactic intervention strategies. Accordingly, a rat model of neurogenic heterotopic ossification induced by combined traumatic brain injury and achillotenotomy was developed to address these two issues. Histological examination of the injured tendon revealed the coexistence of ectopic calcification and fibroblast pyroptosis. The relationships among brain-derived extracellular vesicles, fibroblast pyroptosis and ectopic calcification were further investigated in vitro and in vivo. Intravenous injection of the pyroptosis inhibitor Ac-YVAD-cmk reversed the development of neurogenic heterotopic ossification in vivo. The present work highlights the role of brain-derived extracellular vesicles in the pathogenesis of neurogenic heterotopic ossification and offers a potential strategy for preventing neurogenic heterotopic ossification after traumatic brain injury. Brain-derived extracellular vesicles (BEVs) are released after traumatic brain injury. These BEVs contain pathogens and participate in interorgan communication to initiate secondary injury in distal tissues. After achillotenotomy, the phagocytosis of BEVs by fibroblasts induces pyroptosis, which is a highly inflammatory form of lytic programmed cell death, in the injured tendon. Fibroblast pyroptosis leads to an increase in calcium and phosphorus concentrations and creates a microenvironment that promotes osteogenesis. Intravenous injection of the pyroptosis inhibitor Ac-YVAD-cmk suppressed fibroblast pyroptosis and effectively prevented the onset of heterotopic ossification after neuronal injury. The use of a pyroptosis inhibitor represents a potential strategy for the treatment of neurogenic heterotopic ossification.

Regional distribution prevalence of heterotopic ossification in the elbow joint: a 3D study of patients after surgery for traumatic elbow injury.

BACKGROUND: Heterotopic ossification (HO) is a common complication after elbow fracture surgery and can lead to severe upper extremity disability. The radiographic localization of postoperative HO has been reported previously. However, there is no literature examining the distribution of postoperative HO at the three-dimensional (3D) level. This study aimed to investigate 1) the distribution characteristics of postoperative HO and 2) the possible risk factors affecting the severity of postoperative HO at a 3D level. METHODS: A retrospective review was conducted of patients who presented to our institution with HO secondary to elbow fracture between 13 January 2020 and 16 February 2023. Computed tomography scans of 56 elbows before elbow release surgery were reconstructed in 3D. HO was identified using density thresholds combined with manual identification and segmentation. The elbow joint and HO were divided into six regions according to three planes: the transepicondylar plane, the lateral ridge of the trochlear plane, and the radiocapitellar joint and coronoid facet plane. The differences in the volume of regional HO associated with different initial injuries were analyzed. RESULTS: Postoperative HO was predominantly present in the medial aspect of the capsule in 52 patients (93%), in the lateral aspect of the capsule in 45 patients (80%), in the medial supracondylar in 32 patients (57%), and in the lateral supracondylar, radial head, and ulnar region in the same number of 28 patients (50%). The median and interquartile range volume of total postoperative HO was 1683 (777-4894) mm3. The median and interquartile range volume of regional postoperative HO were: 584 (121-1454) mm3 at medial aspect of capsule, 207 (5-568) mm3 at lateral aspect of capsule, 25 (0-449) mm3 at medial supracondylar, 1 (0-288) at lateral supracondylar, 2 (0-478) at proximal radius and 7 (0-203) mm3 at the proximal ulna. In the subgroups with Injury Severity Score > or = 16, Gustilo-Anderson II, normal uric acid levels, elevated alkaline phosphatase, and body mass index > or = 24, the median HO volume exceeds that of the respective control groups. CONCLUSION: The medial aspect of the capsule was the area with the highest frequency and median volume of postoperative HO among all initial elbow injury types. Patients with higher Gustilo-Anderson grade, Injury Severity Score, alkaline phosphatase or Body Mass Index had higher median volume of postoperative HO.

Bony encasement of the ulnar nerve secondary to heterotopic ossification of the elbow: an evaluation of long-term outcomes.

BACKGROUND: Ulnar neuropathy at the elbow caused by heterotopic ossification (HO) is a rare condition. This retrospective study aims to report on 32 consecutive cases of ulnar nerve encasement caused by elbow HO and evaluate long-term outcomes of operative management and a standardized postoperative rehabilitation regimen. METHODS: A retrospective case series was conducted on 32 elbows (27 patients) that underwent operative management of bony ulnar nerve encasement. All procedures were performed in the inpatient setting at an Academic Level 1 Trauma Center from September 1999 to July 2021 by one of 3 fellowship-trained shoulder and elbow. Postoperatively, all patients received formal physical therapy, HO prophylaxis (30 received indomethacin, 2 received radiation), and a structured continuous passive motion machine regimen. Patient demographics, age, gender, type of injury, history of tobacco use, and medical comorbidities were obtained to include in the analysis. Long-term follow-up examinations were performed to evaluate elbow flexion-extension arc of motion, Mayo Elbow Performance Score, and visual analog scale pain scores. RESULTS: Thirty-two elbows with complete bony ulnar nerve encasement secondary to HO were identified (14 from burns, 15 from trauma, 3 closed head injuries). Following surgery, the mean flexion-extension arc of motion improved significantly, increasing from 21° to 100° at long-term follow-up (average 8.7 years, range 2-17 years), with statistically significant improvements in preoperative vs. long-term postoperative elbow extension (P < .001), flexion (P < .001), and total arc of motion (P < .001). There was a statistically significant improvement in pre- vs. postprocedure ulnar nerve function, as demonstrated by a decrease in average McGowan grade (1.2-0.7; P = .002). Additionally, 63% of patients with preoperative ulnar neuropathy symptoms (20/32) had either complete resolution or subjective improvement after surgery. The mean time from injury to surgery was 518 days (range 65-943 days). Age, gender, time to surgery, and medical comorbidities were not associated with outcomes. The complication rate was 9% (3/32). Patients had an average flexion-extension arc of motion of 97° and average Mayo Elbow Performance Score of 80 ("good") at long-term follow-up. CONCLUSIONS: The combination of operative management, postoperative HO prophylaxis, and a regimented rehabilitation program has proven to be a durable solution for treating and ensuring good long-term functional outcomes for patients with elbow HO and bony ulnar nerve encasement. This treatment approach leads to superior range of motion, improved or resolved ulnar neuropathy, and good to excellent long-term functional outcomes.

The Quality of Life of the Patients with Thoracic Ossification of the Ligamentum Flavum after Surgery Using EQ-5D-5L.

OBJECTIVE: There is a lack of studies on the quality of life (QoL) after posterior laminectomy in patients with thoracic ossification of the ligamentum flavum (TOLF), and risk factors associated with poor prognosis remain controversial. Therefore, the present study was conducted to illustrate the QoL for TOLF patients after surgery and determine its relationship with their demographic, surgery-related, clinical characteristics and imaging data. METHODS: One hundred and eighteen patients diagnosed with thoracic myelopathy because of TOLF were enrolled in this retrospective study. They all underwent posterior decompressive laminectomy from August 2010 to January 2022. The QoL was evaluated based on the EQ-5D-5L. Collecting gender, age, number of operations, compressed segments, Frankel grade, complications, body mass index (BMI), symptoms and duration, modified Japanese Orthopaedic Association (mJOA) score (preoperative), follow-up time and type of ossification, increased signal on Sagittal T2-weighted Images (ISST2I), occupancy rate and analyzing by Mann-Whitney U-test, Kruskal-Wallis test, the χ2 -test, and logistic regression tests. RESULTS: Average follow-up 70.8 months (18-149), the mean age was 59.74 ± 9.81 years and the mean score for the QoL based on the EQ-5D-5 L and visual analogue scale (VAS) score were 0.71 ± 0.28 and 78.88 ± 10.21 at the final follow-up. Moderate and severe problems were found in the pain/discomfort in 22.0% of the patients. These mobility and usual activities numbers were slightly higher (24.6% and 30.4%, respectively). The mean scores for QoL and VAS were significantly higher in patients with mild and moderate neurological impairment, normal BMI, <60 years of age, no dural tears, symptom relief at hospital discharge, unilateral and bilateral ossification on axial CT scan, ≤ 50% spinal canal occupancy on CT and MRI, and none or fuzzy on ISST2I. CONCLUSION: QoL after posterior laminectomy in TOLF patients is generally satisfactory compared to preoperative levels. Preoperative mJOA score, Age, comorbid diabetes, the major symptom is activity limitation, BMI, ISST2I, Intraoperative dural tears and spinal canal occupancy rate correlate significantly with the corresponding dimensions and are predictive. Age, spinal canal occupancy rate, ISST2I, preoperative mJOA score, BMI are significantly associated with and have predictive value for overall postoperative QoL.

Elbow stiffness: Arthritis and heterotopic ossification.

In elbow stiffness, pre-operative assessments should identify the articular and peri-articular tissues involved and, more specifically, they should determine how preserved the articular surfaces and osteo-articular congruity are. We will focus on the most important conditions and tissue reactions after trauma in order to understand the causes of joint stiffness. A logical surgical planning is based upon a deep knowledge of the anatomical obstacles and of the associated lesions that the trauma provoked with. The peri-articular soft tissue contractures. The osteo-articular incongruity.

Suppression of Overactive Insulin-Like Growth Factor 1 Attenuates Trauma-Induced Heterotopic Ossification in Mice.

Heterotopic ossification (HO) is the ectopic bone formation in soft tissues. Aside from hereditary HO, traumatic HO is common after orthopedic surgery, combat-related injuries, severe burns, or neurologic injuries. Recently, mammalian target of rapamycin (mTOR) was demonstrated to be involved in the chondrogenic and osteogenic processes of HO formation. However, its upstream signaling mechanism remains unknown. The current study used an Achilles tendon puncture-induced HO model to show that overactive insulin-like growth factor 1 (IGF-1) was involved in the progression of HO in mice. Micro-computed tomography imaging showed that IGF-1 not only accelerated the rate of osteogenesis and increased ectopic bone volume but also induced spontaneous ectopic bone formation in undamaged Achilles tendons. Blocking IGF-1 activity with IGF-1 antibody or IGF-1 receptor inhibitor picropodophyllin significantly inhibited HO formation. Mechanistically, IGF-1/IGF-1 receptor activates phosphatidylinositol 3-kinase (PI3K)/Akt signaling to promote the phosphorylation of mTOR, resulting in the chondrogenic and osteogenic differentiation of tendon-derived stem cells into chondrocytes and osteoblasts in vitro and in vivo. Inhibitors of PI3K (LY294002) and mTOR (rapamycin) both suppressed the IGF-1-stimulated mTOR signal and mitigated the formation of ectopic bones significantly. In conclusion, these results indicate that IGF-1 mediated the progression of traumatic HO through PI3K/Akt/mTOR signaling, and suppressing IGF-1 signaling cascades attenuated HO formation, providing a promising therapeutic strategy targeting HO.

Disease aggravation following surgery in a rare patient suspected to Fibrodysplasia (Myositis) ossificans progressiva: a case report.

BACKGROUND: Fibrodysplasia ossificans progressiva (FOP) as a rare and heritable disorder with the infrequent genetic transmission of the condition is a catastrophic disorder of heterotopic ossification (HO) and a cause of extraskeletal bone formation in humans. Given the lack of effective treatment for this disease, the important point is to avoid aggravating factors such as bone biopsy, surgery, and intramuscular injection. CASE PRESENTATION: In this report, we present a 52-year-old female patient, Kurdish ethnic, suspected to FOP who had a surgical intervention on the second toe of the right foot, which subsequently, it caused further deterioration of the disease in the person including necrosis and amputation of the distal phalanx of the second toe. CONCLUSIONS: Although, based on our investigation and the available scientific evidence, surgery may a cause for faster progression and worsening of the FOP disorder, but its proof requires further studies.

Inhibition of focal adhesion kinase 2 results in a macrophage polarization shift to M2 which attenuates local and systemic inflammation and reduces heterotopic ossification after polysystem extremity trauma.

Introduction: Heterotopic ossification (HO) is a complex pathology often observed in combat injured casualties who have sustained severe, high energy polytraumatic extremity injuries. Once HO has developed, prophylactic therapies are limited outside of surgical excision. Tourniquet-induced ischemia injury (IR) exacerbates trauma-mediated musculoskeletal tissue injury, inflammation, osteogenic progenitor cell development and HO formation. Others have shown that focal adhesion kinase-2 (FAK2) plays a key role in regulating early inflammatory signaling events. Therefore, we hypothesized that targeting FAK2 prophylactically would mitigate extremity trauma induced IR inflammation and HO formation. Methods: We tested whether the continuous infusion of a FAK2 inhibitor (Defactinib, PF-573228; 6.94 µg/kg/min for 14 days) can mitigate ectopic bone formation (HO) using an established blast-related extremity injury model involving femoral fracture, quadriceps crush injury, three hours of tourniquet-induced limb ischemia, and hindlimb amputation through the fracture site. Tissue inflammation, infiltrating cells, osteogenic progenitor cell content were assessed at POD-7. Micro-computed tomography imaging was used to quantify mature HO at POD-56. Results: In comparison to vehicle control-treated rats, FAK2 administration resulted in no marked wound healing complications or weight loss. FAK2 treatment decreased HO by 43%. At POD-7, marked reductions in tissue proinflammatory gene expression and assayable osteogenic progenitor cells were measured, albeit no significant changes in expression patterns of angiogenic, chondrogenic and osteogenic genes. At the same timepoint, injured tissue from FAK-treated rats had fewer infiltrating cells. Additionally, gene expression analyses of tissue infiltrating cells resulted in a more measurable shift from an M1 inflammatory to an M2 anti-inflammatory macrophage phenotype in the FAK2 inhibitor-treated group. Discussion: Our findings suggest that FAK2 inhibition may be a novel strategy to dampen trauma-induced inflammation and attenuate HO in patients at high risk as a consequence of severe musculoskeletal polytrauma.

Lamina-Lifting Suspension Modification in Bridge Crane Technique in Treatment of Severe Thoracic Ossification of the Ligamentum Flavum (TOLF).

BACKGROUND The aim of this study was to investigate the effectiveness and potential complications of combining a lamina-lifting suspension system with the bridge crane technique in treating thoracic ossification of the ligamentum flavum (TOLF) with thoracic myelopathy. MATERIAL AND METHODS A patient with severe TOLF and myelopathy was treated using a lamina-lifting suspension system combined with bridge crane technique. The brief surgical procedure involved implantation of internal fixation, separation of laminae, installation of cross-bridges, reverse lifting, and fixation of cross-bridges. The modified Japanese Orthopaedic Association (mJOA) scale, Hirabayashi recovery rate, and ASIA grade of the patient were recorded. The canal occupation ratio (COR) and spinal cord status were evaluated by imaging data. RESULTS The surgical intervention significantly enhances the patient's lower limb function, as evidenced by an increase in mJOA score from 5 preoperatively to 11 at terminal follow-up. The Hirabayashi recovery rate after surgery ranges between 25% and 50%. Additionally, ASIA classification improved to grade E. Imaging data showed that the ossification of the thoracic vertebrae had subsided, while the volume of the local spinal canal had recovered and the spinal cord injury had been completely relieved. No adverse effects or complications were observed. CONCLUSIONS The lamina-lifting suspension system preserves the benefits of bridge crane technique while also augmenting the traction of a post laminae-OLF complex (LOC) suspension, rendering it more secure and manageable. Nevertheless, further sample analysis and research are required in the future.

Tranexamic acid in patients with post-traumatic elbow stiffness: protocol for a randomised, double-blind, placebo-controlled trial investigating the effectiveness of tranexamic acid at reducing the recurrence of heterotopic ossification after open elbow arthrolysis.

INTRODUCTION: Exaggerated inflammatory response is one of the main mechanisms underlying heterotopic ossification (HO). It has been suggested that the antifibrinolytic drug tranexamic acid (TXA) can exert a significant anti-inflammatory effect during orthopaedic surgery. However, no prospective studies have yet investigated the effects of TXA on HO recurrence in patients following open elbow arthrolysis (OEA). METHODS AND ANALYSIS: Here, we present a protocol for a single-centre, randomised, double-blind, placebo-controlled trial to investigate the effectiveness of TXA on HO recurrence after OEA in a single hospital. A minimum sample size of 138 eligible and consenting participants randomised into treatment and control groups in a 1:1 manner will be included. Patients will receive 2 g of intravenous TXA (experimental group) or placebo (normal saline, control group) administered before skin incision. The primary outcome is HO recurrence rate within 12 months after surgery. The secondary outcomes are the serum immune-inflammatory cytokines including erythrocyte sedimentation rate, C reactive protein, interleukin (IL)-6, IL-1ß, IL-13 at the first and third day postoperatively, and elbow range of motion and functional score at 1.5, 6, 9 and 12 months after surgery. After completion of the trial, the results will be reported in accordance with the extensions of the Consolidated Standards of Reporting Trials Statement for trials. The results of this study should determine whether TXA can reduce the rates of HO occurrence after OEA. ETHICS AND DISSEMINATION: Ethical approval has been granted by the Medical Ethics Committee of the Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (reference number 2022-123-(1)). The results of this study will be disseminated through presentations at academic conferences and publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ChiCTR2300068106.

Efficacy of ibuprofen and indomethacin as prophylaxis of heterotopic ossification: a comparative study.

The prophylactic action of non-steroidal anti-inflammatory drugs (NSAIDs) in heterotopic ossification (HO) was first described following analgesic therapy with indomethacin. Following that evidence, several compounds have been successfully used for prophylaxes of HO. Ibuprofen has been also proposed for the prevention of HO following THA. The present study compared the administration of ibuprofen for three weeks versus indomethacin as prophylaxis for HO following primary THA. In all THA procedures, pre- and post-operative protocols were conducted in a highly standardized fashion. The type of HO prophylaxis (indomethacin 100 mg/daily or ibuprofen 100 mg/daily) was chosen according to a chronological criterion: from 2017 to 2019 indomethacin was used, whereas from 2019 to 2022 ibuprofen was administered. In case of allergy or intolerance to NSAIDs, no prophylaxis was performed, and patients were included as a control group. All patients who underwent an anteroposterior radiography of the pelvis at a minimum of 12 months following THA were considered for inclusion. On admission, the age and sex of the patients were recorded. Moreover, the causes of osteoarthritis and the date of surgery were recorded. The grade of HO was assigned by a blinded assessor who was not involved in the clinical management of the patients. The modified Brooker Staging System was used to rate the efficacy of the interventions. Data from 1248 patients were collected. 62% (767 of 1248 patients) were women. The mean age was 67.0 ± 2.9 years. The mean follow-up was 21.1 ± 10.8 months. In the ibuprofen group, 73% of patients evidenced Brooker 0, 17% Brooker I, and 10% Brooker II. In the indomethacin group, 77% of patients evidenced Brooker 0, 16% Brooker I, 6% Brooker II. No patient in the ibuprofen and indomethacin group developed Brooker III or IV. In the control group, 64% of patients evidenced Brooker 0, 21% Brooker I, 3% Brooker II, and 12% Brooker III. No patient in the control group developed Brooker IV HO. Concluding, three weeks of administration of ibuprofen demonstrated similar efficacy to indomethacin in preventing HO following primary THA. The prophylaxis with ibuprofen or indomethacin was more effective in preventing HO compared to a control group who did not receive any pharmacological prophylaxis.