Showing papers by "Nuffield Orthopaedic Centre published in 2021"

The EBJIS definition of periprosthetic joint infection.

Abstract: Aims The diagnosis of periprosthetic joint infection (PJI) can be difficult. All current diagnostic tests have problems with accuracy and interpretation of results. Many new tests have been propose...

Management of critical-sized bone defects in the treatment of fracture-related infection: a systematic review and pooled analysis

Abstract: This systematic review determined the reported treatment strategies, their individual success rates, and other outcome parameters in the management of critical-sized bone defects in fracture-related infection (FRI) patients between 1990 and 2018. A systematic literature search on treatment and outcome of critical-sized bone defects in FRI was performed. Treatment strategies identified were, autologous cancellous grafts, autologous cancellous grafts combined with local antibiotics, the induced membrane technique, vascularized grafts, Ilizarov bone transport, and bone transport combined with local antibiotics. Outcomes were bone healing and infection eradication after primary surgical protocol and recurrence of FRI and amputations at the end of study period. Fifty studies were included, describing 1530 patients, the tibia was affected in 82%. Mean age was 40 years (range 6–80), with predominantly male subjects (79%). Mean duration of infection was 17 months (range 1–624) and mean follow-up 51 months (range 6–126). After initial protocolized treatment, FRI was cured in 83% (95% CI 79–87) of all cases, increasing to 94% (95% CI 92–96) at the end of each individual study. Recurrence of infection was seen in 8% (95% CI 6–11) and amputation in 3% (95% CI 2–3). Final outcomes overlapped across treatment strategies. Results should be interpreted with caution due to the retrospective and observational design of most studies, the lack of clear classification systems, incomplete data reports, potential underreporting of adverse outcomes, and heterogeneity in patient series. A consensus on classification, treatment protocols, and outcome is needed to improve reliability of future studies.

Percutaneous microwave ablation of bone tumors: a systematic review.

Abstract: To systematically review microwave ablation (MWA) protocols, safety, and clinical efficacy for treating bone tumors. A systematic literature search was conducted using PubMed, the Cochrane Library, EMBASE, and Web of Science database. Data concerning patient demographics, tumor characteristics, procedure, complications, and clinical outcomes were extracted and analyzed. Seven non-comparative studies (6 retrospective, 1 prospective) were included accounting for 249 patients and 306 tumors (244/306 [79.7%] metastases; 25/306 [8.2%] myelomas, and 37/306 [12.1%] osteoid osteomas [OO]). In malignant tumors, MWA power was 30–70 W (except in one spinal tumors series where a mean power of 13.3 W was used) with pooled mean ablation time of 308.3 s. With OO, MWA power was 30–60 W with mean ablation time of 90–102 s. Protective measures were very sporadically used in 5 studies. Additional osteoplasty was performed in 199/269 (74.0%) malignant tumors. Clinically significant complications were noted in 10/249 (4.0%) patients. For malignant tumors, estimated pain reduction on the numerical rating scale was 5.3/10 (95% confidence intervals [95%CI] 4.6–6.1) at 1 month; and 5.3/10 (95% CI 4.3–6.3) at the last recorded follow-up (range 20–24 weeks in 4/5 studies). For OO, at 1-month follow-up, effective pain relief was noted in 92.3–100% of patients. MWA is effective in achieving pain relief at short- (1 month) and mid-term (4–6 months) for painful OO and malignant bone tumors, respectively. Although MWA seems safe, further prospective studies are warranted to further assess this aspect, and to standardize MWA protocols. • Large heterogeneity exists across literature about ablation protocols used with microwave ablation applied for the treatment of benign and malignant bone tumors. • Although microwave ablation of bone tumors appears safe, further studies are needed to assess this aspect, as current literature does not allow definitive conclusions. • Nevertheless, microwave ablation is effective in achieving pain relief at short- (1 month) and mid-term (4–6 months) for painful osteoid osteomas and malignant bone tumors, respectively.

Will virtual multidisciplinary team meetings become the norm for musculoskeletal oncology care following the COVID-19 pandemic? - experience from a tertiary sarcoma centre.

Abstract: Like with all cancers, multidisciplinary team (MDT) meetings are the norm in bone and soft tissue tumour (BST) management too. Problem in attendance of specialists due to geographical location is the one of the key barriers to effective functioning of MDTs. To overcome this problem, virtual MDTs involving videoconferencing or telemedicine have been proposed, but however this has been seldom used and tested. The COVID-19 pandemic forced the implementation of virtual MDTs in the Oxford sarcoma service in order to maintain normal service provision. We conducted a survey among the participants to evaluate its efficacy. An online questionnaire comprising of 24 questions organised into 4 sections was circulated among all participants of the MDT after completion of 8 virtual MDTs. Opinions were sought comparing virtual MDTs to the conventional face-to-face MDTs on various aspects. A total of 36 responses were received and were evaluated. 72.8% were satisfied with the depth of discussion in virtual MDTs and 83.3% felt that the decision-making in diagnosis had not changed following the switch from face-to-face MDTs. About 86% reported to have all essential patient data was available to make decisions and 88.9% were satisfied with the time for discussion of patient issues over virtual platform. Three-fourths of the participants were satisfied (36.1% - highly satisfied; 38.9% - moderately satisfied) with virtual MDTs and 55.6% of them were happy to attend MDTs only by the virtual platform in the future. Regarding future, 77.8% of the participants opined that virtual MDTs would be the future of cancer care and an overwhelming majority (91.7%) felt that the present exercise would serve as a precursor to global MDTs involving specialists from abroad in the future. Our study shows that the forced switch to virtual MDTs in sarcoma care following the unprecedented COVID-19 pandemic to be a viable and effective alternative to conventional face-to-face MDTs. With effective and efficient software in place, virtual MDTs would also facilitate in forming extended MDTs in seeking opinions on complex cases from specialists abroad and can expand cancer care globally.

Five-Minute Five-Sequence Knee MRI Using Combined Simultaneous Multislice and Parallel Imaging Acceleration: Comparison with 10-Minute Parallel Imaging Knee MRI.

Abstract: Comparisons of 5-minute five-sequence knee MRI using simultaneous multislice and parallel imaging acceleration and 10-minute five-sequence knee MRI using parallel imaging acceleration only suggest ...

The influence of duration of infection on outcome of debridement and implant retention in fracture-related infection.

Abstract: Aims The principle strategies of fracture-related infection (FRI) treatment are debridement, antimicrobial therapy, and implant retention (DAIR) or debridement, antimicrobial therapy, and implant r...

Revision knee replacement for prosthetic joint infection: Epidemiology, clinical outcomes and health-economic considerations

Abstract: Prosthetic joint infection (PJI) is a devastating complication of knee replacement surgery. Recent evidence has shown that the burden of disease is increasing as more and more knee replacement procedures are performed. The current incidence of revision total knee replacement (TKR) for PJI is estimated at 7.5 cases per 1000 primary joint replacement procedures at 10 years. Revision TKR for PJI is complex surgery, and is associated to a high rate of post-operative complications. The 5-year patient mortality is comparable to some common cancer diagnoses, and more than 15% of patients require re-revision by 10 years. Patient-reported outcome measures (PROMs) including joint function may be worse following revision TKR for PJI than for aseptic indications. The complexity and extended length of the treatment pathway for PJI places a significant burden on the healthcare system, highlighting it as an area for future research to identify the most clinically and cost-effective interventions.

Benefits outweigh the risks: a consensus statement on the risks of physical activity for people living with long-term conditions.

Abstract: Introduction The benefits of physical activity for people living with long-term conditions (LTCs) are well established. However, the risks of physical activity are less well documented. The fear of exacerbating symptoms and causing adverse events is a persuasive barrier to physical activity in this population. This work aimed to agree clear statements for use by healthcare professionals about medical risks of physical activity for people living with LTCs through expert consensus. These statements addressed the following questions: (1) Is increasing physical activity safe for people living with one or more LTC? (2) Are the symptoms and clinical syndromes associated with common LTCs aggravated in the short or long term by increasing physical activity levels? (3) What specific risks should healthcare professionals consider when advising symptomatic people with one or more LTCs to increase their physical activity levels? Methods Statements were developed in a multistage process, guided by the Appraisal of Guidelines for Research and Evaluation tool. A patient and clinician involvement process, a rapid literature review and a steering group workshop informed the development of draft symptom and syndrome-based statements. We then tested and refined the draft statements and supporting evidence using a three-stage modified online Delphi study, incorporating a multidisciplinary expert panel with a broad range of clinical specialties. Results Twenty-eight experts completed the Delphi process. All statements achieved consensus with a final agreement between 88.5%–96.5%. Five ‘impact statements’ conclude that (1) for people living with LTCs, the benefits of physical activity far outweigh the risks, (2) despite the risks being very low, perceived risk is high, (3) person-centred conversations are essential for addressing perceived risk, (4) everybody has their own starting point and (5) people should stop and seek medical attention if they experience a dramatic increase in symptoms. In addition, eight symptom/syndrome-based statements discuss specific risks for musculoskeletal pain, fatigue, shortness of breath, cardiac chest pain, palpitations, dysglycaemia, cognitive impairment and falls and frailty. Conclusion Clear, consistent messaging on risk across healthcare will improve people living with LTCs confidence to be physically active. Addressing the fear of adverse events on an individual level will help healthcare professionals affect meaningful behavioural change in day-to-day practice. Evidence does not support routine preparticipation medical clearance for people with stable LTCs if they build up gradually from their current level. The need for medical guidance, as opposed to clearance, should be determined by individuals with specific concerns about active symptoms. As part of a system-wide approach, consistent messaging from healthcare professionals around risk will also help reduce cross-sector barriers to engagement for this population.

Providing an Evidence Base for Tissue Sampling and Culture Interpretation in Suspected Fracture-Related Infection.

Abstract: Background The recent consensus definition for the diagnosis of fracture-related infection (FRI) includes the identification of indistinguishable microorganisms in at least 2 surgical deep-tissue specimens as a confirmatory criterion. However, this cut-off, and the total number of specimens from a patient with suspected FRI that should be sent for microbiological testing, have not been validated. We endeavored to estimate the accuracy of different numbers of specimens and diagnostic cut-offs for microbiological testing of deep-tissue specimens in patients undergoing surgical treatment for possible FRI. Methods A total of 513 surgical procedures in 385 patients with suspected FRI were included. A minimum of 2 surgical deep-tissue specimens were submitted for microbiological testing; 5 or more specimens were analyzed in 345 procedures (67%). FRI was defined by the presence of any confirmatory criteria other than microbiology. Resampling was utilized to model the sensitivity and specificity of diagnostic cut-offs for the number of surgical specimens yielding indistinguishable microorganisms and for the total number of specimens. The likelihood of detecting all clinically relevant microorganisms was also assessed. Results A diagnostic cut-off of at least 2 of 5 specimens with indistinguishable microorganisms identified by culture was 68% sensitive (95% confidence interval [CI], 62% to 74%) and 87% specific (95% CI, 81% to 94%) for the diagnosis of FRI. Two out of 3 specimens were 60% sensitive (95% CI, 55% to 66%) and 92% specific (95% CI, 88% to 96%). Submitting only 3 deep-tissue specimens risked missing clinically relevant microorganisms in at least 1 in 10 cases. Conclusions The present study was the first to validate microbiological criteria for the diagnosis of FRI, supporting the current confirmatory diagnostic criteria for FRI. Analysis of at least 5 deep-tissue specimens in patients with possible FRI is recommended. Level of evidence Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Effectiveness, Patient Satisfaction, and Cost Reduction of Virtual Joint Replacement Clinic Follow-Up of Hip and Knee Arthroplasty.

Abstract: Background Total hip and knee arthroplasties are increasingly performed operations, and routine follow-up places huge demands on orthopedic services. This study investigates the effectiveness, patients’ satisfaction, and cost reduction of Virtual Joint Replacement Clinic (VJRC) follow-up of total hip arthroplasty and total knee arthroplasty patients in a university hospital. VJRC is especially valuable when in-person appointments are not advised or feasible such as during the COVID-19 pandemic. Methods A total of 1749 patients who were invited for VJRC follow-up for knee or hip arthroplasty from January 2017 to December 2018 were included in this retrospective study. Patients were referred to VJRC after their 6-week postoperative review. Routine VJRC postoperative review was undertaken at 1 and 7 years and then 3-yearly thereafter. We evaluated the VJRC patient response rate, acceptability, and outcome. Patient satisfaction was measured in a subgroup of patients using a satisfaction survey. VJRC costs were calculated compared to face-to-face follow-up. Results The VJRC had a 92.05% overall response rate. Only 7.22% required further in-person appointments with only 3% being reviewed by an orthopedic consultant. VJRC resulted in an estimated saving of £42,644 per year at our institution. The patients’ satisfaction survey showed that 89.29% of the patients were either satisfied or very satisfied with VJRC follow-up. Conclusion VJRC follow-up for hip and knee arthroplasty patients is an effective alternative to in-person clinic assessment which is accepted by patients, has high patient satisfaction, and can reduce the cost to both health services and patients.

Definition of long-bone nonunion: A scoping review of prospective clinical trials to evaluate current practice.

Abstract: Aim Although nonunions are among the most common complications after long-bone fracture fixation, the definition of fracture nonunion remains controversial and varies widely. The aim of this study was to identify the definitions and diagnostic criteria used in the scientific literature to describe nonunions after long-bone fractures. Methods A comprehensive literature search was performed in PubMed, Cochrane Library, Web of Science, and Embase. Prospective clinical studies, in which adult long-bone fracture nonunions were investigated as main subject, were included in this analysis. Data on nonunion definitions described in each study were extracted and collected in a database. Results Although 148 studies met the inclusion criteria, only 50% (74/148) provided a definition for their main study subject. Nonunion was defined in these studies based on time-related criteria in 85% (63/74), on radiographic criteria in 62% (46/74), and on clinical criteria in 45% (33/74). A combination of clinical, radiographic and time-related criteria for definition was found in 38% (28/74). The time interval between fracture and the time point when authors defined an unhealed fracture as a nonunion showed considerable heterogeneity, ranging from three to twelve months. Conclusion In the current orthopaedic literature, we found a lack of consensus with regard to the definition of long-bone nonunions. Without valid and reliable definition criteria for nonunion, standardization of diagnostic and treatment algorithms as well as the comparison of clinical studies remains problematic. The lack of a clear definition emphasizes the need for a consensus-based approach to the diagnosis of fracture nonunion centred on clinical, radiographical and time-related criteria.

Serious postoperative complications and reoperation after carpal tunnel decompression surgery in England: a nationwide cohort analysis.

Abstract: Summary Background Carpal tunnel decompression surgery to treat carpal tunnel syndrome is a common procedure, yet data on safety and effectiveness of the operation in the general population remain scarce. We aimed to estimate the incidence of reoperation and serious postoperative complications (requiring admission to hospital or further surgery) following carpal tunnel decompression in routine clinical practice and to identify the patient factors associated with these adverse outcomes. Methods We did a nationwide cohort analysis including all carpal tunnel decompression surgeries in patients aged 18 years or older, done in the National Health Service in England between April 1, 1998, and March 31, 2017, using the Hospital Episode Statistics dataset linked to mortality records. Patients were followed-up until death or until the end of the study (March 31, 2017). Primary outcomes were the overall incidence of carpal tunnel decompression reoperation and serious postoperative complications (surgical site infection or dehiscence, or neurovascular or tendon injury, requiring admission to hospital or further surgery) within 30 days and 90 days after surgery. Multivariable Cox regression analysis was used to identify factors influencing complications and reoperation, and the Fine and Gray method was used to adjust for the competing risk of mortality. This study is registered with ClinicalTrials.gov , NCT03573765 . Findings 855 832 carpal tunnel decompression surgeries were done between April 1, 1998, and March 31, 2017 (incidence rate 1·10 per 1000 person-years [95% CI 1·02–1·17]). 29 288 procedures (3·42%) led to carpal tunnel decompression reoperation (incidence rate 3·18 per 1000 person-years [95% CI 3·12–3·23]). Of the 855 832 initial surgeries, 620 procedures (0·070% [95% CI 0·067–0·078]) led to a serious complication within 30 days after surgery, and 698 procedures (0·082% [0·076–0·088]) within 90 days. Local complications within 90 days after surgery were associated with male sex (adjusted hazard ratio 2·32 [95% CI 1·74–3·09]) and age category 18–29 years (2·25 [1·10–4·62]). Male sex (adjusted subhazard ratio 1·09 [95% CI 1·06–1·13]), old age (>80 years vs 50–59 years: 1·09 [1·03–1·15]), and greater levels of comorbidity (Charlson score ≥5 vs 0: 1·25 [1·19–1·32]) and socioeconomic deprivation (most deprived 10% vs least deprived 10%: 1·18 [1·10–1·27]) were associated with increased reoperation risk. Interpretation To our knowledge, this is the largest national study on carpal tunnel decompression to date, providing strong evidence on serious postoperative complication and reoperation rates. Carpal tunnel decompression appears to be a safe operation in most patients, with an overall serious complication rate (requiring admission to hospital or further surgery) of less than 0·1%. Funding Versus Arthritis; Medical Research Council; Royal College of Surgeons of England and National Joint Registry research fellowship; University of Oxford; National Institute for Health Research; and National Institute for Health Research Biomedical Research Centre, Oxford.

Spinal metastases treated with bipolar radiofrequency ablation with increased (>70°C) target temperature: Pain management and local tumor control.

Abstract: Purpose To investigate the safety and clinical efficacy of bipolar radiofrequency ablation (b-RFA) with increased (> 70 °C) target temperature for the treatment of spine metastases with the intent of achieving pain relief or local tumor control. Materials and methods Thirty-one patients with a total of 37 metastases who were treated with b-RFA with increased temperature and vertebroplasty from January 2016 to May 2019 were retrospectively included. There were 20 women and 11 men with a mean age of 62.4 ± 10.5 (SD) years (range: 40–78 years). Patients and metastases characteristics, procedure details and clinical outcomes were analyzed. Results Metastases were predominantly located in lumbar (22/37; 59.5%) or thoracic spine (13/37; 35.1%). Mean target temperature was 88.4 ± 3.5 (SD) °C (range: 70–90 °C). Technical success was 100% (37/37 metastases). One (1/37; 2.7%) major complication unrelated to b-RFA was reported. One (1/37; 2.7%) metastasis was lost to follow-up. Favorable outcome was noted in patients receiving b-RFA for pain management (16/20 metastases; 80%; mean follow-up, 3.4 ± 2.9 [SD] months) or with oligometastatic/oligoprogressive disease (6/6 metastases; 100%; mean follow-up, 5.0 ± 4.6 [SD] months). In patients receiving b-RFA to prevent complications, favorable outcome was noted in 6/10 metastases (60%; mean follow-up, 3.8 ± 4.8 [SD] months). Conclusions B-RFA with increased target temperature has an excellent safety profile and results in high rates of pain relief and local metastasis control in patients with oligometastatic/oligoprogressive disease. Suboptimal results are achieved in patients receiving b-RFA to prevent complications related to the growth of the index tumor.

Risk factors influencing fracture characteristics in postoperative periprosthetic femoral fractures around cemented stems in total hip arthroplasty : a multicentre observational cohort study on 584 fractures.

Abstract: Aims This study evaluates risk factors influencing fracture characteristics for postoperative periprosthetic femoral fractures (PFFs) around cemented stems in total hip arthroplasty. Methods Data w...

Interdisciplinary consensus statements on imaging of scapholunate joint instability.

Abstract: The purpose of this agreement was to establish evidence-based consensus statements on imaging of scapholunate joint (SLJ) instability by an expert group using the Delphi technique. Nineteen hand surgeons developed a preliminary list of questions on SLJ instability. Radiologists created statements based on the literature and the authors’ clinical experience. Questions and statements were revised during three iterative Delphi rounds. Delphi panellists consisted of twenty-seven musculoskeletal radiologists. The panellists scored their degree of agreement to each statement on an eleven-item numeric scale. Scores of ‘0’, ‘5’ and ‘10’ reflected complete disagreement, indeterminate agreement and complete agreement, respectively. Group consensus was defined as a score of ‘8’ or higher for 80% or more of the panellists. Ten of fifteen statements achieved group consensus in the second Delphi round. The remaining five statements achieved group consensus in the third Delphi round. It was agreed that dorsopalmar and lateral radiographs should be acquired as routine imaging work-up in patients with suspected SLJ instability. Radiographic stress views and dynamic fluoroscopy allow accurate diagnosis of dynamic SLJ instability. MR arthrography and CT arthrography are accurate for detecting scapholunate interosseous ligament tears and articular cartilage defects. Ultrasonography and MRI can delineate most extrinsic carpal ligaments, although validated scientific evidence on accurate differentiation between partially or completely torn or incompetent ligaments is not available. Delphi-based agreements suggest that standardized radiographs, radiographic stress views, dynamic fluoroscopy, MR arthrography and CT arthrography are the most useful and accurate imaging techniques for the work-up of SLJ instability. • Dorsopalmar and lateral wrist radiographs remain the basic imaging modality for routine imaging work-up in patients with suspected scapholunate joint instability. • Radiographic stress views and dynamic fluoroscopy of the wrist allow accurate diagnosis of dynamic scapholunate joint instability. • Wrist MR arthrography and CT arthrography are accurate for determination of scapholunate interosseous ligament tears and cartilage defects.

Patient-Reported Function and Quality of Life After Revision Total Knee Arthroplasty: An Analysis of 10,727 Patients from the NHS PROMs Program.

Abstract: Background The aim of the study was to investigate changes in patient-reported outcome measures (PROMs) after revision total knee arthroplasty (rTKA). Methods A total of 10,727 patients undergoing elective rTKA were recruited from the UK National Health Service PROMs data set from 2013 to 2019. PROMs were collected at baseline and six months to assess joint function (Oxford Knee Score, OKS) and quality of life (EQ-5D). Associations with a change in the OKS (COKS) were investigated through multiple linear regression. Results The mean COKS was 12.4 (standard deviation 10.7) points. A total of 6776 of 10,329 (65.6%) patients demonstrated increase in the OKS above the minimal important change of 7.5 points. The median change in the EQ-5D utility was 0.227 (interquartile range 0.000 to 0.554). A total of 4917 of 9279 (53.0%) patients achieved a composite endpoint of improvement greater than the minimal important change for joint function and ‘better’ QoL as per the Paretian analysis. A total of 7477 of 10,727 (69.7%) patients reported satisfaction with rTKA. A total of 7947 of 10,727 (74.1%) patients felt surgery was a success. A total of 4888 of 10,632 (46.0%) patients reported one or more adverse events. A higher preoperative OKS was associated with a lower COKS (coefficient −0.63 [95% confidence interval −0.67 to −0.60]). Other factors associated with a lower COKS were postoperative complication(s), age under 60 years, longer duration of knee problems, patients who identified as disabled, problems in EQ-5D dimensions of anxiety/depression and self-care, comorbid conditions (circulatory problems, diabetes, and depression), and earlier year of procedure in the data set. Conclusion Two-thirds of patients experienced a meaningful improvement in joint function after rTKA. However, there was a high frequency of patient-reported complications. These findings may enable better informed discussion of the risks and benefits of discretionary rTKA.

Ultrasonographic Halo Score in giant cell arteritis: association with intimal hyperplasia and ischaemic sight loss.

Abstract: Objectives We investigated the relationship between the ultrasonographic Halo Score and temporal artery biopsy (TAB) findings in GCA. Methods This is a prospective study including 90 patients suspected of having GCA. Ultrasonography of temporal/axillary arteries and a TAB were obtained in all patients at baseline. An experienced pathologist evaluated whether TAB findings were consistent with GCA, and whether transmural inflammation, giant cells and intimal hyperplasia were present. Ultrasonographic Halo Scores were determined. Receiver operating characteristic analysis was performed. Results Twenty-seven patients had a positive TAB, while 32 patients with a negative TAB received a clinical diagnosis of GCA after 6 months of follow-up. Patients with a positive TAB showed higher Halo Scores than patients with a negative TAB. The presence of intimal hyperplasia in the biopsy, rather than the presence of transmural inflammation or giant cells, was associated with elevated Halo Scores in patients with GCA. The Halo Score discriminated well between TAB-positive patients with and without intimal hyperplasia, as indicated by an area under the curve of 0.82 in the receiver operating characteristic analysis. Patients with a positive TAB and intimal hyperplasia more frequently presented with ocular ischaemia (40%) than the other patients with GCA (13-14%). Conclusion The ultrasonographic Halo Score may help to identify a subset of GCA patients with intimal hyperplasia, a TAB feature associated with ischaemic sight loss.

MCAT Mutations Cause Nuclear LHON-like Optic Neuropathy.

Abstract: Pathological variants in the nuclear malonyl-CoA-acyl carrier protein transacylase (MCAT) gene, which encodes a mitochondrial protein involved in fatty-acid biogenesis, have been reported in two siblings from China affected by insidious optic nerve degeneration in childhood, leading to blindness in the first decade of life. After analysing 51 families with negative molecular diagnostic tests, from a cohort of 200 families with hereditary optic neuropathy (HON), we identified two novel MCAT mutations in a female patient who presented with acute, sudden, bilateral, yet asymmetric, central visual loss at the age of 20. This presentation is consistent with a Leber hereditary optic neuropathy (LHON)-like phenotype, whose existence and association with NDUFS2 and DNAJC30 has only recently been described. Our findings reveal a wider phenotypic presentation of MCAT mutations, and a greater genetic heterogeneity of nuclear LHON-like phenotypes. Although MCAT pathological variants are very uncommon, this gene should be investigated in HON patients, irrespective of disease presentation.

A retrospective cohort study comparing clinical outcomes and healthcare resource utilisation in patients undergoing surgery for osteomyelitis in England: a case for reorganising orthopaedic infection services.

Abstract: . Aims: An investigation of the impact of a multidisciplinary bone infection unit (BIU) undertaking osteomyelitis surgery with a single-stage protocol on clinical outcomes and healthcare utilisation compared to national outcomes in England. Patients and Methods: A tertiary referral multidisciplinary BIU was compared to the rest of England (ROE) and a subset of the 10 next busiest centres based on osteomyelitis treatment episode volume (Top Ten), using the Hospital Episodes Statistics database (HES). A total of 25 006 patients undergoing osteomyelitis surgery between April 2013 and March 2017 were included. Data on secondary healthcare resource utilisation and clinical indicators were extracted for 24 months before and after surgery. Results: Patients treated at the BIU had higher orthopaedic healthcare utilisation in the 2 years prior to their index procedure, with more admissions ( p 0.001) and a mean length of stay (LOS) over 4 times longer than other groups (10.99 d, compared to 2.79 d for Top Ten and 2.46 d for the ROE, p 0.001). During the index inpatient period, the BIU had fewer mean theatre visits (1.25) compared to the TT (1.98, p 0.001) and the ROE (1.64, p= 0.001). The index inpatient period was shorter in the BIU (11.84 d), 33.6 % less than the Top Ten (17.83 d, p 0.001) and 29.9 % shorter than the ROE (16.88 d, p 0.001). During follow-up, BIU patients underwent fewer osteomyelitis-related reoperations than Top Ten centres ( p= 0.0139) and the ROE ( p= 0.0137). Mortality was lower (4.71 %) compared to the Top Ten (20.06 %, p 0.001) and the ROE (22.63 %, p 0.001). The cumulative BIU total amputation rate was lower (6.47 %) compared to the Top Ten (15.96 %, p 0.001) and the ROE (12.71 %, p 0.001). Overall healthcare utilisation was lower in the BIU for all inpatient admissions, LOS, and Accident and Emergency (A&E) attendances. Conclusion: The benefits of managing osteomyelitis in a multi-disciplinary team (MDT) specialist setting included reduced hospital stays, lower reoperation rates for infection recurrence, improved survival, lower amputation rates, and lower overall healthcare utilisation. These results support the establishment of centrally funded multidisciplinary bone infection units that will improve patient outcomes and reduce healthcare utilisation.

The challenge of equipoise in trials with a surgical and non-surgical comparison: a qualitative synthesis using meta-ethnography.

Abstract: Background Randomised controlled trials in surgery can be a challenge to design and conduct, especially when including a non-surgical comparison. As few as half of initiated surgical trials reach their recruitment target, and failure to recruit is cited as the most frequent reason for premature closure of surgical RCTs. The aim of this qualitative evidence synthesis was to identify and synthesise findings from qualitative studies exploring the challenges in the design and conduct of trials directly comparing surgical and non-surgical interventions. Methods A qualitative evidence synthesis using meta-ethnography was conducted. Six electronic bibliographic databases (Medline, Central, Cinahl, Embase and PsycInfo) were searched up to the end of February 2018. Studies that explored patients’ and health care professionals’ experiences regarding participating in RCTs with a surgical and non-surgical comparison were included. The GRADE-CERQual framework was used to assess confidence in review findings. Results In total, 3697 abstracts and 49 full texts were screened and 26 published studies reporting experiences of patients and healthcare professionals were included. The focus of the studies (24/26) was primarily related to the challenge of recruitment. Two studies explored reasons for non-compliance to treatment allocation following randomisation. Five themes related to the challenges to these types of trials were identified: (1) radical choice between treatments; (2) patients’ discomfort with randomisation: I want the best treatment for me as an individual; (3) challenge of equipoise: patients’ a priori preferences for treatment; (4) challenge of equipoise: clinicians’ a priori preferences for treatment and (5) imbalanced presentation of interventions. Conclusion The marked dichotomy between the surgical and non-surgical interventions was highlighted in this review as making recruitment to these types of trials particularly challenging. This review identified factors that increase our understanding of why patients and clinicians may find equipoise more challenging in these types of trials compared to other trial comparisons. Trialists may wish to consider exploring the balance of potential factors influencing patient and clinician preferences towards treatments before they start recruitment, to enable issues specific to a particular trial to be identified and addressed. This may enable trial teams to make more efficient considered design choices and benefit the delivery of such trials.

Perspectives on the Genetic Associations of Ankylosing Spondylitis

Abstract: Ankylosing spondylitis (AS) is a common form of inflammatory spinal arthritis with a complex polygenic aetiology. Genome-wide association studies have identified more than 100 loci, including some involved in antigen presentation (HLA-B27, ERAP1, and ERAP2), some in Th17 responses (IL6R, IL23R, TYK2, and STAT3), and others in macrophages and T-cells (IL7R, CSF2, RUNX3, and GPR65). Such observations have already helped identify potential new therapies targeting IL-17 and GM-CSF. Most AS genetic associations are not in protein-coding sequences but lie in intergenic regions where their direct relationship to particular genes is difficult to assess. They most likely reflect functional polymorphisms concerned with cell type-specific regulation of gene expression. Clarifying the nature of these associations should help to understand the pathogenic pathways involved in AS better and suggest potential cellular and molecular targets for drug therapy. However, even identifying the precise mechanisms behind the extremely strong HLA-B27 association with AS has so far proved elusive. Polygenic risk scores (using all the known genetic associations with AS) can be effective for the diagnosis of AS, particularly where there is a relatively high pre-test probability of AS. Genetic prediction of disease outcomes and response to biologics is not currently practicable.

Respiratory subtype of relapsing polychondritis frequently presents as difficult asthma: a descriptive study of respiratory involvement in relapsing polychondritis with 13 patients from a single UK centre.

Abstract: Introduction Relapsing polychondritis is a rare multisystem vasculitis characterised by recurrent cartilage inflammation. Respiratory involvement, of which tracheobronchomalacia (TBM) is the commonest form, is difficult to treat and is linked to increased mortality. We describe 13 patients with respiratory involvement. Methods This is a retrospective study of all the patients with relapsing polychondritis at University Hospitals Coventry and Warwickshire NHS Trust (UHCW), a secondary care provider for ∼500 000. Only patients with respiratory involvement were included in this study. Results We identified 13 patients who fulfilled the inclusion criteria. Most patients were identified from the “difficult asthma” clinic. TBM was seen in 11 patients, whilst two patients had pleural effusions which resolved with immunosuppression and one patient had small airways disease. Computed tomography scans (inspiratory and expiratory) and bronchoscopy findings were useful in diagnosing TBM. Pulmonary function testing revealed significant expiratory flow abnormalities. All patients were treated with corticosteroids/disease-modifying anti-rheumatic drugs (DMARDs) and some were given cyclophosphamide or biological agents, although the response to cyclophosphamide (1 out of 4) or biologicals (2 out of 4) was modest in this cohort. Ambulatory continuous positive airway pressure ventilation was successful in four patients. Conclusions Relapsing polychondritis may be overlooked in “difficult asthma” clinics with patients having TBM (not asthma) and other features of relapsing polychondritis. Awareness of this condition is crucial to enable early diagnosis and interventions to reduce the risk of life-threatening airway collapse. A number of patients respond well to DMARDs and are able to minimise corticosteroid use.

Proximal adductor avulsions are rarely isolated but usually involve injury to the PLAC and pectineus: descriptive MRI findings in 145 athletes.

Abstract: The purpose of the study is to review the MRI findings in a cohort of athletes who sustained acute traumatic avulsions of the adductor longus fibrocartilaginous entheses, and to investigate related injuries namely the pyramidalis–anterior pubic ligament–adductor longus complex (PLAC). Associated muscle and soft tissue injuries were also assessed. The MRIs were reviewed for a partial or complete avulsion of the adductor longus fibrocartilage, as well as continuity or separation of the adductor longus from the pyramidalis. The presence of a concurrent partial pectineus tear was noted. Demographic data were analysed. Linear and logistic regression was used to examine associations between injuries. The mean age was 32.5 (SD 10.9). The pyramidalis was absent in 3 of 145 patients. 85 of 145 athletes were professional and 52 competed in the football Premier League. 132 had complete avulsions and 13 partial. The adductor longus was in continuity with pyramidalis in 55 athletes, partially separated in seven and completely in 81 athletes. 48 athletes with a PLAC injury had a partial pectineus avulsion. Six types of PLAC injuries patterns were identified. Associated rectus abdominis injuries were rare and only occurred in five patients (3.5%). The proximal adductor longus forms part of the PLAC and is rarely an isolated injury. The term PLAC injury is more appropriate term. MRI imaging should assess all the anatomical components of the PLAC post-injury, allowing recognition of the different patterns of injury. Level III.

Trends and developments in hip and knee arthroplasty technology.

Abstract: The developments in hip and knee arthroplasty over recent years have aimed to improve outcomes, reduce complications and improve implant survival. This review describes some of the most interesting trends and developments in this important and fast-moving field. Notable developments have included ceramic hip resurfacing, mini hip stems, cementless knee replacement and the wider adoption of the dual mobility articulation for hip arthroplasty. Advances in additive manufacturing and the surface modification of joint replacements offer increasing options for more challenging arthroplasty cases. Robotic assisted surgery is one of the most interesting developments in hip and knee surgery. The recent growth in the use of this technology is providing data that will help determine whether this approach should become the standard of care for hip and knee arthroplasty in the future.

Safety and Oncologic Outcomes of Magnetic Resonance Imaging-Guided Cryoablation of Renal Cell Carcinoma: A 10-Year Single-Center Experience.

Abstract: OBJECTIVES Magnetic resonance imaging guidance has been sporadically reported for renal tumor cryoablation (CA); therefore, clinical experience with this modality is still limited.The aim of this study is to retrospectively analyze our 10-year experience with renal tumor CA performed on a 1.5 T magnetic resonance imaging unit with the intent of reporting procedural safety and oncologic outcomes. MATERIALS AND METHODS We included 143 patients (102 men; 41 women; median age, 73 years; range, 34-91 years) with 149 tumors (median size, 2.6 cm; range, 0.6-6.0 cm), treated between 2009 and 2019. Patient, tumor, procedure, and follow-up data were collected and analyzed. The Kaplan-Meier method was used to estimate local recurrence-free (LRFS), metastasis-free (MFS), disease-free (DFS), cancer-specific, and overall (OS) survival. Univariate and multivariate models were used to identify factors associated with complications, LRFS, MFS, DFS, and OS. RESULTS The overall complication rate was 10.7% (16/149 tumors), with 1 major (1/149 [0.7%]; 95% confidence interval, 0.0%-3.7%) hemorrhagic complication. Other minor complications (15/149 [10.1%]; 95% confidence interval, 0.6%-16.1%) did not include any cases of injury to nearby organs. There were no factors associated with complications.Five-year estimates of LRFS (primary/secondary), MFS, DFS, cancer-specific survival, and OS were 82.8%/91.5%, 91.1%, 75.1%, 98.2%, and 89.6%, respectively. Increasing tumor size (hazard radio [HR], 1.8; P = 0.02) and intraparenchymal tumor location (HR, 5.6; P < 0.01) were associated with lower LRFS; increasing patient's age (HR, 0.5; P = 0.01), high tumor grade (HR, 23.3; P < 0.01) and non-clear-cell/nonpapillary histology (HR, 20.1; P < 0.01) with metastatic disease; and high tumor grade (HR, 3.2; P = 0.04) with lower DFS. CONCLUSION Magnetic resonance imaging-guided CA of renal tumors is associated with acceptable morbidity and high survival estimates at 5-year follow-up. Given the absence of complications resulting from injuries to nearby organs, further studies are required to evaluate whether the potential reduced incidence of these adverse events justifies large-scale implementation of this interventional modality.

Preoperative Anemia in Primary Arthroplasty Patients-Prevalence, Influence on Outcome, and the Effect of Treatment.

Abstract: Background This study aims to: 1) Determine the prevalence of preoperative anemia in arthroplasty; 2) Assess whether preoperative anemia is associated with inferior outcomes; and 3) Ascertain whether optimization in a dedicated blood management program (BMP) is associated with improved outcomes. Methods All primary arthroplasties performed at an academic, tertiary-care, arthroplasty center between 2012 and 2017 were reviewed. Hemoglobin level obtained in the preoperative assessment clinic was recorded. Patients with anemia were then considered for further review in BMP. Outcomes included improvement in hemoglobin level post-BMP; length of stay; perioperative transfusion; 90-day readmission, complication, and reoperation rates. The effect of preoperative anemia and the effect of treatment at the BMP on outcomes were evaluated through multivariable regression analysis controlling for relevant covariates. Results 17% of patients (932/5384) were found to have anemia; 115/357 patients who attended the BMP were no longer anemic. Thus, at time of operation, 15% of patients (817/5384) had anemia. Anemic patients were 4.09 times more likely (95% CI: 2.64-6.35) to require a transfusion; 1.42 times more likely (95% CI: 0.99-2.03) to sustain complications and had 19% longer (95% CI: 13%-26%) length of stay. Those who attended the BMP were less likely to receive a transfusion (OR = 0.32, 95% CI: 0.16-0.66), suffer from postoperative complications (OR = 0.30, 95% CI: 0.14-0.63), or require readmission compared with anemic patients not seen in the BMP (OR = 0.25, 95% CI: 0.09-0.71). Conclusions The prevalence of anemia in this arthroplasty cohort was 15%. Preoperative, timely, optimization of anemia should be strongly considered as it is likely to reduce “anemia-associated burden” after arthroplasty.

Functional Genomic Analysis of a RUNX3 Polymorphism Associated with Ankylosing Spondylitis.

Abstract: OBJECTIVE To investigate the functional consequences of the single-nucleotide polymorphism rs4648889 in a putative enhancer upstream of the RUNX3 promoter associated with susceptibility to ankylosing spondylitis (AS). METHODS Using nuclear extracts from Jurkat cells and primary human CD8+ T cells, the effects of rs4648889 on allele-specific transcription factor (TF) binding were investigated by DNA pull-down assay and quantitative mass spectrometry (qMS), with validation by electrophoretic mobility shift assay (EMSA), Western blotting of the pulled-down eluates, and chromatin immunoprecipitation (ChIP)-quantitative polymerase chain reaction (qPCR) analysis. Further functional effects were tested by small interfering RNA knockdown of the gene for interferon regulatory factor 5 (IRF5), followed by reverse transcription-qPCR (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA) to measure the levels of IFNγ messenger RNA (mRNA) and protein, respectively. RESULTS In nuclear extracts from CD8+ T cells, results of qMS showed that relative TF binding to the AS-risk A allele of rs4648889 was increased 3.7-fold (P < 0.03) for Ikaros family zinc-finger protein 3 (IKZF3; Aiolos) and components of the NuRD complex, including chromodomain helicase DNA binding protein 4 (CHD4) (3.6-fold increase; P < 0.05) and retinoblastoma binding protein 4 (RBBP4) (4.1-fold increase; P < 0.03). In contrast, IRF5 bound significantly more to the AS-protective G allele compared to the AS-risk A allele (fold change 8.2; P = 0.003). Validation with Western blotting, EMSA, and ChIP-qPCR confirmed the differential allelic binding of IKZF3, CHD4, RBBP4, and IRF5. Silencing of IRF5 in CD8+ T cells increased the levels of IFNγ mRNA as measured by RT-qPCR (P = 0.03) and IFNγ protein as measured by ELISA (P = 0.02). CONCLUSION These findings suggest that the association of rs4648889 with AS reflects allele-specific binding of this enhancer-like region to certain TFs, including IRF5, IKZF3, and members of the NuRD complex. IRF5 may have crucial influences on the functions of CD8+ lymphocytes, a finding that could reveal new therapeutic targets for the management of AS.