Effects of corticosteroids and platelet-rich plasma on synoviocytes in IL-1ß-induced inflammatory condition.

AIMS: Corticosteroid injections are used to treat shoulder pain. Platelet-rich plasma (PRP) is known to have anti-inflammatory and anabolic effects, as well as cytoprotective effects against corticosteroids. Thus, this study was to investigate the effects of co-treatment of corticosteroid and PRP on anti-inflammatory and matrix homeostasis of synoviocytes in IL-1ß-induced inflammatory conditions. MATERIALS AND METHODS: Synoviocytes were cultured with 1 ng/mL IL-1ß, 1 µM dexamethasone, and 10% (vol/vol) Platelet-poor plasma (PPP), PRP200, PRP1000, and PRP4000 X 103/µL. Gene expressions of pro-inflammatory and anti-inflammatory cytokines, degradative enzymes, and their inhibitors were evaluated and protein synthesis of degradative enzymes and their inhibitors were also examined. RESULTS: Corticosteroid modulated anti-inflammatory and pro-inflammatory cytokines, and subsequent PRP treatment did not interfere with the effect of a corticosteroid and modulated the gene expressions of cytokines such as TNF-α and IL-4, which were not regulated by the corticosteroid alone. Gene expressions and protein expressions of degradative enzymes and their inhibitors were suppressed by corticosteroid. Additional PRPs did not alter the gene expression and protein regulated by the corticosteroid and inhibited the gene expression of ADAMTS-5 and protein synthesis of MMP-9 and ADAMTS-5, which were not modulated by the corticosteroid alone. CONCLUSION: Corticosteroid regulated the inflammation and synovial homeostasis. When PRP and the corticosteroid were used together, it exhibited synergistic effects on synoviocytes by regulating the parts that were not controlled by corticosteroid alone while not interfering with the effects of the corticosteroid in an inflammatory condition.

The diagnostic value of SPECT/CT in predicting the occurrence of osteonecrosis following femoral neck fracture: a prospective cohort study.

BACKGROUNDS: One of the most significant complications after a femoral neck fracture is osteonecrosis of the femoral head (ONFH). The concomitant use of single-photon emission computed tomography (SPECT) with computed tomography (CT) increases the sensitivity for detecting the anatomic location and severity of ONFH. In this study, we evaluated the diagnostic value of SPECT/CT for the occurrence of ONFH by quantifying the perfusion status of the femoral head. METHODS: A total of 30 patients who had multiple pinnings for femur neck fractures were included in this study. We classified the perfusion status into three groups: normal perfusion, decreased perfusion, and avascular groups, and compared the occurrence of femoral head necrosis between them. For quantitative analysis, we evaluated the uptake ratio of both femur heads (head-to-head uptake ratio). If the patient's contralateral hip was incomparable, we measured the uptake ratio from the superior dome of the ipsilateral acetabulum (head-to-acetabulum uptake ratio). RESULTS: Twenty-four patients out of 30 achieved bone union, whereas the others developed ONFH. When the population was divided into intact and defective perfusion groups on scintigraphy, the sensitivity, specificity, and accuracy of the test were 83.3, 75.0, and 76.7%, respectively. The mean head-to-head uptake ratio value with a 95% confidence interval (CI) was 1.10 (95% CI: 0.85-1.36). In the osteonecrosis group, the mean value of the head-to-head uptake ratio was 0.33 (95% CI: 0.28-0.38). In contrast, the ratio was 1.30 (95% CI: 1.03-1.57) in the non-osteonecrosis group, demonstrating a significant difference in the uptake ratio (P < 0.001). When the cutoff value of the uptake ratio was set to 0.5, both the sensitivity and specificity were 100%. There was also a significant difference in the head-to-acetabulum uptake ratio between the two groups (P <  0.001). CONCLUSIONS: SPECT/CT was useful in evaluating the perfusion status of the femoral head, showing high accuracy in predicting the occurrence of avascular necrosis. To demonstrate the reliability and validity of SPECT/CT, further prospective studies on a larger scale are warranted.

Intratendinous Injection of Mesenchymal Stem Cells for the Treatment of Rotator Cuff Disease: A 2-Year Follow-Up Study.

PURPOSE: To assess the mid-term safety and efficacy of an intratendinous injection of autologous adipose tissue-derived mesenchymal stem cells (AD MSCs) for rotator cuff disease at 2-year follow-up. METHODS: The first part of the study consisted of 3 dose-escalation groups, with 3 patients each, for the evaluation of safety: low-dose (1.0 × 107 cells), mid-dose (5.0 × 107), and high-dose (1.0 × 108) groups. For the second part, we planned to include 9 patients receiving the high dose for the evaluation of exploratory efficacy. Clinical outcomes were assessed according to pain, range of motion, muscle strength, functional scores, overall satisfaction and function, and presence of failure. Structural outcomes included changes in volume of tendon defects measured using magnetic resonance imaging. RESULTS: This study enrolled 19 patients (9 for the first part and 10 for the second part) with partial-thickness rotator cuff tears. There were no treatment-related adverse events at minimum 2-year follow-up. Intratendinous injection of AD MSCs reduced shoulder pain by approximately 90% at 1 and 2 years in the mid- and high-dose groups. The strength of the supraspinatus, infraspinatus, and teres minor significantly increased by greater than 50% at 2 years in the high-dose group. Shoulder function measured with 6 commonly used scores improved for up to 2 years in all dose groups. Structural outcomes evaluated with magnetic resonance imaging showed that the volume of bursal-sided defects in the high-dose group nearly disappeared at 1 year and did not recur at up to 2 years. No failures-defined as the performance of any kind of shoulder surgery or return of the Shoulder Pain and Disability Index score to the preinjection level-occurred during follow-up. CONCLUSIONS: This study showed continued safety and efficacy of an intratendinous injection of AD MSCs for the treatment of partial-thickness rotator cuff tears over a 2-year period through regeneration of tendon defects. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Intratendinous Injection of Autologous Adipose Tissue-Derived Mesenchymal Stem Cells for the Treatment of Rotator Cuff Disease: A First-In-Human Trial.

Despite relatively good results of current symptomatic treatments for rotator cuff disease, there has been an unmet need for fundamental treatments to halt or reverse the progress of disease. The purpose of this study was to assess the safety and efficacy of intratendinous injection of autologous adipose tissue-derived mesenchymal stem cells (AD MSCs) in patients with rotator cuff disease. The first part of the study consists of three dose-escalation cohorts; the low- (1.0 × 107 cells), mid- (5.0 × 107 ), and high-dose (1.0 × 108 ) groups with three patients each for the evaluation of the safety and tolerability. The second part included nine patients receiving the high-dose for the evaluation of the exploratory efficacy. The primary outcomes were the safety and the shoulder pain and disability index (SPADI). Secondary outcomes included clinical, radiological, and arthroscopic evaluations. Twenty patients were enrolled in the study, and two patients were excluded. Intratendinous injection of AD MSCs was not associated with adverse events. It significantly decreased the SPADI scores by 80% and 77% in the mid- and high-dose groups, respectively. Shoulder pain was significantly alleviated by 71% in the high-dose group. Magnetic resonance imaging examination showed that volume of the bursal-side defect significantly decreased by 90% in the high-dose group. Arthroscopic examination demonstrated that volume of the articular- and bursal-side defects decreased by 83% and 90% in the mid- and high-dose groups, respectively. Intratendinous injection of autologous AD MSCs in patient with a partial-thickness rotator cuff tear did not cause adverse events, but improved shoulder function, and relieved pain through regeneration of rotator cuff tendon. Stem Cells 2018;36:1441-1450.

Intra-articular injection of mesenchymal stem cells for the treatment of osteoarthritis of the knee: a proof-of-concept clinical trial.

Mesenchymal stem cells (MSCs) are known to have a potential for articular cartilage regeneration. However, most studies focused on focal cartilage defect through surgical implantation. For the treatment of generalized cartilage loss in osteoarthritis, an alternative delivery strategy would be more appropriate. The purpose of this study was to assess the safety and efficacy of intra-articular injection of autologous adipose tissue derived MSCs (AD-MSCs) for knee osteoarthritis. We enrolled 18 patients with osteoarthritis of the knee and injected AD MSCs into the knee. The phase I study consists of three dose-escalation cohorts; the low-dose (1.0 × 10(7) cells), mid-dose (5.0 × 10(7)), and high-dose (1.0 × 10(8)) group with three patients each. The phase II included nine patients receiving the high-dose. The primary outcomes were the safety and the Western Ontario and McMaster Universities Osteoarthritis index (WOMAC) at 6 months. Secondary outcomes included clinical, radiological, arthroscopic, and histological evaluations. There was no treatment-related adverse event. The WOMAC score improved at 6 months after injection in the high-dose group. The size of cartilage defect decreased while the volume of cartilage increased in the medial femoral and tibial condyles of the high-dose group. Arthroscopy showed that the size of cartilage defect decreased in the medial femoral and medial tibial condyles of the high-dose group. Histology demonstrated thick, hyaline-like cartilage regeneration. These results showed that intra-articular injection of 1.0 × 10(8) AD MSCs into the osteoarthritic knee improved function and pain of the knee joint without causing adverse events, and reduced cartilage defects by regeneration of hyaline-like articular cartilage.

Subchondral insufficiency fracture of the femoral head in elderly people.

We evaluated the clinical course of subchondral insufficiency fracture of the femoral head (SIFFH) and its characteristic findings with special regard to joint space narrowing (JSN). Thirty-one cases of SIFFH of mean age 68.9 yr initially underwent limited weight-bearing conservative treatment. During the follow-up period, the patients with intractable pain underwent total hip arthroplasty (THA). For radiographic evaluation, lateral center-edge angle, JSN and femoral head collapse (FHC) were documented, and the extent of FHC was classified as mild (<2 mm), moderate (2-4 mm), and severe (>4 mm). The progression or new development of FHC more than 2 mm was evaluated on sequential plain radiographs. The relationship between radiographic parameters and clinical outcomes were evaluated. THAs were performed in 15 cases (48.4%). There was no significant correlation between clinical outcomes and the extent of initial FHC. However, a significantly larger proportion of patients that underwent THA showed JSN and FHC progression compared to the symptom improvement group. The risk factor significantly associated with failed conservative treatment was JSN (P=0.038; OR, 11.8; 95% CI, 1.15-122.26). Clinical results of conservative treatment for SIFFH in elderly patients are relatively poor. The patients with JSN are at higher risk of failed conservative treatment.

Epidemiology of hip replacements in Korea from 2007 to 2011.

We analyzed national data collected by the Health Insurance Review and Assessment Service in Korea from 2007 to 2011; 1) to document procedural numbers and procedural rate of bipolar hemiarthroplasty (BH), primary and revision total hip arthroplasties (THAs), 2) to stratify the prevalence of each procedure by age, gender, and hospital type, and quantified, 3) to estimate the revision burden and evaluate whether the burden is changed over time. Our final study population included 60,230 BHs, 40,760 primary THAs, and 10,341 revision THAs. From 2007 to 2011, both the number and the rate of BHs, primary THAs increased steadily, whereas there was no significant change in revision THAs. Over the 5 yr, the rate of BHs and primary THAs per 100,000 persons significantly increased by 33.2% and 21.4%, respectively. The number of revision THAs was consistent over time. The overall annual revision burden for THA decreased from 22.1% in 2007 to 18.9% in 2011. In contrast to western data, there were no changes in the number and rate of revision THAs, and the rates of primary and revision THAs were higher for men than those for women. Although 5 yr is a short time to determine a change in the revision burden, there have been significant decreases in some age groups.

Revision of ceramic head fracture after third generation ceramic-on-ceramic total hip arthroplasty.

We performed 24 revisions of fractures of third generation ceramic heads. The stem was not changed in 20 revisions; a new ceramic-on-ceramic bearing was used in four and a metal-on-polyethylene bearing in 16. The stem was changed in four revisions; a new ceramic-on-ceramic bearing was used in three and a metal-on-polyethylene bearing in one. During the follow-up of 57.5 months, complications occurred in five hips among the 20 stem retained revisions: a fracture of the new ceramic head in two, metallosis with pseudocyst in two, and femoral osteolysis with stem loosening in one. However, there were no complications in the four revisions where the stem was changed. Revision surgery after ceramic head fracture shows high rates of early complications. We recommend stem revision in cases of THA failure due to fracture of a modern ceramic head.

Comparative evaluation of in vivo osteogenic differentiation of fetal and adult mesenchymal stem cell in rat critical-sized femoral defect model.

Mesenchymal stem cells (MSCs) can be obtained from various sources. MSCs from different origins appear to have different preferences for differentiation. In this study, we have compared the in vivo osteogenic potential of adult MSCs from adipose tissue (AT) and bone marrow (BM) with fetal MSCs from umbilical cord (UC) and umbilical cord blood (UCB) by using a rat critical-sized femoral defect model. We have also sought to determine whether pretreatment with an osteogenic medium promotes osteogenesis in MSCs. Study groups were divided as follows: (1) defect only, (2) scaffold only, (3) AT MSCs in scaffolds, (4) BM MSCs in scaffolds, (5) UC MSCs in scaffolds and (6) UCB MSCs in scaffolds. Groups with MSCs were further divided with respect to their pretreatment. At 12 weeks after surgery, in vivo osteogenesis was measured radiographically and by micro-computed tomography (CT). Based on quantitative assessment by micro-CT, no significant difference of the mean bone volume fraction value (BV/TV) was seen between adult MSCs (AT and BM MSCs) and fetal MSCs (UC and UCB MSCs). The mean BV/TVs were significantly higher in non-pretreated BM MSC (14.2±1.4%) and UCB MSC (14.0±1.2%) and pretreated UC MSC (14.8±2.0%) than in those with the scaffold only (11.3±1.3%; P<0.05). In addition, AT (from 10.4±1.2% to 13.1±2.2%) and UC (from 10.3±0.7% to 14.8±2.0%) MSCs from solid tissues showed a significant increase in the mean BV/TV with pretreatment (P<0.05). In contrast, BM MSC (from 14.2±1.4% to 10.9±1.2%) and UCB MSC (from 14.0±1.2% to 11.6±1.0%) from non-solid tissues showed a significant decrease with pretreatment (P<0.05).

Revision total hip arthroplasty using an alumina-on-alumina bearing surface in patients with osteolysis.

We evaluated the outcomes of 64 consecutive revision total hip arthroplasties with an alumina-on-alumina bearing surface in 61 patients with osteolysis. No implants had been rerevised nor was osteolysis detected at a mean of 9.8 years (range, 7.0-13.1 years) postoperatively. There was 1 case of stem loosening but no cup loosening or alumina bearing fractures. Two surgical procedures were performed for an infection in 1 patient. Three dislocations occurred in 3 hips; all were treated with closed reduction and abduction bracing for 3 months. No further dislocations occurred. With any reoperation or radiographic evidence of osteolysis or loosening as the end point, the 7-year survival rate was 96.9% (95% confidence interval, 90.8%-100%). The alumina-on-alumina bearing surfaces used for revision total hip arthroplasty in patients with osteolysis were found to produce encouraging clinical results and implant survival rates at a minimum of 7 years postoperatively.

Optimizing platelet-rich plasma gel formation by varying time and gravitational forces during centrifugation.

Despite the increasing clinical use of topical platelet-rich plasma (PRP) to enhance tissue healing and regeneration, there is no properly standardized method of autologous PRP gel preparation. This study examined the effect of the centrifugation time and gravitational force (g) on the platelet recovery ratio of PRP and determined the most effective centrifugation conditions for preparing PRP. Two-step centrifugations for preparing PRP were used in 39 subjects who had consented prior to the study's start. The separating centrifugation (Step 1, used to separate whole blood into its two main components: red blood cells and plasma) was tested from 500g to 1900g at 200g increments for 5 minutes (min), and from 100g to 1300g at 200g increments for 10 minutes. After separating centrifugation, upper plasma layer was transferred to another plain tube for the condensation centrifugation and remaining lower cell layer was discarded. The condensation centrifugation (Step 2, used to condense the platelets in the separated plasma) was tested at 1000g for 15 min, 1500g for 15 min, 2000g for 5 min and 3000g for 5 min, additionally at 1000g for 10 min and 1500g for 10 min. Platelet gelation was induced by adding 10% calcium gluconate to final PRP with volume ratio of 1:10. The optimal separating centrifugation conditions were followed by 900g for 5 minutes and the condensation conditions were followed by 1500g for 15 minutes, of which recovery ratios were 92.0 ± 3.1% and 84.3 ± 10.0%, respectively.

Case report: multifocal subchondral stress fractures of the femoral heads and tibial condyles in a young military recruit.

BACKGROUND: Subchondral stress fractures of the femoral head may be either of the insufficiency-type with poor quality bone or the fatigue-type with normal quality bone but subject to high repetitive stresses. Unlike osteonecrosis, multiple site involvement rarely has been reported for subchondral stress fractures. We describe a case of multifocal subchondral stress fractures involving femoral heads and medial tibial condyles bilaterally within 2 weeks. CASE DESCRIPTION: A 27-year-old military recruit began having left knee pain after 2 weeks of basic training, without any injury. Subsequently, right knee, right hip, and left hip pain developed sequentially within 2 weeks. The diagnosis of multifocal subchondral stress fracture was confirmed by plain radiographs and MR images. Nonoperative treatment of the subchondral stress fractures of both medial tibial condyles and the left uncollapsed femoral head resulted in resolution of symptoms. The collapsed right femoral head was treated with a fibular strut allograft to restore congruity and healed without further collapse. LITERATURE REVIEW: There has been one case report in which an insufficiency-type subchondral stress fracture of the femoral head and medial femoral condyle occurred within a 2-year interval. CLINICAL RELEVANCE: Because the incidence of bilateral subchondral stress fractures of the femoral head is low and multifocal involvement has not been reported, multifocal subchondral stress fractures can be confused with multifocal osteonecrosis. Our case shows that subchondral stress fractures can occur in multiple sites almost simultaneously.

Alumina-on-alumina THA performed in patients younger than 30 years: a 10-year minimum followup study.

BACKGROUND: THA in patients younger than 30 years presents challenges because of uncertainties regarding the long-term survivorship of prostheses. Alumina-on-alumina bearings, which exhibit little long-term wear, may be a reasonable option but the long-term survivorship is unknown. QUESTIONS/PURPOSES: We determined (1) the survival rate of alumina-on-alumina bearings in patients younger than 30 years after a 10-year followup, (2) the incidence of audible hip clicking and squeaking, (3) radiographic evidence of osteolysis, and (4) the effects on pregnancy, childbirth, and career choice. METHODS: We retrospectively reviewed 62 patients who had 75 THAs with alumina-on-alumina bearings followed more than 10 years (average, 11.5; range, 10-13.5 years). Mean patient age at the time of surgery was 24 years (range, 18-30 years). All operations were performed using the same cementless implant at a single center. We determined survival, presence of osteolysis, and function (Harris hip score, WOMAC). RESULTS: The 10-year survival rate of alumina-on-alumina bearings in THAs, with revision for any reason as the end point, was 98.9%. Audible hip clicking and squeaking were identified in 10 hips and two hips, respectively. No osteolysis was detected. None of the 11 patients who became pregnant had been affected by their THA during pregnancy or childbirth. Seven of the 14 patients who were unemployed at the time of index surgery stated that their THA affected their job choice. CONCLUSIONS: We found a high 10-year survival of cementless alumina-on-alumina bearings in THAs in patients younger than 30 years. Lifetime events such as job choice, pregnancy, and childbirth should be considered when choosing THA for patients younger than 30 years. LEVEL OF EVIDENCE: Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

Malignant fibrous histiocytoma at the site of an alumina-on-alumina-bearing total hip arthroplasty mimicking infected trochanteric bursitis.

Although the incidence of malignant tumors in patients undergoing total hip arthroplasties (THAs) is known to be lower than the general population, there exist several reports on the development of malignant tumors at the site of THAs. We report another case of malignant fibrous histiocytoma at the site of a THA, which was developed in an older patient who presented a cystic mass around the total hip prosthesis using a ceramic-on-ceramic bearing system, even without evidence of osteolysis or loosening of implants. This is the second case associated with an aluminum oxide prosthesis in English literature.

The effect of tranexamic acid in open reduction and internal fixation of pelvic and acetabular fracture: A systematic review and meta-analysis.

BACKGROUND: Pelvic bone fractures may cause extensive bleeding; however, the efficacy of tranexamic acid (TXA) usage in pelvic fracture surgery remains unclear. In this systematic review and meta-analysis, we aimed to evaluate the efficacy of TXA in open reduction and internal fixation surgery for pelvic and acetabular fracture. METHODS: MEDLINE, Embase, and Cochrane Library databases were systematically searched for studies published before April 22, 2020, that investigated the effect of TXA in the treatment of pelvic and acetabular fracture with open reduction and internal fixation. A pooled analysis was used to identify the differences between a TXA usage group and a control group in terms of estimated blood loss (EBL), transfusion rates, and postoperative complications. RESULTS: We included 6 studies involving 764 patients, comprising 293 patients who received TXA (TXA group) and 471 patients who did not (control group). The pooled analysis showed no differences in EBL between the groups (mean difference -64.67, 95% confidence interval [CI] -185.27 to -55.93, P = .29). The study period transfusion rate showed no significant difference between the groups (odds ratio [OR] 0.77, 95% CI 0.19-3.14, P = .71, I2 = 82%), nor in venous thromboembolism incidence (OR 1.53, 95% CI 0.44-5.25, P = .50, I2 = 0%) or postoperative infection rates (OR 1.15, 95% CI 0.13-9.98, P = .90, I2 = 48%). CONCLUSIONS: Despite several studies having recommended TXA administration in orthopedic surgery, our study did not find TXA usage to be more effective than not using TXA in pelvic and acetabular fracture surgery, especially in terms of EBL reduction, transfusion rates, and the risk of postoperative complications.

The effect of multiple channeling on the structural integrity of repaired rotator cuff.

PURPOSE: The purpose of this study was to investigate the effect of adding multiple channeling of the greater tuberosity on the structural integrity of the repaired rotator cuff tendon. METHODS: Fifty-six consecutive patients who underwent arthroscopic rotator cuff repair and postoperative computed tomography arthrography (CTA) were included in this study; 31 consecutive patients that underwent conventional repair and 25 subsequent patients that underwent conventional repair with multiple channeling. Using CTA, the repaired rotator cuff was evaluated as either intact, incomplete, or complete leakage at the insertion and in the tendon separately. The integrity type and overall integrity was then determined by the combination of the insertion and tendon grade. Factors affecting integrity were also evaluated. RESULTS: At the insertion, multiple channeling significantly improved integrity; complete leakage in 35.5% in the conventional group and 4.0% in the multiple channeling group (P = 0.017). In the tendon, no significant difference was observed between the two groups. Integrity types were significantly different between the two groups (P = 0.009). For overall integrity, discontinuity was more frequently identified in the conventional group (35.5%) than in the multiple channeling group (16.0%), but it was not statistically significant. With regard to causes of discontinuity, all were due to retears in the conventional group, while 75% were due to new tears in the multiple channeling group (P = 0.009). CONCLUSION: Multiple channeling is simple and easily performed without any special instrument and might augment the healing of repaired rotator cuff tendons. It could be a useful technique in rotator cuff repair helping healing.

Two-stage total hip arthroplasty following skeletal traction after extensive soft tissue release for severe limb-length discrepancy.

INTRODUCTION: To maximise limb-length discrepancy (LLD) resolution during total hip arthroplasty (THA) for untreated developmental hip dysplasia or septic hip sequelae, THA following limb lengthening was introduced using different methods. We aimed to evaluate 2-stage THA results following limb lengthening via skeletal traction after extensive soft tissue release. METHOD: In total, 24 hips with severe LLD in 10 men and 14 women (mean age, 49.6 ± 15.2 years) underwent 2-stage THA and were followed thereafter (mean 6.3 ± 3.7 years). The entire abductor muscle origin was subperiosteally released from the ilium, and the soft tissue around the hip joint, including the psoas tendon, short external rotator, joint capsule, and adductor tendon, was extensively released. 2-stage THA was performed after 2-week skeletal traction using proximal tibial pins. During the final THA, 7 hips necessitated subtrochanteric shortening osteotomy (STO) for hip joint reduction. We evaluated the clinical and radiological results and especially focused on LLD and neurological complications. RESULTS: The Harris Hip Score improved from 57.1 ± 9.6 to 88.3 ± 6.3 points. No patients showed worse abductor power. LLD improved from 5.0 ± 2.0 to 1.4 ± 1.0 cm. No permanent neurological complications occurred except for 1 transient peroneal nerve palsy during traction, which resolved fully after cessation of traction. There were 2 hips with STO nonunion treated with osteosynthesis and stem revision. CONCLUSION: 2-stage THA following skeletal traction after extensive soft tissue release showed favourable results in terms of neurologic complication prevention and LLD resolution. However, a large proportion of patients still necessitated shortening osteotomy with a risk for nonunion at the osteotomy site. Though surgical procedures might be complicated and necessitate longer hospital stays, 2-stage THA with extensive soft tissue release might be an alternative treatment option for patients with severe LLD willing to resolve their limb length discrepancy.

Allogenic Pure Platelet-Rich Plasma Therapy for Adhesive Capsulitis: A Bed-to-Bench Study With Propensity Score Matching Using a Corticosteroid Control Group.

BACKGROUND: While platelet-rich plasma (PRP) has been widely studied for musculoskeletal disorders, few studies to date have reported its use for adhesive capsulitis (AC). Fully characterized and standardized allogenic PRP may provide clues to solve the underlying mechanism of PRP with respect to synovial inflammation and thus may clarify its clinical indications. PURPOSE: To clinically evaluate the safety and efficacy of a fully characterized pure PRP injection in patients with AC and to assess the effects of pure PRP on synoviocytes with or without inflammation in vitro. STUDY DESIGN: Controlled laboratory study and cohort study; Level of evidence, 3. METHODS: For the clinical analysis, a total of 15 patients with AC received an ultrasonography-guided intra-articular PRP injection and were observed for 6 months. Pain, range of motion (ROM), muscle strength, shoulder function, and overall satisfaction in the patients were evaluated using questionnaires at 1 week as well as at 1, 3, and 6 months after the PRP injection and results were compared with the results of a propensity score-matched control group that received a corticosteroid injection (40 mg triamcinolone acetonide). For the in vitro analysis, synoviocytes were cultured with or without interleukin-1ß (IL-1ß) and PRP. The gene expression of proinflammatory and anti-inflammatory cytokines as well as matrix enzymes and their inhibitors was evaluated. RESULTS: At 6-month follow-up, pure PRP significantly decreased pain and improved ROM, muscle strength, and shoulder function to levels comparable with those after a corticosteroid injection. All pain values, strength measurements, and functional scores significantly improved up to 6 months in the PRP group, but these measures improved up to 3 months and then were decreased at 6 months in the corticosteroid group. ROM was significantly improved in the 2 groups at 6 months compared with baseline. Allogenic PRP did not cause adverse events. For the in vitro findings, PRP induced inflammation but significantly improved the IL 1ß-induced synovial inflammatory condition by decreasing proinflammatory cytokines such as IL-1ß, tumor necrosis factor-α, IL-6, cyclooxygenase-2, and microsomal prostaglandin E synthase-1 and decreased matrix enzymes (matrix metalloproteinase-1, -3, and -13 as well as a disintegrin and metalloproteinase with thrombospondin motifs-4 and -5) and further increasing anti-inflammatory cytokines such as vasoactive intestinal peptide. CONCLUSION: This study showed that PRP decreased pain and improved shoulder ROM and function to an extent comparable with that of a corticosteroid in patients with AC. Allogenic pure PRP acted in a pleiotropic manner and decreased proinflammatory cytokines only in the inflammatory condition. CLINICAL RELEVANCE: Allogenic PRP could be a treatment option for the inflammatory stage of AC.

Culture-Expanded Autologous Adipose-Derived Mesenchymal Stem Cell Treatment for Osteonecrosis of the Femoral Head.

BACKGROUD: Outcomes of traditional treatment for osteonecrosis of the femoral head (ONFH) are not always satisfactory. Hence, cell-supplementation therapy has been attempted to facilitate necrotic-tissue regeneration. Adipose-derived mesenchymal stem cell (ADMSC) transplantation is potentially advantageous over bone marrow-derived MSC implantation, but its outcomes for ONFH remain unclear. The aim of this study was to determine 2-year radiological and clinical outcomes of culture-expanded autologous ADMSC implantation for ONFH. METHODS: Eighteen hips with necrotic lesions involving ≥ 30% of the femoral head were included. ADMSCs were harvested by liposuction and culture expanded for 3 passages over 3 weeks. With a 6-mm single drilling, ADMSCs were implanted into the necrotic zone. All patients underwent magnetic resonance imaging (MRI), single-photon emission computed tomography/computed tomography (SPECT/CT) at screening and 6 months, 12 months, and 24 months postoperatively. The primary outcome was the change in the size of necrotic area on MRI. Secondary outcomes were changes in clinical scores and radioisotope uptake on SPECT/CT. Conversion total hip arthroplasty (THA) was defined as the endpoint. RESULTS: Preoperatively, the necrotic lesion extent was 63.0% (38.4%-96.7%) of the femoral head. The mean Harris hip score was 89.2, the University of California at Los Angeles (UCLA) score was 5.6, and Western Ontario and McMaster Universities Arthritis index (WOMAC) was 79.4. Three patients underwent THA and 1 patient died in an accident. Finally, 11 patients (14 hips) were available for ≥ 2-year follow-up. At the last follow-up, no surgery-related complications occurred, and 14 of 17 hips (82%) were able to perform daily activities without THA requirement. There was no significant decrease in lesion size between any 2 intervals on MRI. However, widening of high signal intensity bands on T2-weighted images inside the necrotic lesion was observed in 9 of 14 hips (64%); 11 of 14 hips (79%) showed increased vascularity on SPECT/CT at 2 years postoperatively. No significant differences were observed between preoperative and 24-month mean Harris hip score (89.2 vs. 88.6), WOMAC (79.4 vs. 75.7), and UCLA score (5.6 vs. 6.2). CONCLUSIONS: Our outcomes suggest that culture-expanded ADMSC implantation is a viable option for ONFH treatment without adverse events.

Differences in donor CXCR4 expression levels are correlated with functional capacity and therapeutic outcome of angiogenic treatment with endothelial colony forming cells.

CXCR4 expression is important for cell migration and recruitment, suggesting that the expression levels of CXCR4 may be correlated with functional activity of implanted cells for therapeutic neovascularization. Here, we examined differences between umbilical cord blood (CB) donors in the CXCR4 levels of endothelial colony forming cells (ECFCs), which are a subtype of endothelial progenitor cells (EPCs). We investigated the relationships between CXCR4 expression level and SDF-1alpha-induced vascular properties in vitro, and their in vivo contributions to neovascularization. We found that ECFCs isolated from different donors showed differences in CXCR4 expression that were linearly correlated with SDF-1alpha-induced migratory capacity. ECFCs with high CXCR4 expression showed enhanced ERK and Akt activation in response to SDF-1alpha. In addition, SDF-1alpha-induced migration and ERK1/2, Akt, and eNOS activation were reduced by AMD3100, a CXCR4-specific peptide antagonist, or by siRNA-CXCR4. Administration of high-CXCR4-expressing ECFCs resulted in a significant increase in therapeutic potential for blood flow recovery, tissue healing and capillary density compared to low-CXCR4-expressing ECFCs in hindlimb ischemia. Taken together, the functional differences among ECFCs derived from different donors depended on the level of CXCR4 expression, suggesting that CXCR4 expression levels in ECFCs could be a predictive marker for success of ECFC-based angiogenic therapy.