We performed a meta-analysis of modern total joint replacement (TJR) to determine the post-operative mortality and the cause of death using different thromboprophylactic regimens as follows: 1) no routine chemothromboprophylaxis (NRC); 2) Potent anticoagulation (PA) (unfractionated or low-molecular-weight heparin, ximelagatran, fondaparinux or rivaroxaban); 3) Potent anticoagulation combined (PAC) with regional anaesthesia and/or pneumatic compression devices (PCDs); 4) Warfarin (W); 5) Warfarin combined (WAC) with regional anaesthesia and/or PCD; and 6) Multimodal (MM) prophylaxis, including regional anaesthesia, PCDs and aspirin in low-risk patients. Cause of death was classified as autopsy proven, clinically certain or unknown. Deaths were grouped into cardiopulmonary excluding pulmonary embolism (PE), PE, bleeding-related, gastrointestinal, central nervous system, and others (miscellaneous). Meta-analysis based on fixed effects or random effects models was used for pooling incidence data. In all, 70 studies were included (99 441 patients; 373 deaths). The mortality was lowest in the MM (0.2%) and WC (0.2%) groups. The most frequent cause of death was cardiopulmonary (47.9%), followed by PE (25.4%) and bleeding (8.9%). The proportion of deaths due to PE was not significantly affected by the thromboprophylaxis regimen (PA, 35.5%; PAC, 28%; MM, 23.2%; and NRC, 16.3%). Fatal bleeding was higher in groups relying on the use of anticoagulation (W, 33.8%; PA, 9.4%; PAC, 10.8%) but the differences were not statistically significant. Our study demonstrated that the routine use of PA does not reduce the overall mortality or the proportion of deaths due to PE

The aims of this study were to identify the early in-hospital mortality rate after hip fracture, identify factors associated with this mortality, and identify the cause of death in these patients. A retrospective cohort study was performed on 4426 patients admitted to our institution between the 1 January 2006 and 31 December 2013 with a hip fracture (1128 male (26%), mean age 82.0 years (60 to 105)). Admissions increased annually, but despite this 30-day mortality decreased from 12.1% to 6.5%; 77% of these were in-hospital deaths. Male gender (odds ratio (OR) 2.0, 95% confidence interval (CI) 1.3 to 3.0), increasing age (age ≥ 91; OR 4.1, 95% CI 1.4 to 12.2) and comorbidity (American Society of Anesthesiologists grades 3 to 5; OR 4.2, 95% CI 2.0 to 8.7) were independently and significantly associated with increased odds of in-hospital mortality. From 220 post-mortem reports, the most common causes of death were respiratory infections (35%), ischaemic heart disease (21%), and cardiac failure (13%). A sub-group of hip fracture patients at highest risk of early death can be identified with these risk factors, and the knowledge of the causes of death can be used to inform service improvements and the development of a more didactic care pathway, so that multidisciplinary intervention can be focused for this sub-group in order to improve their outcome. Cite this article: Bone Joint J 2015;97-B:246–51

Aims. The aim of this study was to compare the rate of mortality and causes of death in Korean patients who undergo surgery for a fracture of the hip, up to 11 years after the injury, with a control group from the general population. Materials and Methods. National cohort data from Korean Health Insurance Review and Assessment Service – National Sample Cohort were used. A ratio of 1:4 matched patients with a fracture who underwent surgery (3383, fracture group) between 2003 and 2012, and controls (13 532) were included. The matches were processed for age, gender, income, and region of residence. We also undertook analyses of subgroups according to age and gender. The mean follow-up was 4.45 years (1 to 11). Results. The prevalence of hypertension, diabetes, and stroke was significantly higher in the fracture group and dyslipidemia in the controls. Both crude and adjusted hazard ratios (HR) for the rate of mortality in the fracture group were > 2 (crude HR 2.03, 95% confidence interval (CI) 1.91 to 2.17, p < 0.001; adjusted HR 2.07, 95% CI 1.94 to 2.21, p < 0.001). The HRs were also > 2 for both men and women, and for both those aged ≥ 50 years and < 50 years. However, for those aged < 50 years, they were insignificant. The rates of mortality due to all 11 major causes of death classified following Korean standard classification of diseases were significantly higher in the fracture group compared with the control group, except those in the mental and behavioral disorders category. Conclusion. The rate of mortality in the fracture group was significantly higher than in the control group up to 11 years after the surgery. The rate of death due to almost every major cause was significantly higher in the fracture group compared with the control group. Cite this article: Bone Joint J 2018;100-B:436–42

Aims. Traumatic central cord syndrome (CCS) typically follows a hyperextension injury and results in motor impairment affecting the upper limbs more than the lower, with occasional sensory impairment and urinary retention. Current evidence on mortality and long-term outcomes is limited. The primary aim of this study was to assess the five-year mortality of CCS, and to determine any difference in mortality between management groups or age. Methods. Patients aged ≥ 18 years with a traumatic CCS between January 2012 and December 2017 in Wales were identified. Patient demographics and data about injury, management, and outcome were collected. Statistical analysis was performed to assess mortality and between-group differences. Results. A total of 65 patients were identified (66.2% male (n = 43), mean age 63.9 years (SD 15.9)). At a minimum of five years’ follow-up, 32.3% of CCS patients (n = 21) had died, of whom six (9.2%) had died within 31 days of their injury. Overall, 69.2% of patients (n = 45) had been managed conservatively. There was no significant difference in age between conservatively and surgically managed patients (p = 0.062). Kaplan-Meier analysis revealed no significant difference in mortality between patients managed conservatively and those managed surgically (p = 0.819). However, there was a significant difference in mortality between the different age groups (< 50 years vs 50 to 70 years vs > 70 years; p = 0.001). At five years’ follow-up, 55.6% of the patient group aged > 70 years at time of injury had died (n = 15). Respiratory failure was the most common cause of death (n = 9; 42.9%). Conclusion. Almost one-third of patients with a traumatic CCS in Wales had died within five years of their injury. The type of management did not significantly affect mortality but their age at the time of injury did. Further work to assess the long-term functional outcomes of surviving patients is needed to generate more reliable prognostic information. Cite this article: Bone Joint J 2023;105-B(8):920–927

Aims. Pigment epithelium-derived factor (PEDF) is known to induce several types of tissue regeneration by activating tissue-specific stem cells. Here, we investigated the therapeutic potential of PEDF 29-mer peptide in the damaged articular cartilage (AC) in rat osteoarthritis (OA). Methods. Mesenchymal stem/stromal cells (MSCs) were isolated from rat bone marrow (BM) and used to evaluate the impact of 29-mer on chondrogenic differentiation of BM-MSCs in culture. Knee OA was induced in rats by a single intra-articular injection of monosodium iodoacetate (MIA) in the right knees (set to day 0). The 29-mer dissolved in 5% hyaluronic acid (HA) was intra-articularly injected into right knees at day 8 and 12 after MIA injection. Subsequently, the therapeutic effect of the 29-mer/HA on OA was evaluated by the Osteoarthritis Research Society International (OARSI) histopathological scoring system and changes in hind paw weight distribution, respectively. The regeneration of chondrocytes in damaged AC was detected by dual-immunostaining of 5-bromo-2'-deoxyuridine (BrdU) and chondrogenic markers. Results. The 29-mer promoted expansion and chondrogenic differentiation of BM-MSCs cultured in different defined media. MIA injection caused chondrocyte death throughout the AC, with cartilage degeneration thereafter. The 29-mer/HA treatment induced extensive chondrocyte regeneration in the damaged AC and suppressed MIA-induced synovitis, accompanied by the recovery of cartilage matrix. Pharmacological inhibitors of PEDF receptor (PEDFR) and signal transducer and activator of transcription 3 (STAT3) signalling substantially blocked the chondrogenic promoting activity of 29-mer on the cultured BM-MSCs and injured AC. Conclusion. The 29-mer/HA formulation effectively induces chondrocyte regeneration and formation of cartilage matrix in the damaged AC. Cite this article: Bone Joint Res 2024;13(4):137–148

Aims. Staphylococcus aureus is a major cause of septic arthritis, and in vitro studies suggest α haemolysin (Hla) is responsible for chondrocyte death. We used an in vivo murine joint model to compare inoculation with wild type S. aureus 8325-4 with a Hla-deficient strain DU1090 on chondrocyte viability, tissue histology, and joint biomechanics. The aim was to compare the actions of S. aureus Hla alone with those of the animal’s immune response to infection. Methods. Adult male C57Bl/6 mice (n = 75) were randomized into three groups to receive 1.0 to 1.4 × 10. 7. colony-forming units (CFUs)/ml of 8325-4, DU1090, or saline into the right stifle joint. Chondrocyte death was assessed by confocal microscopy. Histological changes to inoculated joints were graded for inflammatory responses along with gait, weight changes, and limb swelling. Results. Chondrocyte death was greater with 8325-4 (96.2% (SD 5.5%); p < 0.001) than DU1090 (28.9% (SD 16.0%); p = 0.009) and both were higher than controls (3.8% (SD 1.2%)). Histology revealed cartilage/bone damage with 8325-4 or DU1090 compared to controls (p = 0.010). Both infected groups lost weight (p = 0.006 for both) and experienced limb swelling (p = 0.043 and p = 0.018, respectively). Joints inoculated with bacteria showed significant alterations in gait cycle with a decreased stance phase, increased swing phase, and a corresponding decrease in swing speed. Conclusion. Murine joints inoculated with Hla-producing 8325-4 experienced significantly more chondrocyte death than those with DU1090, which lack the toxin. This was despite similar immune responses, indicating that Hla was the major cause of chondrocyte death. Hla-deficient DU1090 also elevated chondrocyte death compared to controls, suggesting a smaller additional deleterious role of the immune system on cartilage. Cite this article: Bone Joint Res 2022;11(9):669–678

Aims. The place of thromboprophylaxis in arthroplasty surgery remains controversial, with a challenging requirement to balance prevention of potentially fatal venous thrombo-embolism with minimising wound-related complications leading to deep infection. We compared the incidence of fatal pulmonary embolism in patients undergoing elective primary total hip arthroplasty (THA) between those receiving aspirin, warfarin and low molecular weight heparin (LMWH) for the chemical component of a multi-modal thromboprophylaxis regime. Patients and Methods. A prospective audit database was used to identify patients who had died within 42 and 90 days of surgery respectively between April 2000 and December 2012. A case note review was performed to ascertain the causes of death. Results. During this period 7983 THAs were performed. The rate of mortality was 0.43% and 0.58% at 42 and 90 days respectively. The groups comprised 1571 patients (19.7%) on warfarin, 1838 (23.0%) on LMWH and 4574 (57.3%) on aspirin. The 90-day mortality for these three groups was 0.38%, 1.09% and 0.43% respectively. The higher mortality rate for LMWH was significant (p < 0.05). There were six fatal pulmonary emboli (PEs) (0.08%). A total of three occurred within 42 days, all in the LMWH group. A total of three occurred between 42 and 90 days; one on warfarin, two on LMWH. The leading causes of death in all three groups were lower respiratory tract infections and myocardial infarction. Conclusion. We confirmed that fatal PE following elective THA with a multi-modal prophylaxis regime is rare. We further found that LMWH conferred no benefit over aspirin in this context, and is associated with a higher all-cause rate of mortality. Take home message: This study proposes that aspirin may be an appropriate thromboprophylaxis agent when used as part of a multi-modal regimen, suggesting current guidelines should be reviewed. Cite this article: Bone Joint J 2016;98-B:585–8

Patients with osteoarthritis undergoing knee replacement have been reported to have an overall reduced mortality compared with that of the general population. This has been attributed to the selection of healthier patients for surgery. However, previous studies have had a maximum follow-up time of ten years. We have used information from the Swedish Knee Arthroplasty Register to study the mortality of a large national series of patients with total knee replacement for up to 28 years after surgery and compared their mortality with that of the normal population. In addition, for a subgroup of patients operated on between 1980 and 2002 we analysed their registered causes of death to determine if they differed from those expected. We found a reduced overall mortality during the first 12 post-operative years after which it increased and became significantly higher than that of the general population. Age-specific analysis indicated an inverse correlation between age and mortality, where the younger the patients were, the higher their mortality. The shift at 12 years was caused by a relative over-representation of younger patients with a longer follow-up. Analysis of specific causes of death showed a higher mortality for cardiovascular, gastrointestinal and urogenital diseases. The observation that early onset of osteoarthritis of the knee which has been treated by total knee replacement is linked to an increased mortality should be a reason for increased general awareness of health problems in these patients

Objectives. Staphylococcus aureus (S. aureus) is the most commonly implicated organism in septic arthritis, a condition that may be highly destructive to articular cartilage. Previous studies investigating laboratory and clinical strains of S. aureus have demonstrated that potent toxins induced significant chondrocyte death, although the precise toxin or toxins that were involved was unknown. In this study, we used isogenic S. aureus mutants to assess the influence of alpha (Hla)-, beta (Hlb)-, and gamma (Hlg)-haemolysins, toxins considered important for the destruction of host tissue, on in situ bovine chondrocyte viability. Methods. Bovine cartilage explants were cultured with isogenic S. aureus mutants and/or their culture supernatants. Chondrocyte viability was then assessed within defined regions of interest in the axial and coronal plane following live- and dead-cell imaging using the fluorescent probes 5-chloromethylfluorescein diacetate and propidium iodide, respectively, and confocal laser-scanning microscopy. Results. Hla-producing mutants caused substantial chondrocyte death compared with the toxin-deficient control (Hla-Hlb-Hlg-), whilst mutants producing Hlb and Hlg in the absence of Hla induced minimal chondrocyte death. Coronal studies established that Hla-induced chondrocyte death started in the superficial zone of cartilage and spread to deeper layers, whereas Hlb and Hlg toxins were without significant effect. Conclusion. This study identified Hla as a highly potent S. aureus toxin that caused rapid chondrocyte death in bovine cartilage, with other toxins or metabolic products produced by the bacteria playing a minor role. The identification of Hla in mediating chondrocyte death may assist in the development of therapeutic strategies aimed at reducing the extent of cartilage damage during and after an episode of septic arthritis. Cite this article: I. D. M. Smith, K. M. Milto, C. J. Doherty, S. G. B. Amyes, A. H. R. W. Simpson, A. C. Hall. A potential key role for alpha-haemolysin of Staphylococcus aureus in mediating chondrocyte death in septic arthritis. Bone Joint Res 2018;7:457–467. DOI: 10.1302/2046-3758.77.BJR-2017-0165.R1

Antibiotic resistance represents a threat to human health. It has been suggested that by 2050, antibiotic-resistant infections could cause ten million deaths each year. In orthopaedics, many patients undergoing surgery suffer from complications resulting from implant-associated infection. In these circumstances secondary surgery is usually required and chronic and/or relapsing disease may ensue. The development of effective treatments for antibiotic-resistant infections is needed. Recent evidence shows that bacteriophage (phages; viruses that infect bacteria) therapy may represent a viable and successful solution. In this review, a brief description of bone and joint infection and the nature of bacteriophages is presented, as well as a summary of our current knowledge on the use of bacteriophages in the treatment of bacterial infections. We present contemporary published in vitro and in vivo data as well as data from clinical trials, as they relate to bone and joint infections. We discuss the potential use of bacteriophage therapy in orthopaedic infections. This area of research is beginning to reveal successful results, but mostly in nonorthopaedic fields. We believe that bacteriophage therapy has potential therapeutic value for implant-associated infections in orthopaedics. Cite this article: Bone Joint J 2021;103-B(2):234–244

Aims. The aim of this study was to present data on 11 459 patients who underwent total hip (THA), total knee (TKA) or unicompartmental knee arthroplasty (UKA) between November 2002 and April 2014 with aspirin as the primary agent for pharmacological thromboprophylaxis. . Patients and Methods. We analysed the incidence of deep vein thrombosis (DVT) and pulmonary embolism (PE) then compared the 90-day all-cause mortality with the corresponding data in the National Joint Registry for England and Wales (NJR). . Results. The incidence of PE was 0.6% after THA, 1.47% after TKA and 1.2% after UKA. The 90-day mortality was 0.39% after THA and 0.44% after TKA. No deaths occurred after UKA. The main causes of death were ischaemic heart disease and respiratory failure. PE was responsible for only 18% of deaths. There was a decline in 90-day mortality, from 0.64% between 2002 and 2007, to 0.21% between 2008 and 2013 after THA, and from 0.47% to 0.39% after TKA for the corresponding period. The standardised mortality ratio (SMR) declined from 86.5 (confidence interval (CI) 63.0 to 137.7) to 39.7 (CI 31.2 to 54.3) p = 0.024. The incidence of proximal DVT was 0.3%. . Take home message: With individualised risk assessment and as part of a multimodal approach, Aspirin is safe to use as the main thromboprophylactic agent in primary arthroplasty. It is not associated with an increased incidence of symptomatic DVT, PE or death. . Cite this article: Bone Joint J 2016;98-B:341-8

Aims. It has been suggested that cemented fixation of total hip arthroplasty (THA) is associated with an increased peri-operative mortality compared with cementless THA. Our aim was to investigate this through a nationwide matched cohort study adjusting for age, comorbidity, and socioeconomic background. Patients and Methods. A total of 178 784 patients with osteoarthritis who underwent either cemented or cementless THA from the Swedish Hip Arthroplasty Register were matched with 862 294 controls from the general population. Information about the causes of death, comorbidities, and socioeconomic background was obtained. Mortality within the first 90 days after the operation was the primary outcome measure. Results. Patients who underwent cemented THA had an increased risk of death during the first 14 days compared with the controls (hazard ratio (HR) 1.3, confidence interval (CI) 1.11 to 1.44), corresponding to an absolute increase in risk of five deaths per 10 000 observations. No such early increase of risk was seen in those who underwent cementless THA. Between days 15 and 29 the risk of mortality was decreased for those with cemented THA (HR 0.7, CI 0.62 to 0.87). Between days 30 and 90 all patients undergoing THA, irrespective of the mode of fixation, had a lower risk of death than controls. Patients selected for cementless fixation were younger, healthier and had a higher level of education and income than those selected for cemented THA. A supplementary analysis of 16 556 hybrid THAs indicated that cementation of the femoral component was associated with a slight increase in mortality up to 15 days, whereas no such increase in mortality was seen in those with a cemented acetabular component combined with a cementless femoral component. Conclusion. This nationwide matched cohort study indicates that patients receiving cemented THA have a minimally increased relative risk of early mortality that is reversed from day 15 and thereafter. The absolute increase in risk is very small. Our findings lend support to the idea that cementation of the femoral component is more dangerous than cementation of the acetabular component. Cite this article: Bone Joint J 2017;99-B:37–43

Aims. We chose unstable extra-capsular hip fractures as our study group because these types of fractures suffer the largest blood loss. We hypothesised that tranexamic acid (TXA) would reduce total blood loss (TBL) in extra-capsular fractures of the hip. . Patients and Methods. A single-centre placebo-controlled double-blinded randomised clinical trial was performed to test the hypothesis on patients undergoing surgery for extra-capsular hip fractures. For reasons outside the control of the investigators, the trial was stopped before reaching the 120 included patients as planned in the protocol. . Results. In all 72 patients (51 women, 21 men; 33 patients in the TXA group, 39 in the placebo group) were included in the final analysis, with a significant mean reduction of 570.8 ml (p = 0.029) in TBL from 2100.4 ml (standard deviation (. sd). = 1152.6) in the placebo group to 1529.6 ml (. sd. = 1012.7) in the TXA group. . The 90-day mortality was 27.2% (n = 9) in the TXA group and 10.2% (n = 4) in the placebo group (p = 0.07). We were not able to ascertain a reliable cause of death in these patients. . Discussion. TXA significantly reduced TBL in extra-capsular hip fractures, but concerns regarding its safety in this patient group must be investigated further before the use of TXA can be recommended. Take home message: We present a randomised clinical trial that is unique in the literature. We evaluate the effect of TXA in very homogenous population - extra-capsular fractures operated with short intramedullary nails. Cite this article: Bone Joint J 2016;98-B:747–53

Total hip replacement causes a short-term increase in the risk of mortality. It is important to quantify this and to identify modifiable risk factors so that the risk of post-operative mortality can be minimised. We performed a systematic review and critical evaluation of the current literature on the topic. We identified 32 studies published over the last 10 years which provide either 30-day or 90-day mortality data. We estimate the pooled incidence of mortality during the first 30 and 90 days following hip replacement to be 0.30% (95% CI 0.22 to 0.38) and 0.65% (95% CI 0.50 to 0.81), respectively. We found strong evidence of a temporal trend towards reducing mortality rates despite increasingly co-morbid patients. The risk factors for early mortality most commonly identified are increasing age, male gender and co-morbid conditions, particularly cardiovascular disease. Cardiovascular complications appear to have overtaken fatal pulmonary emboli as the leading cause of death after hip replacement. Cite this article: Bone Joint Res 2014;3:175–82

Aims

Ankle fracture is one of the most common musculoskeletal injuries sustained in the UK. Many patients experience pain and physical impairment, with the consequences of the fracture and its management lasting for several months or even years. The broad aim of ankle fracture treatment is to maintain the alignment of the joint while the fracture heals, and to reduce the risks of problems, such as stiffness. More severe injuries to the ankle are routinely treated surgically. However, even with advances in surgery, there remains a risk of complications; for patients experiencing these, the associated loss of function and quality of life (Qol) is considerable. Non-surgical treatment is an alternative to surgery and involves applying a cast carefully shaped to the patient’s ankle to correct and maintain alignment of the joint with the key benefit being a reduction in the frequency of common complications of surgery. The main potential risk of non-surgical treatment is a loss of alignment with a consequent reduction in ankle function. This study aims to determine whether ankle function, four months after treatment, in patients with unstable ankle fractures treated with close contact casting is not worse than in those treated with surgical intervention, which is the current standard of care.

Aims

Cementing in arthroplasty for hip fracture is associated with improved postoperative function, but may have an increased risk of early mortality compared to uncemented fixation. Quantifying this mortality risk is important in providing safe patient care. This study investigated the association between cement use in arthroplasty and mortality at 30 days and one year in patients aged 50 years and over with hip fracture.

Aims

Hip fracture commonly affects the frailest patients, of whom many are care-dependent, with a disproportionate risk of contracting COVID-19. We examined the impact of COVID-19 infection on hip fracture mortality in England.

We performed a retrospective study of a departmental database to assess the efficacy of a new model of orthopaedic care on the outcome of patients with a fracture of the proximal femur. All 1578 patients admitted to a university teaching hospital with a fracture of the proximal femur between December 2007 and December 2009 were included. The allocation of Foundation doctors years 1 and 2 was restructured from individual teams covering several wards to pairs covering individual wards. No alterations were made in the numbers of doctors, their hours, out-of-hours cover, or any other aspect of standard patient care. Outcome measures comprised 30-day mortality and cause, complications and length of stay. Mortality was reduced from 11.7% to 7.6% (p = 0.007, Cox’s regression analysis); adjusted odds ratio was 1.559 (95% confidence interval 1.128 to 2.156). Reductions were seen in Clostridium difficile colitis (p = 0.017), deep wound infection (p = 0.043) and gastrointestinal haemorrhage (p = 0.033). There were no differences in any patient risk factors (except the prevalence of chronic obstructive pulmonary disease), cause of death and length of stay before and after intervention. The underlying mechanisms are unclear, but may include improved efficiency and medical contact time. These findings may have implications for all specialties caring for patients on several wards, and we believe they justify a prospective trial to further assess this effect

Aims

Gram-negative infections are associated with comorbid patients, but outcomes are less well understood. This study reviewed diagnosis, management, and treatment for a cohort treated in a tertiary spinal centre.

Aims

The primary aim was to assess whether preoperative health-related quality of life (HRQoL) was associated with postoperative mortality following total hip arthroplasty (THA) and knee arthroplasty (KA). Secondary aims were to assess whether patient demographics/comorbidities and/or joint-specific function were associated with postoperative mortality.