Preoperative patient's expectations and clinical outcomes after rheumatoid forefoot deformity reconstruction by joint sacrificing surgery.

Objective: To study the clinical and radiologic factors related with overall patient satisfaction of joint scarifying reconstruction on severe rheumatoid forefoot deformity (RFD). Methods: Forty cases of RFD were retrospectively enrolled. A questionnaire on the factors for patient's expectations and satisfactions of the greater and lesser toes was administered, including repression of relapse in deformity (D), pain reduction (P), improvement in shoe wearing (S), barefoot activity (B), and appearance (A). Overall satisfaction were assessed using the 5-digit-scale. Hallux valgus angle, 1, 2 intermetatarsal angle, and other radiologic parameters were measured. Pearson's correlation and multiple linear regression analyses were used to evaluate the relationships between these factors and overall satisfaction. Results: Overall satisfaction was 4.0±0.82. Postoperative radiologic parameters were corrected in adequate range. Visual analog scale (VAS) was reduced from 7.2±2.1 to 2.2±1.8. For the greater toe, patient's expectations (D, P, S, B, and A) were 4.2, 4.1, 3.0, 2.5, 2.7 and satisfactions were 4.2, 4.0, 3.4, 3.5, 3.3, respectively. For the lesser toes, patient's expectations (D, P, S, B, and A) were 3.9, 4.1, 3.4, 3.0, 2.8, and satisfactions were 3.4, 4.0, 3.4, 3.6, 2.9, respectively. Satisfactions with P and B, and reduction amounts of VAS were significantly correlated with overall satisfaction. Conclusion: Although forefoot reconstruction with a joint sacrificing procedure is non-physiological, it could be a good surgical option for severe RFD. Each patient's expectations and satisfactions with this procedure could vary. Thus, it seems important to inform patients preoperatively that expectation could be fulfilled well or less.

Myosin heavy chain 2 (MYH2) expression in hypertrophic chondrocytes of soft callus provokes endochondral bone formation in fracture.

AIMS: Muscle-bone interactions during fracture healing are rarely known. Here we investigated the presence and significance of myosin heavy chain 2 (MYH2), a component of myosin derived from muscles, in fracture healing. MAIN METHODS: We collected five hematoma and seven soft callus tissues from patients with distal radius fractures patients, randomly selected three of them, and performed a liquid chromatography-mass spectrometry (LC-MS) proteomics analysis. Proteomic results were validated by histological observation, immunohistochemistry, and immunofluorescence for MYH2 expression. These findings were further confirmed in a murine femoral fracture model in vivo and investigated using various methods in vitro. KEY FINDINGS: The LC-MS proteomics analysis showed that MYH proteins were enriched in human soft calluses compared to hematoma. Notably, MYH2 protein is upregulated as high rank in each soft callus. The histological examination showed that MYH2 expression was elevated in hypertrophic chondrocytes within the human soft callus. Consistent with human data, Myh2 were significantly co-localized with Sox9 in hypertrophic chondrocytes of murine femoral fracture, in comparison to pre-hypertrophic and proliferating chondrocytes. Soluble MYH2 protein treatment increased MMP13 and RUNX2 expression in chondrocytes. In soluble MYH2 treatment, proliferation of chondrocytes was not altered, but the osteogenic and chondrogenic features of chondrocytes increased and decreased during differentiation, respectively. SIGNIFICANCE: These findings indicate the potential of soluble MYH2 protein as a promising therapeutic strategy for promoting endochondral bone formation in chondrocytes following fracture.

Trends and Risk Factors for Surgical Site Infection after Treatment of the Ankle Fracture: National Cohort Study.

Surgical site infection (SSI) is a major complication after the surgical treatment of ankle fractures that can result in catastrophic consequences. This study aimed to determine the incidence of SSI in several cohorts from national insurance databases over the past 12 years and identify its predictors. The claimed data for patients (n = 1,449,692) with ankle fractures between 2007 and 2019 were investigated, and a total of 41,071 patients were included in the final analysis. The covariates included were age, sex, season, fracture type (closed vs. open), type of surgical fixation procedure, and comorbidities of each patient. All subjects were divided into two groups according to the SSI after the surgical fixation of the ankle fracture (no infection group vs. infection group). The number of SSIs after the surgical treatment of ankle fractures was 874 (2.13%). Open fractures [odds ratio, (OR) = 4.220] showed the highest risk for SSI, followed by the male sex (OR = 1.841), an increasing number of comorbidities (3-5, OR = 1.484; ≥6, OR = 1.730), a history of dementia (OR = 1.720) or of myocardial infarction (OR = 1.628), and increasing age (OR = 1.010). The summer season (OR = 1.349) showed the highest risk among the four seasons for SSI after ankle fracture surgery.

Abnormal kynurenine level contributes to the pathological bone features of ankylosing spondylitis.

OBJECTIVE: Ankylosing spondylitis (AS) exhibits paradoxical bone features typically characterized by new bone formation and systemic bone loss. Although abnormal kynurenine (Kyn), a tryptophan metabolite, has been closely linked to the disease activity of AS, the distinct role of its pathological bone features remains unknown. METHODS: Kynurenine sera level was collected from healthy control (HC; n = 22) and AS (n = 87) patients and measured by ELISA. In the AS group, we analyzed and compared the Kyn level based on the modified stoke ankylosing spondylitis spinal score (mSASSS), MMP13, and OCN. Under osteoblast differentiation, the treatment with Kyn in AS-osteoprogenitors conducted cell proliferation, alkaline phosphatase activity, bone mineralization-related alizarin red s (ARS), von kossa (VON), hydroxyapatite (HA) staining, and mRNA expression markers (ALP, RUNX2, OCN, and OPG) for bone formation. TRAP and F-actin staining was used for osteoclast formation of mouse osteoclast precursors. RESULTS: Kyn sera level was significantly elevated in the AS group compared to the HC. In addition, Kyn sera level was correlated with mSASSS (r = 0.03888, p = 0.067), MMP13 (r = 0.0327, p = 0.093), and OCN (r = 0.0436, p = 0.052). During osteoblast differentiation, treatment with Kyn exhibited no difference in cell proliferation and alkaline phosphate (ALP) activity for bone matrix maturation but promoted ARS, VON, and HA staining for bone mineralization. Interestingly, osteoprotegerin (OPG) and OCN expressions of AS-osteoprogenitors were augmented in the Kyn treatment during differentiation. In growth medium, Kyn treatment of AS-osteoprogenitors resulted in induction of OPG mRNA, protein expression, and Kyn-response genes (AhRR, CYP1b1, and TIPARP). Secreted OPG proteins were observed in the supernatant of AS-osteoprogenitors treated with Kyn. Notably, the supernatant of Kyn-treated AS-osteoprogenitors interrupted the RANKL-mediated osteoclastogenesis of mouse osteoclast precursor such as TRAP-positive osteoclast formation, NFATc1 expression, and osteoclast differentiation markers. CONCLUSION: Our results revealed that elevated Kyn level increased the bone mineralization of osteoblast differentiation in AS and decreased RANKL-mediated osteoclast differentiation by inducing OPG expression. Out study have implication for potential coupling factors linking osteoclast and osteoblast where abnormal Kyn level could be involved in pathological bone features of AS.

Platelet-Derived Growth Factor B Is a Key Element in the Pathological Bone Formation of Ankylosing Spondylitis.

Enthesophyte formation plays a crucial role in the development of spinal ankylosis in ankylosing spondylitis (AS). We aimed to investigate the role of platelet-derived growth factor B (PDGFB) in enthesophyte formation of AS using in vitro and in vivo models and to determine the association between PDGFB and spinal progression in AS. Serum PDGFB levels were measured in AS patients and healthy controls (HC). Human entheseal tissues attached to facet joints or spinous processes were harvested at the time of surgery and investigated for bone-forming activity. The impact of a pharmacological agonist and antagonist of platelet-derived growth factor B receptor (PDGFRB) were investigated respectively in curdlan-treated SKG mice. PDGFB levels were elevated in AS sera and correlated with radiographic progression of AS in the spine. Mature osteoclasts secreting PDGFB proteins were increased in the AS group compared with HC and were observed in bony ankylosis tissues of AS. Expression of PDGFRB was significantly elevated in the spinous enthesis and facet joints of AS compared with controls. Moreover, recombinant PDGFB treatment accelerated bone mineralization of enthesis cells, which was pronounced in AS, whereas PDGFRB inhibition efficiently reduced the PDGFB-induced bone mineralization. Also, PDGFRB inhibition attenuated the severity of arthritis and enthesophyte formation at the joints of curdlan-treated SKG mice. This study suggests that regulating PDGFB/PDGFRB signaling could be a novel therapeutic strategy to block key pathophysiological processes of AS. © 2022 American Society for Bone and Mineral Research (ASBMR).

Long-Term Survival Analysis of 5619 Total Ankle Arthroplasty and Patient Risk Factors for Failure.

BACKGROUND: Total ankle arthroplasty (TAA) has higher complication and failure rates compared to other surgical joint replacement procedures despite technological advances. This study aimed to find the long-term survivability of the TAA procedure and identify the patient risk factors for failure with one of the largest cohorts of patients in the literature. METHODS: This retrospective cohort study involving cases between 2007 and 2018 analyzed patients who received an index primary TAA procedure in Korea. A total of 5619 cases were included in the final analysis. The TAA failure was defined as either a case with revision arthroplasty or a case with TAA implant removal and arthrodesis performed after primary TAA. RESULTS: During the study period, the 5-year survival rate was 95.4% (95% CI, 94.7-96.1%), and the 10-year survival rate was 91.1% (95% CI, 89.1-93.1%). A younger age (<55 years, adjusted hazard ratio [AHR], 1.725; 55-64 years, AHR, 1.812; p < 0.001 for both), chronic pulmonary disease (AHR, 1.476; p = 0.013), diabetes (AHR, 1.443; p = 0.014), and alcohol abuse (AHR, 1.524; p = 0.032) showed a significantly high odds ratio for primary TAA failure in Cox regression analysis. CONCLUSION: The 10-year TAA survivorship rate was 91.1%. A younger age, chronic pulmonary disease, diabetes, and heavy alcohol consumption are risk factors for TAA.

Scaffold-induced compression enhances ligamentization potential of decellularized tendon graft reseeded with ACL-derived cells.

Anterior cruciate ligament (ACL) reconstruction is often performed using a tendon graft. However, the predominant synthesis of fibrotic scar tissue (type III collagen) occurs during the healing process of the tendon graft, resulting in a significantly lower mechanical strength than that of normal ACL tissue. In this study, ACL-derived cells were reseeded to the tendon graft, and scaffold-induced compression was applied to test whether the compressive force results in superior cell survival and integration. Given nanofiber polycaprolactone (PCL) scaffold-induced compression, ACL-derived cells reseeded to a tendon graft demonstrated superior cell survival and integration and resulted in higher gene expression levels of type I collagen compared to non-compressed cell-allograft composites in vitro. Translocation of Yes-associated protein (YAP) into the nucleus was correlated with higher expression of type I collagen in the compression group. These data support the hypothesis of a potential role of mechanotransduction in the ligamentization process.

Comparison of ligamentization potential between anterior cruciate ligament-derived cells and adipose-derived mesenchymal stem cells reseeded to acellularized tendon allograft.

AIMS: To test the hypothesis that reseeded anterior cruciate ligament (ACL)-derived cells have a better ability to survive and integrate into tendon extracellular matrix (ECM) and accelerate the ligamentization process, compared to adipose-derived mesenchymal stem cells (ADMSCs). METHODS: Acellularized tibialis allograft tendons were used. Tendons were randomly reseeded with ACL-derived cells or ADMSCs. ACL-derived cells were harvested and isolated from remnants of ruptured ACLs during reconstruction surgery and cultured at passage three. Cell suspensions (200 µl) containing 2 × 106 ACL-derived cells or ADMSCs were prepared for the purpose of reseeding. At days 1, 3, and 7 post-reseeding, graft composites were assessed for repopulation with histological and immunohistochemical analysis. Matrix protein contents and gene expression levels were analyzed. RESULTS: In the graft reseeded with ACL-derived cells, a large number of elongated cells that integrated into the matrix were evident at day 3 and day 7. However, in the graft reseeded with ADMSCs, only a small number of elongated cells were found integrated into the matrix. Immunofluorescence for Ki-67 and type I collagen confirmed the pronounced production of type I collagen by Ki-67-positive ACL-derived cells integrated into the ECM. A messenger RNA (mRNA) expression assay demonstrated significantly higher gene expression levels of types I (p = 0.013) and III (p = 0.050) collagen in the composites reseeded with ACL-derived cells than ADMSCs. CONCLUSION: ACL-derived cells, when reseeded to acellularized tendon graft, demonstrated earlier better survival and integration in the tendon ECM and resulted in higher gene expression levels of collagen, which may be essential to the normal ligamentization process compared to ADMSCs.Cite this article: Bone Joint Res 2022;11(11):777-786.

Effect of Muscle Cell Preservation on Viability and Differentiation of Hamstring Tendon Graft In Vitro.

Muscle tissue is often removed during hamstring tendon graft preparation for anterior cruciate ligament (ACL) reconstruction. The purpose of the study was to test whether preservation of muscle remnants on a tendon graft is beneficial to the graft healing process following ACL reconstruction. Co-culturing of tendon-derived cells (TDCs) and muscle-derived cells (MDCs) was performed at various ratios, and their potential for cell viability and multilineage differentiation was compared to a single TDC cell group. Ligamentous and chondrogenic differentiation was most enhanced when a small population of MDCs was co-cultured with TDCs (6:2 co-culture group). Cell viability and osteogenic differentiation were proportionally enhanced with increasing MDC population size. MDCs co-cultured with TDCs possess both the ability to enhance cell viability and differentiate into other cell lineages.

The Epidemiology and Trends of Primary Total Ankle Arthroplasty and Revision Procedure in Korea between 2007 and 2017.

BACKGROUND: The aim of this study was to investigate the surgical trends of primary total ankle arthroplasty (TAA) and revision procedure in Korea from 2007 to 2017 using national population-based data. METHODS: We reviewed the National Health Insurance data of Korea from 2007 to 2017. The data included diagnosis codes, procedure codes, prescriptions, medical costs, and other demographic data. Trends of primary diagnosis for primary TAA were evaluated. Annual trends and incidences per 100,000 person-years of primary TAA and revision procedures as well as compound annual growth rate (CAGR) during the study period were analysed. Surgical trends according to patients' age, hospital grades, and insurance systems were also evaluated. RESULTS: Primary diagnosis for primary TAA was mostly degenerative arthritis (6,501 cases; 90.5%). From 2007 to 2017, the total number of cases of primary TAA and revision procedures was 7,183 and 585, respectively. The number of cases in 2007 of primary TAA was 313; there were no cases of revision. The number of cases in 2017 of primary TAA were 986 and of revision were 108. The CAGR during this period was 28.6% for primary TAA and 44.6% for revision procedures. Incidences per 100,000 person-years in 2017 were 1.91 for primary TAA and 0.21 for revision procedures. The average cost paid by patients themselves was USD 813 (19%) and by the National Health Insurance Service was USD 3,480 (81%). CONCLUSION: The incidence of primary TAA and revision procedures steadily increases in Korea during the 11-year study period.

Extraskeletal osteosarcoma misdiagnosed as heterotopic ossification after periprosthetic femoral fracture: A case report.

Extraskeletal osteosarcoma is a malignant tumor of soft tissue characterized by osteoid production and has a very low prevalence, comprising approximately 4% of all osteosarcomas and about 1% of all soft tissue sarcomas, and a total of about 350 cases have been reported until now. Heterotopic ossification is a pathological finding of bony tissue in soft tissue regions such as muscle, skin and subcutaneous tissue. We report a case of an 86-year-old woman with a history of total hip arthroplasty (THA), in which open reduction and internal fixation were done for periprosthetic femoral Fracture. The ossified lesion misdiagnosed as heterotopic ossification initially was diagnosed as extraskeletal osteosarcoma at 6 months after the surgery. Both extraskeletal osteosarcoma and heterotopic ossification have no definite symptoms, but show radiopaque shadows on simple radiograph. Therefore, careful attention and thorough evaluation with multiple imaging tests may be necessary for the differential diagnosis of these entities.

Anterior cruciate ligament remnant cells have different potentials for cell differentiation based on their location.

Histological and cytological observations of the human anterior cruciate ligament (ACL) had been described, but the differentiation potency based on their location is still unknown. To determine and compare proliferation and differentiation potential of cells derived from distal and middle thirds of the ACL remnant, ACL remnant was initially marked at the distal third (within 10 mm from the tibial insertion) and middle third (between 10-20 mm from the tibial insertion) and then dissected. Both the middle and distal third regions of ACL remnant were analyzed using CD34+ cell counting. Cell proliferation rate did not differ in both middle and distal third regions of ACL remnant, but they showed different characteristics in cell differentiation depending on their location. The distal third region of the ACL remnant had a tendency for chondrogenic differentiation with higher expression of CD34+ cells. On the other hand, the middle third region of ACL remnant had a strong tendency for osteogenic and ligamentous differentiation. Characteristics of the ACL remnant tissues should be considered when performing remnant-preserving or harvesting ACL remnants for tissue engineering.

Application of acellular human dermis and skin grafts for lower extremity reconstruction.

OBJECTIVE: To use both acellular human dermis and skin grafting simultaneously for improved skin grafting without contracture. The study also aims to address the lack of research on the application of an acellular human dermis in diverse clinical cases. METHOD: The study examined patients who had received acellular human dermis (CGDerm, CGBio, Seoul, Korea) and split-thickness skin grafting (STSG) simultaneously for lower limb, full-thickness skin defects between September 2012 and June 2014. The researchers performed chart reviews retrospectively and examined the patients based on the following factors: gender, age, injury mechanism, size, exposed structure, pre-coverage dressing method, coverage method, post-operational engraftment and total healing period, contracture development, elasticity, and infection development. RESULTS: A sample of 27 patients with a total of 30 wounds took part in the study. Of these wounds, 29 showed successful engraftment without infection or contracture. In one case, continued seroma was observed and, following new coverage of both the acellular human dermis and STSG, engraftment was successful. CONCLUSION: Human dermis can play an important role in securing the availability of surrounding tissue and in contracture prevention, both of which are key to lower limb reconstruction. Of the types available, acellular human dermis showed lower infection rates than other human dermis types, and its engraftment rate was higher than in STSG-only cases. These findings suggest that acellular human dermis use in STSG is effective and safe in lower limb reconstruction.

The preliminary report about the modified supramalleolar tibial osteotomy for asymmetric ankle osteoarthritis.

OBJECTIVE: Supramalleolar tibial osteotomy (SMO) for asymmetric ankle osteoarthritis (OA) is known to lead to satisfactory. Here, authors present a preliminary report on SMO surgical treatment in patients with asymmetric ankle arthritis. MATERIALS AND METHODS: We reviewed cases of asymmetric ankle OA treated by modified SMO between January 2011 and October 2015. Clinical assessment was performed with the use of the ankle and hindfoot score of the American Orthopedic Foot and Ankle Society (AOFAS), foot function index, and visual analogue scale (VAS). Patient satisfaction with surgery and postoperative subjective symptoms were examined. Radiographic evaluation included preoperative and postoperative tibial anterior surface angle (TAS angle), talar tilt angle (TT angle), and tibial lateral surface angle (TLS angle). Takakura stage was measured. RESULTS: The average follow-up period was 46.3 months. The AOFAS score was 55.7 ± 6.03 preoperatively and 76.0 ± 4.73 postoperatively. Foot function index was 60.7 ± 8.78 preoperatively and 30.8 ± 7.59 postoperatively. VAS was 7.2 ± 0.53 before surgery and 1.9 ± 0.85 after surgery. Clinical evaluations showed statistically significant improvement. The majority of patients reported satisfactory results in the subjective satisfaction evaluation. TAS angle was 84.6 ± 1.82 preoperatively and 94.0 ± 2.79 postoperatively. TLS angle was 78.8 ± 2.11 preoperatively and 81.8 ± 1.80 postoperatively. TT angle was 3.6 ± 1.26 before surgery and 2.1 ± 0.79 after surgery. Thirteen cases showed radiographic improvement of Takakura stage. Complications were not observed. CONCLUSION: Modified SMO is a useful procedure that provides for the union and stability of osteotomy with the advantages of the existing SMO and can be performed without bone graft.

Digital Measurements With Hallux Valgus Before and After Modified Long Oblique Osteotomy.

Radiographic measurements of the hallux valgus (HV) angle (HVA) and the first intermetatarsal angle (IMA1-2) are important for assessing the severity of HV. The purpose of the present study was to digitally investigate the intraobserver and interobserver reliability of various methods for measuring HVA and IMA1-2, as well as each axis composing them, such as axes of the first proximal phalanx (PP1), the first metatarsal (MT1), and the second metatarsal (MT2) in patients with a metatarsal shaft osteotomy-modified long oblique osteotomy. Three orthopedic surgeons measured the HVA, IMA1-2, and the angles between axes of PP1, MT1, and MT2, and the digitally-set reference line (α, ß, and γ, respectively) using 6 different methods for 39 patients with a minimum of 1 year of follow-up after operative treatment. The intraobserver and interobserver intraclass correlation coefficients (ICC) and agreements were calculated. Significant differences were observed within the methods with regard to preoperative HVA, IMA1-2, α, and ß, and postoperative IMA1-2 and ß. Intraobserver and interobserver ICC were high or very high in most methods. For HVA and IMA1-2, the method connecting the center of the head through the center of the base showed the highest agreement. For α, ß, and γ, this method showed the highest agreement, more than 80% intraobserver and interobserver agreement and a discrepancy of <2°. A digital method connecting the center of the head through the center of the base was regarded as the least variable for the HV evaluation and the assessment of the radiographic results in a metatarsal shaft osteotomy-modified long oblique osteotomy.

Radiologic features in symptomatic/asymptomatic heels of patients with ankylosing spondylitis.

AIM: Most heel pain occurs at the posterior or plantar aspect, where main entheses of the heel are located. However, simple radiographs as basic work-up tools, their features based on their association with local symptoms in the heel in ankylosing spondylitis (AS) patients, have rarely been described. METHOD: Forty patients with AS and unilateral heel pain were enrolled to evaluate radiographic differences between symptomatic and asymptomatic heels. The two groups were assessed according to symptom location: posterior (group PS) or plantar (group PL). Typical abnormalities in bone and/or soft tissue on the heel due to inflammation were compared. RESULTS: In group PS (20 cases), 19 (95%) symptomatic feet and 7 (35%) asymptomatic feet showed abnormal findings on the posterior heel and symptomatic feet showed 6 (30%) plantar abnormalities. Erosion of the posterior calcaneal tuberosity, obliteration of the retrocalcaneal recess (RR), and swelling shadows with increased thickness on posterior soft tissue were observed more frequently and significantly in symptomatic feet in group PS (P < 0.05). In group PL (20 cases), 11 (55%) symptomatic feet and 8 (40%) asymptomatic feet showed abnormalities on the plantar heel and symptomatic feet showed 14 (70%) posterior abnormalities, and none showed significant differences between symptomatic and asymptomatic feet. CONCLUSION: Among simple radiographic alterations on heels with AS, such changes around the enthesis of the Achilles as bony erosion and RR obliteration with swollen posterior soft tissue are strongly related to current painful posterior heels. Assessment of enthesitis of the Achilles tendon in AS using plain radiography seems to be valid.

CCAAT/enhancer-binding protein beta (C/EBPß) is an important mediator of 1,25 dihydroxyvitamin D3 (1,25D3)-induced receptor activator of nuclear factor kappa-B ligand (RANKL) expression in osteoblasts.

Receptor activator of nuclear factor kappa B ligand (RANKL) expression in osteoblasts is regulated by 1,25-dihydroxyvitamin D3 (1,25D3). CCAAT/enhancer-binding protein beta (C/EBPß) has been proposed to function as a transcription factor and upregulate RANKL expression, but it is still uncertain how C/EBPß is involved in 1,25D3-induced RANKL expression of osteoblasts. 1,25D3 stimulation increased the expression of RANKL and C/EPBß genes in osteoblasts and enhanced phosphorylation and stability of these proteins. Moreover, induction of RANKL expression by 1,25D3 in osteoblasts was downregulated upon knockdown of C/EBPß. In contrast, C/EBPß overexpression directly upregulated RANKL promoter activity and exhibited a synergistic effect on 1,25D3-induced RANKL expression. In particular, 1,25D3 treatment of osteoblasts increased C/EBPß protein binding to the RANKL promoter. In conclusion, C/EBPß is required for induction of RANKL by 1,25D3. [BMB Reports 2019; 52(6): 391-396].

Lower Extremity Salvage with Thoracodorsal Artery Perforator Free Flap in Condition of Symmetrical Peripheral Gangrene.

Symmetrical peripheral gangrene (SPG) is rare but devastating complication which is characterized by symmetrical ischemic change of the distal extremities. In this report, we describe our management protocol for SPG, focusing on surgical approaches. Between January 2007 and February 2016, 10 thoracodorsal artery perforator (TDAP) free flaps were performed in 6 patients with SPG. Three patients were male and mean age was 56 (range, 44-69) years. All the patients were in shock. The causes of shock were sepsis in 4 cases, respiratory arrest in 1 case, and hypovolemia in 1 case. Eight transmetatarsal amputations and 2 Lisfranc amputations were performed. Flap sizes ranged from 7 × 11 cm to 25 × 15 cm. There were 3 cases of partial necrosis of the flap: two healed conservatively with dressings and one required skin graft. Three of the patients were later able to walk independently at Functional Ambulation Classification (FAC) level 6, one patient could walk independently on level surfaces at FAC level 5, and 2 could walk independently using walking aids, classified at FAC level 4. The average follow-up period was 18 (range, 6-54) months. In patients with SPG, minimal bone amputation and foot salvage with TDAP flaps were successful. Separate reconstruction of bone and soft tissue had good outcomes.

IL-17A induces osteoblast differentiation by activating JAK2/STAT3 in ankylosing spondylitis.

BACKGROUND: IL-17A has recently emerged as a potential target that regulates the extensive inflammation and abnormal bone formation observed in ankylosing spondylitis (AS). Blocking IL-17A is expected to inhibit bony ankylosis. Here, we investigated the effects of anti IL-17A agents in AS. METHODS: TNFα, IL-17A, and IL-12/23 p40 levels in serum and synovial fluid from patients with ankylosing spondylitis (AS), rheumatoid arthritis (RA), osteoarthritis (OA), or healthy controls (HC) were measured by ELISA. Bone tissue samples were obtained at surgery from the facet joints of ten patients with AS and ten control (Ct) patients with noninflammatory spinal disease. The functional relevance of IL-17A, biological blockades, Janus kinase 2 (JAK2), and non-receptor tyrosine kinase was assessed in vitro with primary bone-derived cells (BdCs) and serum from patients with AS. RESULTS: Basal levels of IL-17A and IL-12/23 p40 in body fluids were elevated in patients with AS. JAK2 was also highly expressed in bone tissue and primary BdCs from patients with AS. Furthermore, addition of exogenous IL-17A to primary Ct-BdCs promoted the osteogenic stimulus-induced increase in ALP activity and mineralization. Intriguingly, blocking IL-17A with serum from patients with AS attenuated ALP activity and mineralization in both Ct and AS-BdCs by inhibiting JAK2 phosphorylation and downregulating osteoblast-involved genes. Moreover, JAK2 inhibitors effectively reduced JAK2-driven ALP activity and JAK2-mediated events. CONCLUSIONS: Our findings indicate that IL-17A regulates osteoblast activity and differentiation via JAK2/STAT3 signaling. They shed light on AS pathogenesis and suggest new rational therapies for clinical AS ankylosis.

Reconstruction of diabetic lower leg and foot soft tissue defects using thoracodorsal artery perforator chimeric flaps.

BACKGROUND: Reconstruction of complicated diabetic lower leg and foot defects involving multiple tissue components remains a challenge. The purpose of this report is to introduce thoracodorsal artery perforator (TDAP) chimeric flaps for reconstructing diabetic lower leg and foot soft tissue defects. PATIENTS AND METHODS: Between April 2010 and August 2016, 17 patients with multiple diabetic lower leg and foot defects underwent reconstruction with TDAP chimeric flaps. Nine were women and the mean age of the patients was 57.7 years (range 35-73 years). One patient had 3 separate defects, 14 patients had 2 separate defects, and 2 patients had defects with dead space. The size of the defects ranged from 5 × 3 cm to 20 × 10 cm. RESULTS: Fifteen patients received TDAP chimeric flaps with two components (skin and muscle components), and two received three components (skin, latissimus dorsi (LD), and serratus anterior [SA] components). The skin paddle ranged from 10 × 3 cm to 25 × 14 cm. The LD components ranged from 3 × 5 cm to 20 × 10 cm and SA components ranged from 5 × 2 cm to 8 × 7 cm. All flaps survived except for partial loss of one muscle component. Four patients suffered postoperative complications including wound disruption and infection, all of which healed conservatively. The mean follow-up was 31.3 months (range 8-60 months). Fifteen patients were able to walk, one patient walked with walker, and one patient who had amputation due to Charcot joint infection walked with prosthesis. CONCLUSIONS: The TDAP chimeric flap may be another option for the complicated and complex wound coverage required to reconstruct diabetic lower leg and foot soft tissue defects.