In-Hospital Hip Fractures in a Large Irish Teaching Hospital: Patient Risk Factors and Outcomes.

INTRODUCTION: In-hospital hip fractures follow falls during unrelated admissions. Little data in the Irish setting is available on this vulnerable subset of hip fracture patients. Our objective is to review the incidence of in-hospital hip fractures, identify risk factors, and evaluate outcomes. METHODS: This is a retrospective observational review. We collected patient data in St. James' Hospital using the Hospital In-Patient Enquiry database and Electronic Patient Records for in-hospital hip fractures between 10/02/2017 and 22/04/2020. Comorbidity, survival, and discharge destination data were gathered. RESULTS: We identified 40 fractures, representing 11.5% of all hip fractures treated at our center during the study period. The patients were 60-95 years old. Median age was 77 years for males and 86 years for females. Most (72.5%) were identified as fall risks, and 52% were unwitnessed falls. Many had a history of falls (67.5%), dementia (52.5%), or both (42.5%). Delirium was common (42.5%), and 75% had at least one vascular/coagulation disorder. Mortality was 10.25% at 30 days, 23.1% at 90 days, and 51.4% at 12 months. Although 70% were admitted from home, only 10% were discharged back home. 30% were admitted to a nursing home, and 55% were discharged from a nursing home. CONCLUSION: In-hospital hip fractures accounted for 11.5% of all hip fractures treated at our center, confirming the need for a well-defined hospital protocol. Patients often present with previous falls, dementia, and cardiovascular disease. Outcomes are poor, with 51.4% mortality at 12 months and significant morbidity reflected by a loss of independent living.

Achieving Target Cemented Femoral Stem Anteversion Using a 3-Dimensional Model.

Background: Total hip arthroplasty aims to provide patients with a pain-free and stable hip joint through optimization of biomechanics such as femoral anteversion. There are studies evaluating the limits of cementless stem version, however, none assessing the range of version achieved by a cemented collarless stem. A computed tomography (CT)-based study was performed, utilizing a contemporary robotic planning platform to assess the amount of rotation afforded by a cemented collarless stem, whilst maintaining native biomechanics. Methods: The study utilized 36 cadaveric hips. All had CT scans of the pelvis and hip joints. The CT scans were then loaded into a contemporary robotic planning platform. A stem that restored the patients native femoral offset was selected and positioned in the virtual femur. The stem was rotated while checking for cortical contact at the level of the neck cut. Cortical contact was regarded as the rotation limit, assessed in both anteversion and retroversion. Target range for stem anteversion was 10°-20°. Failure to achieve target version triggered a sequence of adjustments to simulate surgical decisions. Results: Native femoral offset and target version range was obtained in 29 of 36 (80.5%) cases. Following an adjustment sequence, 4 further stems achieved target anteversion with a compromise in offset of 2.3 mm. Overall 33 of 36 (91.7%) stems achieved the target anteversion range of 10°-20°. Conclusions: Target femoral stem anteversion can be achieved using a cemented, collarless stem in a CT-based 3-dimensional model in 80.5% of hips. With a small compromise in offset (mean 2.3 mm), this can be increased to 91.7%.

Seasonal variation in daily activity patterns of snow leopards and their prey.

The daily and seasonal activity patterns of snow leopards (Panthera uncia) are poorly understood, limiting our ecological understanding and hampering our ability to mitigate threats such as climate change and retaliatory killing in response to livestock predation. We fitted GPS-collars with activity loggers to snow leopards, Siberian ibex (Capra sibirica: their main prey), and domestic goats (Capra hircus: common livestock prey) in Mongolia between 2009 and 2020. Snow leopards were facultatively nocturnal with season-specific crepuscular activity peaks: seasonal activity shifted towards night-sunrise during summer, and day-sunset in winter. Snow leopard activity was in contrast to their prey, which were consistently diurnal. We interpret these results in relation to: (1) darkness as concealment for snow leopards when stalking in an open landscape (nocturnal activity), (2) low-intermediate light preferred for predatory ambush in steep rocky terrain (dawn and dusk activity), and (3) seasonal activity adjustments to facilitate thermoregulation in an extreme environment. These patterns suggest that to minimise human-wildlife conflict, livestock should be corralled at night and dawn in summer, and dusk in winter. It is likely that climate change will intensify seasonal effects on the snow leopard's daily temporal niche for thermoregulation in the future.

A Description of Novel Uses of Hip Protectors in an Elderly Hip Fracture Population: A Technical Report.

Hip fractures are a significant cause of morbidity and mortality in the elderly population. The number of hip fractures is set to increase significantly by 2050 as the global population ages. The costs associated with hip fracture patients are significant due to prolonged hospitalisation and rehabilitation. Hip protectors have been advocated as a strategy to reduce the risk of hip fractures in a high-risk population. Evidence suggests that hip protectors are a cost-effective method for reducing the risk of hip fractures. There have, however, been issues with adherence with wearing hip protectors amongst patients and healthcare staff. Despite prevention strategies, many patients continue to present with hip fractures. Many of these patients have cognitive impairment or experience peri-operative delirium. This can cause issues with patients' interference with the operative wound and presents a significant burden to the healthcare team with the need for increased wound monitoring and care in the post-operative period. Applying a well-fitted hip protector provides a substantial additional barrier to protect the surgical wound. Hip fracture surgical wounds can be difficult to manage in these patients and our standard post-operative protocol is to apply compression dressings in this group of patients. We have found that a well-fitted hip protector can provide adequate compression to the surgical site. We describe a brief technical report on a novel use of hip protectors in providing wound security in the agitated patient post-operatively as well as a method of providing compression to the surgical wound site.

A multi-site review of second hip fractures across 6 Dublin teaching hospitals.

INTRODUCTION: Fragility hip fractures are common and costly. Secondary fracture prevention is a treatment goal following hip fracture; however, the number of those that proceed to fracture their contralateral hip in Ireland is unknown. There are plans to introduce a Fracture Liaison Service Database in Ireland which will aim to prevent secondary fractures. To establish a baseline figure for secondary hip fractures, the injury radiographs of 1284 patients from 6 teaching hospitals over a 1-year period were reviewed. METHODS: Irish Hip Fracture Datasheets and corresponding injury radiographs were reviewed locally for all hip fractures within each respective teaching hospital for a 1-year period (2019). RESULTS: A total of 8.7% of all fragility hip fractures across the 6 hospitals were secondary hip fractures (range 4.9-11.5%). 46% occurred within years 1 to 3 following index hip fracture. Forty-eight per cent of patients were started on bone protection medications following their second hip fracture. DISCUSSION/CONCLUSION: Approximately 1 in 11 hip fractures treated across the 6 teaching hospitals assessed in 2019 was a patient's second hip fracture. We advocate for the widespread availability of Fracture Liaison Services to patients throughout Ireland to assist secondary fracture prevention.

Criteria for Return to Play After Hip Arthroscopy in the Treatment of Femoroacetabular Impingement: A Systematic Review.

BACKGROUND: Femoroacetabular impingement (FAI) is a common pathology in athletes that often requires operative management in the form of hip arthroscopy. PURPOSE: To systematically review the rates and level of return to play (RTP) and the criteria used for RTP after hip arthroscopy for FAI in athletes. STUDY DESIGN: Systematic review; Level of evidence, 4. METHODS: A systematic review of the literature, based on the PRISMA guidelines, was performed using PubMed, Embase, and Scopus databases. Studies reporting outcomes after the use of hip arthroscopy for FAI were included. Outcomes analyzed were RTP rate, RTP level, and criteria used for RTP. Statistical analysis was performed using SPSS software. RESULTS: Our review found 130 studies, which included 14,069 patients (14,517 hips) and had a mean methodological quality of evidence (MQOE) of 40.4 (range, 5-67). The majority of patients were female (53.7%), the mean patient age was 30.4 years (range, 15-47 years), and the mean follow-up was 29.7 months (range, 6-75 months). A total of 81 studies reported RTP rates, with an overall RTP rate of 85.4% over a mean period of 6.6 months. Additionally, 49 studies reported the rate of RTP at preinjury level as 72.6%. Specific RTP criteria were reported in 97 studies (77.2%), with time being the most commonly reported item, which was reported in 80 studies (69.2%). A total of 45 studies (57.9%) advised RTP at 3 to 6 months after hip arthroscopy. CONCLUSION: The overall rate of reported RTP was high after hip arthroscopy for FAI. However, more than one-fourth of athletes who returned to sports did not return at their preinjury level. Development of validated rehabilitation criteria for safe return to sports after hip arthroscopy for FAI could potentially improve clinical outcomes while also increasing rates of RTP at preinjury levels.

Repair versus Debridement for Acetabular Labral Tears-A Systematic Review.

PURPOSE: The purpose of this study was to systematically review the evidence in the literature to ascertain whether acetabular labral repair (ALR) or debridement (ALD) resulted in superior patient outcomes. METHODS: The systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Peer-reviewed studies comparing ALR and ALD published in English with full text available were included. Patients undergoing both open and arthroscopic surgery in randomized controlled trials, prospective cohort studies, retrospective cohort studies, and case-control studies were included. Studies were quantified for methodological quality using the MINORS criteria. Clinical outcomes were compared, with qualitative analysis, and quantitative analyses were performed using GraphPad Prism version 7. A P value <.05 was considered to be statistically significant. RESULTS: There were 8 studies included (level of evidence [LOE] I = 1; LOE II = 2; LOE III = 5). The 7 studies compared 364 patients (369 hips) with ALR to 318 patients (329 hips) with ALD, with a mean follow-up time ranging between 32-120 months. Five studies found significantly improved patient reported outcomes with ALR (Harris Hip Score, Merle d'Aubigné, Pain, SF-12). Several studies compared the outcomes after ALR and ALD and found statistical significance in all investigated metrics in favor of ALR. One study found a significant improvement in abduction but no other study found any difference in range of motion. No study found any difference in complication rate, revision rate or conversion to total hip arthroplasty. Although, 2 studies found ALR reduced the rate of osteoarthritic progression. CONCLUSION: Current literature suggests that acetabular labral repair may result in superior patient reported outcomes. However, there appears to be no significant difference in the rate of progression to total hip arthroplasty at up to 10-year follow-up. LEVEL OF EVIDENCE: Level III, systematic review of Level I, II, and III studies.

Perioperative haematological outcomes following total knee arthroplasty in haemophiliacs.

PURPOSE: Patients with haemophilia suffer from recurrent joint haemarthrosis. This can progress to symptomatic arthropathy commonly affecting the knee. While modern coagulation strategies have reduced those proceeding to end-stage arthropathy, total knee arthroplasty (TKA) remains the optimal treatment for some patients. Despite innovation in perioperative haematological management, concerns about the potential for excessive haemorrhage still exist. The aim of this study is to quantify immediate postoperative blood loss and haematological complications in haemophiliacs following TKA. METHODS: A retrospective study of patients with haemophilia types A or B who underwent a TKA over a 12-year period at a single institution was conducted. These patients were compared to both a non-haemophiliac control group and to published standards in non-haemophiliacs undergoing TKA. RESULTS: Twenty-one TKA procedures in 18 patients (72% haemophilia A, 28% haemophilia B) were suitable for inclusion with a mean age of 44 years. The mean haemoglobin drops at 24 and 48 h postoperatively were 2.7 g/dl and 3.8 g/dl respectively. There was no significant difference in haemoglobin drop at 48 h postoperatively when compared to the non-haemophiliac control group (P = 0.2644). There were no immediate perioperative complications and two patients (9.6%) required postoperative transfusion. CONCLUSION: Haemophiliacs undergoing a unilateral primary TKA in a specialised tertiary referral centre appear to have comparable rates of perioperative blood loss when compared to both a non-haemophiliac control group as and published haemostatic standards in non-haemophiliac patients following TKA. Perioperative management with expert orthopaedic and haematological input is recommended to optimise outcomes in this complex patient group.

Incidence of Non-Simultaneous Contralateral Second Hip Fractures: A Single-Center Irish Study.

Introduction Hip fractures are a significant cause of morbidity and mortality in the elderly and are also associated with increased healthcare costs. A second contralateral hip fracture can lead to even more complications and healthcare costs. A significant proportion of the Irish hip fracture population does not receive a bone health assessment or falls specialist assessment to reduce the risk of future falls and fractures. This study aimed to analyze the incidence of a non-simultaneous contralateral hip fracture in an Irish population. Methods We retrospectively analyzed 1,344 patients presenting to our institution with a hip fracture from January 2007 to June 2019. Patients aged ≥ 60 years old presenting with a neck of femur or pertrochanteric fracture were included in our study. We excluded patients who had sub-trochanteric and femoral shaft fractures, high energy fractures, and pathological fractures. We also excluded patients less than 60 years old, as fractures in these younger patients may not be purely related to osteoporosis. Results A total of 1,099 hip fractures meeting the inclusion criteria were treated at our unit during the designated time period. A total of 102 (9.3%) patients experienced a second hip fracture. The mean age at first presentation in our institution was 78.5 years old, with a mean time between first and second hip fractures of 37.2 months. Conclusions Patients presenting with a second hip fracture may represent 9.3% of the Irish hip fracture population. We hope that this study will help inform on the rate of second hip fractures in an Irish population and help advocate for improved resources and implementation of secondary prevention strategies.

The Utility of a Plain Film Arthrogram to Confirm Acute Liner Dissociation in the Setting of Primary Total Hip Arthroplasty.

Acute Liner dissociation is a well-documented, but uncommon complication of total hip arthroplasty, yet the journey to diagnosis remains undefined. This clinical case report outlines the use of plain film arthrogram for diagnosis in a 53-year-old female who presented to the ED following a fall, describing symptoms of increasing groin pain, reduced range of movement, difficulty weight-bearing and a grinding sensation in her left hip, all on a background of total hip replacement two years ago. Examination revealed impaired flexion, rotation and abduction while AP pelvic X-ray confirmed mild eccentric placement of the femoral head, and lateral X-ray proved joint enlocation. An arthrogram of the left hip was performed the following day with injection of 4mls of iodinated contrast injected into the joint. Inferior dissociation of the liner from the shell was evident. The femoral head and liner were replaced two days later, and the liner was found to have shearing and gross plastic deformation at the rim. The patient reported immediate relief from the groin pain and was discharged on the fourth day postoperatively. This shows how plain film imaging fails in diagnosing acute liner dissociation dynamic fluoroscopic tests, post-arthrography CT and metal artifact reduction sequence magnetic resonance imaging (MARS MRI) have previously been proposed despite their associated wait-time, radiation exposure and financial costs. This case report highlights the role of plain film arthrography as a low risk and low-cost diagnostic tool. The report also suggests the incorporation of radio-dense markers in liners to facilitate the use of arthrography when diagnosing dissociation, also raising awareness of prevention and recognition in what may be an under-reported complication of hip arthroplasty.

Predisposing Factors and Outcomes After Prolonged Admission Following Hip Fracture.

Introduction Hip fractures are increasingly prevalent and can result in substantial morbidity, mortality, and cost. Despite the existence of enhanced management strategies, prolonged hip fracture admissions persist. This study's objective was to ascertain characteristics associated with a prolonged length of stay (LOS) and quantify return to baseline once discharged. Methods A retrospective audit of hip fractures over a four-year period was conducted, identifying patients with a LOS over 100 days. Demographics, comorbidities, pre- and post-admission function, and status were assessed. Patients sustaining inpatient hip fractures were excluded to negate the effect of initial admission on LOS. Results Seven hundred and eleven hip fractures were treated, of which 48 (6.8%) were suitable for inclusion. The patients' median age and LOS was 83.5 years and 153 days, respectively. Preoperative American Society of Anesthesiologists - Physical Status (ASA-PS) Grades II and III predominated at 41.7% and 39.6%, respectively. Eighteen of patients had a diagnosis of dementia before admission, increasing to 29 on discharge (P = 0.0026). One patient was in long-term care prior to admission, rising to 30 on discharge (P < 0.0001), with only 25.6% returning to pre-admission residential status (P < 0.0001). Nineteen patients were mobilising unaided prior to admission, decreasing to only two following discharge, with a mere 37.1% returning to their pre-admission mobility baseline (P < 0.0001). Discussion Hip fracture patients with multiple comorbidities or a diagnosis of dementia were most likely to have a prolonged LOS which, in turn, impacted upon return to baseline mobility, cognitive status, and independence. Early identification and management of this cohort may help reduce the potential disease burden and economic effects that a prolonged LOS creates.

Single versus separate implant fixation for concomitant ipsilateral femoral neck and shaft fractures: A systematic review.

Concomitant ipsilateral femoral neck and shaft fractures are uncommon, occurring in 1-9% of femoral shaft fractures. While this injury typically occurs in young patients following high-energy trauma, little consensus has been established regarding the optimal fixation approach. A multitude of treatment strategies exist, with limited evidence as to which is more favorable. The aim of this study was to appraise current evidence, comparing management with either one single or separate devices for both fractures. A systematic review was undertaken in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies published between 1992 and 2018 comparing the rate of postoperative nonunion, malunion, delayed union, avascular necrosis, infection or reoperation between at least one method of single device fixation and one method of separate device fixation were included. Six non-randomized cohort studies assessing 173 patients were suitable for inclusion, each comparing single device cephalomedullary nail fixation of both fractures with a combination of devices. All patients presented following high-energy trauma, at a median age of 32 years. While low complication rate and favorable outcomes were found across both groups, no significant difference could be inferred between either treatment strategy. This injury continues to occur in the traditionally described patient group, and results in acceptable postoperative outcomes. A paucity of randomized studies limits the ability to recommend a single or separate device treatment approach, and as such prospective, randomized trials with adequately powered sample sizes are required to definitively compare surgical management strategies in this rare but complex injury.

Magnetic Resonance Imaging Features of Traumatic Patellofemoral Dislocation.

Acute traumatic patellar dislocations are encountered with relative frequency, making up 3% of all knee injuries. Typically witnessed in younger patients following sporting injuries, this injury can be debilitating, potentially leading to recurrent dislocation, pain, reduction in activity and patellofemoral osteoarthritis. Management of this injury remains controversial, and as such detailed magnetic resonance imaging (MRI) is increasingly recommended to help illustrate the exact nature of osteochondral and soft tissue injury, with a view to assessing the anatomical sequelae of patellar dislocation as well as the potential of recurrence and dictating the need for either conservative or surgical management in the acute setting. As such, awareness of the typical MRI findings in traumatic patellar dislocations may potentially aid in pursuing appropriate intervention for this pathology. This case describes a 33-year-old gentleman presenting to the emergency department following patellar dislocation. After failed departmental closed reduction, this patient progressed on to definitive anatomical MRI assessment followed by acute surgical intervention in the form of medial patellofemoral ligament (MPFL) repair. This case allows for both illustration and discussion of typical radiological features associated with traumatic patellar dislocation.

Canal to diaphysis ratio as a risk factor for hip fractures and hip fracture pattern.

INTRODUCTION: Osteoporosis and related fractures constitute a significant burden on modern healthcare. The standard method of diagnosing osteoporosis with a dual-energy X-ray absorptiometry (DXA) scan is limited by accessibility and expense. The thickness of the cortex of the proximal femur on plain radiographs has been suggested to be a method for indicating osteoporosis and as a risk factor of hip fractures in the elderly. METHODS: A retrospective study was undertaken to assess the usefulness of the canal-diaphysis ratio (CDR) as a risk factor for developing a hip fracture, excluding patients presenting under 50 years old, following high-energy trauma or pathological fractures. The CDR was measured in 84 neck of femur (NOF) fracture patients and 84 intertrochanteric hip fracture patients, and these were subsequently compared to the CDR of 84 patients without a hip fracture. Measurements were taken on two occasions by two members of the orthopaedic team, so as to assess the test's inter- and intraobserver reliability. RESULTS: In comparison to those without a fracture, there was a significant difference in the CDR of patients with a NOF fracture (P < 0.0001) and intertrochanteric fracture (P < 0.0001). Furthermore, the odds of having a CDR above 60.67 and 64.41 were significantly higher in the NOF (OR = 2.214, P = 0.0129) and intertrochanteric fracture (OR = 32.27, P < 0.0001) groups respectively, when compared to the non-fractured group. The analysis of the test's inter- and intraobserver reliability showed strong levels of reproducibility. DISCUSSION: We concluded that a raised CDR was associated with an increased incidence of NOF and intertrochanteric hip fracture. Measuring the CDR can thus be considered as a reproducible and inexpensive method of identifying elderly patients at risk of hip fractures.

Outcomes after quadriceps tendon repair in patients over 80 years of age.

BACKGROUND: Quadriceps tendon (QT) ruptures are uncommon and mostly occur in those who are 50-60 years of age. Timely surgical repair can result in a good functional outcome, however, little is known about the outcome in the older patient. METHODS: A retrospective review of all QT ruptures between 2009 and 2014 was conducted. Patients over the age of 80 were included. Those with penetrating trauma or partial ruptures were excluded. A chart review was undertaken to gather demographic and operative details. The patients were contacted by phone or by mail to have Lysholm and Rougraff scores completed. RESULTS: Of the 32 QT ruptures identified, 6 (19%) patients were eligible for inclusion in our study. They were predominantly (83%) males with a mean age of 81.38 years. The mean follow up was 54 months. The mean Lysholm score at last follow up was 84.8/100, which falls within the range of a good outcome. The mean Rougraff score was 21.3/25, which is an excellent outcome. All patients felt they were close to their premorbid level of mobility. CONCLUSION: Good outcomes can be expected with QT repair in older patients, resulting in restoration of the pre-injury level of mobility. Level of evidence: Level V case series.

Extensive Bone Reaction From Catastrophic Oxidized Zirconium Wear.

The use of alternative bearing surfaces for total hip arthroplasty has become popular to minimize wear and increase longevity, especially in young patients. Oxidized zirconium (Oxinium; Smith & Nephew, Memphis, Tennessee) femoral heads were introduced in the past decade for use in total hip arthroplasty. The advantages of oxidized zirconium include less risk of fracture compared with traditional ceramic heads. This case report describes a patient with a history of bilateral avascular necrosis of the femoral head after chemotherapy for acute lymphoblastic leukemia. Nonoperative management of avascular necrosis failed, and the patient was treated with bilateral total hip arthroplasty. The patient was followed at regular intervals and had slow eccentric polyethylene wear during a 10-year period. After 10 years, the patient had accelerated wear, with femoral and acetabular bone changes as a result of Oxinium and ultrahigh-molecular-weight polyethylene wear during a 6-month period. This article highlights the unusual accelerated bone changes that occurred as a result of Oxinium wear particles.

Association between patella spurs and quadriceps tendon ruptures.

BACKGROUND: quadriceps tendon (QT) ruptures are significant injuries that are relatively uncommon. The diagnosis of QT ruptures is frequently missed or delayed. An association between the presence of a patella spur and QT ruptures has been suggested in the literature. PATIENTS AND METHODS: the Hospital Inpatient Enquiry system was used to gather data on all patients who sustained a QT rupture over a six year period from 2008 to 2014. A retrospective review of the medical notes as well as radiographs was undertaken. We reviewed 200 knee radiographs of patients without QT ruptures to establish the incidence of patella spurs in our normal population. Statistical analysis was performed using SPSS version 11.5 for Windows(®). RESULTS: the records of 20 consecutive patients with 21 QT ruptures were reviewed. The mean age was 60.9 yrs (range 44.9-82.1 yrs) and the majority were male (n=17; 85%). There was one bilateral QT ruptures. Patella spurs were noted in 13 cases (62%) which were significantly higher than in patients without QT rupture 19% (P≤0.05). CONCLUSION: we noted a significantly higher incidence of patella spurs in patients with QT ruptures compared to those without. The presence of a QT rupture should be ruled out in patients with a knee injury and a patella spur on the knee radiographs.

Mechanisms underlying clinical efficacy of Angiotensin II type 2 receptor (AT2R) antagonist EMA401 in neuropathic pain: clinical tissue and in vitro studies.

BACKGROUND: The clinical efficacy of the Angiotensin II (AngII) receptor AT2R antagonist EMA401, a novel peripherally-restricted analgesic, was reported recently in post-herpetic neuralgia. While previous studies have shown that AT2R is expressed by nociceptors in human DRG (hDRG), and that EMA401 inhibits capsaicin responses in cultured hDRG neurons, the expression and levels of its endogenous ligands AngII and AngIII in clinical neuropathic pain tissues, and their signalling pathways, require investigation. We have immunostained AngII, AT2R and the capsaicin receptor TRPV1 in control post-mortem and avulsion injured hDRG, control and injured human nerves, and in cultured hDRG neurons. AngII, AngIII, and Ang-(1-7) levels were quantified by ELISA. The in vitro effects of AngII, AT2R agonist C21, and Nerve growth factor (NGF) were measured on neurite lengths; AngII, NGF and EMA401 effects on expression of p38 and p42/44 MAPK were measured using quantitative immunofluorescence, and on capsaicin responses using calcium imaging. RESULTS: AngII immunostaining was observed in approximately 75% of small/medium diameter neurons in control (n = 5) and avulsion injured (n = 8) hDRG, but not large neurons i.e. similar to TRPV1. AngII was co-localised with AT2R and TRPV1 in hDRG and in vitro. AngII staining by image analysis showed no significant difference between control (n = 12) and injured (n = 13) human nerves. AngII levels by ELISA were also similar in control human nerves (4.09 ± 0.36 pmol/g, n = 31), injured nerves (3.99 ± 0.79 pmol/g, n = 7), and painful neuromas (3.43 ± 0.73 pmol/g, n = 12); AngIII and Ang-(1-7) levels were undetectable (<0.03 and 0.05 pmol/g respectively). Neurite lengths were significantly increased in the presence of NGF, AngII and C21 in cultured DRG neurons. AngII and, as expected, NGF significantly increased signal intensity of p38 and p42/44 MAPK, which was reversed by EMA401. AngII mediated sensitization of capsaicin responses was not observed in the presence of MAP kinase inhibitor PD98059, and the kinase inhibitor staurosporine. CONCLUSION: The major AT2R ligand in human peripheral nerves is AngII, and its levels are maintained in injured nerves. EMA401 may act on paracrine/autocrine mechanisms at peripheral nerve terminals, or intracrine mechanisms, to reduce neuropathic pain signalling in AngII/NGF/TRPV1-convergent pathways.