Early experience and patient-reported outcomes of 503 INFINITY total ankle arthroplasties.

AIMS: This is a multicentre, non-inventor, prospective observational study of 503 INFINITY fixed bearing total ankle arthroplasties (TAAs). We report our early experience, complications, and radiological and functional outcomes. METHODS: Patients were recruited from 11 specialist centres between June 2016 and November 2019. Demographic, radiological, and functional outcome data (Ankle Osteoarthritis Scale, Manchester Oxford Questionnaire, and EuroQol five-dimension five-level score) were collected preoperatively, at six months, one year, and two years. The Canadian Orthopaedic Foot and Ankle Society (COFAS) grading system was used to stratify deformity. Early and late complications and reoperations were recorded as adverse events. Radiographs were assessed for lucencies, cysts, and/or subsidence. RESULTS: In all, 500 patients reached six-month follow-up, 420 reached one-year follow-up, and 188 reached two-year follow-up. The mean age was 67.8 years (23.9 to 88.5). A total of 38 patients (7.5%) presented with inflammatory arthritis. A total of 101 (20.0%) of implantations used patient-specific instrumentation; 167 patients (33.1%) underwent an additional procedure at the time of surgery. A total of seven patients died of unrelated causes, two withdrew, and one was lost to follow-up. The mean follow-up was 16.2 months (6 to 36). There was a significant improvement from baseline across all functional outcome scores at six months, one, and two years. There was no significant difference in outcomes with the use of patient-specific instrumentation, type of arthritis, or COFAS type. Five (1.0%) implants were revised. The overall complication rate was 8.8%. The non-revision reoperation rate was 1.4%. The 30-day readmission rate was 1.2% and the one-year mortality 0.74%. CONCLUSION: The early experience and complications reported in this study support the current use of the INFINITY TAA as a safe and effective implant in the treatment of end-stage ankle arthritis. Cite this article: Bone Joint J 2021;103-B(7):1270-1276.

Competition and community succession link N transformation and greenhouse gas emissions in urine patches.

Nitrous oxide (N2O) is a strong greenhouse gas produced by biotic/abiotic processes directly linked to both fungal and prokaryotic communities that produce, consume or create conditions leading to its emission. In soils exposed to nitrogen (N) in the form of urea, an ecological succession is triggered resulting in a dynamic turnover of microbial populations. However, knowledge of the mechanisms controlling this succession and the repercussions for N2O emissions remain incomplete. Here, we monitored N2O production and fungal/prokaryotic community changes (via 16S and 18S amplicon sequencing) in soil microcosms exposed to urea. Contributions of microbes to emissions were determined using biological inhibitors. Results confirmed that urea leads to shifts in microbial community assemblages by selecting for certain microbial groups (fast growers) as dictated through life history strategies. Urea reduced overall community diversity by conferring dominance to specific groups at different stages in the succession. The diversity lost under urea was recovered with inhibitor addition through the removal of groups that were actively growing under urea indicating that species replacement is mediated in part by competition. Results also identified fungi as significant contributors to N2O emissions, and demonstrate that dominant fungal populations are consistently replaced at different stages of the succession. These successions were affected by addition of inhibitors which resulted in strong decreases in N2O emissions, suggesting that fungal contributions to N2O emissions are larger than that of prokaryotes.

Total ankle arthroplasty.

AIMS: We report the medium-term outcomes of a consecutive series of 118 Zenith total ankle arthroplasties (TAAs) from a single, non-designer centre. METHODS: Between December 2010 and May 2016, 118 consecutive Zenith prostheses were implanted in 114 patients. Demographic, clinical, and patient-reported outcome measures (PROMs) data were collected. The endpoint of the study was failure of the implant requiring revision of one or all of the components. Kaplan-Meier survival curves were generated with 95% confidence intervals (CIs) and the rate of failure calculated for each year. RESULTS: Eight patients (ten ankles) died during follow-up, but none required revision. Of the surviving 106 patients (108 ankles: rheumatoid arthritis (RA), n = 15; osteoarthritis (OA), n = 93), 38 were women and 68 were men, with a mean age of 68.2 years (48 to 86) at the time of surgery. Mean follow-up was 5.1 years (2.1 to 9.0). A total of ten implants failed (8.5%), thus requiring revision. The implant survival at seven years, using revision as an endpoint, was 88.2% (95% CI 100% to 72.9%). There was a mean improvement in Manchester-Oxford Foot and Ankle Questionnaire (MOXFQ) from 85.0 to 32.8 and visual analogue scale (VAS) scores from 7.0 to 3.2, and overall satisfaction was 89%. The three commonest complications were malleolar fracture (14.4%, n = 17), wound healing (13.6%, n = 16), and superficial infection (12.7%, n = 15). The commonest reason for revision was aseptic loosening. No patients in our study were revised for deep infection. CONCLUSION: Our results show that Zenith survival rates are comparable with those in the literature for other implants and in the National Joint Registry (NJR). Overall patient satisfaction was high as were functional outcomes. However, the data highlight potential complications associated with this surgery. The authors believe that these figures support ankle arthroplasty as an option in the treatment of ankle arthritis. Cite this article: Bone Joint J 2021;103-B(4):696-703.

COVID-19 consent and return to elective orthopaedic surgery: allowing a true patient choice?

AIMS: The exact risk to patients undergoing surgery who develop COVID-19 is not yet fully known. This study aims to provide the current data to allow adequate consent regarding the risks of post-surgery COVID-19 infection and subsequent COVID-19-related mortality. METHODS: All orthopaedic trauma cases at the Wrightington Wigan and Leigh NHS Foundation Trust from 'lockdown' (23 March 2020) to date (15 June 2020) were collated and split into three groups. Adult ambulatory trauma surgeries (upper limb trauma, ankle fracture, tibial plateau fracture) and regional-specific referrals (periprosthetic hip fracture) were performed at a stand-alone elective site that accepted COVID-19-negative patients. Neck of femur fractures (NOFF) and all remaining non-NOFF (paediatric trauma, long bone injury) surgeries were performed at an acute site hospital (mixed green/blue site). Patients were swabbed for COVID-19 before surgery on both sites. Age, sex, nature of surgery, American Society of Anaesthesiologists (ASA) grade, associated comorbidity, length of stay, development of post-surgical COVID-19 infection, and post-surgical COVID-19-related deaths were collected. RESULTS: At the elective site, 225 patients underwent orthopaedic trauma surgery; two became COVID-19-positive (0.9%) in the immediate perioperative period, neither of which was fatal. At the acute site, 93 patients underwent non-NOFF trauma surgery, of whom six became COVID-19-positive (6.5%) and three died. A further 84 patients underwent NOFF surgery, seven becoming COVID-19 positive (8.3%) and five died. CONCLUSION: At the elective site, the rate of COVID-19 infection following orthopaedic trauma surgery was low, at 0.9%. At the acute mixed site (typical district general hospital), for non-NOFF surgery there was a 6.5% incidence of post-surgical COVID-19 infection (seven-fold higher risk) with 50% COVID-19 mortality; for NOFF surgery, there was an 8.3% incidence of post-surgical COVID-19 infection, with 71% COVID-19 mortality. This is likely to have significance when planning a resumption of elective orthopaedic surgery and for consent to the patient.Cite this article: Bone Joint Open 2020;1-9:556-561.

Silastic first metatarsophalangeal joint arthroplasty for the treatment of end-stage hallux rigidus.

AIMS: Arthroplasty for end-stage hallux rigidus (HR) is controversial. Arthrodesis remains the gold standard for surgical treatment, although is not without its complications, with rates of up to 10% for nonunion, 14% for reoperation and 10% for metatarsalgia. The aim of this study was to analyze the outcome of a double-stemmed silastic implant (Wright-Medical, Memphis, Tennessee, USA) for patients with end-stage HR. METHODS: We conducted a retrospective review of 108 consecutive implants in 76 patients, between January 2005 and December 2016, with a minimum follow-up of two years. The mean age of the patients at the time of surgery was 61.6 years (42 to 84). There were 104 females and four males. Clinical, radiological, patient reported outcome measures (PROMS) data, a visual analogue score (VAS) for pain, and satisfaction scores were collected. RESULTS: The survivorship at a mean follow-up of 5.3 years (2.1 to 14.1) was 97.2%. The mean Manchester Oxford Foot and Ankle Questionnaire (MOXFQ) scores improved from 78.1 to 11.0, and VAS scores for pain from 7/10 to 1.3/10. The rate of satisfaction was 90.6%. Three implants (2.8%) required revision; one for infection, one-month postoperatively, and two for stem breakage at 10.4 and 13.3 years postoperatively. There was a 1.9% reoperation rate other than revision, 23.1% of patients developed a minor complication, and 21.1% of patients had non-progressive and asymptomatic cysts on radiological review. CONCLUSION: We report a 97.2% survivorship at a mean follow-up of 5.3 years with this implant. We did not find progressive osteolysis, as has been previously reported. These results suggest that this double-stemmed silastic implant provides a predictable and reliable alternative with comparable outcomes to arthrodesis for the treatment of end-stage HR. Cite this article: Bone Joint J 2020;102-B(2):220-226.

Clinical and patient-reported outcomes following Low Intensity Pulsed Ultrasound (LIPUS, Exogen) for established post-traumatic and post-surgical nonunion in the foot and ankle.

BACKGROUND: Biophysical methods including Low Intensity Pulsed Ultrasound (LIPUS) are emerging as potential alternatives to revision surgery for treating established nonunions. We aim to prospectively review the clinical and patient-reported outcomes of patients treated with LIPUS following post-traumatic and post-surgical nonunions in the foot and ankle. METHODS: Forty-seven consecutive patients underwent Exogen treatment. Patient-reported outcome scores included MOXFQ, EQ-5D and VAS. Patients were divided in to 3 groups: fractures (A), hindfoot procedures (B) and midfoot/forefoot procedures (C). RESULTS: Thirty-seven patients (78.7%) clinically united, 4 patients (8.5%) noticed no significant improvement but did not want further intervention and 6 patients (12.8%) underwent revision surgery. The mean duration of Exogen treatment was 6 months. Union rates of 93%, 67% and 78% were noted in the three groups. Significant improvement in functional outcomes and potential cost savings were observed. CONCLUSIONS: Exogen for established nonunion in the foot and ankle is a safe, valuable and economically viable clinical option as an alternative to revision surgery. We observed better results in the fracture and midfoot/forefoot groups and relatively poorer results in the hindfoot fusion group.

A Targeted Mass Spectrometry Strategy for Developing Proteomic Biomarkers: A Case Study of Epithelial Ovarian Cancer.

Protein biomarkers for epithelial ovarian cancer are critical for the early detection of the cancer to improve patient prognosis and for the clinical management of the disease to monitor treatment response and to detect recurrences. Unfortunately, the discovery of protein biomarkers is hampered by the limited availability of reliable and sensitive assays needed for the reproducible quantification of proteins in complex biological matrices such as blood plasma. In recent years, targeted mass spectrometry, exemplified by selected reaction monitoring (SRM) has emerged as a method, capable of overcoming this limitation. Here, we present a comprehensive SRM-based strategy for developing plasma-based protein biomarkers for epithelial ovarian cancer and illustrate how the SRM platform, when combined with rigorous experimental design and statistical analysis, can result in detection of predictive analytes.Our biomarker development strategy first involved a discovery-driven proteomic effort to derive potential N-glycoprotein biomarker candidates for plasma-based detection of human ovarian cancer from a genetically engineered mouse model of endometrioid ovarian cancer, which accurately recapitulates the human disease. Next, 65 candidate markers selected from proteins of different abundance in the discovery dataset were reproducibly quantified with SRM assays across a large cohort of over 200 plasma samples from ovarian cancer patients and healthy controls. Finally, these measurements were used to derive a 5-protein signature for distinguishing individuals with epithelial ovarian cancer from healthy controls. The sensitivity of the candidate biomarker signature in combination with CA125 ELISA-based measurements currently used in clinic, exceeded that of CA125 ELISA-based measurements alone. The SRM-based strategy in this study is broadly applicable. It can be used in any study that requires accurate and reproducible quantification of selected proteins in a high-throughput and multiplexed fashion.

Prediction of colorectal cancer diagnosis based on circulating plasma proteins.

Non-invasive detection of colorectal cancer with blood-based markers is a critical clinical need. Here we describe a phased mass spectrometry-based approach for the discovery, screening, and validation of circulating protein biomarkers with diagnostic value. Initially, we profiled human primary tumor tissue epithelia and characterized about 300 secreted and cell surface candidate glycoproteins. These candidates were then screened in patient systemic circulation to identify detectable candidates in blood plasma. An 88-plex targeting method was established to systematically monitor these proteins in two large and independent cohorts of plasma samples, which generated quantitative clinical datasets at an unprecedented scale. The data were deployed to develop and evaluate a five-protein biomarker signature for colorectal cancer detection.

MSstats: an R package for statistical analysis of quantitative mass spectrometry-based proteomic experiments.

UNLABELLED: MSstats is an R package for statistical relative quantification of proteins and peptides in mass spectrometry-based proteomics. Version 2.0 of MSstats supports label-free and label-based experimental workflows and data-dependent, targeted and data-independent spectral acquisition. It takes as input identified and quantified spectral peaks, and outputs a list of differentially abundant peptides or proteins, or summaries of peptide or protein relative abundance. MSstats relies on a flexible family of linear mixed models. AVAILABILITY AND IMPLEMENTATION: The code, the documentation and example datasets are available open-source at www.msstats.org under the Artistic-2.0 license. The package can be downloaded from www.msstats.org or from Bioconductor www.bioconductor.org and used in an R command line workflow. The package can also be accessed as an external tool in Skyline (Broudy et al., 2014) and used via graphical user interface.

Statistical protein quantification and significance analysis in label-free LC-MS experiments with complex designs.

BACKGROUND: Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) is widely used for quantitative proteomic investigations. The typical output of such studies is a list of identified and quantified peptides. The biological and clinical interest is, however, usually focused on quantitative conclusions at the protein level. Furthermore, many investigations ask complex biological questions by studying multiple interrelated experimental conditions. Therefore, there is a need in the field for generic statistical models to quantify protein levels even in complex study designs. RESULTS: We propose a general statistical modeling approach for protein quantification in arbitrary complex experimental designs, such as time course studies, or those involving multiple experimental factors. The approach summarizes the quantitative experimental information from all the features and all the conditions that pertain to a protein. It enables both protein significance analysis between conditions, and protein quantification in individual samples or conditions. We implement the approach in an open-source R-based software package MSstats suitable for researchers with a limited statistics and programming background. CONCLUSIONS: We demonstrate, using as examples two experimental investigations with complex designs, that a simultaneous statistical modeling of all the relevant features and conditions yields a higher sensitivity of protein significance analysis and a higher accuracy of protein quantification as compared to commonly employed alternatives. The software is available at http://www.stat.purdue.edu/~ovitek/Software.html.

Clopidogrel: is a surgical delay necessary in fractured neck of femur?

INTRODUCTION: This paper assesses the outcomes of patients after surgery for a proximal femur fracture while on clopidogrel. It describes a single-centre retrospective observational study over a two-year period. PATIENTS AND METHODS: A total of 31 surgical patients were included in this study. Of these, 28 were on clopidogrel and 3 on dipyridamole. Patients were split into subgroups based on when surgery took place and the type of hip fracture. The 'early surgery' (<48 hours from admission to theatre) group contained 16 patients (51.6%) and the 'late surgery' (>48 hours) group composed 15 patients (48.4%). Type of surgery performed and pre-and postoperative haemoglobin (Hb) levels were recorded. Furthermore, the number of units of blood transfused per patient as well as complications before and after surgery were noted. RESULTS: A significantly larger mean hb drop occurred in the early surgery group (3.2g/dl) compared with the late surgery group (2.3g/dl) (p=0.027). The mean length of inpatient stay was 21 days in the early and 23 days in the late group (p=0.456). A significantly larger hb mean drop occurred in patients with extracapsular hip fractures (3.4g/dl; n=16) compared with patients with intracapsular fractures (2.3g/dl; n=15) (p=0.020). The extracapsular patients had longer stays in hospital: 24.5 days versus 19.8 days in the intracapsular group (p=0.521). There was no statistical difference in the 30-day mortality between the early surgery (3/16 deaths) and late surgery (2/15 deaths) groups (p=0.481). CONCLUSIONS: Patients with extracapsular fractures, treated with early surgery, appear to be most at risk of complications after surgery.

The present state of ankle arthroplasty.

BACKGROUND: Total ankle arthroplasty (TAA) is being carried out with increasing frequency and manufacturers are releasing new implant designs each year. METHODS: We comment on the various designs and the outcome of the procedure as reported in the literature. No results have so far been published on the majority of the more recent designs and where outcome data are available, the follow up period is very short. RESULTS: For those designs where 5 or 10 year follow-up studies have been performed, the survivorship at 5 years is over 90% in most instances and of the order of 80% at 10 years. The failure rate is lower in ankles that are well aligned at presentation than it is for those with more than 15 degrees varus or valgus deformity pre-operatively. CONCLUSIONS: TAA has definite advantages over fusion for some patients and if selection criteria are adhered to, a long-lasting satisfactory outcome can be achieved.

The use of a local anesthetic foot block in patients undergoing outpatient bony forefoot surgery: a prospective randomized controlled trial.

Foot blocks are known to prolong postoperative pain relief. Consequently, their use has been extended to patients having outpatient surgery, despite little evidence to show improved patient satisfaction. Indeed, patients having outpatient surgery actually may be less satisfied because they will first experience pain at home on the first postoperative night, which may be more severe than anticipated. In this prospective, randomized, blinded study, 42 patients having unilateral outpatient bony forefoot surgery were assigned randomly to either having the surgery under general anesthesia alone or under general anesthesia with supplementary foot block (0.5% bupivicaine). All patients were assessed at home by telephone interview on the first and second postoperative day. There was a significantly longer time to first perceived pain in the foot block group compared with the control group, but no difference in the number of postoperative analgesic tablets consumed, no difference in pain score on the first night, first postoperative or second postoperative day, or any difference in the overall patient satisfaction scores at 2 days. The authors conclude that a local foot block, although prolonging the time to first perceived pain, does not improve patient satisfaction and is not detrimental when used as analgesia in the outpatient setting.