Blood loss and transfusion risk in intramedullary nailing for subtrochanteric fractures.

BACKGROUND: The incidence of hip fractures and subtrochanteric fractures in particular is increasing, along with the globally expanding aging population. Intramedullary nailing remains the 'gold standard' of their treatment. Blood loss can be a result of the original trauma, but also secondary to the subsequent surgical insult, especially during the reaming of the intramedullary canal. OBJECTIVES: The aim of our study was to report on the blood loss and incidence of blood transfusion in patients presenting with a subtrochanteric fracture treated with intramedullary nailing. Most importantly, we aim to identify factors associated with the need for transfusion within the first 48 h post-operatively. METHODS: Following institutional board approval, 431 consecutive patients (131 males; age: 79.03 years old, SD 13.68 years) presenting in a Level 1 Trauma Centre with a subtrochanteric fracture treated with an intramedullary nail were retrospectively identified, over an 8-year period. Exclusion criteria included patients with high energy injuries, pathological fractures, primary operations at other institutions and patients lost to follow-up. To identify risk factors leading to increased risk of transfusion, we first compared patients requiring intra-operative transfusion or transfusion during the first 48 h post-operatively against those who did not require transfusion. This was then followed by multivariate regression analysis adjusted for confounding factors to identify the most important risk factors associated with need for transfusion within the first 48 h post-operatively. RESULTS: Incidence of blood transfusion was 6.0% pre-operatively, compared to 62.7% post-operatively. A total of 230 patients (52.3%) required either intra-operative transfusion or transfusion during the first 48 h following surgery. Patients having a transfusion within the first 48 h post-operatively had a higher incidence of escalation in their care (p = 0.050), LOS (p = 0.015), 30-day (p = 0.033) and one-year mortality (p = 0.004). Multivariate regression analysis adjusted for confounding factors identified that the most important association of a need for transfusion within the first 48 post-operative hours was a pre-operative Hb <100 g/L (OR 6.64); a nail/canal ratio <70% (OR 3.92), followed by need for open reduction (OR 2.66). Fracture involving the lesser trochanter was also implicated with an increased risk (OR 2.08). Additionally, pre-operative moderate/severe renal impairment (OR 4.56), as well as hypoalbuminaemia on admission (OR 2.10) were biochemical predictors of an increased risk of transfusion. Most importantly, the need for transfusion was associated with an increase in 30-day mortality (OR 12.07). CONCLUSION: Several patient, fracture and surgery related factors are implicated with an increased risk for transfusion within the first 48-h post-operatively. Early identification, and where possible correction of these factors can potentially reduce blood loss and risk of transfusion, along with all the associated sequelae and mortality risk. LEVEL OF EVIDENCE: III.

Biological and molecular profile of fracture non-union tissue: A systematic review and an update on current insights.

Fracture non-union represents a common complication, seen in 5%-10% of all acute fractures. Despite the enhancement in scientific understanding and treatment methods, rates of fracture non-union remain largely unchanged over the years. This systematic review investigates the biological, molecular and genetic profiles of both (i) non-union tissue and (ii) non-union-related tissues, and the genetic predisposition to fracture non-union. This is crucially important as it could facilitate earlier identification and targeted treatment of high-risk patients, along with improving our understanding on pathophysiology of fracture non-union. Since this is an update on our previous systematic review, we searched the literature indexed in PubMed Medline; Ovid Medline; Embase; Scopus; Google Scholar; and the Cochrane Library using Medical Subject Heading (MeSH) or Title/Abstract words (non-union(s), non-union(s), human, tissue, bone morphogenic protein(s) (BMPs) and MSCs) from August 2014 (date of our previous publication) to 2 October 2021 for non-union tissue studies, whereas no date restrictions imposed on non-union-related tissue studies. Inclusion criteria of this systematic review are human studies investigating the characteristics and properties of non-union tissue and non-union-related tissues, available in full-text English language. Limitations of this systematic review are exclusion of animal studies, the heterogeneity in the definition of non-union and timing of tissue harvest seen in the included studies, and the search term MSC which may result in the exclusion of studies using historical terms such as 'osteoprogenitors' and 'skeletal stem cells'. A total of 24 studies (non-union tissue: n = 10; non-union-related tissues: n = 14) met the inclusion criteria. Soft tissue interposition, bony sclerosis of fracture ends and complete obliteration of medullary canal are commonest macroscopic appearances of non-unions. Non-union tissue colour and surrounding fluid are two important characteristics that could be used clinically to distinguish between septic and aseptic non-unions. Atrophic non-unions had a predominance of endochondral bone formation and lower cellular density, when compared against hypertrophic non-unions. Vascular tissues were present in both atrophic and hypertrophic non-unions, with no difference in vessel density between the two. Studies have found non-union tissue to contain biologically active MSCs with potential for osteoblastic, chondrogenic and adipogenic differentiation. Proliferative capacity of non-union tissue MSCs was comparable to that of bone marrow MSCs. Rates of cell senescence of non-union tissue remain inconclusive and require further investigation. There was a lower BMP expression in non-union site and absent in the extracellular matrix, with no difference observed between atrophic and hypertrophic non-unions. The reduced BMP-7 gene expression and elevated levels of its inhibitors (Chordin, Noggin and Gremlin) could potentially explain impaired bone healing observed in non-union MSCs. Expression of Dkk-1 in osteogenic medium was higher in non-union MSCs. Numerous genetic polymorphisms associated with fracture non-union have been identified, with some involving the BMP and MMP pathways. Further research is required on determining the sensitivity and specificity of molecular and genetic profiling of relevant tissues as a potential screening biomarker for fracture non-unions.

Subtrochanteric femoral fractures and intramedullary nailing complications: a comparison of two implants.

INTRODUCTION: Intramedullary (IM) nails are considered the 'gold' standard treatment for subtrochanteric femoral fractures. The incidence and risk factors for re-operation in subtrochanteric fractures remain unclear. Furthermore, no studies have compared the outcomes of different nailing systems used to treat subtrochanteric fractures in the same study population. AIMS/OBJECTIVES: Our study aimed to (i) investigate the cumulative incidence and factors associated with an increased risk of re-operation in subtrochanteric fractures treated with a long intramedullary (IM) nail, (ii) compare the outcomes of subtrochanteric fractures treated with long Affixus and Gamma nails, and (iii) establish whether the addition of a proximal anti-rotation screw in the Affixus nail confers any clinical benefit. METHODS: A retrospective review of all adult patients admitted to a level 1 trauma centre with a subtrochanteric femur fracture treated with a long cephalomedullary IM nail over an 8-year period was conducted. Exclusion criteria were primary surgery performed at another institution, prophylactic nailing because of tumours, incomplete fractures, and patients who were lost to follow-up or died before fracture healing. Data variables were assessed for normality prior to determining the use of either parametric or non-parametric tests. Logistic regression analysis was performed to identify potential factors associated with re-operation. For the comparison between the two nail types, patients were matched into two groups of 119 each by age (10-year intervals), gender and mechanism of injury (low energy, high energy and pathological fractures). A p-value < 0.05 was considered significant. The Kaplan-Meier nail survival curve was used to demonstrate the survival of each nail. Data were analysed using the statistical package R (R version 3.6.0). RESULTS: A total of 309 subtrochanteric fractures were treated with a distally locked long IM nail (re-operation rate: 22.33%) over an 8-year period. Logistic regression identified six factors associated with an increased risk of re-operation, including age < 75 years old, use of a long Gamma nail, pre-injury coxa-vara femoral neck shaft angles, an immediate post-operative reduction angle of > 10° varus, deep wound infection and non-union. Following matching, we compared the two long cephalomedullary nailing systems used (Gamma versus Affixus nail). The only differences identified from the unadjusted analysis were a higher overall incidence of nail failure in Gamma nails due to any cause, re-operation, and impingement of the nail tip distally against the anterior femoral cortex. When we corrected for covariates, no significant differences remained evident between the two nails. From the Kaplan-Meier nail survival curves, however, the Affixus nail demonstrated better survivorship up to 5 years post-implantation in terms of nail failure and re-operation for all causes. Finally, the addition of a proximal anti-rotation screw in the Affixus nail did not seem to confer any benefit. CONCLUSION: We reported a 22.3% re-operation rate in our cohort of subtrochanteric fractures treated with a long IM nail. We have identified six risk factors associated with re-operation: age < 75 years old, pre-injury femoral neck shaft angle, choice of nail, varus reduction angle, fracture-related infection and non-union. The addition of a proximal anti-rotation screw in the Affixus nail did not confer any benefit.

In situ three-dimensional printing for reparative and regenerative therapy.

Three-dimensional (3D) bioprinting is an emerging biofabrication technology, driving many innovations and opening new avenues in regenerative therapeutics. The aim of 3D bioprinting is to fabricate grafts in vitro, which can then be implanted in vivo. However, the tissue culture ex vivo carries safety risks and thereby complicated manufacturing equipment and practice are required for tissues to be implanted in the humans. The implantation of printed tissues also adds complexities due to the difficulty in maintaining the structural integrity of fabricated constructs. To tackle this challenge, the concept of in situ 3D bioprinting has been suggested in which tissues are directly printed at the site of injury or defect. Such approach could be combined with cells freshly isolated from patients to produce custom-made grafts that resemble target tissue and fit precisely to target defects. Moreover, the natural cellular microenvironment in the body can be harnessed for tissue maturation resulting in the tissue regeneration and repair. Here, we discuss literature reports on in situ 3D printing and we describe future directions and challenges for in situ 3D bioprinting. We expect that this novel technology would find great attention in different biomedical fields in near future.

The role of peptides in bone healing and regeneration: a systematic review.

BACKGROUND: Bone tissue engineering and the research surrounding peptides has expanded significantly over the last few decades. Several peptides have been shown to support and stimulate the bone healing response and have been proposed as therapeutic vehicles for clinical use. The aim of this comprehensive review is to present the clinical and experimental studies analysing the potential role of peptides for bone healing and bone regeneration. METHODS: A systematic review according to PRISMA guidelines was conducted. Articles presenting peptides capable of exerting an upregulatory effect on osteoprogenitor cells and bone healing were included in the study. RESULTS: Based on the available literature, a significant amount of experimental in vitro and in vivo evidence exists. Several peptides were found to upregulate the bone healing response in experimental models and could act as potential candidates for future clinical applications. However, from the available peptides that reached the level of clinical trials, the presented results are limited. CONCLUSION: Further research is desirable to shed more light into the processes governing the osteoprogenitor cellular responses. With further advances in the field of biomimetic materials and scaffolds, new treatment modalities for bone repair will emerge.

Biological and molecular profile of fracture non-union tissue: current insights.

Delayed bone healing and non-union occur in approximately 10% of long bone fractures. Despite intense investigations and progress in understanding the processes governing bone healing, the specific pathophysiological characteristics of the local microenvironment leading to non-union remain obscure. The clinical findings and radiographic features remain the two important landmarks of diagnosing non-unions and even when the diagnosis is established there is debate on the ideal timing and mode of intervention. In an attempt to understand better the pathophysiological processes involved in the development of fracture non-union, a number of studies have endeavoured to investigate the biological profile of tissue obtained from the non-union site and analyse any differences or similarities of tissue obtained from different types of non-unions. In the herein study, we present the existing evidence of the biological and molecular profile of fracture non-union tissue.

Release of growth factors and the effect of age, sex, and severity of injury after long bone fracture. A preliminary report.

BACKGROUND AND PURPOSE: The systemic response after fracture is regulated by a complex mechanism involving numerous growth factors. In this study, we analyzed the kinetics of key growth factors following lower-limb long bone fracture. MATERIALS AND METHODS: Human serum was isolated from 15 patients suffering from lower-limb long bone fracture (tibia/femur) requiring surgical fixation. The levels of platelet-derived growth factor (PDGF-BB), vascular edothelial growth factor (VEGF), insulin growth factor-I (IGF-I), and transforming growth factor ß1 (TGF-ß1) were assayed by colorimetric ELISA at different time points during the first week after fracture. 10 healthy volunteers made up the control group of the study. Serum levels of the growth factors measured were compared to age, sex, and injury severity score. RESULTS: We found that there was a decline in the levels of PDGF-BB, IGF-I and TGF-ß1 during the first 3 days after fracture. However, VEGF levels remained unchanged. The levels of all the growth factors studied then increased, with the highest concentrations noted at day 7 after surgery. No correlation was found between circulating levels of growth factors and age, injury severity score (ISS), blood loss, or fluid administration. INTERPRETATION: There are systemic mitogenic and osteogenic signals after fracture. Important growth factors are released into the peripheral circulation, but early after surgery it appears that serum levels of key growth factors fall. By 7 days postoperatively, the levels had increased considerably. Our findings should be considered in cases where autologous serum is used for ex vivo expansion of mesenchymal stem cells. There should be further evaluation of the use of these molecules as biomarkers of bone union.

Do nonsteroidal anti-inflammatory drugs affect bone healing? A critical analysis.

Nonsteroidal anti-inflammatory drugs (NSAIDs) play an essential part in our approach to control pain in the posttraumatic setting. Over the last decades, several studies suggested that NSAIDs interfere with bone healing while others contradict these findings. Although their analgesic potency is well proven, clinicians remain puzzled over the potential safety issues. We have systematically reviewed the available literature, analyzing and presenting the available in vitro animal and clinical studies on this field. Our comprehensive review reveals the great diversity of the presented data in all groups of studies. Animal and in vitro studies present so conflicting data that even studies with identical parameters have opposing results. Basic science research defining the exact mechanism with which NSAIDs could interfere with bone cells and also the conduction of well-randomized prospective clinical trials are warranted. In the absence of robust clinical or scientific evidence, clinicians should treat NSAIDs as a risk factor for bone healing impairment, and their administration should be avoided in high-risk patients.

Anatomical reconstruction of the anterior inferior tibiofibular ligament in elite athletes using InternalBrace suture tape.

AIMS: The ideal management of acute syndesmotic injuries in elite athletes is controversial. Among several treatment methods used to stabilize the syndesmosis and facilitate healing of the ligaments, the use of suture tape (InternalBrace) has previously been described. The purpose of this study was to analyze the functional outcome, including American Orthopaedic Foot & Ankle Society (AOFAS) scores, knee-to-wall measurements, and the time to return to play in days, of unstable syndesmotic injuries treated with the use of the InternalBrace in elite athletes. METHODS: Data on a consecutive group of elite athletes who underwent isolated reconstruction of the anterior inferior tibiofibular ligament using the InternalBrace were collected prospectively. Our patient group consisted of 19 elite male athletes with a mean age of 24.5 years (17 to 52). Isolated injuries were seen in 12 patients while associated injuries were found in seven patients (fibular fracture, medial malleolus fracture, anterior talofibular ligament rupture, and posterior malleolus fracture). All patients had a minimum follow-up period of 17 months (mean 27 months (17 to 35)). RESULTS: All patients returned to their pre-injury level of sports activities. One patient developed a delayed union of the medial malleolus. The mean return to play was 62 days (49 to 84) for isolated injuries, while the patients with concomitant injuries returned to play in a mean of 104 days (56 to 196). The AOFAS score returned to 100 postoperatively in all patients. Knee-to-wall measurements were the same as the contralateral side in 18 patients, while one patient lacked 2 cm compared to the contralateral side. CONCLUSION: This study suggests the use of the InternalBrace in the management of unstable syndesmotic injuries offers an alternative method of stabilization, with good short-term results, including early return to sports in elite athletes. Cite this article: Bone Joint J 2022;104-B(1):68-75.

Management of subtrochanteric femur fractures: is open reduction associated with poor outcomes?

PURPOSE: The aim of this study was to identify factors associated with the need for open reduction in subtrochanteric femoral fractures and investigate the effect of cerclage wiring compared to open reduction alone, on the development of complications, especially infection and non-union. METHODS: All consecutive patients with a fracture involving the subtrochanteric region were retrospectively identified, over an 8-year period. Data documented and analysed included patient demographics, fracture characteristics, patient comorbidities, time to fracture union and development of complications. RESULTS: A total of 512 patients met the inclusion criteria (523 fractures). Open reduction was performed in 48% (247) of the fractures. Following matching and regression analysis, we identified diaphyseal extension of the fracture to be associated with an open reduction (OR: 2.30; 95% CI 1.45-3.65; p < 0.001). Open reduction was also associated with an increased risk of superficial infection (OR: 7.88; 95% CI 1.63-38.16; p = 0.010), transfusion within 48 h following surgery (OR: 2.44; 95% CI 1.96-4.87; p < 0.001) and a prolonged surgical time (OR: 3.09; 95% CI 1.96-4.87; p < 0.001). The risk of non-union, deep infection and overall mortality was not increased with open reduction. The use of cerclage wires [50 out of 201 fractures (24.9%) treated with an open reduction] to achieve anatomical reduction as compared to open reduction alone significantly reduced the risk of non-union (OR: 0.20; 95% CI 0.06-0.74; p = 0.015). CONCLUSION: Open reduction of subtrochanteric fractures is not associated with an increased risk of deep infection and non-union, even though it is associated with an increased risk of superficial infection, prolonged surgical time and transfusion. The use of cerclage wire is associated with reduced risk of non-union with little evidence of an increase in complications. LEVEL OF EVIDENCE: III.

Highlights on Advancing Frontiers in Tissue Engineering.

The field of tissue engineering continues to advance, sometimes in exponential leaps forward, but also sometimes at a rate that does not fulfill the promise that the field imagined a few decades ago. This review is in part a catalog of success in an effort to inform the process of innovation. Tissue engineering has recruited new technologies and developed new methods for engineering tissue constructs that can be used to mitigate or model disease states for study. Key to this antecedent statement is that the scientific effort must be anchored in the needs of a disease state and be working toward a functional product in regenerative medicine. It is this focus on the wildly important ideas coupled with partnered research efforts within both academia and industry that have shown most translational potential. The field continues to thrive and among the most important recent developments are the use of three-dimensional bioprinting, organ-on-a-chip, and induced pluripotent stem cell technologies that warrant special attention. Developments in the aforementioned areas as well as future directions are highlighted in this article. Although several early efforts have not come to fruition, there are good examples of commercial profitability that merit continued investment in tissue engineering. Impact statement Tissue engineering led to the development of new methods for regenerative medicine and disease models. Among the most important recent developments in tissue engineering are the use of three-dimensional bioprinting, organ-on-a-chip, and induced pluripotent stem cell technologies. These technologies and an understanding of them will have impact on the success of tissue engineering and its translation to regenerative medicine. Continued investment in tissue engineering will yield products and therapeutics, with both commercial importance and simultaneous disease mitigation.

NSAIDS inhibit in vitro MSC chondrogenesis but not osteogenesis: implications for mechanism of bone formation inhibition in man.

The non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for analgesia but may inhibit bone formation. We investigated whether the reported NSAID effect on bone is related to inhibition of bone marrow mesenchymal stem cell (MSC) proliferation and osteogenic and chondrogenic differentiation and evaluated both cyclooxygenase (COX)-1 and COX-2 specific drugs. The effects of seven COX-1 and COX-2 inhibitors on MSC proliferation and osteogenic and chondrogenic differentiation were tested using Vybrant, sodium 3'-[1-(phenylaminocarbonyl)- 3,4-tetrazolium]-bis (4-methoxy-6-nitro) benzene sulfonic acid hydrate (XTT), functional and quantitative assays of MSC differentiation. The MSC expression of COX-1 and COX-2 and prostaglandin E2 (PGE-2) levels were evaluated serially during lineage differentiation by quantitative PCR and ELISA. None of the NSAIDs at broad range of concentration (range 10(-3) to 100 µg/ml) significantly affected MSC proliferation. Surprisingly, MSC osteogenic differentiation inhibition was not evident. However, NSAIDs affected chondrogenic potential with a reduction in sulphated glycosaminoglycans (sGAG) content by 45% and 55% with diclofenac and ketorolac, respectively (P < 0.05 compared to controls). Parecoxib and meloxicam, more COX-2 specific reagents inhibited sGAG to a lesser degree, 22% and 27% respectively (P < 0.05 compared to controls). Cartilage pellet immunohistochemistry confirmed the above results. Pellet chondrogenesis was associated with increased COX-1 expression levels but not COX-2, and COX-1 specific drugs suppressed MSC PGE-2 more than COX-2 specific inhibitors. These findings suggest that NSAIDs may inhibit bone formation via blockage of MSC chondrogenic differentiation which is an important intermediate phase in normal endochondral bone formation.

NSAIDs inhibit bone healing through the downregulation of TGF-ß3 expression during endochondral ossification.

INTRODUCTION & AIMS: Non Steroidal Anti-Inflammatory drugs (NSAIDs) are potent inhibitors of post-traumatic pain. Several studies have highlighted that NSAIDs could exert a negative effect on bone healing process possibly by down-regulating chondrogenesis and endochondral ossification. The aim of the study is to explore the potential mechanism though which NSAIDs can affect chondrogenesis. M&M: Trabecular bone from the fracture site was isolated from 10 patients suffering from long bone fractures. Mesenchymal Stem Cells (MSCs) were isolated following collagenase digestion and functional assays to assess the effect of diclofenac sodium on chondrogenesis were performed. Gene expression analysis of 84 key molecules was performed. RESULTS: Diclofenac sodium inhibits chondrogenic differentiation and induces a strong inhibition of prostaglandin E-2 (PGE-2) production during chondrogenic differentiation. Replenishment of PGE-2 did not reverse this negative effect. Chondrogenic inhibition is similar in cells treated only for the first week of chondrogenic differentiation or continuously for 3 weeks. Gene analysis shows a strong downregulation of TGF-ß3 and FGF-1 while TNF was upregulated. CONCLUSION: NSAIDs seem to affect the transition phase of mesenchymal stem cells towards functional chondrocytes. This effect is unrelated to the endogenous production of PGE-2. The downregulation of the expression of key molecules like TGF-ß3 seem to be the underlying mechanism.

Development and Validation of a Post-Operative Non-Union Risk Score for Subtrochanteric Femur Fractures.

BACKGROUND: Our objective was to develop and validate a predictive model for non-union following a subtrochanteric fracture of the femur. METHODS: Following institutional board approval, 316 consecutive patients presenting to our institution (84 non-unions) who fulfilled the inclusion criteria were retrospectively identified. To identify potential unadjusted associations with progression to non-union, simple logistic regression models were used, followed by a revised adjusted model of multiple logistic regression. RESULTS: Having established the risk factors for non-union, the coefficients were used to produce a risk score for predicting non-union. To identify the high-risk patients in the early post-operative period, self-dynamisation was excluded. The revised scoring system was the sum of the following: diabetes (6); deep wound infection (35); simple or severe comminution (13); presence of an atypical fracture (14); lateral cortex gap size ≥5 mm (11), varus malreduction (5-10 degrees) (9); varus malreduction (>10 degrees) (20). On the ROC (receiver operating characteristic) curve, the area under the curve (0.790) demonstrated very good discriminatory capability of the scoring system, with good calibration (Hosmer-Lemeshow test; p = 0.291). Moreover, 5-fold cross validation confirmed good fit of the model and internal validity (accuracy 0.806; Kappa 0.416). The cut-point determined by Youden's formula was calculated as 18. CONCLUSION: This study demonstrates that the risk of non-union can be reliably estimated in patients presenting with a subtrochanteric fracture, from the immediate post-operative period. The resulting non-union risk score can be used not only to identify the high-risk patients early, offering them appropriate consultation and in some cases surgical intervention, but also informs surgeons of the modifiable surgery related factors that contribute to this risk.

Surgical Site Infection Following Intramedullary Nailing of Subtrochanteric Femoral Fractures.

Aim: To investigate the incidence, risk factors and pathogenic micro-organisms causing superficial and deep infection in subtrochanteric femoral fractures managed with an intramedullary nail. Materials and Methods: Following institutional board approval, all consecutive patients presenting with a subtrochanteric fracture were retrospectively identified, over an 8-year period. Basic demographics, fracture characteristics, fracture union, revision operation, mortality and other complications were reported and analysed. Variables deemed statistically significant (p-value < 0.05) were then included into a revised adjusted model of logistic regression analysis, where we reported on the odds ratio (OR). Results: The overall incidence of infection was 6.4% (n = 36/561; superficial: 3.7%; deep: 2.7%). Associations with deep infection included: non-union (OR 9.29 (2.56-3.38)), the presence of an open fracture (OR 4.23 (3.18-5.61)), the need for massive transfusion (OR 1.42 (2.39-8.39)), post-operative transfusion (OR 1.40 (1.10-1.79)) and prolonged length of stay (OR 1.04 (1.02-1.06)). The Commonest causes of superficial infection were Staphylococcus aureus (28.5%), enteric flora (23.8%) and mixed flora (23.8%); whereas coliforms (60%) and Staphylococcus aureus (26.7%) were the commonest micro-organisms isolated in deep infection. Polymicrobial infection was identified in 38.5% and 80% of superficial and deep infections, respectively. Conclusion: Causative micro-organisms identified in both superficial and deep infection were similar to those reported in post-traumatic osteomyelitis. In an attempt to minimise infection, the treating clinician should focus on modifiable risk factors with adequate patient optimisation, prompt surgical treatment, adequate antibiotic coverage and wound care when treating patients with subtrochanteric femur fracture.

Mortality and Medical Complications of Subtrochanteric Fracture Fixation.

The aim of this study was to define the incidence and investigate the associations with mortality and medical complications, in patients presenting with subtrochanteric femoral fractures subsequently treated with an intramedullary nail, with a special reference to advancement of age. Materials and Methods: A retrospective review, covering an 8-year period, of all patients admitted to a Level 1 Trauma Centre with the diagnosis of subtrochanteric fractures was conducted. Normality was assessed for the data variables to determine the further use of parametric or non-parametric tests. Logistic regression analysis was then performed to identify the most important associations for each event. A p-value < 0.05 was considered significant. Results: A total of 519 patients were included in our study (age at time of injury: 73.26 ± 19.47 years; 318 female). The average length of hospital stay was 21.4 ± 19.45 days. Mortality was 5.4% and 17.3% for 30 days and one year, respectively. Risk factors for one-year mortality included: Low albumin on admission (Odds ratio (OR) 4.82; 95% Confidence interval (95%CI) 2.08-11.19), dementia (OR 3.99; 95%CI 2.27-7.01), presence of pneumonia during hospital stay (OR 3.18; 95%CI 1.76-5.77) and Charlson comorbidity score (CCS) > 6 (OR 2.94; 95%CI 1.62-5.35). Regarding the medical complications following the operative management of subtrochanteric fractures, the overall incidence of hospital acquired pneumonia (HAP) was 18.3%. Patients with increasing CCS (CCS 6-8: OR 1.69; 95%CI 1.00-2.84/CCS > 8: OR 2.02; 95%CI 1.03-3.95), presence of asthma/chronic obstructive pulmonary disease (COPD) (OR 2.29; 95%CI 1.37-3.82), intensive care unit (ICU)/high dependency unit (HDU) stay (OR 3.25; 95%CI 1.77-5.96) and a length of stay of more than 21 days (OR 8.82; 95%CI 1.18-65.80) were at increased risk of this outcome. The incidence of post-operative delirium was found to be 10.2%. This was associated with pre-existing dementia (OR 4.03; 95%CI 0.34-4.16), urinary tract infection (UTI) (OR 3.85; 95%CI 1.96-7.56), need for an increased level of care (OR 3.16; 95%CI 1.38-7.25), pneumonia (OR 2.29; 95%CI 1.14-4.62) and post-operative deterioration of renal function (OR 2.21; 95%CI 1.18-4.15). The incidence of venous thromboembolism (VTE) was 3.7% (pulmonary embolism (PE): 8 patients; deep venous thrombosis (DVT): 11 patients), whilst the incidence of myocardial infarction (MI)/cerebrovascular accidents (CVA) was 4.0%. No evidence of the so called "weekend effect" was identified on both morbidity and mortality. Regression analysis of these complications did not reveal any significant associations. Conclusions: Our study has opened the field for the investigation of medical complications within the subtrochanteric fracture population. Early identification of the associations of these complications could help prognostication for those who are at risk of a poor outcome. Furthermore, these could be potential "warning shots" for clinicians to act early to manage and in some cases prevent these devastating complications that could potentially lead to an increased risk of mortality.

Recent advances in 3D bioprinting of musculoskeletal tissues.

The musculoskeletal system is essential for maintaining posture, protecting organs, facilitating locomotion, and regulating various cellular and metabolic functions. Injury to this system due to trauma or wear is common, and severe damage may require surgery to restore function and prevent further harm. Autografts are the current gold standard for the replacement of lost or damaged tissues. However, these grafts are constrained by limited supply and donor site morbidity. Allografts, xenografts, and alloplastic materials represent viable alternatives, but each of these methods also has its own problems and limitations. Technological advances in three-dimensional (3D) printing and its biomedical adaptation, 3D bioprinting, have the potential to provide viable, autologous tissue-like constructs that can be used to repair musculoskeletal defects. Though bioprinting is currently unable to develop mature, implantable tissues, it can pattern cells in 3D constructs with features facilitating maturation and vascularization. Further advances in the field may enable the manufacture of constructs that can mimic native tissues in complexity, spatial heterogeneity, and ultimately, clinical utility. This review studies the use of 3D bioprinting for engineering bone, cartilage, muscle, tendon, ligament, and their interface tissues. Additionally, the current limitations and challenges in the field are discussed and the prospects for future progress are highlighted.

Efficacy of minimally invasive techniques for enhancement of fracture healing: evidence today.

The successful treatment of nonunions represents a major challenge for orthopaedic surgeons. Lately, ongoing advances made in the field of molecular medicine and molecular biology have increased our understanding of the pathways and involvement of mediators surrounding the bone healing process. As a result, the surgeon's armamentarium has been increased in terms of options for intervention. This article aims to provide an overview of minimally invasive techniques applicable in the treatment of nonunions of fractures.

Safety Considerations in 3D Bioprinting Using Mesenchymal Stromal Cells.

Three-dimensional (3D) bioprinting has demonstrated great potential for the fabrication of biomimetic human tissues and complex graft materials. This technology utilizes bioinks composed of cellular elements placed within a biomaterial. Mesenchymal stromal cells (MSCs) are an attractive option for cell selection in 3D bioprinting. MSCs can be isolated from a variety of tissues, can pose vast proliferative capacity and can differentiate to multiple committed cell types. Despite their promising properties, the use of MSCs has been associated with several drawbacks. These concerns are related to the ex vivo manipulation throughout the process of 3D bioprinting. The herein manuscript aims to present the current evidence surrounding these events and propose ways to minimize the risks to the patients following widespread expansion of 3D bioprinting in the medical field.