Introduction:. The outcome of previous cemented total hip arthroplasty has been reported to be inferior in renal transplant patients because of poor bone stock resulting from long-term steroid use. Moreover, as renal transplant patients remain on immunosuppressant therapy for life, higher levels of overall morbidity must be considered. We evaluated the mid-term results of cementless total hip arthroplasty in renal transplant recipients with osteonecrosis of the femoral head, and compared those with age and sex matched osteonecrosis patients that had not undergone organ transplantation or been treated with long-term steroid. Materials & Methods:. Between October 1997 and October 2008, 45 consecutive primary cementless total hip arthroplasties were performed in 30 patients with advanced osteonecrosis of the femoral head after renal transplantation. There were 18 males (27 hips) and 12 females (18 hips) of overall mean age 44 years (22 to 68). The clinical and radiographic results of cementless total hip arthroplasty in these 45 hips were compared with those of 96 sex and age-matched osteonecrotic hips of 72 patients that had not undergone organ transplantation or long-term steroid use. Patients were evaluated at surgery and at a mean of 7.2 years (range, 2–13 years) postoperatively. Results:. The mean Harris hip score of patients improved from 48 points preoperatively to 94 points at last follow-up (p < 0.05). Three hips in patient group had massive osteolysis with polyethylene wear requiring revision surgery. One hip in the patient group underwent revision surgery because of recurrent dislocation at 11 years postoperatively. No intergroup differences in overall rates of complications or revisions were observed. However, patients had a significantly higher rate of ectopic ossification. Conclusion:. Despite diffuse osteopenia and chronic immunosuppression in renal transplant patients with osteonecrotic hips, contemporary cementless total hip arthroplasty showed durable implant fixation to bone and did not increase complications

Introduction:. Over the last several decades, life expectancy following solid organ transplant (i.e. kidney, liver, heart, lung, and pancreas) has increased significantly, largely due to improvements in surgical technique, immunosuppressive regimens, patient selection, and postoperative care. As this population ages, many of these transplant patients become candidates for total knee arthroplasty (TKA). However, these patients may be at greater risk of complications following TKA due to immunosuppression and metabolic derangements secondary to organ dysfunction. The purpose of this study was to use a large, nationally representative database to compare morbidity, mortality, length of stay (LOS), and charges for TKA patients with and without a history of solid organ transplant. Methods:. This retrospective study was a review of the Nationwide Inpatient Sample (NIS; the largest all-payer inpatient care United States database representing a 20% stratified sample) from 1998 to 2010. Patients who had a primary TKA (ICD-9-CM 81.54) were included (n = 5,706,675, weighted national frequency). A total of 763,924 cases were excluded for the following: age <18 years, pathologic fracture of lower extremity, malignant neoplasm and/or metastatic cancer, previous and/or bilateral arthroplasty, admission type other than “elective”. The remaining 4,942,751 patients were categorized as transplant (n = 5,245; included only liver, kidney, heart, lung and/or pancreas transplant) or non-transplant group (n = 4,931,017; no history of any transplant including solid organ or tissue). A multivariable regression model was used to identify any association(s) between a history of solid organ transplant and morbidity, mortality, LOS and hospital charges, while adjusting for patient and hospital characteristics. Results:. Between 1998 and 2010, the volume of TKA increased among transplant patients at a rate of 382%, which was significantly higher than that of the non-transplant group (197%; p < 0.01). Patients with a history of transplant had a significantly higher prevalence of renal failure (+69.3%), liver disease (+22.9%), uncomplicated diabetes (+9.0%), hypertension (+8.9%), deficiency anemia (+8.9%) (p < 0.001). Transplant patients suffered 1 or more complication at a rate of 7.3%, which was significantly higher than that of the non-transplant group (5.7%; p < 0.001). A 0.1% mortality rate was observed in the non-transplant group, while no deaths were reported in the transplant group. Unadjusted trends for mean LOS (Figure 1) show that transplant patients have a longer LOS (4.2 days) than non-transplant patients (3.7 days; p < 0.001), although LOS decreased for both groups. Overall mean charges per admission (USD) were significantly higher for the transplant cohort ($ 40,999) than the non-transplant group ($ 35,686; p < 0.001), and both increased over time (Figure 2). After adjusting for patient demographics, hospital characteristics, and comorbidity, transplant patients stayed 0.46 days longer in the hospital (p < 0.01) and had $ 3,480 increased charges (p < 0.01). There was no statistically significant increase in hospital complications (adjusted odds ratio = 1.20; p = 0.13). Conclusions:. While the annual number of TKAs performed in the United States on patients with a history of solid organ transplant is relatively low, the rate is increasing at nearly twice that of non-transplant patients undergoing TKA. Transplant patients have a significantly higher number of comorbidities, longer LOS, and greater charges than patients with no transplant history

Introduction:. Solid organ transplant patients are living longer than in past decades, largely due to improvements in surgical technique, immunosuppressive regimens, patient selection, and postoperative care. As these patients grow older, many of them present for total hip arthroplasty (THA). However, life-long immunosuppressive therapy, metabolic disorders, and post-transplant medications may place transplant patients at higher risk for complications following THA. The objective of this study was to use a national administrative database to compare morbidity, acute complications, in-hospital mortality, length of stay (LOS), and admission costs for THA patients with and without solid organ transplant history. Methods:. The Nationwide Inpatient Sample (NIS), the largest all-payer inpatient care database representing a 20% stratified sample of United States hospitals, was retrospectively queried for primary THA (ICD-9-CM 81.51) patients from 1998 to 2009 (n = 2,567,930; weighted national frequency). Cases were excluded (n = 324,837) for the following: age <18 years, pathologic fracture of lower extremity, malignant neoplasm and/or metastatic cancer, primary diagnosis of femoral neck fracture, admission type other than “elective,” previous and/or bilateral arthroplasty. The remaining 2,243,093 THA patients were assigned to transplant (n = 6,319; liver, kidney, heart, lung and/or pancreas transplant history) or non-transplant groups (n = 2,231,446; no history of any transplant including solid organ or tissue). Acute complications included a variety of organ-specific and procedure-related complications (i.e. mechanical implant failure, dislocation, hematoma, infection, pulmonary embolism, venous thrombosis). Multivariable regression and general estimating equations were developed to study the effect of transplant history on outcomes, adjusting for patient/hospital characteristics and comorbidity. Results:. Between 1998 and 2009, the volume of THA among patients with a history of solid organ transplant grew approximately 40% (444 to 620 cases/year), which was lower than that among non-transplant patients (+102%). Transplant THA patients were significantly sicker than their non-transplant peers, with an elevated Elixhauser comorbidity index (7.69 vs. 1.21; p < 0.001). Transplant and non-transplant patients had similar rates of 1+ inpatient complication(s) following THA (transplant 23.6% vs. non-transplant 24.3%; p = 0.60). There were no in-hospital deaths in the transplant group, while 0.1% (n = 2,855) of non-transplant patients died after THA. Unadjusted trends show that transplant patients have a longer mean LOS (4.5 days) than non-transplant patients (3.9 days; p < 0.001) after THA, although LOS decreased for both groups over time (Figure 1). Also, overall unadjusted mean costs per THA admission were significantly higher for the transplant cohort ($15,518) than the non-transplant group ($14,474; p < 0.001), and both increased over time (Figure 2). After adjusting for confounders, transplant patients had an 8% increase in LOS (0.38 days) compared to non-transplant patients (p < 0.001); however, there were no statistically significant increases in admission costs (p = 0.13) or complications (p = 0.19). Conclusions:. While the annual volume of THA performed in the United States on patients with a history of solid organ transplant is increasing, the rate is less than half that of non-transplant patients undergoing THA. Transplant patients have a significantly higher number of comorbidities and longer LOS after THA compared to non-transplant patients. Admission costs and acute complications are comparable among these populations, after adjusting for patient and hospital characteristics

Aims

Disorders of bone integrity carry a high global disease burden, frequently requiring intervention, but there is a paucity of methods capable of noninvasive real-time assessment. Here we show that miniaturized handheld near-infrared spectroscopy (NIRS) scans, operated via a smartphone, can assess structural human bone properties in under three seconds.

Introduction

Meniscus deficiency leads to the development of early arthritis. Total knee replacement may be the only available treatment option in certain situations. However it is generally best avoided in young patients. We hypothesized that a combination of the two procedures, Allograft Meniscal Transplantation (AMT) and Autologous Chondrocyte Implantation (ACI) would be a solution to treat bone-on-bone arthritis in meniscal deficient knees and postpone the need for a total knee replacement (TKR).

Introduction. The use of vascularised fibula grafts is an accepted method for reconstructing the distal femur following resection of malignant childhood tumours. Limitations relate to the mismatch of the cross-sectional area of the transplanted fibula graft and thel ocal bone, instability of the construct and union difficulties. We present midterm results of a unique staged technique—an immediate defect reconstruction using a double-barrel vascularised fibula graft set in in A-frame configuration and a subsequent intramedullary femoral lengthening. Materials & Methods. We retrospectively included 10 patients (mean age 10 y)with an osteosarcoma of the distal femur, who were treated ac-cording to the above-mentioned surgical technique. All patients were evaluated with regards to consolidation of the transplanted grafts, hypertrophy at the graft-host junctions, leg length discrepancies, lengthening indices, complications as well as functional outcome. Results. The mean defect size after tumour resection was 14.5 cm, the mean length of the harvested fibula graft 22 cm, resulting in a mean (acute) shortening of 4.7 cm (in 8 patients). Consolidation was achieved in all cases, 4 patients required supplementary bone grafting. Hypertrophy at the graft-host junctions was observed in78% of the evaluable junctions. In total 11 intramedullary lengthening procedures in 9 patients had been performed at the last follow up. The mean Muskuloskeletal Society Rating Scale(MSTS) score of the evaluable 9 patients was 85% (57% to 100%)with good or excellent results in 7 patients. Conclusions. A-frame vascularised fibula reconstructions showed encouraging results with respect to defect reconstruction, length as well as function and should therefore be considered a valuable option for reconstruction of the distal femur after osteosarcoma resection. The surgical implementation is demanding though, which is emphasized by the considerable high number of com-plications requiring surgical intervention, even though most were not serious

Background. Joint replacement surgery has been shown to be successful in post solid organ transplantation patients. However, complication rates, revision rates, and overall mortality can be higher in this population compared to patients who have not undergone solid organ transplantation. Many transplant patients have a decreased life expectancy. Therefore, literature suggests that joint replacement surgery be offered to qualifying patients early on when symptomatic. This study compares the outcomes of patients who have undergone solid organ transplantation as well as a joint replacement to patients that have only undergone joint replacement surgery. Methods. We retrospectively gathered 42 transplant (T) patients over a ten year period, 2003–2013, that underwent a liver (21) or kidney (21) transplant as well as primary total knee arthroplasty (TKA) (23) or total hip arthroplasty (THA) (19). We then gathered 42 non-transplant (NT) patients matched for procedure, age, body mass index (BMI), American Society of Anesthesiologists (ASA) score, and age adjusted Charlson co-morbidity index (ACCI) score who only underwent TKA or THA with no transplant. We used Chi-Square, T test, and multivariate analysis to compare the two groups with regard to number of complications (NOC), readmissions at 30 and 90 days post surgery, length of stay (LOS), number of intensive care unit (ICU) admissions, and total direct cost (TDC) per hospital stay. Results. We found no significant difference between the two groups with regard to LOS (P=0.267), readmissions at 30 days (P=0.843) or 90 days (P=0.265), ICU admissions (P=0.326), or TDC per hospital stay (P=0.343). The T group had significantly higher NOC compared to the NT group (P=0.022). The type of transplant was associated with a higher NOC with kidney transplant patients having 6.75 (95% CI 1.318–34.565) times higher odds of complications compared to liver transplant patients (P=0.022). The average time between transplant surgery and joint replacement surgery was 2.9 years. Conclusion. Solid organ transplant patients are considered to be at higher risk for opportunistic infections compared to the general population. Limited data is available regarding the time at which transplant patients are at the highest risk for infection, or if one type of transplant is more at risk for complications than another after THA or TKA. This study suggests that transplant patients undergoing joint replacement surgery at an average of 2.9 years post-transplant are at higher risk for complications than a matched cohort of patients undergoing joint replacement alone, with kidney transplant patients being more at risk to experience a complication than liver transplant patients. To our knowledge, this is the first study to acknowledge the higher risk associated specifically with kidney transplant patients

It has been reported that the total steroid dose and acute rejection episodes after organ transplantation is one of the risk factors for the development of osteonecrosis of the femoral head (ONFH), and ONFH in steroid-iduced subgroup may progress more aggressively to femoral head collapse requiring total hip arthroplasty. Despite inherent medical co-morbidities of solid organ transplantation patients, most authors recently have reported successful outcomes of THAs in those patients. But there are few comparative studies on the outcome of THAs for ONFH after different organ transplantations. The purpose of this study was to evaluate and compare a single tertiary referral institution's experience of performing primary THAs in kidney transplantation (KT) and liver transplantation (LT) patients with specific focus on the total steroid dose, clinical outcomes, and relationship between ONFH and absence or presence of acute rejection (AR). Between 1999 and 2010, 4,713 patients underwent organ transplantations (1,957 KT and 2,756 LT) and AR was occurred in 969 patients (20.6%) after transplantation. Among these patients, 131 patients (191 hips) underwent THA for ONFH, and they were retrospectively reviewed. In KT groups, there were 57 men and 36 women with a mean age of 43.7 years. In LT groups, there were 26 men and 13 women with a mean age of 50.4 years. We investigated the dose of steroid administration on both groups, the time period from transplantation to THA, Harris hips score (HHS), visual analogue scale (VAS) and complications. The mean follow up period was 8.1 years (range, 5 to 14 years). One-hundred and thirty-one (2.8%) patients [93 KT and 38 LT] underwent THA after transplantation. The total steroid dose after transplantations was significantly higher in KT group (10,420 mg) than that in LT group (4,567 mg), but the total steroid dose in the first 2 weeks after transplantation was significantly higher in LT group (3,478 mg) than that in KT group (2,564 mg). Twenty-three (2.4%) patients (19 KT and 4 LT) who underwent THA had an episode of AR. In LT group, the total steroid dose in AR groups was significantly higher than that in non-AR groups, whereas in KT group, there was no significant difference of the total steroid dose between AR group and non-AR group. The rate of THAs for ONFH was similar in both groups (2.4% in AR group, 2.9% in non-AR group). The mean time period from transplantation to THA was 986 days for KT and 1,649 days for LT patients. Both groups showed satisfactory HHS and VAS at final follow up, revealed no differences between the groups. The rate of THAs for ONFH was three times higher in KT patients than that in LT patients, but it was similar in both AR group and non-AR group. The total steroid dose was also higher in KT patients compared to LT patients. The clinical outcomes of THA were satisfactory with few complications in both KT and LT patients. Therefore, THAs seems to be a good option for the patients with symptomatic steroid-induced ONFH after KT and LT

The superficial zone (SFZ) of articular cartilage has unique structural and biomechanical features, and is important for joint long-term function. Previous studies have shown that TGF-β/Alk5 signaling upregulating PRG4 expression maintains articular cartilage homeostasis. However, the exact role and molecular mechanism of TGF-β signaling in SFZ of articular cartilage homeostasis are still lacking. In this study, a combination of in vitro and in vivo approaches were used to elucidate the role of Alk5 signaling in maintaining the SFZ of articular cartilage and preventing osteoarthritis initiation. Mice with inducible cartilage SFZ-specific deletion of Alk5 were generated to assess the role of Alk5 in OA development. Alterations in cartilage structure were evaluated histologically. The chondrocyte apoptosis and cell cycle were detected by TUNEL and Edu staining, respectively. Isolation, culture and treatment of SFZ cells, the expressions of genes associated with articular cartilage homeostasis and TGF-β signaling were analyzed by qRT-PCR. The effects of TGF-β/Alk5 signaling on proliferation and differentiation of SFZ cells were explored by cells count and alcian blue staining. In addition, SFZ cells isolated from C57 mice were cultured in presence of TGF-β1 or SB505124 for 7 days and transplanted subcutaneously in athymic mice. Postnatal cartilage SFZ-specific deletion of Alk5 induced an OA-like phenotype with degradation of articular cartilage, synovial hyperplasia as well as enhanced chondrocyte apoptosis, overproduction of catabolic factors, and decreased expressions of anabolic factors in chondrocytes. qRT-PCR and IHC results confirmed that Alk5 gene was effectively deleted in articular cartilage SFZ cells. Next, the PRG4-positive cells in articular cartilage SFZ were significantly decreased in Alk5 cKO mice compared with those in Cre-negative control mice. The mRNA expression of Aggrecan and Col2 were decreased, meanwhile, expression of Mmp13 and Adamts5 were significantly increased in articular cartilage SFZ cells of Alk5 cKO mice. In addition, Edu and TUNEL staining results revealed that slow-cell cycle cell number and increase the apoptosis positive cell in articular cartilage SFZ of Alk5 cKO mice compared with Cre-negative mice, respectively. Furthermore, all groups of SFZ cells formed ectopic solid tissue masses 1 week after transplantation. Histological examination revealed that the TGF-β1-pretreated tissues was composed of small and round cells and was positive for alcian blue staining, while the SB505124-pretreated tissue contained more hypertrophic cells though it did stain with alcian blue. TGF-β/alk5 signaling is an essential regulator of the superficial layer of articular cartilage by maintaining chondrocyte number, its differentiation properties, and lubrication function. Furthermore, it plays a critical role in protecting cartilage from OA initiation

Introduction. Chronic ruptures of the quadriceps tendon after total knee arthroplasty (TKA) are rare but are a devastating complication. The objective of this study was to validate the use of fresh frozen total fresh quadriceps tendon allografts for quadriceps tendon reconstruction. The hypothesis of this work was that the graft was functional in more than 67% of cases, a higher percentage than the results of conventional treatments. Material – methods. We designed a continuous monocentric retrospective study of all patients operated on between 2009 and 2017 for a chronic rupture of the quadriceps tendon after TKA by quadriceps allograft reconstruction. The usual demographic and perioperative data and the rehabilitation protocols followed were collected. Initial and final radiographs were analyzed to measure patellar height variation. The main criterion was the possibility of achieving an active extension of the knee with a quadriceps contraction force greater than or equal to 3/5 or the possibility of lifting the heel off the ground in a sitting position. Results. 29 patients with 33 allografts were included; 3 iterative allografts were performed on ruptures of the initial transplant and 1 patient was grafted on both sides in one step. There were 21 women and 8 men with a mean age of 73 years, and a mean body mass index of 33 kg/m. 2. Ruptures occurred in 22 cases after chronic periprosthetic infection. Walking was allowed immediately in 29 cases, but free mobilization was delayed in 29 cases. Complications affected 22 cases, but the majority of complications were not related to allograft use (including infectious failures and periprosthetic fractures). After a mean follow-up of 52 months, 28 allografts were still in place, and 22 allografts were considered functional. The active quadriceps extension force was rated on average at 3.5/5. The average pre/post-operative patellar height differential was +2 mm. Discussion. This continuous series of 33 allografts is in line with recent publications on the subject. It confirms their negative impact on the functional outcome of the TKA. The complication rate is high but the specific complication rate is not prohibitive. Two thirds of transplants are functional in the long term. Early rehabilitation procedures can be used in these difficult patients with encouraging results. The management of chronic ruptures of the quadriceps tendon after TKA by quadriceps allograft must be part of the current therapeutic options

Aim. Chronic bone infections and infected fractures are often treated with excision of the dead bone and implantation of biomaterials which elute antibiotics. Gentamicin has been a preferred drug for local delivery, but this could induce renal dysfunction due to systemic toxicity. This is a particular concern in patients with pre-existing chronic renal disease treated with new antibiotic carriers which achieve very high peak levels of gentamicin in the first few days after surgery. Method. 163 patients (109 males; average age 51.6 years) with Cierny-Mader Type 3 or 4 chronic osteomyelitis had a single-stage operation with excision of the dead bone, filling of the osseous defect with a calcium sulphate-hydroxyapatite carrier, containing gentamicin and immediate soft tissue closure. 2. No patient was given systemic gentamicin or other renal toxic antibiotics. Mean carrier volume was 10.9mls (range 1–30mls) and mean gentamicin dosing was 190.75mg (maximum 525mg). Seven patients had pre-existing renal disease (4 diabetic nephropathy, 1 nephrotic syndrome, 1 renal transplant and 1 previous acute kidney injury). Serum creatinine levels were collected pre-operatively and during the first seven days post-operatively. Glomerular filtration rate (GFR) was calculated using the CKD-epi creatinine equation. Renal function was defined using the Chronic Kidney Disease (CKD) Staging system. Results. 155 cases had adequate data to allow calculation of pre- and post-operative GFR. Pre-operative CKD staging demonstrated 118 Class I (normal renal function), 30 Class II, 3 Class IIIa, 3 Class IIIb, and 1 Class V disease. Mean pre-operative GFR (99.7ml/min/1.73m. 2. , SD 21.0) was no different to post-operative GFR (103.2ml/min/1.73m. 2. , SD 21.3), p= 0.0861. Four cases had a >10% decline in GFR below normal, with only one case dropping a CKD stage, from I (normal) to II (mildly decreased). Only 1/7 cases with pre-existing renal disease had a GFR drop of >10% (from 11ml/min/1.73m. 2. to 8ml/min/1.73m. 2. ). 70/155 (45.2%) had a temporary GFR drop post-operatively, with the biggest drop occurring a mean 3.06 days following surgery (SD 2.1). No patient had clinical signs of new acute renal impairment post-operatively. Conclusions. Renal function is not significantly affected by local implantation of gentamicin up to 525mg. The presence of pre-existing renal disease is not a contraindication to local gentamicin therapy

The parameters to be considered in the selection of a cartilage repair strategy are: the diameter of the chondral defect; the depth of the bone defect; the location of the defect (weight bearing); alignment. A chondral defect less than 3 cm in diameter can be managed by surface treatment such as microfracture, autologous chondrocyte transplantation, mosaicplasty, or periosteal grafting. An osteochondral defect less than 3 cm in diameter and less than 1 cm in depth can be managed by autologous chondrocyte transplantation, mosaicplasty or periosteal grafting. An osteochondral defect greater than 3 cm in diameter and 1 cm in depth is best managed by an osteochondral allograft. If there is an associated knee deformity, then an osteotomy should also be performed with all of the aforementioned procedures. In our series of osteochondral allografts for large post-traumatic knee defects realignment osteotomy is performed about 60% of the time in order to off load the transplant. To correct varus we realign the proximal tibia with an opening wedge osteotomy. To correct valgus, we realign the distal femur with a closing wedge osteotomy. Our results with osteochondral allografts for the large osteochondral defects of the knee have been excellent in 85% of patients at an average follow-up of 10 years. The Kaplan-Meier survivorship at 15 years is 72%. At an average follow-up of 22 years in 58 patients with distal femoral osteochondral allograft, 13 have been revised (22%). The 15-year survivorship was 84%. The results for the hip are early. To date we have performed this procedure on 16 patients. Surgical dislocation of the hip is carried out via a trochanteric osteotomy and the defect defined and trephined out. A press-fit fresh osteochondral allograft is inserted using the trephine technique. We have published our early results on a series of 8 patients with 5 good to excellent results, 1 fair result and 2 failures

After meniscetomy there is an increased risk of tibiofemoral arthritis. In recent times there has been an increased emphasis on preservation of healthy meniscal tissue. When this cannot be achieved some patients may benefit from allograft transplantation. This aims to restore meniscal function and so limit pain and the development of arthritis. This is an evolving area with controversy surrounding patient selection, tissue harvesting and sterilisation, longterm outcome and overall efficacy. Twenty-eight patients have undergone 30 meniscal transplants beginning in 2001. All transplants have been performed by the senior author. The mean age at surgery was 37.7 years (range 20–51), there were 16 males and 12 females. At the time of the index operation nine patients underwent additional procedures on the same knee. All patients are scored using recognised knee scoring systems including the Oxford, IKDC and Lysholm scores. All patients are being followed up regularly with clinical assessment and repeat scores. To date the average follow up is 34.3 months (range 6–84). There have been 12 patients requiring further arthroscopy (three with complete meniscal transplant failure). The average increases in Lysholm, Oxford and IKDC scores were 10.7, 7.6 and 8.6 respectively. Lack of donors is the current limitation to performing transplants in Brisbane. 61 patients are currently awaiting suitable menisci and in the last 12 months there have been only three donors. A national registry may address this issue but raises problems related to uniform retrieval, storage, sizing and availability. Early results are encouraging with the majority of patients experiencing pain relief and improvement of function over time

Primary spinal cord injury is followed by secondary, biochemical, immunological, cellular changes in the injured cord. A review article written by Brian Kwon looking critically at the use of hypothermia for SCI. It shows that it is neuroprotective in some settings (i.e. cardiac arrest). However, there are 25 animal studies with mixed results and only eight human SCI studies. Importantly, they are all case series of local, not systemic hypothermia. And the last one published was in 1984. Rho is a critical molecule in SCI. Rho ultimately inhibits axonal growth cone proliferation. Stopping RHO therefore will promote the growth cone. There are two drugs that ultimately targets rho. These are anti nogo antibodies and cethrin both of which ultimately inhibit rho. President Obama lifted the ban on federal funding of stem cell research. This was a monumental occasion and was right around the time that the FDA approved the first trial of hESC for SCI. The FDA trial of Geron is with Thoracic ASIA A SCI patients with transplantation of ESC directly into the cord at 7 to 14 days after injury. Geron has provided evidence to the FDA that there is no teratoma formation with transplantation of a human ESC to a rat or mouse. However, we do not know what will happen in a human to human transplant. In conclusion, use of steroids in setting of SCI is diminishing. There is no clinical evidence to support use of systemic hypothermia. Current clinical trials of pharmacologic therapy include Minocycline and RILUTEK(r) (riluzole) for neuroprotection, Anti-Nogo Antibodies and Cethrin(r) for axonal growth by ultimately inhibiting Rho. There is only one small study supporting safety, not efficacy of OEC transplantation

Periprosthetic joint infection (PJI) is one of the most devastating complications of total joint arthroplasty (TJA). Only a few studies have investigated PJI's impact on the most worrisome of all endpoints, mortality. The purpose of this study was to perform a large-scale study to determine the rates of PJI associated in-hospital mortality, and compare it to other surgical procedures. The Nationwide Inpatient Sample was queried from 2002 to 2010 to assess the risk of mortality for patients undergoing revision for PJI or aseptic failures. Elixhauser comorbidity index and ICD-9 codes were used to obtain patients’ medical conditions and identify PJI. Multiple logistic-regression analyses were used to determine the associated variables with mortality. In-hospital mortality was compared to the followings: coronary-artery bypass graft, mastectomy, prostatectomy, appendectomy, kidney transplant, carotid surgery, cholecystectomy, and coronary interventional procedures. PJI was associated with an increased risk (odds ratio 2.04) of in-hospital mortality (0.77%) compared to aseptic revisions (0.38%). The in-hospital mortality of revision THAs done for PJI (1.38%, 95%CI, 1.12–1.64%) was comparable to or higher than interventional coronary procedure (1.22%, 95%CI, 1.20–1.24%), cholecystectomy (1.13%, 95%CI, 1.11–1.15%), kidney transplantation (0.70%, 95%CI, 0.61%–0.79%) and carotid surgery (0.89%, 95%CI, 0.86%–0.93%) (Figure 1). The following comorbidities were independent risk factors for in-hospital mortality after TJA: liver disease, metastatic disease, fluid and electrolyte disorders, coagulopathy, weight loss and malnutrition, congestive heart failure, pulmonary circulation disorder, renal failure, and peripheral vascular disease. PJI is associated with a two-fold increase in mortality and have mortality rates comparable to kidney transplantation and carotid surgery. Considering the fact that patients with PJI often require multiple surgical procedures, the rate of actual in-hospital mortality for patients with PJI may be considerably higher. Surgeons should be cognizant of the potentially fatal outcome of PJI and must emphasize the importance of infection control to reduce the risk of mortality

Articular cartilage repair remains a challenge in orthopedic surgery, as none of the current clinical therapies can regenerate the functional hyaline cartilage tissue. In this study, we proposed a one-step surgery strategy that uses autologous bone marrow mesenchymal stem cells (MSCs) embedded in type II collagen (Col-II) gels to repair the full thickness chondral defects in minipig models. Briefly, 8 mm full thickness chondral defects were created in both knees separately, one knee received Col-II + MSCs transplantation, while the untreated knee served as control. At 1, 3 and 6 months postoperatively, the animals were sacrificed, regenerated tissue was evaluated by magnetic resonance imaging, macro- and microscopic observation, and histological analysis. Results showed that regenerated tissue in Col-II + MSCs transplantation group exhibited significantly better structure compared with that in control group, in terms of cell distribution, smoothness of surface, adjacent tissue integration, Col-II content, structure of calcified layer and subchondral bone. With the regeneration of hyaline-like cartilage tissue, this one step strategy has the potential to be translated into clinical application

Bone is a connective tissue that undergoes constant remodeling. Any disturbances during this process may result in undesired pathological conditions. A single nucleotide substitution (596T-A) in exon eight which leads to a M199K mutation in human RANKL was found to cause osteoclast-poor autosomal recessive osteopetrosis (ARO). Patients with ARO cannot be cured by hematopoietic stem cell transplantation and, without proper treatments, will die in their early age. To date, how this mutation alters RANKL function has not been characterized. We thus hypothesized that hRANKL M199 residue is a structural determinant for normal RANKL-RANK interaction and osteoclast differentiation. By sharing our findings, we aim to achieve an improved clinical outcome in treating bone-related diseases such as osteoporosis, ARO and osteoarthritis. Site-directed mutagenesis was employed to create three rat RANKL mutants, replacing the methionine 200 (human M199 equivalent residue) with either lysine (M200K), alanine (M200A) or glutamic acid (M200E). Recombinant proteins were subsequently purified through affinity chromatography and visualized by Coomassie blue staining and western blot. MTS was carried out before osteoclastogenesis assay in vitro to measure the cellular toxicity. Bone resorption pit assay, immuno-fluorescent staining, luciferase reporter assay, RT-PCR, western blot and calcium oscillation detection were also conducted to explore the biological effect of rRANKL mutants. Computational modeling, thermal Shift Assay, western blot and protein binding affinity experiments were later carried out for structural analyses. rRANKL mutants M200K/A/E showed a drastically reduced ability to induce osteoclast formation and did not demonstrate features of competitive inhibition against wild-type rRANKL. These mutants are all incapable of supporting osteoclastic polarization and bone resorption or activating RANKL-induced osteoclast marker gene transcription. Consistently, they were unable to induce calcium flux, and also showed a diminished induction of IκBa degradation and activation of NF-kB and NFATc1 transcriptional activity. Furthermore, the transcriptional activation of the antioxidant response element (ARE) crucial in modulating oxidative stress and providing cytoprotection was also unresponsive to stimulation with rM200s. Structural analyses showed that rM200 is located in a hydrophobic pocket critical for protein folding. Thermal shift and western blot assays suggested that rM200 mutants formed unstructured proteins, with disturbed trimerisation and the loss of affinity to its intrinsic receptors RANK and OPG. Taken together, we first demonstrates the underlying cause of M199-meidated ARO in a cellular and molecular level by establishing a phenotype in BMMs similar to observed in human samples. Further investigation hints the structural significance of a hydrophobic pocket within the TNF-like region. Combined with pharmaceutical studies on small-molecule drugs, this finding may represent a therapeutic target motif for future development of anti-resorptive treatments

An established rabbit model was used to preliminarily investigate the effect of acellular triphase, namely bone-cartilage-tendon, scaffold (ATS) sandwiched with autologous bone mesenchymal stem cells (BMSCs) sheets on tendon-bone interface healing. Bone, fibrocartilage and tendon tissue were harvested from the rabbits and sectioned into a book-type scaffold. The scaffolds were decellularized and their characterization was presented. BMSCs were isolated and co-cultured with the scaffolds to verify their cytocompatibility. BMSCs sheets were fabricated and inserted into the book page of the scaffold to construct an autologous BMSCs-sheets/book-type ATS complex. The complex was implated in the right knee of rabbits which operated standard partial patellectomy for TBI regeneration using Imaging, histological and biomechanical examinations. The bone, fibrocartilage and tendon tissue were sectioned into a book-type scaffold before decellularization. Then we decellularized the above tissue and mostly preserved their microstructure and composition of the natural extracellular matrix, including collagen and proteoglycan. After the physicochemical and biological properties of the book-type ATS were evaluated, autologous BMSCs sheets were inserted into the book page of the scaffold to construct an autologous BMSCs-sheets/book-type ATS implants for TBI regeneration. In addition, the ATS has the advantages of non-toxicity, suitable for cell adhesion and growth as well as low immunogenicity while co-cultured with the BMSCs. At the same time, different scaffolds has the ability to induce the osteogenic, chondrogenic and tenogenic differentiation of BMSCs by immunofluorescence, reverse transcription-polymerase chain reaction and western blot analysis. To determine the efficacy of the tissue-engineered implants for TBI regeneration, we transplanted it into a rabbit patella-patellar tendon (PPT) injury model, and the rabbits were sacrificed at postoperative week 8 or 16 for the radiological, histological, and mechanical evaluation. Radiologically, Synchrotron radiation micro-computed tomography (SR-μCT) showed that BMSCs/ATS group significantly increased bone area, BV/TV, trabecular thickness and trabecular number at the healing interface as compared with other groups at postoperative week 8 or 16. Histologically, the BMSCs/ATS group showed more woven bone, and a more robust fibrocartilaginous junction with a characteristic matrix rich in proteoglycans was seen at the PPT healing interface in comparison with other groups after 8 weeks. At week 16, the healing interface in 3 groups displayed better remodeling with respect to postoperative week 8. Healing and remodeling at the PPT junction were almost complete, with a resemblance to a healthy BTI consisting of the characteristic 4 zones in all groups. At last, we used biomechanical test as functional parameters to evaluate the quality of tendon-bone healing. Biomechanical testing indicated that BMSCs/ATS group showed significantly higher failure load and stiffness than other groups at postoperative week 8 and 16. The complex composed of acellular triphase, namely bone-cartilage-tendon, scaffold (ATS) sandwiched with autologous bone mesenchymal stem cells (BMSCs) sheets can simulate the gradient structure of tendon-bone interface, inducing stem cell directional differentiation, so as to promote patella-patellar tendon interface healing effectively after injury

Chondral defects on the patella are a difficult problem in the young active patient and there is no consensus on how to treat these injuries. Fresh osteochondral allografts are a valid option for the treatment of full-thickness osteochondral defects and can be used to restore joint function and reduce pain. The primary purpose of this study was to investigate the clinical and subjective outcomes of a series of patients following fresh osteochondral allograft transplantation for isolated chondral defects of the patella. A series of 5 patients underwent surgery using an open approach for graft transplantation. A strict protocol for the allograft tissue was followed. Transplant recipients must be aged <60, have a full-thickness, isolated chondral lesion and have failed previous traditional treatments. The fresh allografts are hypothermically stored at 4°C in X-VIVO10 media for up to 30 days to maintain cartilage viability. Pre- and post-operative clinical measures including knee stability, range of motion, and quadriceps girth were completed. Post-operative plain radiographs were completed including weight-bearing AP, lateral and skyline views. Patient-centred outcome measures including the Knee Osteoarthritis Outcome Score (KOOS) and the Knee Society Score (KSS) were gathered a minimum of 1-year post-operative. Descriptive and demographic data were collected for all patients. A paired t-test was employed to determine the difference between the pre-operative and post-operative outcomes. All patients were female, with a mean age of 27.4 (SD 3.65). Knee ligament stability was similar pre- and post-operatively. Knee ROM assessment of flexion and extension demonstrated a less than 10° increase from pre to post-operative. Quadriceps girth measurements demonstrated a mean change of 0.5 cm from pre- to post-operative for the surgical limb. Post-operative radiographs demonstrated incorporation of the graft in 4/5 cases within 6-months of surgery. One patient developed fragmentation of the graft after 18-months, and one patient had a subsequent trochleoplasty for persistent pain. The mean KOOS domain scores demonstrated significant improvement (p<0.05) as follows: Symptoms pre-op = 28.57, post-op = 55; Pain pre-op 28.89, post-op = 57.22; ADLs pre-op = 48.92, post-op = 66.18; Sports/Recreation pre-op = 6, post-op = 32; and QoL pre-op = 12.5, post-op = 42.5. Mean pre-op surgical versus non-surgical limb KSS scores were 107.4 and 179 respectively. The mean post-op surgical versus non-surgical limb KSS scores were 166 and 200. Isolated chondral defects of the patella can cause substantial pain, reduced function, and can be challenging to address surgically. This series of 5 cases demonstrated improved function, KOOS and KSS for 4/5 patients. To our knowledge this is a novel biological procedural technique for this problem, which has shown promising results making it a viable treatment option for young active patients with osteochondral defects of the patella

Bone marrow-derived mesenchymal stromal stem cells (BMSCs) are a promising cell source for treating articular cartilage defects. Quality of cartilaginous repair tissue following BMSC transplantation has been shown to correlate with functional outcome. Therefore, tissue-engineering variables, such as cell expansion environment and seeding density of scaffolds, are currently under investigation. The objectives of this study were to demonstrate chondrogenic differentiation of BMSCs seeded within a collagen I scaffold following isolation and expansion in two-dimensional (2D) and three-dimensional (3D) environments, and assess the impact of seeding density on in vitro chondrogenesis. It was hypothesised that both expansion protocols would produce BMSCs capable of hyaline-like chondrogenesis with an optimal seeding density of 10 million cells/cm3. Ovine BMSCs were isolated in a 2D environment by plastic adherence, expanded to passage two in flasks containing expansion medium, and seeded within collagen I scaffolds (6 mm diameter, 3.5 mm thickness and 0.115 ± 0.020 mm pore size; Integra LifeSciences Corp.) at densities of 50, 10, 5, 1, and 0.5 million BMSCs/cm3. For 3D isolation and expansion, bone marrow aspirates containing known quantities of mononucleated cells (BMNCs) were seeded on scaffolds at 50, 10, 5, 1, and 0.5 million BMNCs/cm3 and cultured in expansion medium for an equivalent duration to 2D expansion. All cell-scaffold constructs were differentiated in vitro in chondrogenic medium containing transforming growth factor-beta three for 21 days and assessed with RT-qPCR, safranin O staining, histological scoring using the Bern Score, collagen immunofluorescence, and glycosaminoglycan (GAG) quantification. Two dimensional-expanded BMSCs seeded at all densities were capable of proteoglycan production and displayed increased expressions of aggrecan and collagen II mRNA relative to pre-differentiation controls. Collagen II deposition was apparent in scaffolds seeded at 0.5–10 million BMSCs/cm3. Chondrogenesis of 2D-expanded BMSCs was most pronounced in scaffolds seeded at 5–10 million BMSCs/cm3 based on aggrecan and collagen II mRNA, safranin O staining, Bern Score, total GAG, and GAG/DNA. For 3D-expanded BMSC-seeded scaffolds, increased aggrecan and collagen II mRNA expressions relative to controls were noted with all densities. Proteoglycan deposition was present in scaffolds seeded at 0.5–50 million BMNCs/cm3, while collagen II deposition occurred in scaffolds seeded at 10–50 million BMNCs/cm3. The highest levels of aggrecan and collagen II mRNA, Bern Score, total GAG, and GAG/DNA occurred with seeding at 50 million BMNCs/cm3. Within a collagen I scaffold, 2D- and 3D-expanded BMSCs are capable of hyaline-like chondrogenesis with optimal cell seeding densities of 5–10 million BMSCs/cm3 and 50 million BMNCs/cm3, respectively. Accordingly, these densities could be considered when seeding collagen I scaffolds in BMSC transplantation protocols