We have designed a prospective study to evaluate the usefulness of prolonged incubation of cultures from sonicated orthopaedic implants. During the study period 124 implants from 113 patients were processed (22 osteosynthetic implants, 46 hip prostheses, 54 knee prostheses, and two shoulder prostheses). Of these, 70 patients had clinical infection; 32 had received antibiotics at least seven days before removal of the implant. A total of 54 patients had sonicated samples that produced positive cultures (including four patients without infection). All of them were positive in the first seven days of incubation. No differences were found regarding previous antibiotic treatment when analysing colony counts or days of incubation in the case of a positive result. In our experience, extending incubation of the samples to 14 days does not add more positive results for sonicated orthopaedic implants (hip and knee prosthesis and osteosynthesis implants) compared with a conventional seven-day incubation period. Cite this article: Bone Joint J 2013;95-B:1001–6

The Pavlik harness (PH) is commonly used to treat infantile dislocated hips. Variability exists in the duration of brace treatment after successful reduction of the dislocated hip. In this study we evaluate the effect of prescribed time in brace on acetabular index (AI) at two years of age using a prospective, international, multicenter database. We retrospectively studied prospectively enrolled infants with at least one dislocated hip that were initially treated with a PH and had a recorded AI at two-year follow-up. Subjects were treated at one of two institutions. Institution 1 used the PH until they observed normal radiographic acetabular development. Institution 2 followed a structured 12-week brace treatment protocol. Hip dislocation was defined as less than 30% femoral head coverage at rest on the pre-treatment ultrasound or IHDI grade III or IV on the pre-treatment radiograph. Fifty-three hips met our inclusion criteria. Hips from Institution 1 were treated with a brace 3x longer than hips from institution 2 (adjusted mean 8.9±1.3 months vs 2.6±0.2 months)(p < 0 .001). Institution 1 had an 88% success rate and institution 2 had an 85% success rate at achieving hip reduction (p=0.735). At 2-year follow-up, we observed no significant difference in AI between Institution 1 (adjusted mean 25.6±0.9˚) compared to Institution 2 (adjusted mean 23.5±0.8˚) (p=0.1). However, 19% of patients from Institution 1 and 44% of patients from Institution 2 were at or below the 50th percentile of previously published age- and sex- matched AI normal data (p=0.049). Also, 27% (7/26) of hips from Institution 1 had significant acetabular dysplasia, compared to a 22% (6/27) from Institution 2 (p=0.691). We found no correlation between age at initiation of bracing and AI at 2-year follow-up (p=0.071). Our findings suggest that prolonged brace treatment does not result in improved acetabular index at age two years. Hips treated at Institution 1 had the same AI at age two years as hips treated at Institution 2, while spending about 1/3 the amount of time in a brace. We recommend close follow-up for all children treated for dislocated hips, as ~1/4 of infants had acetabular index measurements at or above the 90th percentile of normal. Continued follow-up of this prospective cohort will be critical to determine how many children require acetabular procedures during childhood. The PH brace can successfully treat dislocated infant hips, however, prolonged brace treatment was not found to result in improved acetabular development at two-year follow-up

Surgical management for acute or impending pathologic fractures in metastatic bone disease (MBD) places patients at high-risk for post-operative venous thromboembolism (VTE). Due to the combination of malignancy, systemic cancer treatment, and surgical treatment, VTE-risk is increased 7-fold in patients with MBD compared to non-cancer patients undergoing the same procedure. The extent and duration of post-operative hypercoagulability in patients with MBD remains unknown and thromboprophylaxis guidelines were developed for non-cancer patients, limiting their applicability to address the elevated VTE-risk in cancer patients. Thrombelastography (TEG) analysis is a point-of-care test that measures clot formation, stabilization, and lysis in whole blood samples. The TEG parameter, maximal amplitude (MA), indicates clot strength and the threshold of ≥65 mm has been used to define hypercoagulability and predict VTE events in non-cancer patients requiring orthopaedic surgery. Therefore, this study aims to quantify the extent and duration of post-operative hypercoagulability in patients with MBD using serial TEG analysis. Consecutive adults (≥18 years) with MBD who required orthopaedic surgery for acute or impending pathologic fractures were enrolled into this single-centre, prospective cohort study. Serial TEG analysis was performed onsite using a TEG®6s haemostasis analyzer (Haemonetics Corporation, Boston, MA) on whole blood samples collected at seven timepoints: pre-operatively; on post-operative day (POD) 1, 3, and 5; and at 2-, 6-, and 12-weeks post-operatively. Hypercoagulability was defined as MA ≥65 mm. Participants received standardized thromboprophylaxis for four weeks and patient-reported compliance with thromboprophylaxis was recorded. VTE was defined as symptomatic DVT or PE, or asymptomatic proximal DVT, and all participants underwent a screening post-operative lower extremity Doppler ultrasound on POD3. Descriptive statistics were performed and difference between pre-operative MA values of participants with VTE versus no VTE was evaluated using Student's t-test (p≤0.05). Twenty-one participants (10 female; 47.6%) with a mean age of 70 ± 12 years were enrolled. Nine different primary cancers were identified amongst participants, with breast (23.8%), colorectal (19.0%), and lung cancer (14.3%) most frequently reported. Most participants (57.1%) were hypercoagulable pre-operatively, and nearly half remained hypercoagulable at 6- and 12-weeks post-operatively (47.1 and 46.7%, respectively). VTE occurred in 5 patients (23.8%) and mean MA was 68.1 ± 4.6 mm at the time of diagnosis. Mean pre-operative MA values were significantly higher (p=0.02) in patients who experienced VTE (68.9 ± 3.5 mm) compared to those who did not (62.7 ± 6.5 mm). VTE incidence was highest in the first week post-operatively, during which time four VTE events (80%) occurred. The proportion of patients in a hypercoagulable state increased at three consecutive timepoints, beginning on POD3 (85.0%), increasing on POD5 (87.5%), and peaking at 2-weeks post-operatively (88.9%). Current thromboprophylaxis guidelines do not consider cancer-associated risk factors that contribute to increased VTE incidence and prescription duration may be inadequate to address prolonged post-operative hypercoagulability in patients with MBD. The high rate of VTE events observed and sustained hypercoagulable state indicate that thromboprophylaxis may be prematurely terminated while patients remain at high risk for VTE. Therefore, extending thromboprophylaxis duration beyond 4-weeks post-operatively in patients with MBD warrants further investigation

Recent studies have described safe outcomes for short-stays in the hospital after total shoulder arthroplasty. The purpose of this study is to identify pre-operative and operative risk factors for hospital admissions exceeding 24 hours. The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database was queried from 2006 to 2016 for the current procedural terminology (CPT) billing code related to total shoulder arthroplasty. Patients were then grouped as either having a length of stay (LOS) equal to or less than 24 hours or greater than 24 hours. Patients admitted to the hospital prior to the day of surgery were excluded. Patient demographics, co-morbidities, and operative time were then analyzed as risk factors for a hospital stay exceeding 24 hours. Pre-operative co-morbidities included body mass index (BMI), diabetes, smoking, chronic obstructive pulmonary disease (COPD), congestive heart failure (CHF), hypertension, dialysis, chronic steroid or immunosuppressant use, bleeding disorders, and American Society of Anesthesiologists (ASA) Classification. Univariate and multivariate analyses were then performed to identify risk factors associated with 30-day readmission. 14,339 patients met inclusion criteria and 6,507 (45.3%) had a hospital LOS less than or equal to 24 hours. The mean length of hospitalization was 1.95 ± 1.88 days, the average age was 69 ± 9.7 years old, and 56.9% of the patients were female. Following a risk adjusted multivariate analysis, increasing age (odds ratio [OR], 1.03, 95% confidence interval [CI], 1.02–1.03), ASA classification (OR, 1.50, 95% CI, 1.41–1.60), diabetes (OR, 1.69, 95% CI, 1.43–1.99), COPD (OR, 1.35, 95% CI, 1.16–1.57), CHF (OR, 2.67, 95% CI, 1.34–5.33), dialysis (OR, 2.47, 95% CI, 1.28, 4.77), history of a bleeding disorder (OR, 1.50, 95% CI, 1.20–1.88), or increasing operative time (OR, 1.01, 95% CI, 1.01–1.01) were identified as independent risk factors for hospital lengths of stay exceeding 24 hours. Male gender was identified as a protective factor for prolonged hospitalization (OR, 0.50, 95% CI, 0.46–0.53). This study identifies patient demographics, co-morbidities, and operative-relative risk factors that are associated with increased risk for a prolonged hospitalization following total shoulder arthroplasty. Female gender, increasing age, ASA classification, operative time, or a history of diabetes, COPD, CHF, or history of a bleeding disorder are risk factors hospitalizations exceeding 24 hours

Introduction. The enhanced recovery after surgery (ERAS) concept in arthroplasty surgery has led to a reduction in postoperative length of stay in recent years. Patients with prolonged length of stay (PLOS) add to the burden of a strained NHS. Our aim was to identify the main reasons. Methods. A PLOS was arbitrarily defined as an inpatient hospital stay of four days or longer from admission date. A total of 2,000 consecutive arthroplasty patients between September 2017 and July 2018 were reviewed. Of these, 1,878 patients were included after exclusion criteria were applied. Notes for 524 PLOS patients were audited to determine predominant reasons for PLOS. Results. The mean total length of stay was 4 days (1 to 42). The top three reasons for PLOS were social services, day-before-surgery admission, and slow to mobilize. Social services accounted for 1,224 excess bed days, almost half (49.2%, 1,224/2,489) of the sum of excess bed days. Conclusion. A preadmission discharge plan, plus day of surgery admission and mobilization on the day of surgery, would have the potential to significantly reduce length of stay without compromising patient care. Cite this article: Bone Joint Open 2020;1-8:488–493

Aim. Allograft bone chips used in complex bone reconstruction procedures are associated with an increased infection risk. The perioperative use of systemic cefazolin is standard to prevent infection, but is less effective in the presence of avascular bone grafts. Bone chips have been described as a carrier for local delivery of antibiotics, but impregnation with cefazolin in a prophylactic setting has not been described. We aimed to obtain a prolonged cefazolin release from bone chips to maximize the prophylactic effect. Method. Three types of bone chips were evaluated: fresh frozen, decellularized frozen and decellularized lyophilized. Bone chips were incubated with 20 mg/ml cefazolin or treated with liquid hydrogel containing either 1 mg/ml fibrin or 1 mg/ml collagen and 20 mg/ml cefazolin. The cefazolin hydrogel was distributed in the porous structure by short vacuum treatment. Bone chips with cefazolin but without hydrogel were incubated for 20 min- 4h under atmospheric pressure or under vacuum. Cefazolin elution of bone chips was carried out in fetal bovine serum and analyzed by Ultra Performance Liquid Chromatography – Diode Array Detection. Results. Without hydrogel, cefazolin release was limited to 4 hours. When vacuum was applied during impregnation, elution of cefazolin exceeding the MIC (minimal inhibitory concentration) from decellularized lyophilized bone chips was obtained for 36 hours. Use of a collagen hydrogel and vacuum treatment resulted in a high concentration at 24 hours, but did not support prolonged release for any of the three types of tested bone chips. In contrast, combination of decellularized frozen bone chips with fibrin hydrogel resulted in an initial release of 533 μg/ml, declining to the MIC at 72 hours, while no longer measurable after 92 hours. Such elution profile is desirable, since high initial levels are important to maximize antibacterial action whereas the complete wash out prevents antibiotic resistance. By increasing the cefazolin concentration during impregnation, elution above the MIC could be obtained for 120 hours. Impregnated bone chips stored at −20° C for 3 months performed similarly to freshly impregnated bone chips. Conclusions. Bone chips processed with the described hydrogel-based impregnation protocol allows tunable delivery of cefazolin for a local prophylactic effect

To prevent infections after orthopedic surgery, intravenous antibiotics are administered perioperatively. Cefazolin is widely used as the prophylactic antibiotic of choice. Systemic antibiotic therapy may however be less effective in longstanding surgery where bone allografts are used. Bone chips have been shown to be an effective carrier for certain types of antibiotics. Bone allografts impregnated with antibiotics may therefore provide the necessary local antibiotic levels for prophylaxis. To be efficient, a prolonged release from these bonechips is required. In contrast to vancomycin, for which prolonged release has clearly been proven effective from Osteomycin®, a commercially available impregnated bone allograft, no prolonged release bone chip preparations have been described so far for cefazolin. We developed a protocol to bind cefazolin in the porous structure of bone chips by means of a hydrogel composed of proteins naturally present in the human body. Three types of bone chips were evaluated: fresh frozen, decellularized frozen and decellularized lyophilized. Bone chips were incubated with 20 mg/ml cefazolin or treated with liquid hydrogel containing either 1 mg/ml fibrin or 1 mg/ml collagen and 20 mg/ml cefazolin. The cefazolin hydrogel was distributed in the porous structure by short vacuum treatment. Bone chips with cefazolin but without hydrogel were either incubated for 20 min- 4h or also treated with vacuum. Cefazolin elution of bone chips was carried out in fetal bovine serum and analyzed by Ultra Performance Liquid Chromatography – Diode Array Detection. Soaking of bone chips without hydrogel resulted in a quick release of cefazolin, which was limited to 4 hours. When vacuum was applied elution of >1 µg/ml cefazolin was measured for up to 36 hours. Combination with collagen hydrogel resulted in a higher cefazolin concentration released at 24 hours (3.9 vs 0.3 µg/ml), but not in a prolonged release. However, combination of decellularized frozen bone chips with fibrin hydrogel resulted in an initial release of 533 µg/ml followed by a gradual decline reaching the minimal inhibitory concentration for S. aureus at 72 hours (1.7 µg/ml), while not measurable anymore after 92 hours. Processed bone chips with hydrogel-cefazolin showed a markedly prolonged cefazolin release. When combined with a fibrin hydrogel, high initial peak levels of cefazolin were obtained, followed by a decreasing release over the following three days. This elution profile is desirable, since high initial levels are important to maximize anti-bacterial action whereas low levels of antibiotic for a limited time may stimulate osteogenesis. It is important that antibiotic release is ending after a few days as prolonged low levels of antibiotics are not clinically helpful and may lead to antibiotic resistance. Further preclinical studies are warranted to show effectiveness of hydrogel-cefazolin impregnated bone chips

Staphylococcus aureus osteo-articular infections (OAI) are frequently accompanied by blood stream infections (BSI) diagnosed by positive blood culture (BC). Microbiological protocols in adults advise prolonged intravenous antibiotics and repeat BC 48-hourly in the presence of a BSI, however evidence to support the systematic employment of these guidelines in paediatric patients is lacking. We aimed to determine whether there was an increased incidence of orthopaedic and systemic complications in patients with s aureus BSI, and whether a shorter duration of intravenous antibiotics was associated with the development of complications. Following ethical approval, the departmental surgical database was searched for patients that underwent surgery for acute OAI over a 5-year period. Patients with no sample taken for BC were excluded, as were those with other or no organisms identified from any site. Demographic and clinical data were captured, including duration of IV antibiotics and development of complications. Statistical significance was set at p<0.05. Following exclusions, 44 patients with a median age of 85 months remained to be analysed. Thirty patients (68%) had a positive BC. A positive BC was associated with a higher rate of systemic complications (p=0.026) but not orthopaedic complications (p=0.159). Patients who had developed any complication had a significantly longer duration of IV antibiotic treatment compared to those without complications (p<0.001). The presenting CRP levels were significantly higher in patients that developed complications (p=0.004). Patients with staphylococcal BSI in association with an OAI are at increased risk of developing systemic complications. In our cohort, a shorter duration of antibiotic use was not associated with the development of complications, which does not support the systematic use of long courses of IV antibiotics in s aureus BSI. Further research will be required to determine the ideal protocol for these patients

We prospectively studied the benefits and risks of prolonged treatment with the Pavlik harness in infants with idiopathic developmental dysplasia of the hip. Bracing was continued as long as abduction improved. It was started at a mean age of four months (1 to 6.9). Outcome measures were the number of successful reductions, the time to reduction, the acetabular index and evidence of avascular necrosis at follow-up at one year. In 50 infants with 62 subluxated and dislocated hips (42 Graf type III and 20 type IV), 37 were reduced successfully with a mean time to reduction of 13.4 weeks (. sd. 6.8). Bracing was successful in 31 type-III (73.8%) and in only six type-IV hips (20%, p = 0.002). Avascular necrosis was seen in ten hips. Prolonged treatment with the Pavlik harness for developmental dysplasia of the hip over the age of one month can be beneficial in type-III hips, but it is unclear as to whether this is the optimal treatment, since it may postpone the need for closed or open reduction to a more unfavourable age. The use of the Pavlik harness in type-IV hips in this age group is questionable, but if used, prolonged bracing is not advised

Aim. To prevent infections after orthopaedic surgery, intravenous antibiotics are administered perioperatively. Cefazolin is widely used as the prophylactic antibiotic of choice. Systemic antibiotic therapy may however be less effective in longstanding surgery where bone allografts are used. Bone chips have been shown to be an effective carrier for certain types of antibiotics and may provide the necessary local antibiotic levels for prophylaxis. To be efficient a prolonged release is required. In contrast to vancomycin with proven efficient prolonged release from Osteomycin, this has not been described for cefazolin. We developed a protocol to bind cefazolin to bone chips by means of a hydrogel composed of proteins naturally present in the human body. Method. Three types of bone chips were evaluated: fresh frozen, decellularized frozen and decellularized lyophilized. Bone chips were incubated with 20 mg/ml cefazolin or treated with liquid hydrogel containing either 1 mg/ml fibrin or 1 mg/ml collagen and 20 mg/ml cefazolin. The cefazolin hydrogel was distributed in the porous structure by short vacuum treatment. Bone chips with cefazolin but without hydrogel were either incubated for 20 min- 4h or also treated with vacuum. Cefazolin elution of bone chips was carried out in fetal bovine serum and analysed by Ultra Performance Liquid Chromatography – Diode Array Detection. Results. Soaking of bone chips without hydrogel resulted in a quick release of cefazolin, which was limited to 4 hours. When vacuum was applied elution of >1 µg/ml cefazolin was measured for up to 36 hours. Combination with collagen hydrogel resulted in a higher cefazolin concentration released at 24 hours (3.9 vs 0.3 µg/ml), but not in a prolonged release. However, combination of decellularized frozen bone chips with fibrin hydrogel resulted in an initial release of 533 µg/ml followed by a gradual decline reaching the minimal inhibitory concentration for S. aureus at 72 hours (1.7 µg/ml), while not measurable anymore after 92 hours. Conclusions. Processed bone chips with hydrogel-cefazolin showed a markedly prolonged cefazolin release. When combined with a fibrin hydrogel, high initial peak levels of cefazolin were obtained, followed by a decreasing release over the following three days. This elution profile seems desirable, with high initial levels to maximize anti-bacterial action and low levels for a limited time to stimulate osteogenesis. Further preclinical studies are warranted to show effectiveness of hydrogel-cefazolin impregnated bone chips

Accurate identification of pathogens is a crucial step for successful treatment of implant-associated infections. Sonication of explanted foreign material and subsequent sonicate-fluid culture is regarded to be more sensitive than conventional tissue culture. However, the duration of incubation of cultures remains controversial. The aim of our study was to evaluate diagnostic yield of prolonged 14-days incubation compared to more classical 7-days incubation. Consecutive sonicate fluid culture results from a 2-years period (2013–2015) were retrospectively analysed. All sonicate fluids were cultured aerobically, anaerobically and using blood culture system for 14 days and inspected for growth on day 1, 2, 7 and 14 days. Terminal subcultivation was performed on day 7 from broth and blood culture system for additional 7 days aerobically and anaerobically. Time of bacterial isolation was recorded. Microbiological significance was determined based on isolate quantity and concomitant growth in conventional tissue cultures. A total of 394 sonicate fluid cultures from 304 patients (8–95 years, mean age 62), 53.9% (n=164) women, were analysed. 51.0% (n=201) were from explanted osteosynthetic material, 37.6% (n=148) from hip prosthesis and 11.4% (n=45) from knee prosthesis. Overall, 57.1% (n=225) of cultures were positive. Among them, 71.1% (n=160) were monomicrobial, 21.3% bimicrobial and 7.6% (n=17) polymicrobial. In total, 312 bacterial isolates were isolated. The most frequently isolated bacteria were coagulase-negative staphylococci (CoNS) 34.6% (n=108), Staphylococcus aureus 16.4% (n=51) and Propionibacterium acnes 11.2% (n=35). Gram-negative bacteria and anaerobes represented 18.3% (n=57) and 14.4% (n=45) of isolates, respectively. Among all sonicate fluid cultures, 92.0% (n=207) were positive after 7 days while 8.0% (n=18) were positive only after prolonged 14-days incubation with P. acnes being the predominant bacteria isolated after prolonged incubation. Among all P. acnes isolates 57.1% (n=20) were isolated within 7 days and 42.9% (n=15) within 14 days. Based on microbiologic criteria, 45.7% (n=16) of them were diagnostic; 37.1% (n=13) among early isolates and 8.6% (n=3) among late isolates, difference being statistically significant (p=0.016). Prolonged 14-days incubation of sonicate fluid culture for the diagnosis of implant-associated infections offers only minor 8.0% improvement with regard to conventional 7-days incubation. The majority of P. acnes isolated after prolonged incubation are non-diagnostic using microbiologic criteria. Caution in an interpretation of significance of P. acnes isolated after 14-days incubation is warranted. However, due to a significant impact on patient management prolonged 14-days incubation is still recommended

Increased operative time has been previously identified as a risk factor for complications following total joint arthroplasty. The purpose of this study was to evaluate the influence of surgical time on 30-day complications following Total Knee Arthroplasty (TKA) and to determine if there were specific time intervals associated with worse outcomes. The American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database was utilized to identify patients ≥18 years who underwent TKA between 2005 and 2016 using procedural codes. Patients with surgical durations >240 minutes were excluded. Patient demographics, operation length, and 30-day major and minor complication rates were captured. Multivariable logistic regression was used to determine if the rate of complications differed depending on length of operation, while adjusting for age, sex, American Society of Anaesthesiologists (ASA) class, functional status, smoking status, comorbidities, anesthesia type, and Body Mass Index (BMI). Multivariable linear regression was used to identify independent predictors of duration of surgery. A total of 213,921 TKA patients (average age 67 ± 10 years) were identified from the database. Within 30-days of the index procedure, 3,321 (1.55%) experienced a major complication, and 6,144 (2.86%) experienced a minor complication. Mean surgical duration was 92 minutes (range 20 – 240). Underweight, or overweight/obese BMI, male sex, hypertension, cancer, dependent functional status, epidural anaesthesia, and ASA class III and IV were determined to be independent predictors of prolonged operation length, while COPD, current smoking, spinal anesthesia, and older age predicted lower operation times. Operation lengths ≥ 90 minutes significantly increased the risk of both major and minor complications (P>0.01). Specifically, the rates of deep vein thrombosis (DVT), unplanned reintubation, surgical site infection (SSI), sepsis, and wound disruption were higher for patients whose operations lasted ≥ 90 minutes (p 0.05). With respect to specific complications, following covariate adjustment, operation lengths ≥ 90 minutes increased the risk of DVT, deep and superficial incisional SSI, and wound disruption, while operation lengths ≥ 120 minutes increased the risk of deep, non-incisional SSI, and sepsis (P < 0 .01). Surgical times of ≥90 minutes independently increase the 30-day risk of DVT, infection, and wound disruption following TKA after controlling for other variables that influence operation length. This study confirms the importance of surgical duration on early outcomes following TKA

Osteoarthritis (OA) is a debilitating disease and the most common joint disorder worldwide. Although the development of OA is considered multifactorial, the mechanisms underlying its initiation and progression remain unclear. A prominent feature in OA is cartilage degradation typified by the progressive loss of extracellular matrix components - aggrecan and type II collagen (Col II). Cartilage homeostasis is maintained by the anabolic and catabolic activities of chondrocytes. Prolonged exposure to stressors such as mechanical loading and inflammatory cytokines can alter the phonotype of chondrocytes favoring cartilage catabolism, and occurs through decreased matrix protein synthesis and upregulation of catabolic enzymes such as aggrecanases (ADAMTS-) 4 and 5 and matrix metalloproteinases (MMPs). More recently, the endoplasmic reticulum (ER) stress response has been implicated in OA. The ER-stress response protects the cell from misfolded proteins however, excessive activation of this system can lead to chondrocyte apoptosis. Acute exposure of chondrocytes to IL-1β has been demonstrated to upregulate ER-stress markers (GADD153 and GRP78), however, it is unclear whether the ER-stress response plays a role on chronic IL-1β exposure. The purpose of this study was to determine whether modulating the ER stress response with tauroursodeoxycholic acid (TUDCA) in human OA chondrocytes during prolonged IL-1β exposure can alter its catabolic effects. Articular cartilage was isolated from donors undergoing total hip or knee replacement. Chondrocytes were recovered from the cartilage of each femoral head or knee by sequential digestion with Pronase followed by Collagenase, and expanded in DMEM-low glucose supplemented with 10% FBS. Chondrocytes were expanded in flasks for one passage before being prepared for micropellet culture. Chondrocyte pellets were cultured in regular growth medium (Control), medium supplemented with IL-1β [10 ng/mL], TUDCA [100 uM] or IL-1β + TUDCA for 12 days. Medium was replaced every three days. Cartilage explants were prepared from the donors undergoing knee replacement, and included cartilage with the cortical bone approximately 1 cm2 in dimension. Explants were cultured in the above mentioned media, however, the incubation period was extended to 21 days. RNA was extracted using Geneaid RNA Mini Kit for Tissue followed by cDNA synthesis. QPCR was performed using Cyber Green mastermix and primers for the following genes: ACAN (aggreacan), COL1A1, COL2A1, COL10A1, ADAMTS-4, ADAMTS-5, MMP-3, and MMP-13, on an ABI 7500 fast qPCR system. Although IL-1β did not significantly decrease the expression of matrix proteins, it did increase the expression of ADAMTS-4, −5, and MMP3 and −13 when compared to controls (Kruskal-Wallis, p < 0 .05, n=3). TUDCA treatment alone did not significantly increase the expression of catabolic enzymes but it did increase the expression of collagen type II. When IL-1β was coincubated with TUDCA, the expression of ADAMTS-4, ADAMTS-5, and MMP-13 significantly decreased by ∼40-fold, ∼10-fold, and ∼3-fold, respectfully. We provide evidence that the catabolic activities of IL-1β on human cartilage can be abrogated through modulation of the ER stress response

Summary Statement. Prolonged presence of VEGF (released from gelatin microspheres) led to a significant increase in scaffold vascularization when applied in vivo. Bioprinted scaffolds with regional VEGF presence retained their architecture and regional vessel formation occurred. Introduction. Tissue-engineered bone constructs need timely vascularization for optimal performance in regeneration. A potent stimulus of vascularization is vascular endothelial growth factor (VEGF), a factor with a short half-life time. Controlled release of VEGF from gelatin microparticles (GMPs) was investigated as a means to prolong VEGF presence at the preferred location within bioprinted scaffolds, and study subsequent vascularization. Methods. Release of VEGF from GMPs was measured with ELISA and bioactivity was assessed using human endothelial progenitor cells (EPC) in Transwell and real-time migration assays. Matrigel scaffolds containing EPCs and VEGF, which was released either in a fast or sustained fashion by application of GMPs, were investigated for their in vivo vasculogenic capacity. In addition, regional differences with respect to VEGF release were introduced in 3D-printed EPC-laden scaffolds. Scaffolds were implanted in subcutaneous pockets in mice for 1 week and analyzed for vessel formation. Results. Release of VEGF from GMPs was continuous for 3 weeks. VEGF bioactivity was confirmed, EPC migration in the presence of GMP-released VEGF was indistinguishable from VEGF added to the medium. Implantation in subcutaneous pockets in mice demonstrated that vessel formation was significantly higher in the VEGF sustained release group when compared to fast release or control groups. In addition, the different regions in the bioprinted scaffolds were retained and vessel formation occurred analogous with the results seen in the Matrigel plugs. Discussion/Conclusion. We conclude that GMPs are suitable to generate sustained release profiles of bioactive VEGF, and that they can be used to generate defined differentiation regions in 3D printed heterogeneous constructs. The prolonged presence of VEGF led to a significant increase in scaffold vascularization when applied in vivo

Purpose: To analyse prolonged combinations of oral intracellular-effective antibiotics plus two-stage exchange surgery for treatment of chronic THA and TKA infections. Materials and Methods: Definition of infected case: more than 3 months from surgery; multiple positive intraoperative cultures and/or active fistulae. 33 patients were treated from 1996 to 2002: 8 THA, 5 hip hemiarthroplasties, 20 TKA. Bacteriology: 24 Staphylococci of which 16 were methycillin-resistant, 7 multi-resistant Gram-negative, 2 Cory-nebacteriae; 7 polymicrobian. Antibiotic therapy: two simultaneous oral antibiotics, selected according to bacterial sensitivity and intracel-lular effectiveness (rifampin, ofloxacin, ciprofloxacin, levofloxacin, trimethoprim-sulfamethoxazole, fosfomicin, linezolid, doxiciclin), were used on an outpatient basis (between 1st and 2nd surgery, and after 2nd surgery until serological normalization). Patients received intravenous antibiotics and were in-hospital only for one week after surgery. Surgery: two-stage exchange with 2nd stage delayed until clinical and serological normalization. Healing of infection: absence of clinical, serological and radiological evidence of infection along all follow-up. Prospective follow-up: 24-96 months. Results: Healing of infection: 32/33 patients (97%). Treatment failure: 1 patient (TKA) (3%). THA: 8/8 infections healed: 1 Girdlestone patient (1st stage of exchange) rejected reimplantation; 7 two-stage exchange (good/excellent objective and subjective result). Hip hemiarthroplasty: 5/5 infections healed: 3 Girdlestone (1st stage of exchange surgery, 2nd stage rejected because of hemiplegia or Alzheimer); 2 two-stage exchange (good/excellent objective and subjective result). TKA: 19/20 infections healed: 3 resection-arthroplasty (1st stage of exchange surgery, 2nd stage rejected because of Buerger, cirrhosis or Alzheimer); 17 two-stage exchange (15 good/excellent objective and subjective results, 1 patient needed a debridement 2 months after 2nd surgery because of prolonged aseptic drainage and healed uneventfully, 1 failure described). Conclusions: Prolonged combinations of oral intracellular-effective antibiotics associated with two-stages exchange surgery is a promising alternative for treating deep chronic THA and TKA infections. Longer follow-up and larger series are necessary

Introduction Although subjects with whiplash associated disorders lack demonstrable physical injury, many exhibit prolonged disability. Disability appears unrelated to the severity of the collision. A prospective study was carried out to identify factors predictive of prolonged disability. Methods One hundred and forty-seven subjects with recent whiplash injury were interviewed for putative disability risk factors. One hundred and thirty-five were re-interviewed 12 months later to assess the degree and duration of disability. Bi-variate and multi-variate analyses were undertaken to measure the association between putative risk factors and measures of outcome. Results The bodily pain score and role emotional scores of the SF-36 health questionnaire showed a consistent significant positive association with better outcomes. After adjustment for bodily pain score and role emotional scores, consulting a lawyer was associated with less improvement in NPOS (p< 0.05), but there was no association with change in VAPS. Consulting a lawyer was associated with a lesser chance of claim settlement (p< 0.01) and a greater chance of still having treatment (p< 0.01) after one year, but there was no significant association with rate of return to work. The degree of damage to the vehicle was not a predictor of outcome. Conclusions SF-36 scores for bodily pain and role emotional are useful means of identifying subjects at risk of prolonged disability. The findings support the implementation of an insurance system designed to minimise litigation. In relation to the conduct of this study, one or more of the authors is in receipt of a research grant from a non-commercial source

Tungsten has been increasing in demand for use in manufacturing and recently, medical devices, as it imparts flexibility, strength, and conductance of metal alloys. Given the surge in tungsten use, our population may be subjected to elevated exposures. For instance, embolism coils made of tungsten have been shown to degrade in some patients. In a cohort of breast cancer patients who received tungsten-based shielding for intraoperative radiotherapy, urinary tungsten levels remained over tenfold higher 20 months post-surgery. In vivo models have demonstrated that tungsten exposure increases tumor metastasis and enhances the adipogenesis of bone marrow-derived mesenchymal stem cells while inhibiting osteogenesis. We recently determined that when mice are exposed to tungsten [15 ppm] in their drinking water, it bioaccumulates in the intervertebral disc tissue and vertebrae. This study was performed to determine the toxicity of tungsten on intervertebral disc. Bovine nucleus pulposus (bNP) and annulus fibrosus (bAF) cells were isolated from bovine caudal tails. Cells were expanded in flasks then prepared for 3D culturing in alginate beads at a density of 1×10. ∧. 6 cells/mL. Beads were cultured in medium supplemented with increasing tungsten concentrations in the form of sodium tungstate [0, 0.5, 5, 15 ug/mL] for 12 days. A modified GAG assay was performed on the beads to determine proteoglycan content and Western blotting for type II collagen (Col II) synthesis. Cell viability was determined by counting live and dead cells in the beads following incubation with the Live/Dead Viability Assay kit (Thermo Fisher Scientific). Cell numbers in beads at the end of the incubation period was determined using Quant-iT dsDNA Assay Kit (Thermo Fisher Scientific). Tungsten dose-dependently decreased the synthesis of proteoglycan in IVD cells, however, the effect was significant at the highest dose of 15 ug/mL. (n=3). Furthermore, although tungsten decreased the synthesis of Col II in IVD cells, it significantly increased the synthesis of Col I. Upregulation of catabolic enzymes ADAMTS4 and −5 were also observed in IVD cells treated with tungsten (n=3). Upon histological examination of spines from mice treated with tungsten [15 ug/mL] in their drinking water for 30 days, disc heights were diminished and Col I upregulation was observed (n=4). Cell viability was not markedly affected by tungsten in both bNP and bAF cells, but proliferation of bNP cells decreased at higher concentration. Surprisingly, histological examination of IVDs and gene expression analysis demonstrated upregulation of NGF expression in both NP and AF cells. In addition, endplate capillaries showed increases in CGRP and PGP9.5 expression as determined on histological sections of mouse IVDs, suggesting the development of sensory neuron invasion of the disc. We provide evidence that prolonged tungsten exposure can induce disc fibrosis and increase the expression of markers associated with pain. Tungsten toxicity may play a role in disc degeneration disease

Introduction: Proximal femur fractures are an important cause of morbidity in the elderly and comprise a significant proportion of acute orthopaedic admissions. Aim: To study the demographics of and factors responsible for prolonged hospital stay following admission with a fractured neck of femur. Methods: We reviewed of a consecutive series of hip fractures presenting to our unit over a five-year period between 2000 and 2004. A complete patient cohort was obtained from the casualty register, the OT register and from a Hospital In-Patient Enquiry (HIPE) database. Pathological, high energy and peri-prosthetic fractures were excluded. We reviewed records to obtain demographic and clinical data including age, sex, length of stay, time to operation and comorbidities. Those who remained in-patients for greater than 14 days were analysed for reasons responsible for prolonged stay. Results: 717 low-energy hip fractures treated in the period 2000–2004. The M:F ratio was 1:3.3. The average age for males and females was 73.6 yrs (SD 11.23) and 79.6 yrs (SD 9.74) respectively. The overall average length of stay was 28 days. 351 patients (49%) stayed in hospital > 14 days. For these, the mean length of stay was 48 days (range 15–443). Reasons for prolonged stay included acute medical and surgical issues (32%), social and placement issues (22%), active chronic disease (17%) and post-operative complications (4%). Conclusion: Hip fractures in the elderly constitute a significant burden on an acute trauma service. Further strategies are needed to address both medical and social reasons for prolonged stay in and delayed discharge from hospital. A national hip fracture audit is required

The efficacy of traction before an attempted closed reduction for patients with developmental dislocation of the hip remains controversial. We treated 55 children (62 dislocations of the hip) by preliminary, prolonged traction for a mean of eight weeks. All were followed up for at least two years in order to observe the development of any avascular changes within the femoral head. Of the 55 children, 27 (31 dislocations) were followed up until they were over six years of age. Fifty-seven of the 62 hips (92%) showed a successful closed reduction. Only one had radiological evidence of avascular necrosis of the femoral head. Of the 31 hips which were followed up to over six years of age, 15 (48%) showed residual subluxation. Our method of prolonged preliminary traction leads to a high rate of successful closed reduction, a low incidence of avascular necrosis and a reduced need for secondary operations

Study design: A prospective study of 135 subjects with whiplash injury. Objectives: To identify factors predictive of prolonged disability following whiplash injury. Summary of background data: Although subjects with whiplash associated disorders lack demonstrable physical injury, many exhibit prolonged disability. Disability appears unrelated to the severity of the collision. Methods: 147 subjects with recent whiplash injury were interviewed for putative risk factors for disability. 135 were re-interviewed 12 months later to assess degree of duration of disability. Bivariate and multivariate analyses were undertaken to measure the association between putative risk factors and measures of outcome. Results: The bodily pain score and role emotional scores of the SF-36 health questionnaire showed a consistent significant positive association with better outcomes. After adjustment for bodily pain score and role emotional scores, consulting a lawyer was associated with less improvement in NPOS (p< 0.01) after one year, but there was no significant association with rate of return to work. The degree of damage to the vehicle was not a predictor of outcome. Conclusions: SF-36 scores for bodily pain and role emotional are useful means of identifying subjects at risk of prolonged disability. The findings support the implementation of an insurance system designed to minimise litigation