Reconstructive surgery after distal fibular resection due to bone tumors: a technical report on surgical strategies and results from the PROSPERO international register of systematic reviews.

Purpose: Primary bone tumors of the fibula are rare. Distal fibular resection has a significant impact on ankle biomechanics and gait, possibly leading to complications such as ankle instability, valgus deformity, and degenerative changes. Question: Is there a need for reconstructive surgery after distal fibular resection, and what reconstructive procedures are available? Materials and methods: The review is registered with the PROSPERO International Register of Systematic Reviews. Inclusion criteria consisted of all levels of evidence, human studies, patients of all ages and genders, publication in English, and resection of the distal portion of the fibula due to tumor pathology. The reviewers defined four different categories of interest by method of treatment. Additional articles of interest during full-text review were also added. Results: The initial search resulted with a total of 2958 records. After screening, a total of 50 articles were included in the study. Articles were divided into 'No reconstruction', 'Soft tissue reconstruction', 'Bone and soft tissue reconstruction', and 'Arthrodesis, arthroplasty or other reconstruction options' groups. Conclusion: Limb salvage surgery should be followed by reconstruction in order to avoid complications. Soft tissue reconstructions should always be considered to stabilize the joint after fibular resection. Bone reconstruction with reversed vascularized fibula is the preferred technique in young patients and in cases of bone defects more than 3 cm, while arthrodesis should be considered in adult patients. Whenever possible for oncologic reason, if a residual peroneal malleolus could be preserved, we prefer augmentation with a sliding ipsilateral fibular graft.

Distinctiveness of Femoral and Acetabular Mesenchymal Stem and Progenitor Populations in Patients with Primary and Secondary Hip Osteoarthritis Due to Developmental Dysplasia.

Primary hip osteoarthritis (pOA) develops without an apparent underlying reason, whereas secondary osteoarthritis arises due to a known cause, such as developmental dysplasia of the hips (DDH-OA). DDH-OA patients undergo total hip arthroplasty at a much younger age than pOA patients (50.58 vs. 65 years in this study). Recently, mesenchymal stem and progenitor cells (MSPCs) have been investigated for the treatment of osteoarthritis due to their immunomodulatory and regenerative potential. This study identified cells in subchondral bone expressing common MSPC markers (CD10, CD73, CD140b, CD146, CD164, CD271, GD2, PDPN) in vivo and compared the proportions of these populations in pOA vs. DDH-OA, further correlating them with clinical, demographic, and morphological characteristics. The differences in subchondral morphology and proportions of non-hematopoietic cells expressing MSPC markers were noted depending on OA type and skeletal location. Bone sclerosis was more prominent in the pOA acetabulum (Ac) in comparison to the DDH-OA Ac and in the pOA Ac compared to the pOA femoral head (Fh). Immunophenotyping indicated diagnosis-specific differences, such as a higher proportion of CD164+ cells and their subsets in DDH-OA, while pOA contained a significantly higher proportion of CD10+ and GD2+ cells and subsets, with CD271+ being marginally higher. Location-specific differences showed that CD271+ cells were more abundant in the Fh compared to the Ac in DDH-OA patients. Furthermore, immunohistochemical characterization of stromal bone-adjacent cells expressing MSPC markers (CD10, CD164, CD271, GD2) in the Ac and Fh compartments was performed. This research proved that immunophenotype profiles and morphological changes are both location- and disease-specific. Furthermore, it provided potentially effective targets for therapeutic strategies. Future research should analyze the differentiation potential of subsets identified in this study. After proper characterization, they can be selectively targeted, thus enhancing personalized medicine approaches in joint disease management.

Specificities in the Structure of the Cartilage of Patients with Advanced Stages of Developmental Dysplasia of the Hip.

Developmental dysplasia of the hip (DDH) presents varying degrees of femoral head dislocation, with severe cases leading to the formation of a new articular surface on the external side of the iliac bone-the neoacetabulum. Despite conventional understanding suggesting otherwise, a tissue resembling hyaline cartilage is found in the neoacetabulum and acetabulum of Crowe III and IV patients, indicating a potential for hyaline cartilage development without mechanical pressure. To test this theory, acetabular and femoral head cartilage obtained from patients with DDH was stained with hematoxylin-eosin and toluidine blue. The immunohistochemical analysis for collagen types II and VI and aggrecan was performed, as well as delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) analysis on a 7.0 T micro-MRI machine. The results obtained from DDH patients were compared to those of the control groups. Hyaline cartilage was found in the neoacetabulum and the acetabulum of patients with DDH. The nature of the tissue was confirmed with both the histological and the MRI analyses. The results of this study proved the presence of hyaline cartilage in patients with DDH at anatomical regions genetically predisposed to be bone tissue and at regions that are not subjected to mechanical stress. This is the first time that the neoacetabular cartilage of patients with advanced stages of DDH has been characterized in detail.

Novel micro-MRI approach for subchondral trabecular bone analysis in patients with hip osteoarthritis is comparable to micro-CT approach.

AIM: To test the agreement between a newly developed micro-magnetic resonance imaging (MRI) analysis of the subchondral bone and the micro-computed tomography (CT) approach. METHODS: Samples obtained from 10 patients with osteoarthritis undergoing total hip arthroplasty were scanned with a 7.0 T micro-MRI. Proton density-weighted images and proton density-weighted images with fat suppression were obtained. The results were validated with a micro-CT device. Micro-MRI and micro-CT scans of the same sample were aligned, and regions of interest were delineated on equal areas of the sample. Bone volume fraction was calculated by using in-house plugins. The agreement between the methods was tested with Bland-Altman analysis. RESULTS: The agreement between the methods was good, with average difference of 2.167%. The differences between the methods were not significant (P=0.272, t test). CONCLUSION: The novel micro-MRI approach could be used for subchondral bone analysis. With further optimization for clinical MRI machines, the approach can be also used in the diagnostics of hip osteoarthritis.

Arthroscopic removal as an effective treatment option for intra-articular osteoid osteoma of the knee.

BACKGROUND: Intra-articular osteoid osteoma (iaOO) can be found in 5.2% up to 10% of cases. They may cause non-specific symptoms, mimicking degenerative or traumatic pathologies. If iaOO is left untreated, it may lead to severe muscle atrophy, tenderness, swelling, and limited range of motion. Therefore, surgical treatment is recommended. The main goal of surgical treatment is complete removal or destruction of iaOO. AIM: To evaluate the efficiency of arthroscopic removal of iaOO of the knee in our cases and cases available in the literature. METHODS: Analysis of available hospital records of four patients with iaOO of the knee treated by arthroscopic removal from August 2005 to December 2015 at our Department was performed. All patients had a diagnosis of iaOO confirmed by histopathologic analysis. Additional literature review of cases of iaOO of the knee available on PubMed and Google Scholar was made. All cases of iaOO of the knee treated by arthroscopic or arthroscopically assisted removal were reviewed in order to further evaluate the efficiency of the method. RESULTS: The average age of patients included in our study was 23.2 (range 16-37) years. The average duration of the symptoms prior to surgery was 14.2 (range 6-24) months. All of the patients had persistent knee pain. Three patients reported worsening of pain during the night, while two reported worsening of pain during activity. Three patients reported alleviation of pain on non-steroidal anti-inflammatory drugs (NSAIDs), while one patient reported partial alleviation of pain on NSAIDs. No intraoperative complications were noted, and the postoperative period was uneventful in all patients. The patients reported immediate pain relief in the postoperative period. No recurrence of the disease was noted in any of the patients during the follow-up period of at least 24 mo. The literature review revealed 14 cases with an average age of 27.6 (range 16-48) years and onset of symptoms 27.7 (range 6-108) months prior to surgery, with recurrence of the disease noted in a single case. CONCLUSION: Arthroscopic removal is an efficient treatment method that allows excision of iaOO that is neither insufficient nor excessive, thus avoiding disease recurrence while obtaining adequate material for histopathologic analysis.

Anterior and Posterior Arthroscopic Treatment of Primary Synovial Chondromatosis of the Ankle.

BACKGROUND: Primary synovial chondromatosis (PSC) is a progressive disorder of unknown etiology resulting in formation of multiple loose bodies. If left untreated, it may lead to degenerative changes or malignant transformation to chondrosarcoma. METHODS: Seventeen patients who underwent combined posterior and anterior ankle arthroscopy within the same operative session and had histologically confirmed PSC were included in this retrospective study. American Orthopaedic Foot & Ankle Society (AOFAS) Ankle-Hindfoot score was used to evaluate ankle function preoperatively and at a final follow-up. A 3-question survey was used to evaluate patient's satisfaction at the final follow-up. RESULTS: In 14 patients, loose bodies were found in both compartments of the ankle, in 2 only in the anterior compartment, and in 1 only in the posterior compartment. All patients had evident signs of synovial inflammation in both compartments. The AOFAS Ankle-Hindfoot score increased from the preoperative median score of 65 (range, 29-90) to 95 (range, 65-100) at the final follow-up. Fourteen patients reported they were extremely satisfied with the outcome, 1 was moderately satisfied, and 2 were dissatisfied. No cases of recurrence of synovitis or loose body formation were noted, nor any signs of malignant transformation during the follow-up period. CONCLUSION: We believe the risk of recurrence of PSC, which is in close relation to malignant transformation, can be minimized by performing a complete synovectomy of the ankle. Our experience and review of literature makes us believe that ankle PSC should be regarded as a whole joint disorder. Performing a combined posterior and anterior arthroscopic procedure within the same operative session should always be considered in patients with ankle PSC. LEVEL OF EVIDENCE: Level IV, retrospective case series.

Accessory Soleus Muscle: Two Case Reports with a Completely Different Presentation Caused by the Same Entity.

Accessory soleus muscle (ASM) is a rare supernumerary anatomical variant that commonly presents as a posteromedial ankle swelling, which may become painful during physical activity. As it may mimic a soft tissue tumor, it is essential to differentiate this condition from ganglion, lipoma, hemangioma, synovioma, and sarcoma. However, ASM may also present with a painful syndrome, characterized by pain and paresthesia of the ankle and foot, mimicking the tarsal tunnel syndrome (TTS). Two cases of ASM are presented in this article. The first case had a typical presentation with painful posteromedial ankle swelling. After the initial assessment, the diagnosis was confirmed by magnetic resonance imaging (MRI), and ASM was treated by complete resection. The second case presented with pain and paresthesia in the right ankle and foot, but no swelling was noticeable. It was initially misdiagnosed by a rheumatologist and afterward overlooked on an MRI by a musculoskeletal radiology specialist and therefore mistreated by numerous physicians before being referred to our outpatient clinic. After further assessment, the diagnosis has been confirmed, and ASM was treated by complete resection combined with tarsal tunnel decompression. To the best of our knowledge, this is the first case reported in which ASM caused symptoms but presented without posteromedial swelling. This might be due to a proximally positioned belly of the ASM, followed by a tendinous insertion on the medial side of the calcaneus.

Current knowledge on the genetic background of developmental dysplasia of the hip and the histomorphological status of the cartilage.

Developmental dysplasia of the hip (DDH) represents a morphological abnormality characterized by the incongruity of femoral head and acetabulum. It ranges from mild dysplastic changes to complete dislocation. DDH has been associated with several hereditary and environmental risk factors, which could explain the incidence variability among different countries. Numerous genes may be involved in the disease etiology and progression. However, there are controversies in the literature regarding some of these genes. DDH-induced secondary osteoarthritis (OA) is characterized by changes in the macromolecule content of the cartilage and the expression of cartilage degradation markers. In addition, it exhibits a pattern of specific histological changes, with several reported differences between primary and DDH-induced secondary OA. The articular cartilage of patients with DDH shows specific radiological characteristics, including changes visible already in infancy, but also at pre-arthritic stages, early stages of OA, and in fully developed DDH-induced secondary OA. Although DDH has been extensively researched in different disease stages, the etiology of the disorder still remains uncertain. This review focuses on the current knowledge on the histomorphological status of the cartilage and the genetic background of DDH.

The neoacetabulum in developmental dysplasia of the hip is covered with hyaline cartilage.

The lack of adequate mechanical stimulation and appropriate contact between acetabulum and femoral head results with developmental dysplasia of the hip (DDH). In DDH, hip joint forms normally during the organogenesis, but deforms during the fetal development. Acetabulum remains comparable in width with normal acetabulum, but has increased length and decreased depth, resulting in a poor coverage of the femoral head. In cases of severe hip subluxation and luxation due to DDH, the femoral head articulates with the external side of the iliac bone, forming a neoacetabulum in the position that was genetically predetermined to become bony tissue. A neoacetabulum is therefore formed under intermittent mechanical pressure, but never has the depth of a physiological acetabulum due to different forces at this new location. Over time, the depth of the neoacetabulum increases, and a crest is formed that obstructs reposition of the femoral head into the anatomic acetabulum. We hypothesize that the neoacetabulum on the iliac bone in DDH patients is formed of hyaline cartilage, despite the lack of genetic predisposition for hyaline cartilage formation in this area. We assume that as the femoral head migrates during development in such patients, joint capsular tissue interposes between the external side of the iliac bone and the femoral head, and a cartilaginous metaplasia of the capsule follows. This results in elongation of the acetabular cartilage in the same direction as the femoral head migrated. This assumption is based on the finding that in patients with hip luxation such interposed joint capsule showed signs of cartilaginous transformation. Furthermore, in the inner part of such joint capsules, proteoglycan production was notably higher than that of other non-cartilaginous tissue. Also, high expression of cartilaginous genes, which are usually not expressed in this tissue, was observed. Confirmation of this hypothesis would put a new perspective on the pathogenesis of DDH and could lead to better management or even prevention of this condition.

A 24-Month Follow-Up Study of the Effect of Intra-Articular Injection of Autologous Microfragmented Fat Tissue on Proteoglycan Synthesis in Patients with Knee Osteoarthritis.

Osteoarthritis (OA) is a widely prevalent disease worldwide, and with an increasingly ageing society, it has become a challenge for the field of regenerative medicine. OA is a disease process involving multiple joint tissues, including those not visible on radiography, and is a complex disease process with multiple phenotypes that require evaluation by a multimodality imaging assessment. The purpose of this study was to evaluate the effect of micro-fragmented fat tissue intra-articular injection 24 months after application in two ways: Indirectly using functional magnetic resonance imaging (MRI) assessment analyzing the glycosaminoglycans (GAG) content in cartilage by means of delayed gadolinium (Gd)-enhanced magnetic resonance imaging of cartilage (dGEMRIC), as well as clinical outcome on observed level of GAG using standard orthopedic physical examination including VAS assessment. In our previous study assessing comprehensive results after 12 months, the dGEMRIC results have drawn attention. The present study explores the long-term effect of intra-articular injection of autologous microfragmented adipose tissue to host chondrocytes and cartilage proteoglycans in patients with knee OA. A prospective, non-randomized, interventional, single-center, open-label clinical trial was conducted from January 2016 to April 2018. A total of 17 patients were enrolled in the study, and 32 knees were assessed in a 12-month follow-up, but only 10 patients of them with 18 knees are included in a 24-month follow-up. The rest of the seven patients dropped out of the study 12 months after follow-up: three patients underwent knee arthroplasty, and the remaining four did not fulfil the basic criteria of 24 months involvement in the study. Surgical intervention (lipoaspiration), followed by tissue processing and intra-articular injection of the final microfragmented adipose tissue product into the affected knee(s), was performed in all patients. Patients were assessed for a visual analog scale (VAS), dGEMRIC at the baseline, three, six, 12 and 24 months after the treatment. A magnetic resonance sequence in dGEMRIC due to infiltration of the anionic, negatively-charged contrast gadopentetate dimeglumine (Gd-DTPA2) into the cartilage indicated that the contents of cartilage glycosaminoglycans significantly increased in specific areas of the treated knee joint. Our results suggest that this method of single intra-articular injection of autologous microfragmented adipose tissue improves GAG content on a significant scale, with over half of the measurements suggesting relevant improvement 24 months after intra-articular injection opposed to the expected GAG decrease over the natural course of the disease.

Applications and critical evaluation of fascia iliaca compartment block and quadratus lumborum block for orthopedic procedures.

Anterior section of the hip joint capsule is innervated by femoral nerve and obturator nerve, and posterior section is innervated by the nerve to quadratus femoris muscle and occasionally by the superior gluteal (posterolateral region) and sciatic nerve (posterosuperior region). One of the regional anesthesia options for hip surgery is the fascia iliaca compartment block (FICB) that affects nerves important for hip innervation and sensory innervation of the thigh - femoral, obturator and lateral femoral cutaneous nerve. FICB can be easily performed and is often a good solution for management of hip fractures in emergency departments. Its use reduces morphine pre-operative requirement for patients with femoral neck fractures and can also be indicated for hip arthroplasty, hip arthroscopy and burn management of the region. Quadratus lumborum block (QLB) is a block of the posterior abdominal wall performed exclusively under ultrasound guidance, with still unclarified mechanism of action. When considering hip surgery and postoperative management, the anterior QLB has shown to reduce lengthy hospital stay and opioid use, it improves perioperative analgesia in patients undergoing hip and proximal femoral surgery compared to standard intravenous analgesia regimen, provides early and rapid pain relief and allows early ambulation, thus preventing deep vein thrombosis and thromboembolic complications etc. However, some nerve branches responsible for innervation of the hip joint are not affected by QLB, which has to be taken into consideration. QLB has shown potential for use in hip surgery and perioperative pain management, but still needs to be validated as a reliable treatment approach.

Immunophenotyping of a Stromal Vascular Fraction from Microfragmented Lipoaspirate Used in Osteoarthritis Cartilage Treatment and Its Lipoaspirate Counterpart.

Osteoarthritis (OA) is a degenerative joint disease accompanied by pain and loss of function. Adipose tissue harbors mesenchymal stem/stromal cells (MSC), or medicinal signaling cells as suggested by Caplan (Caplan, 2017), used in autologous transplantation in many clinical settings. The aim of the study was to characterize a stromal vascular fraction from microfragmented lipoaspirate (SVF-MLA) applied for cartilage treatment in OA and compare it to that of autologous lipoaspirate (SVF-LA). Samples were first stained using a DuraClone SC prototype tube for the surface detection of CD31, CD34, CD45, CD73, CD90, CD105, CD146 and LIVE/DEAD Yellow Fixable Stain for dead cell detection, followed by DRAQ7 cell nuclear dye staining, and analyzed by flow cytometry. In SVF-LA and SVF-MLA samples, the following population phenotypes were identified within the CD45- fraction: CD31+CD34+CD73±CD90±CD105±CD146± endothelial progenitors (EP), CD31+CD34-CD73±CD90±CD105-CD146± mature endothelial cells, CD31-CD34-CD73±CD90+CD105-CD146+ pericytes, CD31-CD34+CD73±CD90+CD105-CD146+ transitional pericytes, and CD31-CD34+CD73highCD90+CD105-CD146- supra-adventitial-adipose stromal cells (SA-ASC). The immunophenotyping profile of SVF-MLA was dominated by a reduction of leukocytes and SA-ASC, and an increase in EP, evidencing a marked enrichment of this cell population in the course of adipose tissue microfragmentation. The role of EP in pericyte-primed MSC-mediated tissue healing, as well as the observed hormonal implication, is yet to be investigated.

Early results of intra-articular micro-fragmented lipoaspirate treatment in patients with late stages knee osteoarthritis: a prospective study.

AIM: To analyze clinical and functional effects of intra-articular injection of autologous micro-fragmented lipoaspirate (MLA) in patients with late stage knee osteoarthritis (KOA). Secondary aims included classifying cell types contributing to the treatment effect, performing detailed MRI-based classification of KOA, and elucidating the predictors for functional outcomes. METHODS: This prospective, non-randomized study was conducted from June 2016 to February 2018 and enrolled 20 patients with late stage symptomatic KOA (Kellgren Lawrence grade III, n=4; and IV, n=16) who received an intra-articular injection of autologous MLA in the index knee joint. At baseline radiological KOA grade and MRI were assessed in order to classify the morphology of KOA changes. Stromal vascular fraction cells obtained from MLA samples were stained with antibodies specific for cell surface markers. Patients were evaluated at baseline and 12-months after treatment with visual analog scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Knee Injury and Osteoarthritis Outcome Score (KOOS). RESULTS: Three patients (15%) received a total knee replacement and were not followed up completely. Seventeen patients (85%) showed a substantial pattern of KOOS and WOMAC improvement, significant in all accounts. KOOS score improved from 46 to 176% when compared with baseline, WOMAC decreased from 40 to 45%, while VAS rating decreased from 54% to 82% (all P values were <0.001). MLA contained endothelial progenitor cells, pericytes, and supra-adventitial adipose stromal cells as most abundant cell phenotypes. CONCLUSION: This study is among the first to show a positive effect of MLA on patients with late stages KOA.

The Effect of Intra-articular Injection of Autologous Microfragmented Fat Tissue on Proteoglycan Synthesis in Patients with Knee Osteoarthritis.

Osteoarthritis (OA) is one of the leading musculoskeletal disorders in the adult population. It is associated with cartilage damage triggered by the deterioration of the extracellular matrix tissue. The present study explores the effect of intra-articular injection of autologous microfragmented adipose tissue to host chondrocytes and cartilage proteoglycans in patients with knee OA. A prospective, non-randomized, interventional, single-center, open-label clinical trial was conducted from January 2016 to April 2017. A total of 17 patients were enrolled in the study, and 32 knees with osteoarthritis were assessed. Surgical intervention (lipoaspiration) followed by tissue processing and intra-articular injection of the final microfragmented adipose tissue product into the affected knee(s) was performed in all patients. Patients were assessed for visual analogue scale (VAS), delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) and immunoglobulin G (IgG) glycans at the baseline, three, six and 12 months after the treatment. Magnetic resonance sequence in dGEMRIC due to infiltration of the anionic, negatively charged contrast gadopentetate dimeglumine (Gd-DTPA2-) into the cartilage indicated that the contents of cartilage glycosaminoglycans significantly increased in specific areas of the treated knee joint. In addition, dGEMRIC consequently reflected subsequent changes in the mechanical axis of the lower extremities. The results of our study indicate that the use of autologous and microfragmented adipose tissue in patients with knee OA (measured by dGEMRIC MRI) increased glycosaminoglycan (GAG) content in hyaline cartilage, which is in line with observed VAS and clinical results.

Systemic inhibition of BMP1-3 decreases progression of CCl4-induced liver fibrosis in rats.

Liver fibrosis is a progressive pathological process resulting in an accumulation of excess extracellular matrix proteins. We discovered that bone morphogenetic protein 1-3 (BMP1-3), an isoform of the metalloproteinase Bmp1 gene, circulates in the plasma of healthy volunteers and its neutralization decreases the progression of chronic kidney disease in 5/6 nephrectomized rats. Here, we investigated the potential role of BMP1-3 in a chronic liver disease. Rats with carbon tetrachloride (CCl4)-induced liver fibrosis were treated with monoclonal anti-BMP1-3 antibodies. Treatment with anti-BMP1-3 antibodies dose-dependently lowered the amount of collagen type I, downregulated the expression of Tgfb1, Itgb6, Col1a1, and Acta2 and upregulated the expression of Ctgf, Itgb1, and Dcn. Mehanistically, BMP1-3 inhibition decreased the plasma levels of transforming growth factor beta 1(TGFß1) by prevention of its activation and lowered the prodecorin production further suppressing the TGFß1 profibrotic effect. Our results suggest that BMP1-3 inhibitors have significant potential for decreasing the progression of fibrosis in liver cirrhosis.