Heterotopic mesenteric ossification caused by trauma:A case report

BACKGROUND Heterotopic mesenteric ossification(HMO)is a clinically rare condition characterized by the formation of bone tissue in the mesentery.The worldwide reporting of such cases is limited to just over 70 instances in the medical literature.The etiology of HMO remains unclear,but the disease is possibly induced by mechanical trauma,ischemia,or intra-left lower quadrant abdominal infection,leading to the differentiation of mesenchymal stem cells into osteoblasts.Here,we present a rare case of HMO that occurred in a 34-year-old male,who presented with left lower quadrant abdominal pain.CASE SUMMARY We report the case of a 34-year-old male patient who presented with left lower abdominal pain following trauma to the left lower abdomen.He subsequently underwent surgical treatment,and the postoperative pathological diagnosis was HMO.CONCLUSION We believe that although there is limited literature and research on HMO,when patients with a history of trauma or surgery to the left lower abdomen present with corresponding imaging findings,clinicians should be vigilant in distinguishing this condition and promptly selecting appropriate diagnostic and therapeutic interventions.

Heterotopic ossification after the use of recombinant human bone morphogenetic protein-7

AIM To present the incidence of heterotopic ossification after the use of recombinant human bone morphogenetic protein-7(rhB MP-7) for the treatment of nonunions.METHODS Bone morphogenetic proteins(BMPs) promote bone formation by auto-induction. Recombinant human BMP-7 in combination with bone grafts was used in 84 patients for the treatment of long bone nonunions. All patients were evaluated radiographicaly for the development of heterotopic ossification during the standard assessment for the nonunion healing. In all patients(80.9%) with radiographic signs of heterotopic ossification, a CT scan was performed. Nonunion site palpation and ROM evaluation of the adjacent jointswere also carried out. Factors related to the patient(age, gender), the nonunion(location, size, chronicity, number of previous procedures, infection, surrounding tissues condition) and the surgical procedure(graft and fixation type, amount of rhB MP-7) were correlated with the development of heterotopic ossification and statistical analysis with Pearsons χ~2 test was performed.RESULTS Eighty point nine percent of the nonunions treated with rh BMP-7, healed with no need for further procedures. Heterotopic bone formation occurred in 15 of 84 patients(17.8%) and it was apparent in the routine radiologi-cal evaluation of the nonunion site, in a mean time of 5.5 mo after the rh BMP-7 application(range 3-12). The heterotopic ossification was located at the femur in 8 cases, at the tibia in 6, and at the humerus in οne patient. In 4 patients a palpable mass was present and only in one patient, with a para-articular knee nonunion treated with rhB MP-7, the size of heterotopic ossification affected the knee range of motion. All the patients with heterotopic ossification were male. Statistical analysis proved that patient's gender was the only important factor for the development of heterotopic ossification(P = 0.007). CONCLUSION Heterotopic ossification after the use of rh BMP-7 in nonunions was common but it did not compromise the final clinical outcome in most cases, and affected only male patients.

Post-laparotomy heterotopic ossification of the xiphoid process: A case report

BACKGROUND Heterotopic ossification(HO)represents all types of extraskeletal ossification in the body.It occurs in various areas,including the skin,subcutaneous tissue,muscle,and joints.Surgical excision is recommended for symptomatic HO.Postoperative radiotherapy,oral nonsteroidal anti-inflammatory drugs,and topical sealants,such as bone wax,have been recommended as preventive measures.As HO is rare in occurrence,these recommendations are based on personal experiences,and there is a lack of information on individualized treatments depending on its location.CASE SUMMARY A 62-year-old male was admitted for symptomatic HO along a laparotomy scar.Surgical excision was performed for an 11 cm-sized ossification originating from the xiphoid process,and bone wax was applied to the excisional margin.However,the surgical wound failed to heal.After several weeks of saline-soaked gauze dressing,delayed wound closure was performed.The patient was finally discharged eight weeks after the excision.Because HO can occur in various areas of the body,a treatment strategy that may be effective for some may not be for others.Bone wax has been used as a topical sealant over excisional margins in the shoulder,elbow,and temporomandibular joints.However,in our case,its application on an abdominal surgical wound delayed its primary healing intention.The valuable lesson was that,when choosing a treatment method for HO based on available research data,its location must be considered.CONCLUSION Complete excision should be the priority treatment option for symptomatic HO along the laparotomy scar.Bone wax application is not recommended.Core Tip:Heterotopic ossification(HO)represents all types of extraskeletal ossification,and occurs in various areas,including the skin,muscle,and joints.There are some suggested treatment and preventive approaches for symptomatic HO,which include surgical excision and preventive measures such as postoperative radiotherapy,oral nonsteroidal anti-inflam-matory drugs,and topical sealants(bone wax).However,these recommendations are based on personal experiences limited to HO in certain locations.It is important to individualize our treatment approaches depending on its location.For symptomatic HO along the laparotomy scar,complete surgical excision should be the priority treatment option,and bone wax application is not recommended.

Neuromuscular electrical stimulation and testosterone did not influence heterotopic ossification size after spinal cord injury: A case series

Neuromuscular electrical stimulation(NMES) and testosterone replacement therapy(TRT) are effective rehabilitation strategies to attenuate muscle atrophy and evoke hypertrophy in persons with spinal cord injury(SCI). However both interventions might increase heterotopic ossification(HO) size in SCI patients. We present the results of two men with chronic traumatic motor complete SCI who also had pre-existing HO and participated in a study investigating the effects of TRT or TRT plus NMES resistance training(RT) on body composition. The 49-year-old male, Subject A, has unilateral HO in his right thigh. The 31-year-old male, Subject B, has bilateral HO in both thighs. Both participants wore transdermal testosterone patches(4-6 mg/d) daily for 16 wk. Subject A also underwent progressive NMES-RT twice weekly for 16 wk. Magnetic resonance imaging scans were acquired prior to and post intervention. Cross-sectional areas(CSA) of thewhole thigh and knee extensor skeletal muscles, femoral bone, and HO were measured. In Subject A(NMES-RT + TRT), the whole thigh skeletal muscle CSA increased by 10%, the knee extensor CSA increased by 17%, and the HO + femoral bone CSA did not change. In Subject B(TRT), the whole thigh skeletal muscle CSA increased by 13% in the right thigh and 6% in the left thigh. The knee extensor CSA increased by 7% in the right thigh and did not change in the left thigh. The femoral bone and HO CSAs in both thighs did not change. Both the TRT and NMES-RT + TRT protocols evoked muscle hypertrophy without stimulating the growth of preexisting HO.

Pulsed Lavage in Cementless Total Hip Arthroplasty Reduces the Incidence ofBrooker Grade 3 and 4 Heterotopic Ossifications

Heterotopic ossification (HO) may cause pain, and can lead to loss of hip motion after total hip arthroplasty (THA). There is evidence that pulsed lavage may lower the incidence of HO formation. We assessed the effect of pulsed lavage on the incidence of HO in 87 male patients after THA. All patients received an uncemented THA through a posterolateral approach. 39 patients were treated with pulsed lavage (index group) and 48 males were treated without pulsed lavage (historical control group, matched on aetiology, gender, surgical approach and type of prosthesis). Both groups followed the same postoperative treatment regimen. HO severity was scored in both groups according to the Brooker classification by three blinded orthopaedic surgeons one year postoperatively. Good inter-observer agreement (Kappa 0.7) for scoring HO was found. The incidence of HO (51%) in the index group did not differ significantly (p = 0.53) from the control group (58%). However, the incidence of clinically relevant HO (Brooker grades 3 and 4) was significantly lower (p = 0.04) in the index group (3%) as compared to the control group (17%). These results suggest a beneficial effect of pulsed lavage on the incidence of severe heterotopic ossification after cementless THA in male patients.

Heterotopic ossification beneath the upper abdominal incision after radical gastrectomy:Two case reports

BACKGROUND Heterotopic ossification(HO)is a rare clinical phenomenon that refers to bone formation in nonossifying tissues.CASE SUMMARY This report presents two cases of HO beneath the upper abdominal median incision after radical gastrectomy.The first patient had postoperative pain below the incision area.There were no signs of anastomotic leakage,and the wound healed.Computed tomography(CT)findings 2 wk postoperatively were negative for HO,but the 6-wk CT showed HO beneath the incision.The patient refused reoperation,and after conservative therapy,the pain was gradually relieved after 2 wk.In the second case,postoperative recovery was uneventful,and HO was only detected on routine follow-up CT after 4 mo.An anti-adhesion membrane was applied beneath the peritoneum in both patients.Our findings suggest that HO beneath the abdominal incision might form at approximately 1 mo postoperatively.It may cause intractable pain;however,reoperation is usually not required.CONCLUSION In our cases,we suspect that HO may be related to the use of foreign materials beneath the peritoneum,which needs to be further investigated.

Bilateral hip heterotopic ossification with sciatic nerve compression on a paediatric patient–An individualized surgical approach: A case report

BACKGROUND Neurogenic heterotopic ossification is an acquired serious complication described in patients with central nervous system disorders and defined by bone formation in non-osseous tissue.CASE SUMMARY We present an unusual case of a 13-yr-old boy presenting with hip pain and severe gait impairment 5 mo after the diagnosis of hemiplegia following a spontaneous intracerebral haemorrhage.Computed tomography revealed bilateral heterotopic ossification of both the paretic and the non-paretic limbs,with entrapment of the sciatic nerve.The choice of surgical or nonsurgical management of such patients depends on the timing of diagnosis,the symptoms,and the extent of maturation of the ossified lesions.Surgical resection remains the only treatment with proven,evidence-based effectiveness.The choice of surgical approach largely depends on the location of the ossified lesions.CONCLUSION We believe the plane of dissection presented is a satisfactory option for resection of a posteromedial mass and sciatic nerve release.

Severe heterotopic ossification in a seronegative spondyloarthritis patient after cervical Bryan disc arthroplasty: A case report

BACKGROUND Cervical disc arthroplasty(CDA)is an alternative treatment to traditional interbody fusion that maintains postoperative cervical spine mobility.However,the CDA postoperative period is impacted by osteolysis,subsidence,metallosis,or heterotopic ossification(HO).We report a case of severe HO in a seronegative spondyloarthritis patient after cervical Bryan disc arthroplasty.CASE SUMMARY A 34-year-old man received hybrid surgery for C4-C5 and C5-C6 arthroplasty with Bryan discs and C6-C7 arthrodesis with polyetheretherketone cage due to traumatic herniation of the intervertebral disc(HIVD).After four years,cervical spine radiographs revealed severe HO around the Bryan discs over the C4-C5 and C5-C6 levels.The magnetic resonance image revealed HIVD over the C3-C4 level with spinal cord compression.Seronegative spondyloarthritis was diagnosed after consultation with a rheumatologist.A second CDA for the adjacent segment disease HIVD with Baguera C disc over the C3-C4 level achieved an excellent outcome.CONCLUSION Minimizing intraoperative tissue trauma and achieving postoperative interbody stability avoid soft tissue traction to prevent HO formation after CDA.

Radiation Therapy Prophylaxis for Heterotopic Ossification in Non-Hip Sites

Background: Radiation therapy prophylaxis for heterotopic ossification is well-established for the hip, either pre or post-operatively. There is limited data for this treatment in non-hip sites. We report our institution’s experience. Methods: From October 2004 to August 2015, a total of 39 non-hip sites in 38 patients were treated with prophylactic radiation therapy for heterotopic ossification at our institution. An IRB approved retrospective review was performed. There were 15 patients who received treatments to the elbow, 13 to the knee (1 bilateral for a total of 14 knees), and 10 to other sites (leg stump (2), pubic symphysis (2), femur (1), foot (1), humerus stump (1), abdominal wall (1), shoulder (1), thigh (1)). All but 1 patient were treated with a single fraction treatment with 700 or 800 cGy. One patient received 2000 cGy in 10 fractions to the abdominal wall for heterotopic ossification extending from the xiphoid process. Results: Fifteen patients underwent treatment to the elbow with a median follow-up of 5 months (0 - 99). Median age for this group was 50 years (37 - 69). Nine (60.0%) patients had evidence of heterotopic ossification prior to surgery. All (100%) of the elbow patients were free from recurrence at last follow-up. There were no acute or late toxicities noted. For treatment to the knee, there were 4 (28.6%) recurrences, all in cases where there were pre-operative heterotopic ossification. There were two other recurrences in the non-hip, elbow or knee sites: one patient who received radiation therapy to the abdominal wall and one patient who underwent treatment to the thigh. Conclusions: Prophylactic radiation therapy with 700 cGy or 800 cGy in 1 fraction either before or after surgery remains a safe and effective treatment for both hip and most non-hip sites. Fractionated treatment may be used for larger treatment fields, however experience is limited.

Post-traumatic heterotopic ossification in front of the ankle joint for 23 years:A case report and review of literature

BACKGROUND Heterotopic ossification(HO)refers to the formation of new bone in non-skeletal tissues such as muscles,tendons or other soft tissues.Severe muscle and soft tissue injury often lead to the formation of HO.However,anterior HO of the ankle is rarely reported.CASE SUMMARY We report a patient with massive HO in front of the ankle joint for 23 years.In 1998,the patient was injured by a falling object on the right lower extremity,which gradually formed a massive heterotopic bone change in the right calf and dorsum of the foot.The patient did not develop gradual ankle function limitations until nearly 36 mo ago,and underwent resection of HO.Even after 23 years and resection of HO,the ankle joint was still able to move.CONCLUSION It is recommended that the orthopedist should be aware of HO and distinguish it from bone tumor.

Non-Traumatic Intracranial Heterotopic Ossification: A Case from Turkey

Heterotopic ossification (HO) is the abnormal, non-neoplastic presence of lamellar bone in soft tissue. The ectopic formation of lamellar bone in non-osseus tissues secondary to traumatic injuries of the spinal cord or the brain is defined as Neurogenic HO. The pathophysiology of HO is not clear. But several theories like overactive humoral mechanisms after fracture healing, imbalance of pro-osteoinductive and anti-osteoinductive mediators located on the soft tissues and gene mutations in such as bone morphogenetic proteins-4 (BMP-4) are proposed. Casualty factors leading to increased risk of HO include older age, blast mechanism of injury, location of injury and traumatic brain injury. The aim of this paper is to demonstrate a case of HO located in the brain without history of trauma or any other risk factors.

Elevated Cobalt, Chromium and Molybdenum Levels in Peripheral Blood Have No Effect on the Development of Heterotopic Ossifications after Metal-on-Metal Total Hip Arthroplasty

Metal debris from metal-on-metal (MoM) total hip arthroplasties (THA) has been suspected to cause periprosthetic heterotopic ossifications (HO). We determined the influence of disseminated cobalt, chromium and molybdenum on the development of HO. Native blood samples from patients with 86 high-carbon and 16 low-carbon Co28Cr6Mo articulations were analysed by high-resolution inductively coupled plasma mass-spectrometry (HR ICP-MS). The results revealed that high-carbon metal-on-metal articulations showed lower metal blood levels (Co 1.03 to 1.60 μg/l, Cr 0.77 to 0.88 μg/l, Mo 0.45 to 0.56 μg/l) whereas low-carbon articulations achieved higher metal blood levels (Co 2.59 to 6.85 μg/l, Cr 1.25 to 3.55 μg/l, Mo 0.45 to 0.64 μg/l), but no correlation between metal ion blood level or carbon content and the development of HO could be found in these MoM articulations. Hence, metal debris from MoM articulation does not stimulate heterotopic bone formation despite other well-known local reactions.

Port-site metastasis of unsuspected gallbladder carcinoma with ossification after laparoscopic cholecystectomy:A case report

BACKGROUND Unsuspected gallbladder carcinoma(UGC)refers to cholecystectomy due to benign gallbladder disease,which is pathologically confirmed as gallbladder cancer during or after surgery.Port-site metastasis(PSM)of UGC following laparoscopic cholecystectomy is rare,especially after several years.CASE SUMMARY A 55-year-old man presenting with acute cholecystitis and gallstones was treated by laparoscopic cholecystectomy in July 2008.Histological analysis revealed unexpected papillary adenocarcinoma of the gallbladder with gallstones,which indicated that the tumor had spread to the muscular space(pT1b).Radical resection of gallbladder carcinoma was performed 10 d later.In January 2018,the patient was admitted to our hospital for a mass in the upper abdominal wall after surgery for gallbladder cancer 10 years ago.Laparoscopic exploration and complete resection of the abdominal wall tumor were successfully performed.Pathological diagnosis showed metastatic or invasive,moderately differentiated adenocarcinoma in fibrous tissue with massive ossification.Immunohistochemistry and medical history were consistent with invasion or metastasis of gallbladder carcinoma.His general condition was well at follow-up of 31 mo.No recurrence was found by ultrasound and epigastric enhanced computed tomography.CONCLUSION PSM of gallbladder cancer is often accompanied by peritoneal metastasis,which indicates poor prognosis.Once PSM occurs after surgery,laparoscopic exploration is recommended to rule out abdominal metastasis to avoid unnecessary surgery.

Intervertebral bridging ossification after kyphoplasty in a Parkinson’s patient with Kummell’s disease:A case report

BACKGROUND The short-term therapeutic efficacy of kyphoplasty on Kummell’s disease is obvious.However,postoperative refracture and adjacent vertebral fracture occur occasionally and are difficult to treat.Parkinson's disease(PD)is a pathological disorder associated with heterotopic ossification.In a patient with PD,an intervertebral bridge was formed in a short period of time after postoperative refracture and adjacent vertebral fracture,providing new stability.CASE SUMMARY A 78-year-old woman had been suffering from PD for more than 10 years.Three months before operation,she developed lower back pain and discomfort.The visual analog scale(VAS)score was 9 points.Preoperative magnetic resonance imaging indicated collapse of the L2 vertebra.Kyphoplasty was performed and significantly decreased the severity of intractable pain.The patient’s VAS score for pain improved from 9 to 2.Fifty days postoperatively,the patient suddenly developed severe back pain,and the VAS score was 9 points.X-ray showed L2 vertebral body collapse,slight forward bone cement displacement,L1 vertebral compression fracture,and severe L1 collapse.The patient was given calcium acetate capsules 0.6 g po qd and alfacalcidol 0.5ug po qd,and bed rest and brace protection were ordered.After conservative treatment for 2 mo,the patient's back pain was alleviated,and the VAS score improved from 9 to 2.Computed tomography at the 7-mo follow-up indicated extensive callus formation around the T12-L2 vertebrae and intervertebral bridging ossification,providing new stability.CONCLUSION Kyphoplasty is currently a conventional treatment for Kummell's disease,with definite short-term effects.However,complications still occur in the long term,and these complications are difficult to address;thus,the treatment needs to be selected carefully.To avoid refracture,an interlaced structure of bone cement with trabeculae should be created to the greatest extent possible during the injection of bone cement.Surgical intervention may not be urgently needed when a patient with PD experiences refracture and adjacent vertebral fracture,as a strong bridge may help stabilize the vertebrae and relieve pain.

Development of an experimental method for well-controlled blast induced traumatic limb fracture in rats

Heterotopic ossification(HO)is a consequence of traumatic bone and tissue damage,which occurs in 65%of military casualties with blast-associated amputations.However,the mechanisms behind blast-induced HO remain unclear.Animal models are used to study blast-induced HO,but developing such models is challenging,particularly in how to use a pure blast wave(primary blast)to induce limb fracture that then requires an amputation.Several studies,including our recent study,have developed platforms to induce limb fractures in rats with blast loading or a mixture of blast and impact loading.However,these models are limited by the survivability of the animal and repeatability of the model.In this study,we developed an improved platform,aiming to improve the animal's survivability and injury repeatability as well as focusing on primary blast only.The platform exposed only one limb of the rat to a blast wave while providing proper protection to the rest of the rat's body.We obtained very consistent fracture outcome in the tibia(location and pattern)in cadaveric rats with a large range of size and weight.Importantly,the rats did not obviously move during the test,where movement is a potential cause of uncontrolled injury.We further conducted parametric studies by varying the features of the design of the platform.These factors,such as how the limb is fixed and how the cavity through which the limb is placed is sealed,significantly affect the resulting injury.This platform and test setups enable well-controlled limb fracture induced directly by pure blast wave,which is the fundamental step towards a complete in vivo animal model for blast-induced HO induced by primary blast alone,excluding secondary and tertiary blast injury.In addition,the platform design and the findings presented here,particularly regarding the proper protection of the animal,have implications for future studies investigating localized blast injuries,such as blast induced brain and lung injuries.

Incidence and risk factors analysis of heterotopic ossification after cervical disc replacement

Background Cervical disc replacement （CDR） as a substitute for traditional fusion surgery has been widely used in treating degenerative cervical disc diseases.The objectives of this study were to assess the clinical and radiological findings for patients with heterotopic ossification （HO） following CDR and to detect the risk factors of HO after CDR.Methods A total of 125 patients with symptomatic cervical single-or double-level disc diseases,who underwent CDR procedure with Discover prosthesis in Department of Spine Surgery,Changzheng Orthopedics Hospital from March 2009 to March 2011,were enrolled in this retrospective study.Occurrence of HO was defined by the McAfee classification on cervical lateral X-rays in this study.Prosthesis vertebral ratio （PVR） was used to determine the matching degree between the cervical disc prosthesis and cervical vertebra.Logistic regression analyses were performed to determine the risk factors of HO.Variables evaluated for their association with HO occurrence included age,gender,high-intensity signal in spinal cord,preoperative range of motion （ROM）,postoperative ROM,operation level number,and PVR.Results Mean follow-up time was （26.4±5.8） months.All the patients had significant symptoms and neurological function improvements during the follow-up period.The ROM of the operated segment from the preoperative period to the last follow-up was relatively well maintained.The rate of HO in this cohort of patients,who underwent Discover disc,was 27.92％ per surgical level and 24.8％ per patient by the last follow-up.There were 19 patients （19.79％） with HO in the single-level group while 12 patients （41.38％） in the double-level group.Conclusions We identified preoperative high-intensity signal in spinal cord,postoperative ROM of surgical level,number of operation level,and PVR as significant risk factors for postoperative HO occurrence.

Heterotopic ossification after arthroscopy for hip impingement syndrome

Background:Heterotopic ossification(HO)is a known complication of hip arthroscopy.We investigated incidence of HO after hip arthroscopy and determined whether revision for HO improved outcome.Methods:A retrospective study was conducted on 242 patients(140 men and 102 women,mean age:36.2±9.5 years)who underwent hip arthroscopy for femoroacetabular impingement(FAI)between January 2016 and January 2018.The average followup period was 22.88±11.74 months(range:11-34 months).Thirteen(5.37%)cases of HO(six men and seven women,five left hips and eight right hips;mean age:37.5±4.7 years)were observed.Among them,four cases with HO with obvious pain symptoms and persistent non-remission underwent revision surgery to remove HO.Monthly follow-up was conducted.Visual analog scale(VAS),modified Harris Hip Score(mHHS),and non-Arthritis Hip Score(NAHS)were evaluated and compared between HO and non-HO patients.Independent sample t test,Mann-Whitney U test and the Chi-square test were used for inter-group comparisons.HO degree was evaluated using Brooker classification.Symptoms and function were evaluated before and after revision.Results:A total of 242 patients were involved in this study.Thirteen cases(5.4%)had imaging evidence of HO.Nine(9/13)were classified as Brooker stageⅠ,three(3/13)Brooker stageⅡ,and one(1/13)Brooker stageⅢ.HO was detected by ultrasonography as early as 3 weeks after operation.After primary surgery,the mHHS of the HO group and non-HO group increased by 13.00(8.50,25.50)and 24.00(14.00,34.50)points(Z=-1.80,P=0.08),NAHS increased by 18.00(9.50,31.50)and 26.00(13.50,36.00)points(Z=-1.34,P=0.18),and VAS decreased by 3.00(2.00,4.00)and 4.00(3.00,4.50)points(Z=-1.55,P=0.12).Average follow-up time after revision was 9.00±2.94 months;mHHS increased by 34.75 points t=-55.23,P<0.01)and NAHS by 28.75 points t=-6.03,P<0.01),and VAS decreased by 4 points t=9.80,P<0.01).HO and non-HO patients were similar for demographic and surgical data,and clinical and functional scores.Conclusion:HO incidence after arthroscopic treatment of FAI is similar to that found in previous studies.Most HO have no effect on clinical symptoms.Patients who undergo revision HO resection show improvement in pain and joint function.

A Systems Biology Approach for Studying Heterotopic Ossification： Proteomic Analysis of Clinical Serum and Tissue Samples

Heterotopic ossification （HO） refers to the abnormal formation of bone in soft tissue. Although some of the underlying processes of HO have been described, there are currently no clinical tests using validated biomarkers for predicting HO formation. As such, the diagnosis is made radiographically after HO has formed. To identify potential and novel biomarkers for HO, we used isobaric tags for relative and absolute quantitation （iTRAQ） and high-throughput antibody arrays to produce a semi-quantitative proteomics survey of serum and tissue from subjects with （HO ＋） and without （HO-） heterotopic ossification. The resulting data were then analyzed using a systems biology approach. We found that serum samples from subjects experiencing traumatic injuries with resulting HO have a different proteomic expression controls. Subsequent quantitative ELISA identified profile compared to those from the matched five blood serum proteins that were differentially regulated between the HO-- and HO- groups. Compared to HO- samples, the amount of insulin-like growth factor I （IGF1） was up-regulated in HO＋ samples, whereas a lower amount of osteopontin （OPN）, myeloperoxidase （MPO）, runt-related transcription factor 2 （RUNX2）,and growth differentiation factor 2 or bone morphogenetic protein 9 （BMP-9） was found in HO ＋ samples （Welch two sample t-test; P 〈 0.05）. These proteins, in combination with potential serum biomarkers previously reported, are key candidates for a serum diagnostic panel that may enable early detection of HO prior to radiographic and clinical manifestations.

Comment on "Heterotopic ossification after arthroscopy for hip impingement syndrome"

We have read with great interest the article "Heterotopic ossification after arthroscopy for hip impingement syndrome" by Gao et al.[1] The authors showed the incidence of heterotopic ossification (HO) is an observed complication after hip arthroscopy for hip impingement syndrome which is not common (5.4%,13/242) and most HO has no or little effect on clinical symptoms.We also agree with them that oral nonsteroidal anti-inflammatory drugs (NSAIDs) are beneficial in the prevention of HO after primary hip arthroscopy.Although we agree with the conclusion similar to our previous studies in the clinic,there are some issues we like to comment on.

Preemptive targeted muscle reinnervation:the single incision approach should be avoided in trans‑tibial traumatic amputation

Dear Editor,Chronic pain is a significant concern after major lower limb amputations that often preclude prosthetic fitting,decrease ambulation,and impact the quality of life[1,2].In the last decade,targeted muscle reinnervation(TMR)has been proposed as a surgical strategy for treating or preventing symptomatic neuromas and phantomlimb phenomena in major amputees[1].This technique involves the transfer of an amputated mixed-motor and sensory nerve to a nearby recipient motor nerve[1,2].Unlike most surgical strategies that aim to hide or protect the neuroma,TMR gives the amputated nerves“somewhere to go and something to do”[2].In a randomized clinical trial on neuroma and phantom pain,Dumanian et al.[1]demonstrated that TMR reduces amputationrelated chronic pain at 1-year post-intervention when compared with the excision and muscle-burying technique,which remains the current gold standard.Valerio et al.[2]also proposed applying TMR at the time of major limb amputation for preventing chronic pain and found that TMR patients experienced less residual limb pain(RLP)and phantom limb pain(PLP)when compared with untreated amputee controls.