How to: assess patient suitability for unlicensed phage therapy in the United Kingdom.

BACKGROUND: Bacteriophage (phage) therapy is a promising alternative antimicrobial approach which has the potential to transform the way we treat bacterial infections. The antibiotic resistance crisis is driving renewed interest in phage therapy. There are currently no licenced phage therapy medicinal products and phage therapy is used in small but growing patient numbers on an unlicensed basis. OBJECTIVES: This article provides guidelines on the assessment of patient suitability for unlicensed phage therapy for clinicians in the United Kingdom. SOURCES: This article builds on Health Improvement Scotland's recommendation for the consideration of phage therapy in difficult-to-treat infection and the experience of the author group who have collectively assessed the suitability of 30 patients for phage therapy. CONTENT: In the UK, unlicensed medicines, including phages, may be considered to meet special clinical needs. The use of unlicensed medicines is governed by national legislation and local NHS Trust policies. Phages can be used in any NHS Trust and decisions about suitability should be made via existing local clinical management pathways. This article sets out guidelines to support local clinical teams in the assessment of patient suitability for phage therapy. Clinical and microbiological considerations are presented, including allergy and pregnancy.

Periprosthetic joint infection of the hip.

Aims: The number of revision arthroplasties being performed in the elderly is expected to rise, including revision for infection. The primary aim of this study was to measure the treatment success rate for octogenarians undergoing revision total hip arthroplasty (THA) for periprosthetic joint infection (PJI) compared to a younger cohort. Secondary outcomes were complications and mortality. Methods: Patients undergoing one- or two-stage revision of a primary THA for PJI between January 2008 and January 2021 were identified. Age, sex, BMI, American Society of Anesthesiologists grade, Charlson Comorbidity Index (CCI), McPherson systemic host grade, and causative organism were collated for all patients. PJI was classified as 'confirmed', 'likely', or 'unlikely' according to the 2021 European Bone and Joint Infection Society criteria. Primary outcomes were complications, reoperation, re-revision, and successful treatment of PJI. A total of 37 patients aged 80 years or older and 120 patients aged under 80 years were identified. The octogenarian group had a significantly lower BMI and significantly higher CCI and McPherson systemic host grades compared to the younger cohort. Results: The majority of patients were planned to undergo two-stage revision, although a significantly higher proportion of the octogenarians did not proceed with the second stage (38.7% (n = 12) vs 14.8% (n = 16); p = 0.003). Although there was some evidence of a lower complication rate in the younger cohort, this did not reach statistical significance (p = 0.065). No significant difference in reoperation (21.6% (n = 8) vs 25.0% (n = 30); p = 0.675) or re-revision rate (8.1% (n = 3) vs 16.7% (n = 20); p = 0.288) was identified between the groups. There was no difference in treatment success between groups (octogenarian 89.2% (n = 33) vs control 82.5% (n = 99); p = 0.444). Conclusion: When compared to a younger cohort, octogenarians did not show a significant difference in complication, re-revision, or treatment success rates. However, given they are less likely to be eligible to proceed with second stage revision, consideration should be given to either single-stage revision or use of an articulated spacer to maximize functional outcomes.

Does delay to theatre influence morbidity or mortality in femoral periprosthetic fractures?

Aims: Femoral periprosthetic fractures are rising in incidence. Their management is complex and carries a high associated mortality. Unlike native hip fractures, there are no guidelines advising on time to theatre in this group. We aim to determine whether delaying surgical intervention influences morbidity or mortality in femoral periprosthetic fractures. Methods: We identified all periprosthetic fractures around a hip or knee arthroplasty from our prospectively collated database between 2012 and 2021. Patients were categorized into early or delayed intervention based on time from admission to surgery (early = ≤ 36 hours, delayed > 36 hours). Patient demographics, existing implants, Unified Classification System fracture subtype, acute medical issues on admission, preoperative haemoglobin, blood transfusion requirement, and length of hospital stay were identified for all patients. Complication and mortality rates were compared between groups. Results: A total of 365 patients were identified: 140 in the early and 225 in the delayed intervention group. Mortality rate was 4.1% at 30 days and 19.2% at one year. There was some indication that those who had surgery within 36 hours had a higher mortality rate, but this did not reach statistical significance at 30 days (p = 0.078) or one year (p = 0.051). Univariate analysis demonstrated that age, preoperative haemoglobin, acute medical issue on admission, and the presence of postoperative complications influenced 30-day and one-year mortality. Using a multivariate model, age and preoperative haemoglobin were independently predictive factors for one-year mortality (odds ratio (OR) 1.071; p < 0.001 and OR 0.980; p = 0.020). There was no association between timing of surgery and postoperative complications. Postoperative complications were more likely with increasing age (OR 1.032; p = 0.001) and revision arthroplasty compared to internal fixation (OR 0.481; p = 0.001). Conclusion: While early intervention may be preferable to reduce prolonged immobilization, there is no evidence that delaying surgery beyond 36 hours increases mortality or complications in patients with a femoral periprosthetic fracture.

Proceedings of the United Kingdom Periprosthetic Joint Infection Meeting 2022: Combined and Arthroplasty Sessions.

Considerable variation in practice exists in the prevention, diagnosis, and treatment of periprosthetic joint infection (PJI), which is a devastating complication for patients and surgeons. The consensus principle has been increasingly embraced by the orthopaedic community to help guide practice, especially where high-level evidence remains unavailable. The third United Kingdom Periprosthetic Joint Infection (UK PJI) Meeting was held in Glasgow on April 1, 2022, with more than 180 delegates in attendance, representing orthopaedics, microbiology, infectious diseases, plastic surgery, anesthetics, and allied health professions, including pharmacy and arthroplasty nurses. The meeting comprised a combined session for all delegates, and separate breakout sessions for arthroplasty and fracture-related infection. Consensus questions for each session were prepared in advance by the UK PJI working group, based upon topics that were proposed at previous UK PJI Meetings, and delegates participated in an anonymized electronic voting process. We present the findings of the combined and arthroplasty sessions of the meeting in this article, and each consensus topic is discussed in relation to the contemporary literature.

Cement-in-cement versus uncemented modular stem revision for Vancouver B2 periprosthetic fractures.

Background: To compare outcomes of revision to a long uncemented stem with cement-in-cement revision for Vancouver B2 periprosthetic fracture (PPF). Methods: Patients undergoing surgery for a Vancouver B2 PPF in a cemented stem from 2008 to 2018 were identified using our prospectively collated database. Results: We identified 43 uncemented and 29 cement-in-cement revisions. Cement-in-cement revision had a shorter operative time, reduction in certain complications, no increased rate of non-union, lower degree of stem subsidence and no difference in re-revision rate. Conclusion: With appropriate patient selection, both cement-in-cement and long uncemented stem revision represent appropriate treatment options for Vancouver B2 fractures.

Survival of the GAP II cage in the management of metastatic disease of the acetabulum.

AIMS: The aim of this study was to assess the clinical and radiological outcomes of an antiprotrusio acetabular cage (APC) when used in the surgical treatment of periacetabular bone metastases. METHODS: This retrospective cohort study using a prospectively collected database involved 56 patients who underwent acetabular reconstruction for periacetabular bone metastases or haematological malignancy using a single APC between January 2009 and 2020. The mean follow-up was 20 months (1 to 143). The primary outcome measure was implant survival. Postoperative radiographs were analyzed for loosening and failure. Patient and implant survival were assessed using a competing risk analysis. Secondary parameters included primary malignancy, oncological treatment, surgical factors, length of stay in hospital, and postoperative complications. RESULTS: A total of 33 patients (59%) died during the study period at a mean of 15 months postoperatively (1 to 63). No patient had radiological evidence of loosening or failure. Acetabular component survival was 100%. Three patients (5.4%) had further surgery; one (1.8%) underwent revision of the femoral component for dislocation, one required debridement with implant retention for periprosthetic joint infection, and one required closed reduction for dislocation. Using death as a competing risk, at 100 months, the probability of revision was 0.036 and the risk of death was 0.84. CONCLUSION: With appropriate patient selection, the antiprotrusio cage offers good implant survival, with a reasonable perioperative complication rate in this high-risk group of patients when managing metastatic disease or haematological malignancy around the acetabulum. Cite this article: Bone Joint J 2022;104-B(4):504-509.

Nanovibrational stimulation inhibits osteoclastogenesis and enhances osteogenesis in co-cultures.

Models of bone remodelling could be useful in drug discovery, particularly if the model is one that replicates bone regeneration with reduction in osteoclast activity. Here we use nanovibrational stimulation to achieve this in a 3D co-culture of primary human osteoprogenitor and osteoclast progenitor cells. We show that 1000 Hz frequency, 40 nm amplitude vibration reduces osteoclast formation and activity in human mononuclear CD14+ blood cells. Additionally, this nanoscale vibration both enhances osteogenesis and reduces osteoclastogenesis in a co-culture of primary human bone marrow stromal cells and bone marrow hematopoietic cells. Further, we use metabolomics to identify Akt (protein kinase C) as a potential mediator. Akt is known to be involved in bone differentiation via transforming growth factor beta 1 (TGFß1) and bone morphogenetic protein 2 (BMP2) and it has been implicated in reduced osteoclast activity via Guanine nucleotide-binding protein subunit α13 (Gα13). With further validation, our nanovibrational bioreactor could be used to help provide humanised 3D models for drug screening.

Improving outcomes in acute and chronic periprosthetic hip and knee joint infection with a multidisciplinary approach.

AIMS: Periprosthetic hip and knee infection remains one of the most severe complications following arthroplasty, with an incidence between 0.5% to 1%. This study compares the outcomes of revision surgery for periprosthetic joint infection (PJI) following hip and knee arthroplasty prior to and after implementation of a specialist PJI multidisciplinary team (MDT). METHODS: Data was retrospectively analyzed from a single centre. In all, 29 consecutive joints prior to the implementation of an infection MDT in November 2016 were compared with 29 consecutive joints subsequent to the MDT conception. All individuals who underwent a debridement antibiotics and implant retention (DAIR) procedure, a one-stage revision, or a two-stage revision for an acute or chronic PJI in this time period were included. The definition of successfully treated PJI was based on the Delphi international multidisciplinary consensus. RESULTS: There were no statistically significant differences in patient demographics or comorbidities between the groups. There was also no significant difference in length of overall hospital stay (p = 0.530). The time taken for formal microbiology advice was significantly shorter in the post MDT group (p = 0.0001). There was a significant difference in failure rates between the two groups (p = 0.001), with 12 individuals (41.38%) pre-MDT requiring further revision surgery compared with one individual (6.67%) post-MDT inception. CONCLUSION: Our standardized multidisciplinary approach for periprosthetic knee and hip joint infection shows a significant reduction in failure rates following revision surgery. Following implementation of our MDT, our success rate in treating PJI is 96.55%, higher than what current literature suggests. We advocate the role of a specialist infection MDT in the management of patients with a PJI to allow an individualized patient-centred approach and care plan, thereby reducing postoperative complications and failure rates. Cite this article: Bone Jt Open 2021;2(7):509-514.

Cement-in-cement femoral component revision : a comparison of two different taper-slip designs with medium-term follow up.

AIMS: Cement-in-cement revision of the femoral component represents a widely practised technique for a variety of indications in revision total hip arthroplasty. In this study, we compare the clinical and radiological outcomes of two polished tapered femoral components. METHODS: From our prospectively collated database, we identified all patients undergoing cement-in-cement revision from January 2005 to January 2013 who had a minimum of two years' follow-up. All cases were performed by the senior author using either an Exeter short revision stem or the C-Stem AMT high offset No. 1 prosthesis. Patients were followed-up annually with clinical and radiological assessment. RESULTS: A total of 97 patients matched the inclusion criteria (50 Exeter and 47 C-Stem AMT components). There were no significant differences between the patient demographic data in either group. Mean follow-up was 9.7 years. A significant improvement in Oxford Hip Score (OHS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and 12-item Short-Form Survey (SF-12) scores was observed in both cohorts. Leg lengths were significantly shorter in the Exeter group, with a mean of -4 mm in this cohort compared with 0 mm in the C-Stem AMT group. One patient in the Exeter group had early evidence of radiological loosening. In total, 16 patients (15%) underwent further revision of the femoral component (seven in the C-Stem AMT group and nine in the Exeter group). No femoral components were revised for aseptic loosening. There were two cases of femoral component fracture in the Exeter group. CONCLUSION: Our series shows promising mid-term outcomes for the cement-in-cement revision technique using either the Exeter or C-Stem AMT components. These results demonstrate that cement-in-cement revision using a double or triple taper-slip design is a safe and reliable technique when used for the correct indications. Cite this article: Bone Joint J 2021;103-B(7):1215-1221.

An Adult Immunization Best Practices Learning Collaborative: Impact, Scale Up, and Spread.

The research objective was to rapidly scale up and spread a proven learning collaborative approach (intervention) for adult vaccination rates for influenza and pneumococcal disease from 7 to 39 US health care organizations and to examine improvement in adult immunization rates after scale-up. Comparative analyses were conducted between intervention and nonintervention propensity score-matched providers on vaccination rates using a difference-in-differences approach. Qualitative data, collected during site visits and in-person and virtual meetings, were used to enhance understanding of quantitative results. In 2017-2018, an analysis of a subset of sites (n = 9) from 2 intervention cohorts (∼20 sites each) demonstrated greater improvement than their matched providers in pneumococcal vaccinations (PV) for patients ages ≥65 years (treatment effect range: 1.4%-3.7%, P < 0.01) and PV for high-risk patients (eg, with immunocompromising conditions) aged 19-64 years (0.8%-1.6%, P < 0.01). Significant effects were observed in one of the study cohorts for PV for at-risk patients (eg, with diabetes) aged 19-64 years (1.7%, P < 0.01), and influenza vaccination rates (2.4%, P < 0.001). Individual health systems demonstrated even greater improvements across all 4 vaccinations: 9.5% influenza; 8.7% PV ages ≥65 years; 11.8% PV high-risk; 16.3% PV at-risk (all P < 0.01). Results demonstrated that a 7-site pilot could be successfully scaled to 39 additional sites, with similar improvements in vaccination rates. Between 2014 and 2018, vaccination improvements among all 46 groups (7 pilot, 39 in subsequent cohorts) resulted in an estimated 5.5 million adult vaccinations administered or documented in 27 states.

Impact of a Learning Collaborative Approach on Influenza and Pneumococcal Immunization Rates in US Adults: A Mixed Methods Approach.

The objective of this research was to test the impact of a learning collaborative model (intervention) on adult vaccination rates for influenza and pneumococcal disease. A mixed methods approach was used to identify changes in adult vaccination rates over time and organizational factors contributing to successful programs. Provider-level propensity scores were used to match intervention to non-intervention providers to control for inherent selection bias of participating organizations. Comparative analyses were conducted between intervention and non-intervention sites on vaccination rates, using a difference-in-differences approach. Qualitative data (eg, semi-structured interviews) were analyzed using a constant comparison approach to identify themes related to successful strategies. From 2014-2016, intervention providers demonstrated greater improvement than their matched providers in pneumococcal vaccinations (PV) for patients aged 65 years and older (treatment effect: 4.3%, P < 0.05) and PV for high-risk patients (eg, with immunocompromising conditions) aged 19-64 years (2.7%, P < 0.001). Significant effects were also observed for PV for at-risk patients (eg, with diabetes) aged 19-64 years (1.7%, P < 0.05). Individual health systems demonstrated even greater improvements (eg, greater increase in PV rates for patients aged 65 years and older), with treatment effects as high as 20.4% (P < 0.05). A learning collaborative approach was demonstrated to be an effective approach to improve adult vaccination rates among participating integrated delivery systems and medical groups. Factors associated with success included organization type (ie, integrated delivery systems) and systems characterized by a positive learning climate and collaborative culture.

Obesity is associated with higher complication rates in revision total hip arthroplasty.

We examined differences in complication rates between obese and non-obese patients undergoing revision total hip arthroplasty. Sixty-five patients with a BMI ≥30 kg/m2 and 54 patients with a BMI of <30 kg/m2 were identified. Obese patients were 2.5 times more likely to suffer a complication than non-obese (38.4% cf 14.8%, p = 0.02). Obese patients were more likely to experience dislocation, leg length discrepancy, fracture, implant loosening, infection and pulmonary embolus. The obese group had a significantly higher revision rate (12.3% cf 1.8%, p = 0.039). Obese patients should be counselled pre-operatively on their elevated risk.

Universal 2 total wrist arthroplasty: high satisfaction but high complication rates.

The Universal 2 total wrist arthroplasty is intended to alleviate wrist pain and restore function. There is limited evidence regarding its success and safety. We report outcomes in 48 wrists of 46 patients with Universal 2 arthroplasty between 2006 and 2014. We recorded range of motion of the operated wrist, patient satisfaction, complication and revision rates, and radiological appearances of the wrists with mean follow-up of 7 years (3.5 to 11 years). We found a significant improvement in DASH scores after surgery, with active range of wrist motion being 33° flexion and 24° extension. Thirty-nine patients would undergo the procedure again if he had similar wrist problems. Twenty-three patients had loosening of at least one component of the implant. Complications were found in 13 wrists; seven underwent revision. We conclude that the Universal 2 arthroplasty produces significant improvements in DASH scores and high levels of satisfaction of the patients. However, the surgery has a high complication rate. LEVEL OF EVIDENCE: IV.

Delays in diagnosis are associated with poorer outcomes in adult hip dysplasia.

Background and Aims Developmental dysplasia of the hip is a common cause of osteoarthritis. Periacetabular osteotomy can restore femoral head coverage; however, it is reserved for patients with minimal articular degeneration. We examined the relationship between delays in diagnosis and outcomes. Methods We identified patients presenting to a hip specialist with a new diagnosis of hip dysplasia. The time taken between patients presenting to their general practitioner and attending the young adult hip clinic was established. Patients were stratified into Early, Moderate and Late Referral groups. Hip and SF-12 questionnaires were completed. Radiographs were graded according to the Tönnis classification system and the outcome following hip specialist review documented. Results Fifty-one patients were identified. Mean time from attending a general practitioner to review at the young adult hip clinic was 40.4 months. Lower hip and SF-12 scores, and higher radiological osteoarthritis grades were found in the Moderate and Late Referral groups. A higher proportion of the Moderate and Late Referral group underwent total hip arthroplasty rather than periacetabular osteotomy. Conclusion Delays in referring a patient to a hip specialist are associated with poorer outcomes. We propose pelvic radiographs are requested early by general practitioners to allow prompt diagnosis and referral to a hip specialist.

Noise production in ceramic-on-ceramic total hip arthroplasty is associated with lower patient satisfaction and hip scores.

BACKGROUND: Ceramic-on-ceramic total hip arthroplasties (THA) are commonly implanted. We investigated the incidence of noise in ceramic-on-ceramic and determined any association with patient satisfaction and hip scores. METHODS: We recruited 140 THA. Questionnaires were completed to assess the incidence and frequency of noise, and satisfaction level. Hip and SF-12 scores were recorded. RESULTS: Forty-two patients (30%) were aware of noise production. Patients with noise production had lower satisfaction, mean hip and SF-12 scores than those with silent hips. CONCLUSION: Given the high incidence of noise in ceramic-on-ceramic THA, patients should be counselled on this risk pre-operatively.

Total Hip Arthroplasty in Systemic Lupus Erythematosus: A Systematic Review.

The prognosis of systemic lupus erythematosus (SLE) has greatly improved in recent years, resulting in an increased number of patients reporting musculoskeletal complications such as osteonecrosis of the femoral head. Total hip arthroplasty (THA) can be utilised to alleviate the pain associated with this; however postoperative outcomes in patients with SLE are uncertain. A systematic review of the literature was conducted to identify articles presenting results of THA in SLE, and nine suitable papers were found. All papers were level IV evidence. Pooling the results, a total of 162 patients underwent 214 total hip arthroplasties. Mean follow-up was 72.5 months. The mean Harris Hip Score improved from 45.5 preoperatively to 88.6 and last follow-up. Seventeen percent of patients experienced at least one complication. Superficial wound infection occurred in 3.3%. Revision was required in 2.8% of cases. The mortality rate was 18.5% however no deaths were attributable to undergoing THA. Given the paucity of data present in the literature, more studies are required to adequately assess the postoperative outcomes of THA in patients with SLE, particularly complication rates.

Growth arrest lines and intra-epiphyseal silhouettes: a case series.

BACKGROUND: Growth arrest lines can develop within the skeleton after physiological stress or trauma. They are usually evident on radiographs as transverse lines in the metaphyses and have been used in fields from palaeontology to orthopaedics. This report consists of three cases, two of which describe growth arrest lines in an intra-epiphyseal site hitherto rarely documented, and a third demonstrating their clinical application. CASE PRESENTATION: Case 1 describes a 9-year-old who suffered a knee hyperflexion injury requiring anterior cruciate ligament and posterior cruciate ligament reattachments. She subsequently developed a marked distal femoral intra-epiphyseal arrest silhouette, as well as metaphyseal arrest lines in the femur, tibia and fibula. Case 2 describes an 8-year-old who sustained a tibial spine fracture and underwent open reduction and internal fixation. Subsequent imaging shows a further example of femoral intra-epiphyseal arrest silhouette as well as tibia and fibula metaphyseal arrest lines. Case 3 describes a 10-year-old who sustained a distal tibia fracture which was managed with open reduction and internal fixation. Subsequently the metaphyseal growth arrest line was parallel to the physis, suggesting no growth arrest (a danger with such a fracture). CONCLUSION: This case series describes two examples of rarely described intra-epiphyseal growth arrest silhouettes and demonstrates the usefulness of arrest lines when assessing for growth plate damage.