Critical size bone defects pose a serious clinical problem, as the intrinsic healing capacity of bone fails due to the size of the defect. Bone healing might be aided by addition of 1,25(OH)2 vitamin D3 (vitD3) to bone tissue engineering scaffolds. VitD3can promote osteogenic differentiation of human stem cells such as adipose stem cells (hASCs), which is a clinical-relevant source of mesenchymal stem cells. However, it is unknown which release kinetics of vitD3, i.e. short or sustained release from scaffolds, leads to the most optimal osteogenic differentiation of hASCs. We hypothesized that sustained release of vitD3 leads to more osteogenic differentiation of hASCs than shorter applications. hASCs (1×105, passage 3–4) were seeded on 20 ± 1 mg of calcium phosphate particles (day 0), cultured for 20 days, and treated with a total amount of 124 ng vitD3. This treatment was provided either during 30 min before seeding (pre-incubation, short stimulation: [200 nM]), after seeding, over the first 2 days (burst- release high: [100 nM]), or over the total culture period of 20 days (sustained-release: [10 nM]). In the extra condition: burst-release low the hASCs were treated for 2 days after seeding with 6.2 ng vitD3 ([10 nM]) per day. Live/dead staining followed by fluorescent microscopy showed that hASCs attached to the calcium phosphate particles and were mostly viable (±75 %) at day 2. VitD3 applied for any duration did not affect the proliferation of hASCs at day 7 and day 20, measured with an alamar blue assay. At day 7, sustained-release increased the release of active alkaline phosphatase on average by 3.5-fold, compared to all the other conditions. At day 20, this was increased 4.3-fold. At both day 7 and day 20 total protein levels were similar in all conditions. Our results suggest that sustained release of VitD3 from bone tissue engineered scaffolds may be beneficial for the osteogenic differentiation of human stem cells for the treatment of critical bone size defects

While mesenchymal stromal cells (MSCs) are a very attractive cell source for cartilage regeneration, an inherent tendency to undergo hypertrophic maturation and endochondral ossification; as well as insufficient extracellular matrix production still prevent their clinical application in cell –based cartilage repair therapies. We recently demonstrated that intermittent treatment of MSC with parathyroid hormone-related protein (PTHrP) during in vitro chondrogenesis significantly enhanced extracellular matrix deposition and concomitantly reduced hypertrophy (1) opposite to constant PTHrP treatment, which strongly suppressed chondrogenesis via the cAMP/PKA pathway (2). Since signal timing seemed to be decisive for an anabolic versus catabolic outcome of the PTHrP treatment, we here aimed to investigate the role of PTHrP pulse frequency, pulse duration and total weekly exposure time in order to unlock the full potential of PTHrP pulse application to enhance and control MSC chondrogenesis. Human bone marrow-derived MSC were subjected to in vitro chondrogenesis for six weeks. From day 7–42, cells were additionally exposed to 2.5 nM PTHrP(1–34) pulses or left untreated (control). Pulse frequency was increased from three times per week (3×6h/week) to daily, thereby maintaining either pulse duration (6h/d, total 42 h/week) or total weekly exposure time (2.6h/d, total 18 h/week). A high frequency of PTHrP-treatment (daily) was important to significantly increase extracellular matrix deposition and strongly suppress ALP activity by 87 %; independent of the pulse duration. A long pulse duration was, however, critical for the suppression of the hypertrophic marker gene IHH, while MEF2C and IBSP were significantly suppressed by all tested pulse duration and frequency protocols. COL10A1, RUNX2 and MMP13 mRNA levels remained unaffected by intermittent PTHrP. A drop of Sox9 levels and a decreased proliferation rate after 6 hours of PTHrP exposure on day 14 indicated delayed chondroblast formation. Decreased IGFBP-2, -3 and -6 expression as well as decreased IGFBP-2 protein levels in culture supernatants suggested IGF-I-related mechanisms behind anabolic matrix stimulation by intermittent PTHrP. The significant improvement of MSC chondrogenesis by the optimization of intermittent PTHrP application timing revealed the vast potential of PTHrP to suppress hypertrophy and stimulate chondrogenic matrix deposition. A treatment with PTHrP for 6 hours daily emerged as the most effective treatment mode. IGF-I and Sox-9 related mechanisms are suggested behind anabolic effects and delayed chondroblasts formation, respectively. Thus, similar to the established osteoporosis treatment, daily injections of PTHrP may become clinically relevant to support cartilage repair strategies relying on MSCs like subchondral bone microfracturing and autologous MSC implantation

Summary Statement. The stable inhibition of miR-214 in the aged osteoporotic rats induced by OVX could be achieved by periodic administration of AntagomiR-214 at a dosage of 4 mg/kg and at an interval of 7 days, which will provide a potential bone anabolic strategy for treatment of osteoprosis. Introduction. MiR-214 has a crucial role in suppressing bone formation and miR-214 inhibition in osteogenic cells may be a potential anabolic strategy for ameliorating osteoporosis (Wang X, et al. 2013). An aged ovariectomised rat has been regarded as a golden model to test bone anabolic agents for reversing established osteoporosis in aged postmenopausal women (Li X, et al. 2009). However, there is still lack of evidence to demonstrate bone anabolic potential of therapeutic inhibition of miR-214 within osteogenic cells in the golden model. So, it should be necessary to establish RNAi-based administration protocol toward stable inhibition of miR-214 at a low level in the golden model. A targeted delivery system specifically facilitating Antagomir-214 approaching osteogenic cells, i.e. (Asp-Ser-Ser). 6. -liposome (Zhang G, et al 2012), was employed in this study. Objectives. This study was to investigate optimal dosage and duration for therapeutic inhibition of miR-214 within osteogenic cells in the aged osteoporotic rats induced by ovariectomy. Materials and Methods. Six-month-old female Sprague-Dawley rats were ovariectomised (OVX) and left untreated for 12 months to establish aged osteoporosis. To determine the optimal dosage for therapeutic inhibition of miR-214, the OVX rats were injected intravenously with the AntagomiR-214 at a dosage of 0.5mg/kg, 1mg/kg, 2mg/kg, 4mg/kg, 6mg/kg and 8mg/kg (n=6 for each dosage group) delivered by (Asp-Ser-Ser). 6. -liposome, respectively. Thereafter, miR-214 expression level in osteogenic cells from bilateral femur was quantified at day 2 post injection by real-time PCR analysis in combination with laser captured dissection (LCM). To determine the optimal duration of miR-214, the OVX rats were intravenously injected with the AntagomiR-214 (AntagomiR-214 group) or non-sense AntagomiR-214 (NC group) delivered by (Asp-Ser-Ser). 6. -liposome at the optimal dosage or (Asp-Ser-Ser). 6. -liposome alone (Vehicle group). Then, the miR-214 level in osteogenic cells from bilateral femur was quantified at 1, 3, 5, 7, 9, 12, 14, 16, 21 day after the single dosing (n=6 for each time-point) by real-time PCR analysis in combination with LCM, respectively. To examine the long-term effect of the AntagomiR-214 after periodic pulsed dosing, the OVX rats were administrated with the AntagomiR-214 at the optimal dosage and duration for 5 repeated injections and then the miR-214 level in osteogenic cells from bilateral femur was quantified by real-time PCR analysis in combination with LCM. Results. The miR-214 level was efficiently decreased in a dose-dependent manner by the AntogomiR-214 and reached the level lower than 10% of the baseline at a dosage of 4 mg/kg at least in the aged osteoporotic rats. The effective duration for miR-214 at a level lower than 50% of the baseline lasted for 7 days in the osteoporotic rats after the single dosing. The miR-214 level was continuously lowered until 28 days and continuously maintained later at the level lower than 10% of the baseline by the 5 pulsed dosing of the AntagomiR-214 at an interval of 7 days and at a dosage of 4 mg/kg in the osteoporotic rats. Conclusions. The stable inhibition of miR-214 for bone anabolic strategy in the aged osteoporotic rats induced by OVX could be achieved by periodic administration of AntagomiR-214 at a dosage of 4 mg/kg and at an interval of 7 days

After knee replacement, therapy resistant, chronic synovitis is common and leads to effusion and pain. A cohort of 55 patients with 57 knee replacements and chronic synovitis underwent radiosynoviorthesis. In summary, 101 joints were treated using 182±9 MBq of 90Y-citrate. The number of radiosynoviorthesis ranged from 1 to 4 (53%, 21%, 23%, and 4%). Every patient received a 99mTc-MDP scintigraphy before and three months after every radiosynoviorthesis. Follow-up ranged from 5.7 to 86.7 months. For qualitative analysis, an four steps scoring was used (0 = no response or worsening, 1 = slight, 2 = good, 3 = excellent response). For quantification, the uptake was determined within the 99mTc-MDP scintigraphy soft tissue phase before and after therapy. At the end of long-term follow-up 27% of patients have an excellent, 24% good, 30% slight and 20% no response. The duration of response was 7.5±8.3 months (maximum 27 months). In repeated treatment, the effect after the first therapy was lesser than in patients who received a single treatment in total. However, three months after the last radiosynoviorthesis, patients with repeated treatment showed a similar effectiveness than single treated patients. At the end of long-term follow-up, patients with repeated radiosynoviorthesis had a higher effectiveness at similar duration response. In the 99mTc-MDP scan 65% of patients showed a reduction of uptake. When comparing subjective and objective response 78% of patients showed a concordance in both, symptoms and scintigraphy. Pilot histological analysis revealed that the synovitis is triggered by small plastic particles. Radiosynoviorthesis is effective in patients with knee replacement and chronic synovitis. It shows good subjective and objective response rates and long response duration. Repeated treatment leads to a stronger long-time response. The chronic synovitis is caused by plastic particles, which result from the abrasion of the polymeric inlay of endoprothesis

Abstract. Introduction. The medial meniscus is crescent shaped and it is wider posteriorly than anteriorly. It covers up to 60 % of the articular surface of medial tibial condyle and helps with the loading distribution in the medial compartment. Meniscal lesions occur in association with ACL tears in 60 % of the time. The posterior aspect of the menisco-capsular junction is known as the meniscal rampzone. If not addressed during surgery, it could lead to unfavourable results. Objective. Incidence of ramp lesion following ACL injuries. Methods. Observational study of 100 patients at EL Hadara Main University Hospital who underwent anterior cruciate ligament reconstruction. MRI and arthroscopic diagnosis was done to detect Ramp lesions associated with ACL ruptures in November 2017 till November 2019. Results. Incidence was 9%. Duration of injury and increased medial meniscal slope were associated with increased incidence of ramp lesion. MRI signs were present in 79% of cases without Ramp lesion, 100% in Cases with ramp lesion. Mode of Injury and presence of locking or giving way symptoms were not associated with increased incidence. Conclusion. The ramp lesion at the posterior aspect of the meniscus is difficult to visualize from standard anterior portals and is, therefore, frequently missed and can be underestimated. Also, there are no specific MRI signs of this lesion. The overall incidence of ramp lesions in 100 cases that had undergone ACL reconstruction in our study was 9 %. It was found also that the longer the duration from injury, the more likely ramp lesion would occur. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

Ankle fractures are among the most common types of fractures. If surgery is not performed within 12 to 24 hours, ankle swelling is likely to develop and delay the operative fixation. This leads to patients staying longer in the ward waiting and increased hospital occupancy. This prolonged stay has significant financial implication as well as it is frustrating for both patients and health care professionals. The aim was to formulate a pathway for the ankle fracture patients coming to the emergency department, outpatients and planned for operative intervention. To identify whether pre-operative hospital admissions of stable ankle fracture patients are reduced with the implementation of the pathway. We formulated an ankle fracture fixation pathway, which was approved for use in December 2020. A retrospective analysis of 6 months hospital admissions of ankle fracture patients in the period between January to June 2020. The duration from admission to the actual surgery was collected to review if some admissions could have been avoided and patients brought directly on the surgery day. A total of 23 patients were included. Mean age was 60.5 years and SD was 17years. 94% of patients were females. 10 patients were appropriately discharged.7 Patients were appropriately admitted. 6 Patients were unnecessarily admitted. These 6 patients were admitted on presentation to ED. Retrospective analysis of this audit showed that this cohort of patients met the safe discharge criteria and could have been discharged. Duration of unnecessary stay ranged from 1 to 11 days (21 days in total). Total saving could have been £6300. Standards were met in 74% of cases. Preoperative hospital admission could be reduced with the proposed pathway. It is a valuable tool to be used and should be implemented to reduce unnecessary hospital admissions

Septic arthritis following anterior cruciate ligament reconstruction (ACLR) is a rare and serious complication. Previous studies have shown that septic arthritis is associated with inferior outcome of ACLR. Despite that, there is no standardized treatment protocol, and the course of the disease has mainly been studied within single institutions with a small number of patients. The aim of the present study is to describe the course of septic arthritis following ACLR in a large nationwide cohort. The hypothesis was that the clinical presentation of septic arthritis following ACLR varies according to the infectious agent. The present cohort represents patients with septic arthritis identified in a previous study that analyzed compensation claims reported to the Swedish national insurance company (Löf) in 2005–2014 (1). The diagnosis was confirmed by medical experts at Löf after review of medical records. We conducted a comprehensive analysis of the medical records as well as data available from the Swedish National Knee Ligament Registry (SNKLR) for the study group. The study involved 158 patients who received compensation due to developing septic arhtirits. 94 (59.9%) patients were infected with Coagulase negative staphylococci (CoNS), and 25 patients by Staphyolococcus Aureus (S.Aureus) (15.9%). There was a significant difference between the groups regarding Maximum CRP (p<0.001), and duration between ACLR and first washout operation (p<0.005). S.aureus group had the higest maximum CRP (281) and the shortest duration between ACLR and first washout operation (12 days). The Clinical presentation of septic arthritis following ACLR can vary according to the agent causing the infection, and low virulent agents are responsible for the majority of the infections. Clinicians need to be aware of these differences and consider them when making diagnosis or treatment decisions

Gait analysis is an indispensable tool for scientific assessment and treatment of individuals whose ability to walk is impaired. The high cost of installation and operation are a major limitation for wide-spread use in clinical routine. Advances in Artificial Intelligence (AI) could significantly reduce the required instrumentation. A mobile phone could be all equipment necessary for 3D gait analysis. MediaPipe Pose provided by Google Research is such a Machine Learning approach for human body tracking from monocular RGB video frames that is detecting 3D-landmarks of the human body. Aim of this study was to analyze the accuracy of gait phase detection based on the joint landmarks identified by the AI system. Motion data from 10 healthy volunteers walking on a treadmill with a fixed speed of 4.5km/h (Callis, Sprintex, Germany) was sampled with a mobile phone (iPhone SE 2nd Generation, Apple). The video was processed with Mediapipe Pose (Version 0.9.1.0) using custom python software. Gait phases (Initial Contact - IC and Toe Off - TO) were detected from the angular velocities of the lower legs. For the determination of ground truth, the movement was simultaneously recorded with the AS-200 System (LaiTronic GmbH, Innsbruck, Austria). The number of detected strides, the error in IC detection and stance phase duration was calculated. In total, 1692 strides were detected from the reference system during the trials from which the AI-system identified 679 strides. The absolute mean error (AME) in IC detection was 39.3 ± 36.6 ms while the AME for stance duration was 187.6 ± 140 ms. Landmark detection is a challenging task for the AI-system as can clearly be seen be the rate of only 40% detected strides. As mentioned by Fadillioglu et al., error in TO-detection is higher than in IC-detection

A painful “dreaded black line” (DBL) has been associated with progression to complete fractures in atypical femur fractures (AFF). Adjacent sclerosis, an unrecognized radiological finding, has been observed in relation to the DBL. We document its incidence, associated features, demographics and clinical progression. We reviewed plain radiographs of 109 incomplete AFFs between November 2006 and June 2021 for the presence of sclerosis adjacent to a DBL. Radiographs were reviewed for location of lesions, and presence of focal endosteal or periosteal thickening. We collected demographical data, type and duration of bisphosphonate therapy, and progression to fracture or need for prophylactic stabilization, with a 100% follow up of 72 months (8 – 184 months). 109 femurs in 86 patients were reviewed. Seventeen sclerotic DBLs were observed in 14 patients (3 bilateral), involving 15.6% of all femora and 29.8% of femora with DBLs. Location was mainly subtrochanteric (41.2%), proximal diaphyseal (35.3%) and mid-diaphyseal (23.5%), and were associated with endosteal or periosteal thickening. All patients were female, mostly Chinese (92.9%), with a mean age of 69 years. 12 patients (85.7%) had a history of alendronate therapy, and the remaining 2 patients had zoledronate and denosumab therapy respectively. Mean duration of bisphosphonate therapy was 62 months. 4 femora (23.5%) progressed to complete fractures that were surgically managed, whilst 6 femora (35.3%) required prophylactic fixation. Peri-lesional sclerosis in DBL is a new radiological finding in AFFs, predominantly found in the proximal half of the femur, at times bilateral, and are always associated with endosteal or periosteal thickening. As a high proportion of patients required surgical intervention, these lesions could suggest non-union of AFFs, similar to the sclerotic margins commonly seen in fractures with non-union. The recognition of and further research into this new feature could shed more light on the pathophysiological progression of AFFs

To determine risk factors of infection in total knee arthroplasty. This descriptive study was conducted in the Department of Orthopedics for a duration of three years from January 2016 to January 2019. All patients undergoing primary total knee replacement were included in the study. Exclusion criteria were all patients operated in another hospital and revision total knee replacement. All patients were followed up at 2, 4, 8, 12 and 24 weeks post-operatively. Signs of inflammation and inflammatory markers such as total leukocyte count (TLC), C-reactive protein (CRP) and ESR were measured. Risk factors like age, body mass index (BMI), ASA, co-morbid conditions were also noted. A total of 78 patients underwent primary unilateral Total Knee Replacement (TKR) during the study period. Of these, 30 (34.09%) were male and 48 (61.54%) female patients. Mean age of patients was 68.32 ± 8.54 years. Average BMI 25.89 Kg/m2 .Osteoarthritis was the pre-dominant cause of total knee replacement (94.87%). Among co-morbid factors 33.33% were diabetic, 28.20% having ischemic heart disease and 12.82% with chronic lung disease. Upon anaesthesia fitness pre-operatively, 91.02% patients had an American society of anaesthesiologist score (ASA) between 0–2 while 07 (8.97%) between 3- 5. Average duration of surgery was 85.62± 4.11 minutes. 6.41% cases got infected. In majority of the infected cases (60%), Staphylococcus aureus was the infective organism. Diabetes Mellitus (p=0.01) and Obesity (p=0.02) had a significant relation to post-operative infection. Pre-operative risk evaluation and prevention strategies along with early recognition of infection and control can greatly reduce the risk of joint infection post-TKR which will not only improve the mobility of patient but also its morbidity and mortality as well. Key Words:. C-reactive protein (CRP), Erythrocyte Sedimentation Rate (ESR), Staphylococcus aureus, Total Knee Arthroplasty (TKA)

Introduction. As per national guidelines for Ankle fractures in the United Kingdom, fractures considered stable can be treated with analgesia, splinting and allowed to weight bear as tolerated. The guidelines also suggest further follow-up not mandatory. This study was aimed at evaluating the current clinical practice of managing stable ankle fractures at a university hospital against national guidelines. Method. The study was undertaken using retrospectively collected data, the inclusion criteria being all adults with stable ankle fracture pattern treated non-operatively between December 2022 and April 2023. Collected data included age of patient, date of injury, type of immobilization, number of clinical visits and any complications. Results. 41 cases were identified and analyzed. The mean age of the cohort was 49.8 years (Standard deviation 20.01). Twelve percent (n = 5) were reviewed in clinic, treated and discharged as stable Weber B type fracture pattern as per national guidelines after the first visit. About 52% (n = 21) were seen in clinic twice before discharge, first visit between 1-2 weeks and the last clinic visit between 5-7 weeks. About a third of patients (30%, n = 12) were seen in clinic on more than two occasions. At the first clinic visit 87% (n = 36) were given a boot and allowed to weight bear as tolerated. Two patients were diagnosed with deep vein thrombosis/pulmonary embolism during the treatment duration. Three patients had extended duration of follow up for ongoing symptoms. None discharged after first or second visit needed surgery for displaced or malunited fracture. Conclusion. Patients discharged from clinic after first or second visit did not need any further surgery. As per national guidelines, patients deemed stable weber B lateral malleolus fracture pattern after weight bearing radiograph can be treated safely with a weight bearing walking boot with no further follow up

Mental disorders in particular depression and anxiety have been reported to be prevalent among patients with spinal pathologies. Goal of the current study was to analyze the relationship of Zung pre- and post-op score to other PROs and length of stay. Secondary outcomes included revision surgery and post-operative infections. Data from the international multicenter prospective spine degenerative surgery data repository, DegenPRO v1.1 (AO Spine Knowledge Forum Degenerative) were utilized. Patients undergoing cervical or lumbar procedure were included. Patient's demographics, Charlson Comorbidity Index, surgical information, Zung score, NDI, pain related PROs and EQ-5D, and complications at surgery and at various post-op time periods. Except for hospital duration, data were analyzed, using multivariable mixed linear models. A robust linear regression model was used to assess the association between Zung score and hospital duration. All models were adjusted for gender and age. 42 patients had Zung score administered. Among those patients 22 (52%) were within normal range, 18 (43%) were mildly and 2 (5%) severely depressed. 62% of the patients had a lumbar pathology with fusion procedures being the most common. Median EQ-5D (3L) score at surgery was significantly higher (0.7, IQR: 0.4-0.7) for patients within normal range than for those with mild (0.4, IGR: 0.3-0.7) or severe depression (0.3, IQR: 0.3-0.3, p-value: 0.05). Compared to patients within normal Zung range, mixed models, indicated lower EQ-5D (3L) score values and higher values for neck and arm pain at surgery with both PROs and EQ-5D (3L) improving in patients with depression over the follow-up time. No association was found between Zung score and hospital length of stay. The initial analysis showed that 43% of the patients were mildly depressed and mainly male patients. Zung score was correlated with post-operative improvements in EQ-5D and arm and neck pain PROs

The current study aims to find the role of Enhance Recovery Pathway (ERP) as a multidisciplinary approach aimed to expedite rapid recovery, reduce LOS, and minimize morbidity associated with Non Fusion Anterior Scoliosis Correction (NFASC) surgery. A retrospective analysis of 35 AIS patients who underwent NFASC with Lenke 1 and Lenke 5 curves with a minimum of 1 year of follow-up was done. Patient demographics, surgical details, postoperative analgesia, mobilization, length of stay (LOS), patient satisfaction survey score with respect to information and care, and 90 days complications were collected. The cohort included 34 females and 1 male with a mean age of 15.2 years at the time of surgery. There were 16 Lenke 1 and 19 Lenke 5 in the study. Mean preoperative major thoracic and thoracolumbar/lumbar Cobb's angle were 52˚±7.6˚ and 51˚±4.5˚ respectively. Average blood loss and surgical time were 102 ±6.4 ml and 168 ± 10.2 mins respectively. Average time to commencing solid food was 6.5±1.5 hrs. Average time to mobilization following surgery was 15.5± 4.3 hrs. The average duration to the stopping of the epidural was 42.5±3.5 hrs. The average dose of opioid consumption intraoperatively was 600.5±100.5 mcg of fentanyl i.v. and 12.5±4.5 mg morphine i.v. Postoperatively opioids were administered via an epidural catheter at a dose of 2 mg of morphine every 24 hours up to 2 days and an infusion of 2mcg/hr of fentanyl along with 0.12-0.15% ropivacaine. The average duration to transition to oral analgesia was 55.5±8.5 hrs .20 patients had urinary catheter and the average time to removal of the catheter was 17.5±1.4 hrs. 25 patients had a chest tube and the average time to remove of chest tube was 25.5±3.2 hrs. The average length of hospital stay was 3.1±0.5 days. No patient had postoperative ileus or requirement of blood transfusion or any other complications. No correlation was found between LOS and initial cobb angle. The application of ERP in AIS patients undergoing NFASC results in reduced LOS and indirectly the cost, reduced post-operative opioid use, and overall improve patient satisfaction score

Adverse events (AEs) are still a major problem in spinal surgery, despite advances in surgical techniques, innovative technologies available and the introduction of checklist and predictive score systems aimed at reducing surgical complications. We previously analysed the results of the introduction of the WHO Safety Surgical Checklist (SSC) in our Institution, comparing the incidence of complications between two periods: from January to December 2010 (without checklist) and from January 2011 and December 2012 (with checklist), in order to assess the checklist effectiveness. The sample size was 917 patients with an average of 30 months of follow-up. Complications were observed in 107 patients (11.6%) among 917 spinal surgery procedures performed, with 159 (17.3%) complications in total. The overall incidence of complications for trauma, infectious pathology, oncology, and degenerative disease was 22.2%, 19.2%, 18.4%, and 15.3%, respectively. We observed a reduction of the overall incidence of complications following the introduction of the WHO Surgical Checklist: in 2010 without checklist, the incidence of complications was 24.2%, while in 2011 and 2012, following the checklist introduction, the incidence of complications was 16.7% and 11.7%, respectively (mean 14.2%) (p<0.0005). Thus, the SSC appeared to be an effective tool to reduce complications in spinal surgery and we proposed to extend the use of checklist system also to the pre-operative and post-operative phases in order to further reduce the incidence of complications. We also believe that a correct capture and classification of complications is fundamental to generate a clinical decision support system aimed at improving patients’ safety in spinal surgery. In the period between January 2017 and January 2018 we prospectively recorded the adverse events and complications of patients undergoing spinal surgery in our department, without using any collection system. Then we retrospectively recorded the intraoperative and postoperative adverse events of surgically treated patients during the same one-year period, using the SAVES v2 system introduced by Rampersaud and collaborators (Rampersaud YR et al. J Neurosurg Spine 2016 Aug; 25 (2): 256-63) to classify them. In the one-year period from January 2017 to January 2018 a total of 336 patients underwent spinal surgery: 223 for degenerative conditions and 113 for spinal tumors. Comorbidities were collected (Charlson Comorbidity Index [CCI]). Overall, a higher number of adverse events (AEs) was recorded using SAVES compared to the prospective recording without the use of any capture system and the increased number was statistically significant for early postoperative AEs (138/336 vs 44/336, p<0.001). 210 adverse events were retrospectively recorded using the SAVES system (30 intraoperative adverse events, 138 early postoperative and 42 late postoperative adverse events). 99 patients (29.5%) on the cohort had at least one complication. Furthermore, the correlation between some risk factors and the onset of complications or the prolonged length of stay was statistically analyzed. The risk factors taken into account were: age, presence of comorbidities (CCI), ASA score, previous surgery at the same level, type of intervention, location of the disease, duration of the surgery. In particular, the duration of the surgery (more than 3 hours) and the presence of previous surgeries resulted to be risk factors for complications in multivariate analyses

Abstract. Introduction. Component mal-positioning in total hip replacement (THR) and total knee replacement (TKR) can increase the risk of revision for various reasons. Compared to conventional surgery, relatively improved accuracy of implant positioning can be achieved using computer assisted technologies including navigation, patient-specific jigs, and robotic systems. However, it is not known whether application of these technologies has improved prosthesis survival in the real-world. This study aimed to compare risk of revision for all-causes following primary THR and TKR, and revision for dislocation following primary THR performed using computer assisted technologies compared to conventional technique. Methods. We performed an observational study using National Joint Registry data. All adult patients undergoing primary THR and TKR for osteoarthritis between 01/04/2003 to 31/12/2020 were eligible. Patients who received metal-on-metal bearing THR were excluded. We generated propensity score weights, using Sturmer weight trimming, based on: age, gender, ASA grade, side, operation funding, year of surgery, approach, and fixation. Specific additional variables included position and bearing for THR and patellar resurfacing for TKR. For THR, effective sample sizes and duration of follow up for conventional versus computer-guided and robotic-assisted analyses were 9,379 and 10,600 procedures, and approximately 18 and 4 years, respectively. For TKR, effective sample sizes and durations of follow up for conventional versus computer-guided, patient-specific jigs, and robotic-assisted groups were 92,579 procedures over 18 years, 11,665 procedures over 8 years, and 644 procedures over 3 years, respectively. Outcomes were assessed using Kaplan-Meier analysis and expressed using hazard ratios (HR) and 95% confidence intervals (CI). Results. For THR, analysis comparing computer-guided versus conventional technique demonstrated HR of 0.771 (95%CI 0.573–1.036) p=0.085, and 0.594 (95%CI 0.297–1.190) p=0.142, for revision for all-causes and dislocation, respectively. When comparing robotic-assisted versus conventional technique, HR for revision for all-causes was 0.480 (95%CI 0.067 –3.452) p=0.466. For TKR, compared to conventional surgery, HR for all-cause revision for procedures performed using computer guidance and patient-specific jigs were 0.967 (95% CI 0.888–1.052) p=0.430, and 0.937 (95% CI 0.708–1.241) p=0.65, respectively. HR for analysis comparing robotic-assisted versus conventional technique was 2.0940 (0.2423, 18.0995) p = 0.50. Conclusions. This is the largest study investigating this topic utilising propensity score analysis methods. We did not find a statistically significant difference in revision for all-causes and dislocation although these analyses are underpowered to detect smaller differences in effect size between groups. Additional comparison for revision for dislocation between robotic-assisted versus conventionally performed THR was not performed as this is a subset of revision for all-causes and wide confidence intervals were already observed for that analysis. It is also important to mention this NJR analysis study is of an observational study design which has inherent limitations. Nonetheless, this is the most feasible study design to answer this research question requiring use of a large data set due to revision being a rare outcome. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

Introduction and Objective. Continuous peripheral nerve blocks (cPNBs) have shown good results in pain management after orthopedic surgeries. However, the variation of performance between different subspecialities is unknown. The aim of this study is to describe our experience with cPNBs after lower limb orthopedic surgeries in different subspecialties. Materials and Methods. This prospective cohort study was performed on collected data from cPNBs after orthopedic surgeries in lower limbs. Catheters were placed by experienced anesthesiologists using sterile technique. After catheterization, the patients were examined daily, by specially educated acute pain service nurses. The characteristics of the patients, duration of catheterization, severity of the post-operative pain, need for additional opioids, and possible complications were registered. Results. We included 246 patients (=547 catheters). 115 (21%) femoral, 162 (30%) saphenous, 66 (12%) sciatic, and 204 (37%) popliteal sciatic nerve catheter were used. The median duration of a catheter was 3 days [IQR = 2 – 5]. The proportion of femoral, sciatic, saphenous, and popliteal nerve catheters with duration of more than two days was 81%, 79%, 73%, and 71% for, respectively. This proportion varied also between different subspecialties. 91% of the catheters remained in place for more than two days in amputations (n=56), 89% in pediatric surgery (n=79), 76% in trauma (n=217), 64% in foot and ankle surgery (n=129), and 59% in limb reconstructive surgery (n=66). The proportion of pain-free patients were 77 – 95% at rest, 63 – 88% at mobilization. 79 – 92% did not need increased opioid doses, and 50 – 67% did not require PRN opioid. 443 catheters (81%) were removed as planned. The cause of unplanned catheter removal was loss of efficacy in 69 (13%), dislodgement in 23 (4.2%), leakage in 8 (1.5%), and erythema in 4 catheters (0.73%). No major complication occurred. Conclusions. 81% of catheters remained in place until planned removal and opioid usage after surgery was lower than expected. Catheters were efficient in both adult and pediatric surgery; however, a variation was seen between orthopaedic subspecialities regarding duration of nerve catheter usage

Abstract. Objective. To investigate the safety and cost-effectiveness of interscalene brachial plexus block/regional anaesthesia (ISB-RA) in patients undergoing reverse total shoulder replacement. Methods. This retrospective study included 15 patients with symptomatic rotator cuff arthropathy who underwent reverse total shoulder arthroplasty (rTSA) under ISB-RA without general anaesthesia in the beach chair position from 2010 to 2018. The mean patient age was 77 years (range 59–82 years). Patients had associated medical comorbidities: American Society of Anesthesiologists (ASA) grade 2–4. Assessed parameters were: duration of anaesthesia, intra-operative systolic blood pressure variation, sedation and vasopressor use, duration of post-operative recovery, recovery scores, length of stay, and complications. A robust cost analysis was also performed. Results. The mean (range) duration of anaesthesia was 38.66 (20–60) min. Maximum and minimum intra-operative systolic blood pressure ranges were 130–210 and 75–145 mmHg, respectively (mean [range] drop, 74.13 [33–125] mmHg). Mean (range) propofol dose was 1.74 (1–3.0) mg/kg/h. The Median (interquartile range) post-operative recovery time was 30 (20–50) min. The mean (range) postoperative recovery score (local scale, range 5–28 where lower values are superior) was 5.2 (5–8). The mean (range) length of stay was 8 (1–20 days); the two included patients with ASA grade 2 were both discharged within 24 hours. One patient with predisposing history developed pneumonia; however, there were no complications related to ISB-RA. The mean (range) cost per patient was £101.36 (£59.80-£132.20). Conclusions. Our data demonstrate that rTSA under ISB-RA is safe, cost-effective and a potentially viable alternative for patients with multiple comorbidities. Notably, patients with ASA grade 2 who underwent rTSA under ISB-RA had a reduced length of stay and were discharged within 24 hours

Skeletal muscle tissue engineering has made progress towards production of functional tissues in line with the development in materials science and fabrication techniques. In particular, combining the specificity of 3D printing with smart materials has introduced a new concept called the 4D printing. Inspired by the unique properties of smart/responsive materials, we designed a bioink made of gelatin, a polymer with well-known cell compatibility, to be 3D printed on a magnetically responsive substrate. Gelatin was made photocrosslinkable by the methacrylate reaction (GELMA), and its viscosity was finetuned by blending with alginate which was later removed by alginate lyase treatment, so that the printability of the bioink as well as the cell viability can be finetuned. C2C12 mouse myoblasts-laden bioink was then 3D printed on a magnetic substrate for 4D shape-shifting. The magnetic substrate was produced using silicon rubber (EcoFlex) and carbonyl iron powders. After 3D printing, the bioink was crosslinked on the substrate, and the substrate was rolled with the help of a permanent magnet. Unrolled (Open) samples were used as the control group. The stiffness of the bioink matrix was found to be in the range of 13–45 kPa, which is the appropriate value for the adhesion of C2C12 cells. In the cell viability analysis, it was observed that the cells survived and could proliferate within the 7-day duration of the experiment. As a result of the immunofluorescence test, compared to the Open Group, more cell nuclei were observed overlapping MyoD1 expression in the Rolled Group; this indicated that the cells in these samples had more cell-cell interactions and therefore tended to form more myotubes. Acknowledgements: This research was supported by the TÜBİTAK 2211-A and YÖK 100/2000 scholarship programs

To test and evaluate the effectiveness of local injection of autologous fat-derived mesenchymal stem cells (MSCs) into fracture site to prevent non-union in a clinically relevant model. 5 male Wistar rats underwent the same surgical procedure of inducing non-union. A mid-shaft tibial osteotomy was made with 1mm non-critical gap. Periosteum was stripped around the two fracture ends. Then, the fracture was fixed by ante-grade intramedullary nail. The non-critical gap was maintained by a spacer with minimal effect on the healing surface area. At the same surgical time, subcutaneous fat was collected from the ipsilateral inguinal region and stem cells were isolated and cultured in vitro. Within three weeks postoperatively, the number of expanded stem cells reached 5×10. 6. and were injected into the fracture site. Healing was followed up for 8 weeks and the quality was measured by serial x-rays, microCT, mechanical testing and histologically. Quality of healing was compared with that of previously published allogenic, xenogeneic MSCs and Purified Buffered Saline (PBS) controls. All the five fractures united fully after 8 weeks. There was a progressive increase in the callus radiopacity during the eight-week duration, the average radiopacity in the autologous fat-MSC injected group was significantly higher than that of the allogeneic MSCs, xenogeneic MSCs and the control group, P < 0.0001 for treatment, time after injection, and treatment-time interaction (two-way repeated measure ANOVA). MicroCT, mechanical testing and histology confirmed radiological findings. The autologous fat-MSCs are effective in prevention of atrophic non-union by stimulation of the healing process leading to a solid union. The quality and speed of repair are higher than those of the other types of cell transplantation tested

Low back pain affects 80% of the population with half of cases attributed to intervertebral disc (IVD) degeneration. However, the majority of treatments focus on pain management, with none targeting the underlying pathophysiological causes. PCRX-201 presents a novel gene therapy approach that addresses this issue. PCRX-201 codes for interleukin-1 receptor antagonist (IL-1Ra), the natural inhibitor of the pro-inflammatory cytokine IL-1, which orchestrates the catabolic degeneration of the IVD. Our objective here is to determine the ability of PCRX-201 to infect human nucleus pulposus (NP) cells and tissue to increase the production of IL-1Ra and assess downstream effects on catabolic protein production. Degenerate human NP cells and tissue explants were infected with PCRX-201 at 0 or 3000 multiplicities of infection (MOI) and subsequently cultured for 5 days in monolayer (n=7), 21 days in alginate beads (n=6) and 14 days in tissue explants (n=5). Cell culture supernatant was collected throughout culture duration and downstream targets associated with pain and degeneration were assessed using ELISA. IL-1Ra production was increased in NP cells and tissue infected with PCRX-201. The production of downstream catabolic proteins such as IL-1β, IL-6, MMP3, ADAMTS4 and VEGF was decreased in both 3D-cultured NP cells and tissue explants. Here, we have demonstrated that a novel gene therapy, PCRX-201, is able to infect and increase the production of IL-1Ra in degenerate NP cells and tissue in vitro. The increase of IL-1Ra also resulted in a decrease in the production of a number of pro-inflammatory and catabolic proteins, suggesting PCRX-201 enables the inhibition of IL-1-driven IVD degeneration. At present, no treatments for IVD degeneration target the underlying pathology. The ability of FX201 to elicit anti-catabolic responses is promising and warrants further investigation in vitro and in vivo, to determine the efficacy of this exciting, novel gene therapy