A National audit of the care of patients with acute kidney injury in England and Wales in 2019 and the association with patient outcomes.

BACKGROUND: Acute kidney injury (AKI) is a common complication of hospitalisations. This national audit assessed the care received by patients with AKI in hospital Trusts in England and Wales. METHODS: Twenty four hospital Trusts across England and Wales took part. Patients with AKI stage2/3 were identified using the UK Renal Registry AKI master patient index. Data was returned through a secure portal with linkage to hospital episode statistic mortality and hospitalisation data. Completion rates of AKI care standards and regional variations in care were established. RESULTS: 989 AKI episodes were included in the analyses. In-hospital 30-day mortality was 31-33.1% (AKI 2/3). Standard AKI interventions were completed in >80% of episodes. Significant inter-hospital variation remained in attainment of AKI care standards after adjustment for age and sex. Recording of urinalysis (41.9%) and timely imaging (37.2%) were low. Information on discharge summaries relating to medication changes/re-commencement and follow-up blood tests associated with reduced mortality. No quality indicators relating to clinical management associated with mortality. Better communication on discharge summaries associated with reduced mortality. CONCLUSIONS: Outcomes for patients with AKI in hospital remain poor. Regional variation in care exists. Work is needed to assess whether improving and standardising care improves patient outcomes.

Advance care planning for patients with end-stage kidney disease on dialysis: narrative review of the current evidence, and future considerations.

Patients with end-stage kidney disease (ESKD) have a high symptom-burden and high rates of morbidity and mortality. Despite this, evidence has shown that this patient group does not have timely discussions to plan for deterioration and death, and at the end of life there are unmet palliative care needs. Advance care planning is a process that can help patients share their personal values and preferences for their future care and prepare for declining health. Earlier, more integrated and holistic advance care planning has the potential to improve access to care services, communication, and preparedness for future decision-making and changing circumstances. However, there are many barriers to successful implementation of advance care planning in this population. In this narrative review we discuss the current evidence for advance care planning in patients on dialysis, the data around the barriers to advance care planning implementation, and interventions that have been trialled. The review explores whether the concepts and approaches to advance care planning in this population need to be updated to encompass current and future care. It suggests that a shift from a problem-orientated approach to a goal-orientated approach may lead to better engagement, with more patient-centred and satisfying outcomes.

The effect of a novel, digital physical activity and emotional well-being intervention on health-related quality of life in people with chronic kidney disease: trial design and baseline data from a multicentre prospective, wait-list randomised controlled trial (kidney BEAM).

BACKGROUND: Physical activity and emotional self-management has the potential to enhance health-related quality of life (HRQoL), but few people with chronic kidney disease (CKD) have access to resources and support. The Kidney BEAM trial aims to evaluate whether an evidence-based physical activity and emotional wellbeing self-management programme (Kidney BEAM) leads to improvements in HRQoL in people with CKD. METHODS: This was a prospective, multicentre, randomised waitlist-controlled trial, with health economic analysis and nested qualitative studies. In total, three hundred and four adults with established CKD were recruited from 11 UK kidney units. Participants were randomly assigned to the intervention (Kidney BEAM) or a wait list control group (1:1). The primary outcome was the between-group difference in Kidney Disease Quality of Life (KDQoL) mental component summary score (MCS) at 12 weeks. Secondary outcomes included the KDQoL physical component summary score, kidney-specific scores, fatigue, life participation, depression and anxiety, physical function, clinical chemistry, healthcare utilisation and harms. All outcomes were measured at baseline and 12 weeks, with long-term HRQoL and adherence also collected at six months follow-up. A nested qualitative study explored experience and impact of using Kidney BEAM. RESULTS: 340 participants were randomised to Kidney BEAM (n = 173) and waiting list (n = 167) groups. There were 96 (55%) and 89 (53%) males in the intervention and waiting list groups respectively, and the mean (SD) age was 53 (14) years in both groups. Ethnicity, body mass, CKD stage, and history of diabetes and hypertension were comparable across groups. The mean (SD) of the MCS was similar in both groups, 44.7 (10.8) and 45.9 (10.6) in the intervention and waiting list groups respectively. CONCLUSION: Results from this trial will establish whether the Kidney BEAM self management programme is a cost-effective method of enhancing mental and physical wellbeing of people with CKD. TRIAL REGISTRATION: NCT04872933. Registered 5th May 2021.

Falanga: The clinical correlates of surgical outcomes as a result of foot whipping in a resource poor setting.

BACKGROUND: Falanga is a punishment that involves hitting the bare soles of a person's feet. The consequences of this punishment may be limb and life-threatening. Post-traumatic acute kidney injury (AKI) secondary to rhabdomyolysis is a well-documented complication. Patients often require prompt surgical intervention and renal replacement therapy (RRT). The clinical and biochemical presentation of these patients and subsequent outcomes are poorly understood. AIMS: This prospective observational study describes the clinical presentation and effects of foot whipping on patient outcomes. METHODOLOGY: Prospective data were collected over a one-year period for 135 patients presenting following blunt force assault admitted to a single centre. Presenting clinical characteristics and patient outcomes were recorded and correlations between presenting clinical characteristics and surgical and clinical outcomes were assessed. RESULTS: Of 138 patients presenting following blunt force assault 96% were male with a mean age of 28.8 ± 8.01. Thirty-six out of the 138 patients presenting following blunt force assault had received foot-whipping only (falanga group, FG). Ten of these 36 patients in the FG group required surgical intervention, with one requiring a below knee amputation, compared with only two patients who required surgical intervention in the group who experienced blunt force trauma not restricted to foot whipping (Sjambok group). Average length of stay was 4 days (range 2-38) in FG group compared with 5 (range 1-21) in SG group, with no mortalities in either group. For patients in the FG, Hb was higher at presentation compared to patients in the SG group (135.2 33.7 vs 124.2 21.3, p = 0.03) and correlated positively with the need for surgical intervention (r = 0.6, p < 0.01). In this same group, the presenting characteristics of CK (4251.3 3087.4, p = 0.1 vs 7422.6 12347.7, p = 0.1) and urine output (0.95 0.4 vs 0.7 0.4) positively correlated with RRT [CK r = 0.6, p < 0.01, UO r = 0.46, p < 0.01]. CONCLUSION: Patients who present following falanga frequently require surgical intervention and the related healthcare utilisation and morbidity is high. Clinical indicators of a greater systemic injury at presentation may correlate with an increased likelihood of requiring surgical intervention or RRT.

A systematic review of immune checkpoint inhibitor-related neurological adverse events and association with anti-neuronal autoantibodies.

Introduction: Immune checkpoint inhibitors (ICI) therapy has led to a paradigm shift in cancer drug development and in the clinical evaluation of approaches to combination cancer treatment. Dysregulation of the immune system by ICI therapy may also elicit autoimmune phenomena and consequently manifest clinically as immune-related adverse events (irAEs) including neurological irAEs. Areas Covered: The purpose of this review is to explore the role of autoantibodies in the diagnosis and prediction of neurological irAEs and to evaluate their pathogenicity. We searched Pubmed and Embase for neurological irAEs and associated autoantibodies and found 28 patients with central and peripheral neurological irAEs. Of these patients, up to 40% had encephalitis, 34.4% with myasthenia gravis and 22% of patients with peripheral neuropathy and Guillain-Barre Syndrome had autoantibodies. Expert Opinion: Overall, our survey suggested a causal relationship between neurological irAEs and autoantibodies. Detection of autoantibodies may help to diagnose neurological irAEs and inform their clinical management.

Association between native T1 mapping of the kidney and renal fibrosis in patients with IgA nephropathy.

INTRODUCTION: IgA nephropathy (IgAN) is the commonest global cause of glomerulonephritis. Extent of fibrosis, tubular atrophy and glomerulosclerosis predict renal function decline. Extent of renal fibrosis is assessed with renal biopsy which is invasive and prone to sampling error. We assessed the utility of non-contrast native T1 mapping of the kidney in patients with IgAN for assessment of renal fibrosis. METHODS: Renal native T1 mapping was undertaken in 20 patients with IgAN and 10 healthy subjects. Ten IgAN patients had a second scan to assess test-retest reproducibility of the technique. Native T1 times were compared to markers of disease severity including degree of fibrosis, eGFR, rate of eGFR decline and proteinuria. RESULTS: All patients tolerated the MRI scan and analysable quality T1 maps were acquired in at least one kidney in all subjects. Cortical T1 times were significantly longer in patients with IgAN than healthy subjects (1540 ms ± 110 ms versus 1446 ± 88 ms, p = 0.038). There was excellent test-retest reproducibility of the technique, with Coefficient-of-variability of axial and coronal T1 mapping analysis being 2.9 and 3.7% respectively. T1 correlated with eGFR and proteinuria (r = - 0.444, p = 0.016; r = 0.533, p = 0.003 respectively). Patients with an eGFR decline > 2 ml/min/year had increased T1 times compared to those with a decline < 2 ml/min/year (1615 ± 135 ms versus 1516 ± 87 ms, p = 0.068), and T1 time was also higher in patients with a histological 'T'-score of > 0, compared to those with a 'T'-score of 0 (1575 ± 106 ms versus 1496 ± 105 ms, p = 0.131), though not to significance. CONCLUSIONS: Cortical native T1 time is significantly increased in patients with IgAN compared to healthy subjects and correlates with markers of renal disease. Reproducibility of renal T1 mapping is excellent. This study highlights the potential utility of native T1 mapping in IgAN and other progressive nephropathies, and larger prospective studies are warranted.

A comparison of the reproducibility of two cine-derived strain software programmes in disease states.

BACKGROUND: Systolic strain and peak-early diastolic strain rate (PEDSR) measure subclinical cardiac dysfunction. These parameters can be derived from cardiovascular magnetic resonance (CMR) cine images using new software packages, but the comparative test-retest reproducibility of these software in disease states is unknown. This study compared the test-retest reproducibility of strain measures derived from two software packages (feature-tracking software (FT) and tissue-tracking (TT)) in disease populations with preserved ejection fractions. METHODS: This was a prospective study of 10 patients with aortic stenosis (AS), 10 haemodialysis patients and 10 diabetic patients at 1.5 and 3-Tesla. 30 subjects underwent test-retest reproducibility scans of global circumferential strain (GCS), global longitudinal strain (GLS), circumferential-PEDSR and longitudinal-PEDSR calculated using TT and FT software. RESULTS: Test-retest reproducibility of GCS and GLS were similar for FT and TT across patient groups. Coefficient of variability (CoV) for FT-derived GCS 8.1%, 5% and 7.9% for AS, diabetic and haemodialysis patients, compared to 3.3%, 9.2% and 5.4% for TT-derived GCS, with CoV for FT-derived GLS 8%, 6.4% and 8.2% for AS, diabetic and haemodialysis patients, compared to 5.3%, 4.8% and 7% for TT-derived GLS). Reproducibility of FT-derived circumferential and longitudinal-PEDSR was worse than TT-derived circumferential and longitudinal-PEDSR (CoV for FT-derived circumferential-PEDSR 18.2%, 18% and 17.4% for AS, diabetic and haemodialysis patients, compared to 6.1%, 11.7% and 11% for TT-derived circumferential-PEDSR with CoV for FT-derived longitudinal PEDSR 18.2%, 18.9%, 18.3% for AS, diabetic and haemodialysis patients, compared to 8.9%, 9.1% and 11.4% for TT-derived longitudinal-PEDSR). Bland-Altman analysis revealed no systematic bias with tighter limits of agreement for TT-derived strain measures. CONCLUSIONS: Reproducibility of GCS and GLS are excellent with FT and TT software across diseases. TT had superior test-retest reproducibility for quantification of longitudinal and circumferential-PEDSR than FT-derived PEDSR across diseases.

Defining myocardial fibrosis in haemodialysis patients with non-contrast cardiac magnetic resonance.

BACKGROUND: Extent of myocardial fibrosis (MF) determined using late gadolinium enhanced (LGE) predicts outcomes, but gadolinium is contraindicated in advanced renal disease. We assessed the ability of native T1-mapping to identify and quantify MF in aortic stenosis patients (AS) as a model for use in haemodialysis patients. METHODS: We compared the ability to identify areas of replacement-MF using native T1-mapping to LGE in 25 AS patients at 3 T. We assessed agreement between extent of MF defined by LGE full-width-half-maximum (FWHM) and the LGE 3-standard-deviations (3SD) in AS patients and nine T1 thresholding-techniques, with thresholds set 2-to-9 standard-deviations above normal-range (1083 ± 33 ms). A further technique was tested that set an individual T1-threshold for each patient (T11SD). The technique that agreed most strongly with FWHM or 3SD in AS patients was used to compare extent of MF between AS (n = 25) and haemodialysis patients (n = 25). RESULTS: Twenty-six areas of enhancement were identified on LGE images, with 25 corresponding areas of discretely increased native T1 signal identified on T1 maps. Global T1 was higher in haemodialysis than AS patients (1279 ms ± 5.8 vs 1143 ms ± 12.49, P < 0.01). No signal-threshold technique derived from standard-deviations above normal-range associated with FWHM or 3SD. T11SD correlated with FWHM in AS patients (r = 0.55) with moderate agreement (ICC = 0.64), (but not with 3SD). Extent of MF defined by T11SD was higher in haemodialysis vs AS patients (21.92% ± 1 vs 18.24% ± 1.4, P = 0.038), as was T1 in regions-of-interest defined as scar (1390 ± 8.7 vs 1276 ms ± 20.5, P < 0.01). There was no difference in the relative difference between remote myocardium and regions defined as scar, between groups (111.4 ms ± 7.6 vs 133.2 ms ± 17.5, P = 0.26). CONCLUSIONS: Areas of MF are identifiable on native T1 maps, but absolute thresholds to define extent of MF could not be determined. Histological studies are needed to assess the ability of native-T1 signal-thresholding techniques to define extent of MF in haemodialysis patients. Data is taken from the PRIMID-AS (NCT01658345) and CYCLE-HD studies (ISRCTN11299707).

Imaging of Myocardial Fibrosis in Patients with End-Stage Renal Disease: Current Limitations and Future Possibilities.

Cardiovascular disease in patients with end-stage renal disease (ESRD) is driven by a different set of processes than in the general population. These processes lead to pathological changes in cardiac structure and function that include the development of left ventricular hypertrophy and left ventricular dilatation and the development of myocardial fibrosis. Reduction in left ventricular hypertrophy has been the established goal of many interventional trials in patients with chronic kidney disease, but a recent systematic review has questioned whether reduction of left ventricular hypertrophy improves cardiovascular mortality as previously thought. The development of novel imaging biomarkers that link to cardiovascular outcomes and that are specific to the disease processes in ESRD is therefore required. Postmortem studies of patients with ESRD on hemodialysis have shown that the extent of myocardial fibrosis is strongly linked to cardiovascular death and accurate imaging of myocardial fibrosis would be an attractive target as an imaging biomarker. In this article we will discuss the current imaging methods available to measure myocardial fibrosis in patients with ESRD, the reliability of the techniques, specific challenges and important limitations in patients with ESRD, and how to further develop the techniques we have so they are sufficiently robust for use in future clinical trials.

Intestinal Barrier Disturbances in Haemodialysis Patients: Mechanisms, Consequences, and Therapeutic Options.

There is accumulating evidence that the intestinal barrier and the microbiota may play a role in the systemic inflammation present in HD patients. HD patients are subject to a number of unique factors, some related to the HD process and others simply to the uraemic milieu but with common characteristic that they can both alter the intestinal barrier and the microbiota. This review is intended to provide an overview of the current methods for measuring such changes in HD patients, the mechanisms behind these changes, and potential strategies that may mitigate these modifications. Lastly, intradialytic exercise is an increasingly employed intervention in HD patients; however the potential implications that this may have for the intestinal barrier are not known; therefore future research directions are also covered.

Development of a transmission alpha particle dosimetry technique using A549 cells and a Ra-223 source for targeted alpha therapy.

PURPOSE: In targeted radionuclide therapy, regional tumors are targeted with radionuclides delivering therapeutic radiation doses. Targeted alpha therapy (TAT) is of particular interest due to its ability to deliver alpha particles of high linear energy transfer within the confines of the tumor. However, there is a lack of data related to alpha particle distribution in TAT. These data are required to more accurately estimate the absorbed dose on a cellular level. As a result, there is a need for a dosimeter that can estimate, or better yet determine the absorbed dose deposited by alpha particles in cells. In this study, as an initial step, the authors present a transmission dosimetry design for alpha particles using A549 lung carcinoma cells, an external alpha particle emitting source (radium 223; Ra-223) and a Timepix pixelated semiconductor detector. METHODS: The dose delivery to the A549 lung carcinoma cell line from a Ra-223 source, considered to be an attractive radionuclide for alpha therapy, was investigated in the current work. A549 cells were either unirradiated (control) or irradiated for 12, 1, 2, or 3 h with alpha particles emitted from a Ra-223 source positioned below a monolayer of A549 cells. The Timepix detector was used to determine the number of transmitted alpha particles passing through the A549 cells and DNA double strand breaks (DSBs) in the form of γ-H2AX foci were examined by fluorescence microscopy. The number of transmitted alpha particles was correlated with the observed DNA DSBs and the delivered radiation dose was estimated. Additionally, the dose deposited was calculated using Monte Carlo code SRIM. RESULTS: Approximately 20% of alpha particles were transmitted and detected by Timepix. The frequency and number of γ-H2AX foci increased significantly following alpha particle irradiation as compared to unirradiated controls. The equivalent dose delivered to A549 cells was estimated to be approximately 0.66, 1.32, 2.53, and 3.96 Gy after 12, 1, 2, and 3 h irradiation, respectively, considering a relative biological effectiveness of alpha particles of 5.5. CONCLUSIONS: The study confirmed that the Timepix detector can be used for transmission alpha particle dosimetry. If cross-calibrated using biological dosimetry, this method will give a good indication of the biological effects of alpha particles without the need for repeated biological dosimetry which is costly, time consuming, and not readily available.

Induction treatment of previously undiagnosed ANCA-associated vasculitis in a renal transplant patient with Rituximab.

We report the case of a 40-year-old female transplant patient with undiagnosed ANCA-associated vasculitis (AAV) and renal allograft dysfunction who achieved disease remission with restoration of transplant function following induction therapy with rituximab. There are currently no trial data looking at the use of rituximab for induction of remission of renal transplant patients with AAV. Although recurrence of AAV following renal transplantation is rare, such patients have invariably had multiple previous exposures to induction and maintenance immunosuppressive regimens, often limiting treatment options post-transplantation. In this case, rituximab was well tolerated with no side effects, and was successful in salvaging transplant function. Optimal treatment regimens for relapsed AAV in the transplant population are not known, and clinical trials are needed to evaluate the efficacy and safety of rituximab at inducing and maintaining disease remission in relapsed AAV following transplantation.

Design and methods of CYCLE-HD: improving cardiovascular health in patients with end stage renal disease using a structured programme of exercise: a randomised control trial.

BACKGROUND: There is emerging evidence that exercise training could positively impact several of the cardiovascular risk factors associated with sudden cardiac death amongst patients on haemodialysis. The primary aim of this study is to evaluate the effect of an intradialytic exercise programme on left ventricular mass. METHOD AND DESIGN: Prospective, randomised cluster open-label blinded endpoint clinical trial in 130 patients with end stage renal disease on haemodialysis. Patients will be randomised 1:1 to either 1) minimum of 30 min continuous cycling thrice weekly during dialysis or 2) standard care. The primary outcome is change in left ventricular mass at 6 months, assessed by cardiac MRI (CMR). In order to detect a difference in LV mass of 15 g between groups at 80 % power, a sample size of 65 patients per group is required. Secondary outcome measures include abnormalities of cardiac rhythm, left ventricular volumes and ejection fraction, physical function measures, anthropometric measures, quality of life and markers of inflammation, with interim assessment for some measures at 3 months. DISCUSSION: This study will test the hypothesis that an intradialytic programme of exercise leads to a regression in left ventricular mass, an important non-traditional cardiovascular risk factor in end stage renal disease. For the first time this will be assessed using CMR. We will also evaluate the efficacy, feasibility and safety of an intradialytic exercise programme using a number of secondary end-points. We anticipate that a positive outcome will lead to both an increased patient uptake into established intradialytic programmes and the development of new programmes nationally and internationally. TRIAL REGISTRATION NUMBER: ISRCTN11299707 (registration date 5(th) March 2015).

A randomized, controlled phase III trial of nab-Paclitaxel versus dacarbazine in chemotherapy-naïve patients with metastatic melanoma.

BACKGROUND: The efficacy and safety of nab-paclitaxel versus dacarbazine in patients with metastatic melanoma was evaluated in a phase III randomized, controlled trial. PATIENTS AND METHODS: Chemotherapy-naïve patients with stage IV melanoma received nab-paclitaxel 150 mg/m(2) on days 1, 8, and 15 every 4 weeks or dacarbazine 1000 mg/m(2) every 3 weeks. The primary end point was progression-free survival (PFS) by independent radiologic review; the secondary end point was overall survival (OS). RESULTS: A total of 529 patients were randomized to nab-paclitaxel (n = 264) or dacarbazine (n = 265). Baseline characteristics were well balanced. The majority of patients were men (66%), had an Eastern Cooperative Oncology Group status of 0 (71%), and had M1c stage disease (65%). The median PFS (primary end point) was 4.8 months with nab-paclitaxel and 2.5 months with dacarbazine [hazard ratio (HR), 0.792; 95.1% confidence interval (CI) 0.631-0.992; P = 0.044]. The median OS was 12.6 months with nab-paclitaxel and 10.5 months with dacarbazine (HR, 0.897; 95.1% CI 0.738-1.089; P = 0.271). Independently assessed overall response rate was 15% versus 11% (P = 0.239), and disease control rate (DCR) was 39% versus 27% (P = 0.004) for nab-paclitaxel versus dacarbazine, respectively. The most common grade ≥3 treatment-related adverse events were neuropathy (nab-paclitaxel, 25% versus dacarbazine, 0%; P < 0.001), and neutropenia (nab-paclitaxel, 20% versus dacarbazine, 10%; P = 0.004). There was no correlation between secreted protein acidic and rich in cysteine (SPARC) status and PFS in either treatment arm. CONCLUSIONS: nab-Paclitaxel significantly improved PFS and DCR compared with dacarbazine, with a manageable safety profile.

Circumferential hoof clamp method of lameness induction in the horse.

A circumferential hoof clamp method to induce controlled and reversible lameness in the forelimbs of eight horses was assessed. Peak vertical forces and vertical impulses were recorded using a force plate to verify induced lameness. Video recordings were used by blinded observers to determine subjective lameness using a 0-5 scale and any residual lameness following clamp loosening. Tightening of clamps resulted in consistent, visible lameness in the selected limbs in all horses. Lameness was confirmed by significant decreases from baseline in the peak vertical force (P <0.01). Lameness was also confirmed subjectively by elevated median scores (0 at baseline and 2 during lameness). Lameness was not immediately reversible after clamp loosening (median score 1.5), but horses were not obviously lame after clamp removal and were no different from initial baseline (median score 0.5) approximately 3 days later.

Realising opportunities for evidence-based cancer service delivery and research: linking cancer registry and administrative data in Australia.

The traditional roles of Australian cancer registries have been incidence, mortality and survival surveillance although increasingly, roles are being broadened to include data support for health-service management and evaluation. In some Australian jurisdictions, cancer stage and other prognostic data are being included in registry databases and this is being facilitated by an increase in structured pathology reporting by pathology and haematology laboratories. Data linkage facilities are being extended across the country at national and jurisdictional level, facilitating data linkage between registry data and data extracts from administrative databases that include treatment, screening and vaccination data, and self-reported data from large population cohorts. Well-established linkage protocols exist to protect privacy. The aim is to gain better data on patterns of care, service outcomes and related performance indicators for health-service management and population health and health-services research, at a time of increasing cost pressures. Barriers include wariness among some data custodians towards releasing data and the need for clearance for data release from large numbers of research ethics committees. Progress is being made though, and proof of concept is being established.

Vascular perfusion of the dorsal and palmar condyles of the equine third metacarpal bone.

REASONS FOR PERFORMING STUDY: Palmar osteochondral disease (POD) is an overload arthrosis that commonly affects fetlock joints of racing Thoroughbreds (TB) but the aetiopathogenesis of the disease has not been well defined. OBJECTIVES: The aim of this study was to compare India ink perfusion in the dorsal and palmar condyles of the third metacarpal bone (McIII) in both passively flexed and maximally extended fetlock joints from paired equine cadaver limbs. STUDY DESIGN: Descriptive cadaver study comparing perfusion of condyles of McIII in paired cadaver limbs in flexion (control group) and maximal extension (intervention group). METHODS: Pairs of forelimbs were acquired from 5 TB horses subjected to euthanasia for reasons unrelated to lameness. Limb pairs were perfused intra-arterially with India ink and then randomly assigned to passive flexion or maximal extension of the fetlock joint. Limbs were sectioned sagittally in 3 mm sections through the fetlock and 12 sections per limb processed using a modified tissue-clearing technique. Sections were subsequently digitally imaged and bone perfusion evaluated with image analysis software. RESULTS: Greater perfusion of the dorsal condyle than of palmar condyle was observed in 78% of sections from limbs in passive flexion and 92% of maximally extended sections. Perfusion to the palmar aspect of the condyle was significantly decreased (P < 0.0001) when the limbs were placed in maximal extension compared to passive flexion. CONCLUSIONS: The palmar condyle of McIII had less perfusion than the dorsal condyle when the fetlock joint was in passive flexion and this difference was exacerbated by maximal extension. Based on the anatomical location of POD lesions, perfusion differences between the dorsal and palmar condyles of McIII may be associated with development of these lesions.

Non-terminal animal model of post-traumatic osteoarthritis induced by acute joint injury.

OBJECTIVE: Develop a non-terminal animal model of acute joint injury that demonstrates clinical and morphological evidence of early post-traumatic osteoarthritis (PTOA). METHODS: An osteochondral (OC) fragment was created arthroscopically in one metacarpophalangeal (MCP) joint of 11 horses and the contralateral joint was sham operated. Eleven additional horses served as unoperated controls. Every 2 weeks, force plate analysis, flexion response, joint circumference, and synovial effusion scores were recorded. At weeks 0 and 16, radiographs (all horses) and arthroscopic videos (OC injured and sham joints) were graded. At week 16, synovium and cartilage biopsies were taken arthroscopically from OC injured and sham joints for histologic evaluation and the OC fragment was removed. RESULTS: OC fragments were successfully created and horses were free of clinical lameness after fragment removal. Forelimb gait asymmetry was observed at week 2 (P = 0.0012), while joint circumference (P < 0.0001) and effusion scores (P < 0.0001) were increased in injured limbs compared to baseline from weeks 2 to 16. Positive flexion response of injured limbs was noted at multiple time points. Capsular enthesophytes were seen radiographically in injured limbs. Articular cartilage damage was demonstrated arthroscopically as mild wear-lines and histologically as superficial zone chondrocyte death accompanied by mild proliferation. Synovial hyperemia and fibrosis were present at the site of OC injury. CONCLUSION: Acute OC injury to the MCP joint resulted in clinical, imaging, and histologic changes in cartilage and synovium characteristic of early PTOA. This model will be useful for defining biomarkers of early osteoarthritis and for monitoring response to therapy and surgery.