H Duhem

D Viglino

A Bellier

Stéphane Tanguy

V Descombe

F Boucher

Philippe Chaffanjon

G Debaty
email: gdebaty@gmail.com

; Tanguy

BS ; Descombe

; Boucher

; Chaffanjon

; Debaty

Guillaume Debaty Samu

Cadaver models for cardiac arrest: A systematic review and perspectives

Keywords: Heart arrest, Resuscitation, Cadaver, Cardiac arrest, Cardiopulmonary resuscitation CPR, cardiopulmonary resuscitation, HCM, human cadaver model

de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

INTRODUCTION

Although progress has been made in cardiac arrest response and management, patients' outcome has barely improved over the last 30 years [START_REF] Sandroni | In-hospital cardiac arrest: incidence, prognosis and possible measures to improve survival[END_REF][START_REF] Chen | American Heart Association's Get With the Guidelines-Resuscitation (formerly the National Registry of Cardiopulmonary Resuscitation) Investigators. Association between a hospital's rate of cardiac arrest incidence and cardiac arrest survival[END_REF]. The fine pathophysiology of cardiac arrest remains unclear, especially the interaction between ventilatory and circulatory support during resuscitation [START_REF] Ashoor | Effectiveness of different compression-to-ventilation methods for cardiopulmonary resuscitation: A systematic review[END_REF].

Several limits need to be taken into account to explain the complexity of experimental and clinical research in this field [START_REF] Nichol | Trial of Continuous or Interrupted Chest Compressions during CPR[END_REF]. First, cardiac arrest mainly occurs out of hospitals and physiologic parameters change quickly after occurrence, which results in difficulties exploring the pathophysiology of this event. Second, ethical concerns may be an obstacle to research with these patients, who obviously are not able to give their consent prior to the intervention and for whom medical care has to be optimal and efficient. Lastly, the heterogeneity of patients and their precipitating pathologies are also a constraint.

Animal research, mainly on swine models, has provided some translational discoveries but also has several limitations [START_REF] Vognsen | Contemporary animal models of cardiac arrest: A systematic review[END_REF][START_REF] Bk | Animal models of cardiac arrest: A systematic review of bias and reporting[END_REF]. Even if swine, among other animal models, appears to have the most similar thorax shape to humans, the slight differences in chest morphology make it difficult to extrapolate the effect of chest compressions. The differences in global cardiopulmonary physiology also restricts the comparability of the models [START_REF] Prat | Comparison of thoracic wall behavior in large animals and human cadavers submitted to an identical ballistic blunt thoracic trauma[END_REF][START_REF] Idris | Utstein-style guidelines for uniform reporting of laboratory CPR research. A statement for healthcare professionals from a Task Force of the American Heart Association, the American College of Emergency Physicians, the American College of Cardiology, the European Resuscitation Council, the Heart and Stroke Foundation of Canada, the Institute of Critical Care Medicine, the Safar Center for Resuscitation Research, and the Society for Academic Emergency Medicine[END_REF][START_REF] Swindle | Swine as models in experimental surgery[END_REF].

Manikin trials are widely used for training purposes in the field of cardiac arrest [START_REF] Heitz | Simulation in medical student education: survey of clerkship directors in emergency medicine[END_REF][START_REF] Okuda | National growth in simulation training within emergency medicine residency programs, 2003-2008[END_REF][START_REF] Mclaughlin | Simulation in graduate medical education 2008: a review for emergency medicine[END_REF], although the transfer of skills learned on simulation tools into clinical practice is still being discussed [START_REF] Cook | Technology-Enhanced Simulation for Health Professions Education: A Systematic Review and Meta-analysis[END_REF][START_REF] Ilgen | Technology-enhanced Simulation in Emergency Medicine: A Systematic Review and Meta-Analysis[END_REF]. Some manikin-based studies also intended to explore cardiopulmonary resuscitation (CPR) pathophysiology [START_REF] Wenzel | Influence of tidal volume on the distribution of gas between the lungs and stomach in the nonintubated patient receiving positive-pressure ventilation[END_REF]. Even if findings obtained on manikin-based studies are sometimes directly extrapolated to clinical practice [START_REF] Koster | European Resuscitation Council Guidelines for Resuscitation 2010 Section 2. Adult basic life support and use of automated external defibrillators[END_REF], this needs to be done cautiously. Manikin models are an approximate representation of physiological observations and measurements made on patients [START_REF] Eichhorn | Development and validation of an improved mechanical thorax for simulating cardiopulmonary resuscitation with adjustable chest stiffness and simulated blood flow[END_REF] and therefore cannot be used to explore pathophysiology to achieve a better understanding.

Since human cadavers are not typically used for resuscitation training or research, the aim of this review was to reference studies on cardiac arrest or CPR using human cadaver models (HCMs) and to give a complete overview of their characteristics. Potential limiters of an HCM are the condition of the body, how it is stored and prepared, time interval since death and its accessibility. However, HCMs have the potential to provide new information related to the mechanics of CPR, especially when trying to elucidate the mechanisms of interactions between anatomic elements. Additionally, this model allows sophisticated physiologic monitoring that could not be attained in a consistent methodological design in live humans.

Finally, HCMs make it possible to explore various resuscitation techniques on the same model, in comparison with animal models which often require a new animal for each test.

No systematic review has yet been published on this subject. We therefore aimed to [START_REF] Sandroni | In-hospital cardiac arrest: incidence, prognosis and possible measures to improve survival[END_REF] report a precise analysis of the cadaver models used in the field of cardiac arrest research, (2) list the research fields explored in those studies, (3) synthesise the advantages and drawbacks mentioned by the authors of each HCM and finally (4) imagine an ideal HCM based on previous observations.

METHODS

Eligibility Criteria

Studies concerning the use of a cadaver model to explore cardiac arrest pathophysiology or to assess the effectiveness of a new CPR method, as well as studies using HCMs to simulate cardiac arrest for learning and/or teaching goals, were eligible for this systematic review.

Cadaver models used for any fields other than CPR or cardiac arrest and studies on animals were excluded. Cadaver models that could be included in this study were identified through a systematic literature review (Fig. 1). It was conducted in accordance with current guidelines on systematic literature reviews and it complied with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement [START_REF] Liberati | The PRISMA Statement for Reporting Systematic Reviews and Meta-Analyses of Studies That Evaluate Health Care Interventions: Explanation and Elaboration[END_REF].

Search Strategies and Data Extraction

Studies were identified through electronic databases. The following key words were used: "heart arrest", "cardiac arrest", "cardiopulmonary resuscitation", "cadaver". Only articles with the full text available in English or French were selected. No type of document restriction was applied and no methodology filters were used. All studies published until February 2019 were eligible for inclusion. This search was applied to Medline and adapted to Embase, Current Contents and Pascal electronic databases. We also searched the grey literature (Open SIGLE). The precise research approach for identifying potential eligible studies is described in Appendix A. One author (HD) conducted the literature search with the help of a professional librarian (VD) to produce a database of references. Finally, a secondary search was conducted by scanning the reference lists of the original articles retrieved.

Two review authors (HD, GD) independently and blindly screened the titles and abstracts of all the records identified by the search strategy, in accordance with the Cochrane recommendations [START_REF] Higgins | Cochrane Handbook for Systematic Reviews of Interventions[END_REF]. For this initial screening, all search results were imported into reference management software and duplicates were removed. The screening process assessed whether the citation: (1) reported data from an original research study using HCMs and (2) focused on cardiac arrest or cardiopulmonary resuscitation. If both criteria were met, the study was considered eligible. The two review authors rated each citation using a "relevant", "irrelevant" or "unsure" designation. Only full-text articles that received a "relevant" or "unsure" classification from at least one of the two review authors were retrieved for citations. Out of 244 records identified, discrepancies of eligibility assessment between authors were encountered for 14 references. Full-text articles of records identified as being potentially relevant were independently assessed by the two authors for inclusion.

Disagreements on eligibility were resolved in discussion between the reviewers. The reasons for excluding studies were recorded. A PRISMA-style flow diagram was drawn to illustrate the process of primary study selection from identification to inclusion in the systematic review (Fig. 1).

The following data were collected for each study eligible when available: the type of cadaver and its characteristics and the intended purpose of the study. We also reported if chest compressions were applied and their modalities, if ventilation was performed, if declotting or perfusion techniques were used and if any other kind of equipment was used on the cadaver. Finally, we looked for any mention of the model's quality assessment or limitations reported in those studies.

Risk of Bias (Quality) Assessment

To provide an overview of the quality level of the studies included, we used the Cochrane RoB Tool developed by the Cochrane Collaboration [START_REF] Higgins | The Cochrane Collaboration's tool for assessing risk of bias in randomised trials[END_REF] to report the risk of bias (Appendix B). This tool evaluates seven different quality domains: (1) random sequence generation, (2) allocation concealment, (3) blinding of participants and personnel, (4) blinding of outcome assessment, (5) incomplete outcome data, (6) selective reporting and (7) other biases. The Cochrane RoB Tool was developed for randomised clinical trials and is not completely adequate for studies on cadaver models which include experimental studies. This means that some aspects of the quality assessment process needed to be adapted to the characteristics of the studies using HCMs. When the risk of bias for a specific domain was considered irrelevant in a given study by the authors, it was graded as "low". We graded as "unclear risk of other biases" studies lacking a description of the model's characteristics, preparation or storage conditions in a way resulting in non-reproducible study conditions.

Statistical Analysis

The results were reported as numbers and percentages for categorical variables and means and standard deviations or minimum and maximum values for continuous variables.

RESULTS

Literature Search

A total of 283 citations were identified in the database search (Fig. 1). The secondary search yielded 12 additional records, identified from citation and reference tracking. After removing duplicates, a total of 244 studies were screened on the basis of the title and abstract. The full text of 40 articles was retrieved for a more thorough eligibility review. Eleven citations did not fulfil the inclusion criteria and were excluded. Finally, 29 articles were included. Four different cadaver preparation models were used.

Characteristics of the Studies Included

Sixteen (55%) studies used fresh cadavers, six (21%) used "newly deceased" cadavers, four (14%) used Thiel-embalmed cadavers and three (10%) used fresh-frozen cadavers. No study used formalin-embalmed cadavers. A brief technical description of each model is summarised in Table 1. The number of cadavers used in each study was 12±11. Within studies, interventions were performed several times on the same cadaver with an average number of uses of 6±11 times. The age of cadavers was indicated in 15 (52%) studies, with a mean of 71 years (range, 58-84). Only five studies specified the cadaver storage temperature, four of them used fresh cadavers, not frozen, and cadavers were kept at 4°C in three of these, one study kept them at 22°C for a very short time. One study using Thielembalmed cadavers mentioned a storage temperature of 20°C. Ten (34%) studies used automated chest compressions, seven (24%) used manual chest compressions, three (10%) used open chest cardiac massage and four (14%) used a combination of the above. Thirteen (45%) studies used ventilation on cadavers, either manual or mechanical (Table 3).

The studies explored seven main domains: ventilation and airway management, 14 (48%); haemodynamics, five (17%); thoraco(s)tomy, two (7%); mechanical properties of the chest, four (14%); defibrillation safety, two (7%); bispectral index monitoring, one (3%); and intraosseous access, one (3%) (Table 2). All relevant studies were interventional in design.

Risk of Bias Within Studies

The risk of bias assessment is summarised in Appendix B. The main issue was that considering the main outcome measured, 22 (76%) studies were not able to blind participants to the intervention type. In addition, there was either unclear or no blinding of assessors in 25 (86%) studies. The model description was considered adequate if at least five out of eight of the following criteria were specified in the study: type of cadaver, storage temperature, number of cadavers used, number of uses per cadaver, age, weight, gender and post-mortem time interval. Nine (31%) studies were considered as non-reproducible due to insufficient model description. There was insufficient information on the sequence generation process and/or allocation concealment in five studies (17%). One study [START_REF] Skinner | Resuscitation following prolonged cardiac arrest[END_REF] seemed to incompletely report its outcomes. Finally, there was substantial (25%) unexplained drop-out in one study [START_REF] Lemkin | Electrical exposure risk associated with hands-on defibrillation[END_REF] and 27% of the data were missing in one of the interventions in a crossover study [START_REF] Wei | Cardiopulmonary Resuscitation in Prone Position: A Simplified Method for Outpatients[END_REF].

Fresh Cadavers

Fresh cadavers entail a human body never frozen or embalmed post-mortem, generally kept for up to 72 h in a refrigerated area and then used for research or teaching. No preparation or declotting is performed. In this systematic review, 16 (55%) studies used fresh cadavers, and these records studied six main research areas: airway management, seven studies (44%) [START_REF] Truszewski | A comparison of a traditional endotracheal tube versus ETView SL in endotracheal intubation during different emergency conditions[END_REF][START_REF] Truszewski | Ability of paramedics to perform endotracheal intubation during continuous chest compressions: a randomized cadaver study comparing Pentax AWS and Macintosh laryngoscopes[END_REF][START_REF] Cho | Airway scope vs Macintosh laryngoscope during chest compressions on a fresh cadaver model[END_REF][START_REF] Segal | Effect of continuous oxygen insufflation on inducedgastric air volume during cardiopulmonary resuscitation in a cadaveric model[END_REF][START_REF] Coats | End-tidal CO2 detection during cadaveric ventilation[END_REF][START_REF] Piegeler | Evaluation of six different airway devices regarding regurgitation and pulmonary aspiration during cardio-pulmonary resuscitation (CPR) -A human cadaver pilot study[END_REF][START_REF] Ruetzler | Regurgitation and pulmonary aspiration during cardio-pulmonary resuscitation (CPR) with a laryngeal tube : A pilot crossover human cadaver study[END_REF]; mechanical properties of the chest, three studies (19%) [START_REF] Eichhorn | Development and validation of an improved mechanical thorax for simulating cardiopulmonary resuscitation with adjustable chest stiffness and simulated blood flow[END_REF][START_REF] Segal | Chest compliance is altered by static compression and decompression as revealed by changes in anteroposterior chest height during CPR using the ResQPUMP in a human cadaver model[END_REF][START_REF] Baubin | Chest injuries after active compression-decompression cardiopulmonary resuscitation (ACD-CPR) in cadavers[END_REF]; haemodynamics, two studies (12.5%) [START_REF] Moore | Consistent head up cardiopulmonary resuscitation haemodynamics are observed across porcine and human cadaver translational models[END_REF][START_REF] Rutty | Could post-mortem computed tomography angiography inform cardiopulmonary resuscitation research?[END_REF]; defibrillation safety, two studies (12.5%) [START_REF] Lemkin | Electrical exposure risk associated with hands-on defibrillation[END_REF][START_REF] Wampler | A randomized control hands-on defibrillation study-Barrier use evaluation[END_REF], intraosseous access, one study (6%) [START_REF] Szarpak | A Randomized Cadaver Study Comparing First-Attempt Success Between Tibial and Humeral Intraosseous Insertions Using NIO Device by Paramedics: A Preliminary Investigation[END_REF]; and one study explored bispectral index monitoring and used a fresh cadaver for artefact control (6%) [START_REF] Fatovich | An observational study of bispectral index monitoring for out of hospital cardiac arrest[END_REF]. The main advantages reported of using fresh cadavers were: its accurate morphology and tissue conservation making it possible, for example, to reflect the conditions of endotracheal intubation, accurately estimate regurgitation risks in humans having CPR, obtain a stable transthoracic impedance over time and characterise thoracic viscoelastic properties. The authors also reported good results in haemodynamic simulations since they were able to measure a pressure rise during chest compressions; one study assessed achievement of venous circulation from a peripheric vessel to pulmonary vessels with automated chest compressions [START_REF] Rutty | Could post-mortem computed tomography angiography inform cardiopulmonary resuscitation research?[END_REF], and another one reported haemodynamic findings similar to pigs during ventricular fibrillation [START_REF] Moore | Consistent head up cardiopulmonary resuscitation haemodynamics are observed across porcine and human cadaver translational models[END_REF]. On the other hand, the limitations of this model were that no right-to-left circulation was achieved, nor left-to-right capillary flow, resulting in blood flow measurement being impossible. Moreover, the authors reported that the loss of vascular tone, the modified biomechanics of the tissues and the modification of lung compliance due to beginning rigor mortis were also limitations to the realism of the model. Finally, one group regretted that human cadavers consisted of elderly patients with a low body mass index, which could reduce the comparability with cardiac arrest patients, and one study decided to use fresh-frozen cadavers because they considered fresh cadavers too expensive [START_REF] Mckay | Are chest compressions safe for the patient reconstructed with sternal plates? Evaluating the safety of cardiopulmonary resuscitation using a human cadaveric model[END_REF].

Fresh-Frozen Cadavers

Fresh-frozen cadavers consist of human bodies frozen a few hours after death (only one study mentioned the post-mortem interval between death and freezing: 36 h ± 12) and then thawed before use. Like fresh cadavers, no preparation or declotting techniques are used. In this systematic review, three studies used fresh-frozen cadavers (10%), one explored the mechanical properties of the chest (33%) [START_REF] Mckay | Are chest compressions safe for the patient reconstructed with sternal plates? Evaluating the safety of cardiopulmonary resuscitation using a human cadaveric model[END_REF], one assessed an open chest cardiac massage device (33%) [START_REF] Hanouz | Insertion of the minimally invasive direct cardiac massage device (MIDCM): training on human cadavers[END_REF] and one studied ventilation (33%) [START_REF] Silvestri | Endotracheal tube placement confirmation: 100% sensitivity and specificity with sustained four-phase capnographic waveforms in a cadaveric experimental model[END_REF]. None of them specified the freezing temperature. One study exploring capnographic waveforms during ventilation pointed out the advantage of the similarity of cadaver models with the low-or no-perfusion state observed in cardiac arrest patients [START_REF] Silvestri | Endotracheal tube placement confirmation: 100% sensitivity and specificity with sustained four-phase capnographic waveforms in a cadaveric experimental model[END_REF]. The authors reported a lack of realism of the lung and chest compliance and the frailty of the cadavers compared to patients or fresh cadavers. Once again, the lack of circulation was found to be a strong limitation of the model since complications such as bleeding could not be simulated, as well as the lack of a real gas exchange despite ventilation. One study mentioned high cost as a limitation to the number of specimens used and therefore to the power of the study [START_REF] Mckay | Are chest compressions safe for the patient reconstructed with sternal plates? Evaluating the safety of cardiopulmonary resuscitation using a human cadaveric model[END_REF].

Thiel-Embalmed Cadavers

Thiel-embalmed cadavers are soft-embalmed cadavers using a method described by Walter Thiel in 1992 [START_REF] Thiel | The preservation of the whole corpse with natural color[END_REF] and updated in 2002 [START_REF] Thiel | Supplement to the conservation of an entire cadaver according to W. Thiel[END_REF]. It consists in the application of an intravascular injection formula containing glycol, various salts, boric acid, chlorocresol, alcohol and low levels of formaldehyde, and maintaining the corpses submerged for a determinate period of time in the immersion solution in a tank. After immersion, it is possible to maintain the corpses in a hermetically sealed container, thus avoiding dehydration outside the tank.

Cadavers embalmed with Thiel methods can be used repeatedly and be preserved for up to 3 years, in contrast with fresh and fresh-frozen cadavers. In this review, four studies used Thiel-embalmed cadavers (14%), three of them were conducted by the same research team and studied ventilation (75%) [START_REF] Grieco | Intrathoracic Airway Closure Impacts CO2 Signal and Delivered Ventilation During Cardiopulmonary Resuscitation[END_REF][START_REF] Charbonney | A new physiological model for studying the effect of chest compression and ventilation during cardiopulmonary resuscitation: The Thiel cadaver[END_REF][START_REF] Savary | Capnographic waveforms obtained in experimental Thiel cadaver model after intubation[END_REF] and one studied thoracotomy training (25%) [START_REF] Puchwein | Clamshell thoracotomy and open heart massage-A potential life-saving procedure can be taught to emergency physicians[END_REF]. All the studies included using Thiel-embalmed cadavers were published after 2015, even though this embalming method has been known since 1992. The main advantages reported concerning the use of Thiel-embalmed cadavers were the lifelike aspect of the anatomy and mechanical properties, in particular the preserved elasticity and flexibility of the tissues as well as lung and chest wall compliance and resistance that were found to be comparable to values reported in critically ill patients. In addition, this model also had the advantage of being stable over time in terms of resistance and compliance and reproduces the airway opening and collapse phenomenon observed in cardiac arrest patients. Once again, the lack of blood flow and perfusion was reported by the authors as a shortcoming. Charbonney et al. [START_REF] Charbonney | A new physiological model for studying the effect of chest compression and ventilation during cardiopulmonary resuscitation: The Thiel cadaver[END_REF] also mentioned that Thiel-embalmed cadavers seemed to be particularly prone to pulmonary derecruitment. The other disadvantage reported was the fact that Thielembalmed method requires expertise available in only certain laboratories.

Newly Deceased Cadavers

Six records used newly deceased cadavers (21%) to study ventilation and airway management [START_REF] Davis | Lung Compliance Following Cardiac Arrest[END_REF][START_REF] Langhelle | Airway pressure with chest compressions versus Heimlich manoeuvre in recently dead adults with complete airway obstruction[END_REF][START_REF] Lufkin | Mouth-to-mouth ventilation of cardiac arrested humans using a barrier mask[END_REF] and haemodynamics [START_REF] Skinner | Resuscitation following prolonged cardiac arrest[END_REF][START_REF] Wei | Cardiopulmonary Resuscitation in Prone Position: A Simplified Method for Outpatients[END_REF][START_REF] Rieder | A study of the techniques of cardiac massage with the abdomen open[END_REF]. These studies were carried out in the minutes following death in ICU and emergency departments, or on organ donors. No description of the models was provided, but the authors report that the cadaver population used could differ from cardiac arrest patients given that most of the subjects died of multiorgan failure or had severe pulmonary complications before death. One study noted that the model was found to be unstable over time [START_REF] Rieder | A study of the techniques of cardiac massage with the abdomen open[END_REF]. As for ethical concerns, four studies reported or implied that informed consent was not required by ethics committees, one study mentioned that permission was obtained with the permit for organ retrieval [START_REF] Rieder | A study of the techniques of cardiac massage with the abdomen open[END_REF] and consent of the family was obtained in one study [START_REF] Wei | Cardiopulmonary Resuscitation in Prone Position: A Simplified Method for Outpatients[END_REF]. Interestingly enough, all studies using newly deceased cadavers except one [START_REF] Wei | Cardiopulmonary Resuscitation in Prone Position: A Simplified Method for Outpatients[END_REF] were published before the beginning of the 21st century.

DISCUSSION

To our knowledge, this review is the first to describe the different human cadaver models that have been used to date in cardiac arrest research. We found that four different models were used -newly deceased, fresh cadavers, fresh-frozen cadavers and Thiel-embalmed cadavers with the specific advantage and limitations for each model. The majority of the studies were conducted on fresh cadavers.

Understanding the physiology of cardiopulmonary resuscitation during cardiac arrest has been a challenge for many years. Pre-clinical research in this field is often long and fastidious. Although animal studies have tried to reflect the clinical scenario, these models fail to properly simulate human cardiopulmonary pathophysiology. Likewise, manikin simulation cannot be extrapolated with certainty to patients in cardiac arrest because it is only a representation of physiological observations and measurements taken on patients. It has been shown that the results obtained on manikins may fail to translate to actual out-ofhospital cardiac arrest patients [START_REF] De Luca | Reliability of manikin-based studies: an evaluation of manikin characteristics and their impact on measurements of ventilatory variables[END_REF][START_REF] Tomte | Advanced life support performance with manual and mechanical chest compressions in a randomized, multicentre manikin study[END_REF][START_REF] Hallstrom | Manual Chest Compression vs Use of an Automated Chest Compression Device During Resuscitation Following Out-of-Hospital Cardiac Arrest: A Randomized Trial[END_REF]. This might be a root cause for the negative results of many clinical studies with promising experimental findings [START_REF] Cariou | Early High-Dose Erythropoietin Therapy After Out-of-Hospital Cardiac Arrest: A Multicenter, Randomized Controlled Trial[END_REF][START_REF] Kim | Effect of prehospital induction of mild hypothermia on survival and neurological status among adults with cardiac arrest: a randomized clinical trial[END_REF][START_REF] Argaud | Effect of Cyclosporine in Nonshockable Out-of-Hospital Cardiac Arrest: The CYRUS Randomized Clinical Trial[END_REF][START_REF] Debaty | Impact of intra-arrest therapeutic hypothermia in outcomes of prehospital cardiac arrest: a randomized controlled trial[END_REF]. High-quality postresuscitation care is the key component to improve survival with good neurological outcome [START_REF] Nolan | European Resuscitation Council and European Society of Intensive Care Medicine Guidelines for Post-resuscitation Care 2015: Section 5 of the European Resuscitation Council Guidelines for Resuscitation 2015[END_REF][START_REF] Sunde | Predicting survival with good neurologic recovery at hospital admission after successful resuscitation of out-ofhospital cardiac arrest: the OHCA score[END_REF]. Human cadaver models provide new perspectives in resuscitation research through their ability to enable sophisticated physiologic monitoring that could not be attained in a clinical setting. In addition, their human morphology allows researchers to overcome anatomical differences which might burden animal studies.

The studies included in this review explored two main areas, ventilation and airway management, and haemodynamics. Most studies using Thiel-embalmed cadavers explored ventilation and showed promising results, particularly concerning the similarity of respiratory system behavior with cardiac arrest patients. Haemodynamics was studied using either fresh cadavers or newly deceased cadavers. Three studies measured blood pressure in cadaver models, two of them using newly deceased cadavers were evaluated with a high risk of bias [START_REF] Wei | Cardiopulmonary Resuscitation in Prone Position: A Simplified Method for Outpatients[END_REF][START_REF] Rieder | A study of the techniques of cardiac massage with the abdomen open[END_REF]. One study with good methodology [START_REF] Moore | Consistent head up cardiopulmonary resuscitation haemodynamics are observed across porcine and human cadaver translational models[END_REF] measured arterial blood pressure in a fresh cadaver model and reported encouraging findings of similar blood pressure curves to those obtained on pigs in ventricular fibrillation. Nevertheless, the lack of circulation was almost systematically reported as a limit to HCM and research in this area should be pursued.

Taking into account the weaknesses and strong points underlined by the authors, we have described an "ideal" cadaver model of cardiac arrest. What seemed important for the realism and accuracy of the model was its lifelike anatomy and tissue conservation as well as similarity with cardiac arrest patients in terms of chest and lung compliance and resistance.

Stability over time appeared as another important point to be emphasised given that human cadaver research can be expensive. The lack of circulation was definitely the most common and important limitation of the models described; therefore we suggest that this ideal model should enable left-to-right circulation. To reproduce circulation, the use of a fresh cadaver seemed to be a reasonable option as haemodynamic studies have already reported satisfactory results [START_REF] Moore | Consistent head up cardiopulmonary resuscitation haemodynamics are observed across porcine and human cadaver translational models[END_REF][START_REF] Rutty | Could post-mortem computed tomography angiography inform cardiopulmonary resuscitation research?[END_REF]. The drawback of this model, as previously reported, is the lack of embalming, which requires the cadaver to be disposed of after the procedure. Moreover, although it has not been reported in the studies included, prolonged cardiac massage on a perfused cadaver inevitably leads to pulmonary and limb oedema due to the altered vascular permeability of fresh cadavers. An interesting lead to explore could be to try and reproduce circulation on a Thiel-embalmed cadaver since this model shows greater similarities in terms of lung and chest compliance and resistance, with critically ill patients, and is more stable over time compared to fresh cadavers. This has never been done to explore cardiac arrest pathophysiology, but one team has successfully perfused the aorta of a Thiel-embalmed cadaver to simulate aortic endovascular procedures [START_REF] Mcleod | Human Thiel-Embalmed Cadaveric Aortic Model with Perfusion for Endovascular Intervention Training and Medical Device Evaluation[END_REF].

Even if human cadavers are not yet traditionally used for resuscitation training or research, it is interesting to note that 60% of the studies included in this review were published in the past 4 years, which confirms a definite trend towards this approach in cardiac arrest research (Fig. 2). Furthermore, "time for procedure" was found to be the main outcome measured in a fair number of the studies included [START_REF] Truszewski | A comparison of a traditional endotracheal tube versus ETView SL in endotracheal intubation during different emergency conditions[END_REF][START_REF] Truszewski | Ability of paramedics to perform endotracheal intubation during continuous chest compressions: a randomized cadaver study comparing Pentax AWS and Macintosh laryngoscopes[END_REF][START_REF] Cho | Airway scope vs Macintosh laryngoscope during chest compressions on a fresh cadaver model[END_REF][START_REF] Szarpak | A Randomized Cadaver Study Comparing First-Attempt Success Between Tibial and Humeral Intraosseous Insertions Using NIO Device by Paramedics: A Preliminary Investigation[END_REF][START_REF] Hanouz | Insertion of the minimally invasive direct cardiac massage device (MIDCM): training on human cadavers[END_REF][START_REF] Puchwein | Clamshell thoracotomy and open heart massage-A potential life-saving procedure can be taught to emergency physicians[END_REF], underscoring the fact that cadaver models are used in feasibility studies to test new medical devices. In extension, this also opens the door to the idea that an HCM could be used for training and education in cardiac arrest management. Indeed, their lifelike features could enable realistic training and simulation of invasive procedures and/or new CPR strategies in a controlled and risk-free environment.

A strong limitation reported by the authors was that cadaver research could be expensive and therefore limits the size of the samples used. We attempted to evaluate the cost of each cadaver model but the literature in this field is poorly documented. We must admit that maintenance of a cadaver lab, storage, technical support, operative equipment and embalming fluids has cost implications that might be too complex to calculate a cost per cadaver. We identified three studies mentioning "preparation" costs of cadaver models, all of them concerning surgical training. Benkhadra et al. [START_REF] Benkhadra | Is Thiel's embalming method widely known? A world survey about its use[END_REF] estimated the price of a Thielembalmed cadaver at about 300 € while Hammer et al. [START_REF] Hammer | Comparison of modified thiel embalming and ethanol-glycerin fixation in an anatomy environment: Potentials and limitations of two complementary techniques[END_REF] proposed a modified Thiel embalming method which could almost cut the price in half. This modified Thiel method was estimated around 437 €, which is inconsistent with Benkhadra et al.'s findings. Both studies estimated the price of formaldehyde-based cadavers near 30 €. Finally, Mitchell et al. [START_REF] Mitchell | A fresh cadaver laboratory to conceptualize troublesome anatomic relationships in vascular surgery[END_REF] priced a fresh cadaver model between 900 € and 1800 € depending on the presence or absence of the extremities and head, as opposed to a porcine model's cost, which was estimated at 350 € per animal. Comparatively, another study using swine models in burn research estimated the price at 517 € per animal. Once again, this estimation does not include technical support, storage or operative equipment [START_REF] Abdullahi | Animal Models in Burn Research[END_REF]. Cadaver-related costs, however, can be mitigated using the same cadaver for other purposes and by other disciplines. In this way, the Thiel-embalmed cadaver could be the most sustainable model used in these studies because it was found to be reusable after investigation and stable over time.

Finally, an "ideal" cadaver model is probably an unrealistic goal, as no single HCM can encompass the complexity of a cardiac arrest patient. Various models are essential to answer specific research questions. Based on the findings of this systematic review, we consider fresh cadaver models as the most appropriate model to investigate hemodynamic during CPR, even if Thiel-embalmed cadavers have never been tested for this purpose.

However, Thiel-embalmed cadavers could represent strong models to study ventilation in cardiac arrest, and it should probably be researchers' first choice for such studies.

Investigators should adapt their choice of HCM in accordance with the scientific question at hand, but their methodology must be reported and well documented to enable reproducibility. The lack of uniform reporting limits our ability to compare the results obtained in these studies. Such discrepancy might be further enhanced by the large period of literacy search. Studies that were performed almost 60 years ago substantially differ from the more recent ones, due at least partly to the fact that the methodology of research in this field has greatly improved. Accordingly, comparison might be challenging. Nevertheless, there is a need to standardise cardiac arrest research and reporting on human cadaver models. Ideally, the Utstein-Style Guidelines for Uniform Reporting of Laboratory CPR Research [START_REF] Idris | Utstein-style guidelines for uniform reporting of laboratory CPR research. A statement for healthcare professionals from a Task Force of the American Heart Association, the American College of Emergency Physicians, the American College of Cardiology, the European Resuscitation Council, the Heart and Stroke Foundation of Canada, the Institute of Critical Care Medicine, the Safar Center for Resuscitation Research, and the Society for Academic Emergency Medicine[END_REF] could be adapted to research on cadaver models. These guidelines were published in 1996 with the aim of standardising the reporting of animal cardiac arrest research. Similar guidelines for studies on cadavers might improve comparability and reproducibility of such studies.

CONCLUSION

Four types of cadaver models were reported, newly deceased, fresh cadavers, fresh-frozen cadavers and Thiel-embalmed cadavers. The majority of the studies used fresh cadavers.

Ventilation and airway management was the most common topic explored. The lack of circulation was found to be the main drawback of human cadavers regardless of the type of model. The studies included lacked uniform reporting, which limited our ability to compare the results obtained.

Bispectral index monitoring

Fatovich et al.

Intraosseous access

Szarpak et al.

FIGURES:Figure 1 :( 2 )( 3 )Figure 2 :

 1232 FIGURES:

Table 1 -

 1 Models' description

	Type of cadavers	Preservative	Time between	Storage	Period of use
		agents	death and use
	Fresh	None	A few hours (less	4°C	Days
			than 72h usually)
	Fresh-frozen	None	Days	Ca.-18°C	Days
	Thiel-embalmed	Glycol, various	A few months	20°C	Years
		salts, boric acid,	(immersion time)
		chlorocresol,
		formaldehyde,
		alcohol
	Newly deceased	None	Immediatly after	None	Hours
			death
	Formalin-	Formaldehyde+/-	Hours	20°C	Years
	embalmed	phenol and
		glycerine

Table 2 -

 2 Domains of study

		Fresh	Fresh-frozen	Thiel-embalmed	Newly deceased
	Ventilation and airways'	Truszewski et al.	Silvestri et al.	Charbonney et al.	Davis et al.
	management	Truszewski et al.		Grieco et al.	Langhelle et al.
		(2)		Savary et al.	Lufkin et al.
		Cho et al.
		Segal et al. (2)
		Coats et al.
		Piegeler et al.
		Ruetzler et al.
	Haemodynamics	Moore et al.			Wei et al.
		Rutty et al.			Rieder et al.
					Skinner et al.
	Thoraco(s)tomy		Hanouz et al.	Puchwein et al.
	Mechanical properties of	Segal et al.	McKay et al.
	the chest	Baubin et al.
		Eichhorn et al.
	Defibrillation safety	Wampler et al.
		Lemkin et al.

Conflict of Interest

The authors declare that they have no conflict of interest in connection with the article.

Role of the funding source

The study was funded by an internal grant and the University Grenoble Alps.


MD Marion Aribert
email: maribert@chu-grenoble.fr

D Corcella

M Bouyer

Denis

MD Corcella

MD Michael Bouyer

and lunate cartilage lesions: advantages of a skin paddle Lambeau libre composite ostéo-chondro-cutané de trochlée fémorale médiale dans les lésions cartilagineuses du scaphoïde et du lunatum : avantages d'une palette cutanée

Keywords: Medial femoral trochlea flap, Scaphoid nonunion, Osteocartilagenous autograft, Descending genicular artery flap, Skin island flap Lambeau de trochlée fémorale médiale, Pseudarthrose du pôle proximal du

ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

Introduction

The free medial femoral condyle (MFC) flap is a corticoperiosteal flap, vascularized by the descending genicular artery (DGA), initially described in the late 1980s [START_REF] Hertel | The reverse flow medial knee osteoperiosteal flap for skeletal reconstruction of the leg. Description and anatomical basis[END_REF][START_REF] Masquelet | Vascularized periosteal grafts. Anatomic description, experimental study, preliminary report of clinical experience[END_REF]. Thereafter, the MFC flap was improved and used for various bone reconstructions, mostly scaphoid nonunion, with good results [START_REF] Doi | Free vascularized bone graft for nonunion of the scaphoid[END_REF]. Derived from the MFC flap, a cartilage-bone graft with the same vascularization (by the DGA) was described in 2008 [START_REF] Kälicke | A new vascularized cartilage-bone-graft for scaphoid nonunion with avascular necrosis of the proximal pole. Description of a new type of surgical procedure[END_REF][START_REF] Higgins | The use of osteochondral flaps in the treatment of carpal disorders[END_REF][START_REF] Higgins | Medial femoral trochlea osteochondral flap: applications for scaphoid and lunate reconstruction[END_REF]: the free medial femoral trochlea (MFT) flap.

The MFT flap is a composite chondrocorticoperiosteal flap. It was developed for the reconstruction of cartilage lesions and can be used for various articular defects [START_REF] Higgins | Osteochondral flaps from the distal femur: expanding applications, harvest sites, and indications[END_REF]. The most common application is reconstruction of nonunion of the scaphoid's proximal pole [START_REF] Kälicke | A new vascularized cartilage-bone-graft for scaphoid nonunion with avascular necrosis of the proximal pole. Description of a new type of surgical procedure[END_REF][START_REF] Higgins | The use of osteochondral flaps in the treatment of carpal disorders[END_REF][START_REF] Higgins | Medial femoral trochlea osteochondral flap: applications for scaphoid and lunate reconstruction[END_REF][START_REF] Higgins | Osteochondral flaps from the distal femur: expanding applications, harvest sites, and indications[END_REF][START_REF] Bürger | Vascularized medial femoral trochlea osteocartilaginous flap reconstruction of proximal pole scaphoid nonunions[END_REF][START_REF] Capito | Scaphoid overstuffing: the effects of the dimensions of scaphoid reconstruction on scapholunate alignment[END_REF][START_REF] Higgins | Proximal scaphoid arthroplasty using the medial femoral trochlea flap[END_REF][START_REF] Windhofer | Knee donor site morbidity following harvest of medial femoral trochlea osteochondral flaps for carpal reconstruction[END_REF] and advanced avascular necrosis of the lunate in Kienböck disease [START_REF] Higgins | The use of osteochondral flaps in the treatment of carpal disorders[END_REF][START_REF] Higgins | Medial femoral trochlea osteochondral flap: applications for scaphoid and lunate reconstruction[END_REF][START_REF] Higgins | Osteochondral flaps from the distal femur: expanding applications, harvest sites, and indications[END_REF][START_REF] Capito | Scaphoid overstuffing: the effects of the dimensions of scaphoid reconstruction on scapholunate alignment[END_REF][START_REF] Higgins | Proximal scaphoid arthroplasty using the medial femoral trochlea flap[END_REF][START_REF] Bürger | Vascularized medial femoral trochlea osteochondral flap reconstruction of advanced Kienbock disease[END_REF]. MFC and MFT flaps may be associated with a skin island flap to monitor its vascularization. This surgical technique has been thoroughly studied and described [START_REF] Doi | Free vascularized bone graft for nonunion of the scaphoid[END_REF][START_REF] Windhofer | Knee donor site morbidity following harvest of medial femoral trochlea osteochondral flaps for carpal reconstruction[END_REF][START_REF] Iorio | Cutaneous angiosome territory of the medial femoral condyle osteocutaneous flap[END_REF]]. However, only 10 studies (totaling 50 patients) briefly report the postoperative outcome of the skin paddle in MFC flap cases and only one on 2 patients [START_REF] Tremp | The medial femoral trochlea flap with a monitor skin island. Report of two cases[END_REF] for the MFT flap. The few studies examining the MFC flap assessed the success of the flap for bone union without considering good flap vascularization. Only one study has related the immediate postoperative condition and utility of the skin paddle.

We report three cases of the MFT flap being used with a skin paddle to replace an injured proximal scaphoid and lunate pole.

Cases reports

Between May 2017 and August 2017, three males were treated with a free osteochondral cutaneous graft harvested from the MFT (Table 1) [START_REF] Schernberg | Classification of fractures of the carpal scaphoid. An anatomoradiologic study of characteristics[END_REF][START_REF] Alnot | Fractures and non-unions of the proximal pole of the carpal scaphoid bone. Internal fixation by a proximal to distal screw[END_REF][START_REF] Lichtman | Staging and its use in the determination of treatment modalities for Kienbock's disease[END_REF]. None of the patients had undergone previous surgery. Avascularity of the proximal pole of the scaphoid was present in both cases of scaphoid nonunion (Fig. 1).

In all three cases, the flap was designed and removed according to the technique described by Iorio et al. and Bürger et al. [8,[START_REF] Iorio | Cutaneous angiosome territory of the medial femoral condyle osteocutaneous flap[END_REF] (Table 1) (Figs. 2 and3). All donor sites were closed directly. At the wrist, the approaches were dorsal (between the second and third extensor compartments, to set the graft) and radial (according to the Henry approach, for vascular anastomosis) with a pedicle tunneled between the two.

Each patient followed our postoperative free flap protocol consisting in wrist immobilization in a loose window bandage, 250 mg of acetylsalicylic acid daily, 300 mg of piribedil twice a day, and 40 mg of enoxaparin sodium daily until walking was resumed.

Patients were instructed to have strict bed rest for 5 days, no cold exposure, no stimulants or other arterial blood pressure variators. Skin color was monitored every 2 hours for 5 days with evaluation of paddle coloring, pulse, heat, bleeding, and Doppler signal (if spotted preoperatively). Knee physical therapy was started on the first postoperative day.

After a mean of 10 weeks postoperative, CT scan showed complete healing and the pins were removed (Fig. 4).

Discussion

Vascular anatomy and consequences

MFT flap vascularization originates proximally to the medial condyle from the descending genicular artery (DGA), which is the last branch of the superficial femoral artery (SFA). The DGA originates proximally or distally to the adductor hiatus and divides into three different vessels with great anatomic variability, classified by Dubois et al. [START_REF] Dubois | The corticoperiosteal medial femoral supracondylar flap: anatomical study for clinical evaluation in mandibular osteoradionecrosis[END_REF] into seven types. There is the muscular branch (to the vastus medialis), the saphenous artery branch (SAB) (which is cutaneous), and the osteoarticular branch, commonly called the DGA. The osteoarticular branch divides as well into three branches: the cutaneous branch from the DGA (DGA-CB), the longitudinal periosteal branch, and the transverse periosteal branch.

The latter transverse branch supplies the convex cartilage-bearing trochlea of the medial patellofemoral joint, where the MFT flap is harvested.

In about 90% of cases, a skin island flap, overlying the medial area of the knee, could be combined with the MFT flap [START_REF] Iorio | Cutaneous angiosome territory of the medial femoral condyle osteocutaneous flap[END_REF][START_REF] Dubois | The corticoperiosteal medial femoral supracondylar flap: anatomical study for clinical evaluation in mandibular osteoradionecrosis[END_REF][START_REF] Garcia-Pumarino | Anatomical variability of descending genicular artery[END_REF]. Its vascularization can arise from the SAB or the DGA-CB or sometimes both (20% of cases). The skin paddle is most often based on the DGA-CB because it is easy to expose and dissect [START_REF] Iorio | Cutaneous angiosome territory of the medial femoral condyle osteocutaneous flap[END_REF]. In about 10% of cases, a skin paddle cannot be combined with the MFT flap because neither the SAB nor the DGA communicating branch is adequate for perfusion of a skin segment [START_REF] Hertel | The reverse flow medial knee osteoperiosteal flap for skeletal reconstruction of the leg. Description and anatomical basis[END_REF][START_REF] Iorio | Cutaneous angiosome territory of the medial femoral condyle osteocutaneous flap[END_REF][START_REF] Dubois | The corticoperiosteal medial femoral supracondylar flap: anatomical study for clinical evaluation in mandibular osteoradionecrosis[END_REF][START_REF] Garcia-Pumarino | Anatomical variability of descending genicular artery[END_REF][START_REF] Scheibel | A detailed anatomical description of the subvastus region and its clinical relevance for the subvastus approach in total knee arthroplasty[END_REF][START_REF] Martin | Mandibular reconstruction using a free vascularised osteocutaneous flap from the internal condyle of the femur[END_REF][START_REF] Ballmer | The reversed-flow medio-distal fasciocutaneous island thigh flap: anatomic basis and clinical applications[END_REF].

The DGA-CB most commonly arises from the longitudinal periosteal branches, but it can also leave the osteoarticular branch at the supracondylar region. The DGA-CB always arises distally to the SAB origin and can always be elevated anteriorly to the sartorius muscle and adductor tendon. These distal skin-carrying vessels seem to be present in about 94% of cases but cannot always be used [START_REF] Iorio | Cutaneous angiosome territory of the medial femoral condyle osteocutaneous flap[END_REF]. The DGA-CB has a small skin-vascularized area (70 cm 2 ) on the inner side of the knee joint. The SAB exists in around 97% of cases, and its origin is 14 ± 2.1 cm from the joint line.

Three types of anatomic variations of the SAB origin were identified by Dubois et al. [START_REF] Dubois | The corticoperiosteal medial femoral supracondylar flap: anatomical study for clinical evaluation in mandibular osteoradionecrosis[END_REF], which impact flap harvesting. The type-1 pattern (around 70% of cases) will not affect raising the flap because the SAB and the osteoarticular branch originate from the same trunk. Type-2 patterns (around 20% of cases) make it difficult to raise all flaps on a single suitable-length pedicle because the SAB or the osteoarticular branches originate separately from the SFA. This type is manageable with technical adaptations and requires careful distal dissection because the SAB runs anterior or posterior to the sartorius muscle and adductor tendon, close to the saphenous nerve. A type-3 pattern (10% of cases) does not always allow association of a skin paddle because the SAB and the osteoarticular branch originate separately from the SFA. The SAB has a large vascularized territory, particularly distally, which overlaps the DGA-CB territory (361 cm 2 ) [START_REF] Iorio | Cutaneous angiosome territory of the medial femoral condyle osteocutaneous flap[END_REF]. The variability of the DGA branching means the feasibility and difficulty of harvesting a skin flap with the MFT (or MFC) flap is difficult to predict [START_REF] Dubois | The corticoperiosteal medial femoral supracondylar flap: anatomical study for clinical evaluation in mandibular osteoradionecrosis[END_REF][START_REF] Garcia-Pumarino | Anatomical variability of descending genicular artery[END_REF]. However, in about 70% of cases, the skin paddle on the SAB is feasible [START_REF] Iorio | Cutaneous angiosome territory of the medial femoral condyle osteocutaneous flap[END_REF][START_REF] Dubois | The corticoperiosteal medial femoral supracondylar flap: anatomical study for clinical evaluation in mandibular osteoradionecrosis[END_REF][START_REF] Garcia-Pumarino | Anatomical variability of descending genicular artery[END_REF] with short harvest time (about 28 min) [START_REF] Rancy | Tibial bone grafting for wrist reconstruction[END_REF]. No study has assessed the presence and availability of a skin paddle on the DGA-CB, but it seems to be at least as frequent as on the SAB [START_REF] Iorio | Cutaneous angiosome territory of the medial femoral condyle osteocutaneous flap[END_REF][START_REF] Dubois | The corticoperiosteal medial femoral supracondylar flap: anatomical study for clinical evaluation in mandibular osteoradionecrosis[END_REF][START_REF] Garcia-Pumarino | Anatomical variability of descending genicular artery[END_REF].

Advantages of skin paddle on the MFT flap

The DGA's vascular tree is the source vessel for a large number of reconstructive flap options. Its numerous branches have led to the description of free skin, tendon, nerve, periosteal, corticoperiosteal, and osteochondral flaps [START_REF] Higgins | The use of osteochondral flaps in the treatment of carpal disorders[END_REF][START_REF] Higgins | Medial femoral trochlea osteochondral flap: applications for scaphoid and lunate reconstruction[END_REF][START_REF] Higgins | Osteochondral flaps from the distal femur: expanding applications, harvest sites, and indications[END_REF][START_REF] Kazmers | Upper and lower extremity reconstructive applications utilizing free flaps from the medial genicular arterial system: A systematic review[END_REF]. This flap is particularly well suited for conservative reconstruction of small bone defects and nonunion, such as in the wrist, with an excellent bone union rate [START_REF] Rancy | Tibial bone grafting for wrist reconstruction[END_REF][START_REF] Kazmers | Upper and lower extremity reconstructive applications utilizing free flaps from the medial genicular arterial system: A systematic review[END_REF]. It allows larger bone defects to be filled than with Zaidemberg's vascularized radial graft [START_REF] Zaidemberg | A new vascularized bone graft for scaphoid nonunion[END_REF] and the vascularized bone graft pedicle on the volar carpal artery described by Kuhlmann et al. [START_REF] Kuhlmann | Vascularized bone graft pedicled on the volar carpal artery for non-union of the scaphoid[END_REF].

A skin paddle allows monitoring of flap viability, clinically and with Doppler, which are ideal to monitor the buried osteochondroperiosteal graft during the immediate postoperative phase. The literature includes a dozen studies reporting cases of a skin paddle being associated with a MFC flap and only one study with a MFT flap, reporting 50 cases. Except Tremp and al. [START_REF] Tremp | The medial femoral trochlea flap with a monitor skin island. Report of two cases[END_REF], the best of these studies briefly describes the skin paddle mostly at the end of follow-up (Table 2) [START_REF] Doi | Free vascularized bone graft for nonunion of the scaphoid[END_REF][START_REF] Iorio | Cutaneous angiosome territory of the medial femoral condyle osteocutaneous flap[END_REF][START_REF] Tremp | The medial femoral trochlea flap with a monitor skin island. Report of two cases[END_REF][START_REF] Martin | Mandibular reconstruction using a free vascularised osteocutaneous flap from the internal condyle of the femur[END_REF][START_REF] Sakai | Free vascularized thin corticoperiosteal graft[END_REF][START_REF] Kobayashi | Use of vascularized corticoperiosteal flap from the femur for reconstruction of the orbit[END_REF][START_REF] Doi | Vascularized periosteal bone graft from the supracondylar region of the femur[END_REF][START_REF] Piñal | Vascularised corticoperiosteal grafts from the medial femoral condyle for difficult nonunions of the upper limb[END_REF][START_REF] Gaggl | Free microvascular transfer of segmental corticocancellous femur for reconstruction of the alveolar ridge[END_REF][START_REF] Pelzer | Osteo-periosteal-cutaneous flaps of the medial femoral condyle: a valuable modification for selected clinical situations[END_REF][START_REF] Elgammal | Vascularized medial femoral condyle graft for management of scaphoid non-union[END_REF]. None describe the surgical recovery in cases of vascular abnormality of the skin paddle and a possible delay of bone union in case of skin paddle necrosis. The paddle serves as an early beacon of the vascular anastomosis. This is one element of the immediate postoperative monitoring of the microsurgical anastomosis. It provides an indirect indication of the perfusion status of the flap of interest (the chondrocortical flap); any deviation must be carefully interpreted. Skin paddle vascular damage does not necessarily mean the osteochondral graft is avascular; the flap may end up being a valuable, non-vascularized, bone reconstruction graft. Indeed, small osteochondral grafts can heal without being vascularized by a pedicle [START_REF] Salon | Conservative surgery in Kienbock's disease with perilunatearthrosis : articular resurfacing using resected carpal bones[END_REF][START_REF] Mall | Cartilage defect of lunate facet of distal radius after fracture treated with osteochondral autograft from knee[END_REF][START_REF] Fowler | Osteochondral resurfacing with proximal row carpectomy : 8-year follow-up[END_REF]. Unfortunately, there is no data on this subject in the literature, particularly about MFC and MFT flaps.

If flap vascularization fails, without a skin paddle, the graft could behave like a conventional graft, with the risk of cartilage degradation and then osteoarthritis. In addition to the ability to monitor the flap, the skin paddle ensures the graft is vascularized, potentially allowing rescue, and therefore the graft's success. It serves an early means of evaluating union, before and as a supplement to bone union imaging.

The skin segment is mostly harvested as an ellipse, centered over the MFC flap.

Tremp et al. published a good description of two skin paddles associated with a MFT flap [START_REF] Tremp | The medial femoral trochlea flap with a monitor skin island. Report of two cases[END_REF]. Closure of the skin over the anastomosis without excessive tension is facilitated, preventing vessel compression by the periosteum and edema. Furthermore, the gain of skin area transferred seems ideally suited for post-radiation-induced fractures or chronic bone nonunion with a concomitant small skin defect or damaged and scarred skin. The paddle could easily cover the skin defect given the large rotation arc with thin and flexible skin.

A sensory skin flap using the saphenous nerve seems feasible in cases of bone and soft tissue loss around the hand.

Composite osteochondrocutaneous MFT flap consolidation and complications

Skin paddle vascularization can be compromised for several reasons; excessive pedicle traction, vessel plication area, caliber disparity and the proximity to a collateral vessel causing hemodynamic turbulence, appear to be related to the vessels' anastomosis thrombosis. Repositioning the pedicle after vessel thrombosis as a shortcut to reanastomosis in a healthy zone eliminated the risk of new thrombosis.

The literature reports an approximately 6% rate of major complications, with flap loss or unplanned reoperation in MFT and MFC flaps used for upper extremity reconstruction [START_REF] Kazmers | Upper and lower extremity reconstructive applications utilizing free flaps from the medial genicular arterial system: A systematic review[END_REF].

At the recipient site, the scaphoid and lunate bone union rate is 97.8% and 94%, respectively, with an average of 3.2 months without major complications [START_REF] Kazmers | Upper and lower extremity reconstructive applications utilizing free flaps from the medial genicular arterial system: A systematic review[END_REF]. In 4.4% of cases, there are heterotopic calcifications, not affecting wrist motion, due to the periosteum's strong osteogenic capacity. This can be avoided by meticulous dissection of the vascular bundle to the graft and by not leaving a periosteal sleeve under the vessels at the graft's margin [START_REF] Vedung | Ectopic bone formation after medial femoral condyle graft to scaphoid nonunion[END_REF].

Windhofer et al. [START_REF] Windhofer | Knee donor site morbidity following harvest of medial femoral trochlea osteochondral flaps for carpal reconstruction[END_REF] reported low donor site morbidity of the MFT flap in 45 patients.

No early postoperative donor site complications were found (infection, hematoma, iatrogenic fracture, wound dehiscence). At the last follow-up of 27 months, all patients had stable operated knee and patella, range of motion was equal to that of the contralateral side, and the functional outcome scores were very good. Patients reported an average of 56 postoperative painful days and 3 months before the knee returned to normal. One patient could not kneel down and 50% of the patients had physical therapy after surgery. There were no pathological changes on the X-rays and MRI taken on 35 patients; the MFT harvest site appeared completely filled and resurfaced with fibrocartilage [START_REF] Windhofer | Knee donor site morbidity following harvest of medial femoral trochlea osteochondral flaps for carpal reconstruction[END_REF].

Early clinical and radiological results

At a mean of 1 year postoperative, our three patients no longer had wrist pain (VAS = 0.5/10) and had no discomfort in their knee. While they still had restricted wrist mobility (68% flexion-extension range of the opposite side), but this is expected to improve over time. Loss of postoperative wrist mobility is probably caused partly by adhesions created by the flap's periosteum bulk. Therefore, to decrease periosteum volume, it seems useful to dissect the pedicle a little more or keep only one periosteal artery of the two. Also, considering the excellent bone union rates and the possibility of performing stable bone fixation, rehabilitation could be started earlier to improve postoperative ROM.

We reconstructed the scaphoid with an osteochondral graft larger than the original size of the proximal pole and tried to preserve most of the scapholunate ligament. This overstuffing is intended to make up for the lack of scapholunate ligament integrity and participate in preventing DISI [START_REF] Bürger | Vascularized medial femoral trochlea osteocartilaginous flap reconstruction of proximal pole scaphoid nonunions[END_REF][START_REF] Capito | Scaphoid overstuffing: the effects of the dimensions of scaphoid reconstruction on scapholunate alignment[END_REF][START_REF] Bürger | Vascularized medial femoral trochlea osteochondral flap reconstruction of advanced Kienbock disease[END_REF]. In our two cases, there was no misalignment of the first carpal row, which theoretically should protect wrist joint against the onset of osteoarthritis [START_REF] Bürger | Vascularized medial femoral trochlea osteocartilaginous flap reconstruction of proximal pole scaphoid nonunions[END_REF].

Conclusion

The MFT flap is indicated for conservative surgical treatment of small osteocartilaginous defects and nonunion. It is suitable in hand reconstruction with excellent bone union rates. Associating a skin paddle is often easy and has numerous benefits such as flap monitoring, preventing vessel compression, and replacing damaged skin without high donor site morbidity. The MFT flap with a cutaneous skin paddle may contribute to preventing carpal arthritis following wrist bone nonunion or necrosis in the presence of cartilage destruction.

Figures legends

Fig.

1 .

 1 Fig. 1. Wrist scaphoid nonunion in a 25-year-old man with avascular necrosis of the proximal pole (case 3) shown on MRI.

Fig. 2 .Fig. 3 .

 23 Fig. 2. Composite osteo-chondro-cutaneous graft with bipedicled skin paddle vascularization (case 3). DGA: descending geniculate artery; P: periosteum; OC GRAFT: osteochondral graft; DGA-CB: cutaneous branch from the DGA; SAB: saphenous artery branch; SP: skin paddle.

Fig. 4 .

 4 Fig.[START_REF] Kälicke | A new vascularized cartilage-bone-graft for scaphoid nonunion with avascular necrosis of the proximal pole. Description of a new type of surgical procedure[END_REF]. Postoperative CT 3 months after surgery (case 3). Note the radiographic appearance of step off between the lunate and reconstructed scaphoid due to the thickness of the trochlea cartilage layer[START_REF] Bürger | Vascularized medial femoral trochlea osteocartilaginous flap reconstruction of proximal pole scaphoid nonunions[END_REF].

Table titles Table 1 .

 titles1 Summary of preoperative, intraoperative and postoperative data from our series of 3 cases of MFT skin paddle

Table 2 .

 2 Published studies of MFC and MFT skin paddles

Table 1 .

 1 Summary of preoperative, intraoperative and postoperative data from our series of 3 cases of MFT skin paddle

		Case 1	Case 2	Case 3
	Age (years)	31	19	25
	Disease	Scaphoid nonunion	Kienböck	Scaphoid nonunion
	(classifications)	(Schoenberg 3, Alnot 4)	(Lichtman 3A)	(Schernberg 1, Alnot 2A)
	Smoker	No	Yes	Yes
	Dominant hand	Yes	Yes	No
	Preoperative
	Arc F -E (%/Clt)	60° -65° (84%/Clt)	50°-50° (74%/Clt)	75°-70° (97%/Clt)
	Arc RD -UD (%/Clt)	15°-50° (84%/Clt)	25°-35° (85%/Clt)	20°-40° (100%/Clt)
	Pronation-supination	90°-90° (100%/Clt)	60°-90° (83%/Clt)	90°-90° (100%/Clt)
	Grip strength (%/Clt)	25 Kg (39%/Clt)	26 Kg (52%/Clt)	40 Kg (80%/Clt)
	Pain on VAS	6	7	1
	Last follow-up	15 months	9 months	13 months
	Arc F -E (%/Clt)	50°-50° (68%/Clt)	60°-35° (70%/Clt)	50°-50° (68%/Clt)
	Arc RD -UD (%/Clt)	10°-44° (70%/Clt)	20°-30° (71%/Clt)	30°-10° (67%/Clt)
	Pronation-supination	90°-90° (100%/Clt)	90°-90° (100%/Clt)	90°-90° (100%/Clt)
	Grip strength (%/Clt)	35 Kg (55%/Clt)	40 Kg (74%/Clt)	38 Kg (86%/Clt)
	Pain on VAS	1	0	0
	Skin paddle
	-size	-2 x 2 cm	-5 x 3 cm	-6 x 3 cm
	-vascularization	-DGA-CB	-SAB	-DGA-CB and SAB
	MFT flap
	-size (length x wide x	-3 cm x 1 cm x 8 mm	-1.5 cm x 1.5 cm x 8 mm	-3 cm x 1 cm x 8 mm
	height)	-longitudinal and	-transverse periosteal	-longitudinal and
	-vascularization	transverse periosteal	branches	transverse periosteal
		branches		branches
	Anastomoses -arterial -venous	-end-to-side on radial artery -end-to-end on superficial vein	-T-shaped anastomosis on radial artery -end-to-end on superficial vein	-end-to-end on radiopalmar artery -end-to-end on superficial vein
	Relevant surgical	Preservation of dorsal	Preservation of dorsal	Detachment and reinsertion
	details	portion of scapholunate	scapholunate and	of radial part of
		ligament	lunotriquetral ligaments	scapholunate ligament
		-1 compression screw	-3 K-wires (1 trans-	-1 compression screw
	Bone fixation	-2 K-wires (1 trans-scapholunate and 1 trans-	scapholunate and 2 trans-triquetrolunate)	-2 K-wires (1 trans-scapholunate and 1 trans-
		scaphocapitate)		scaphocapitate)
		After 15 hrs., venous		After 16 hrs., arterial
	Skin paddle monitoring	thrombosis was found and repaired. Skin paddle was removed (damage and	No problems	thrombosis was found and repaired (caliber disparity). Skin paddle was preserved.
		obvious ecchymosis).
	Union time	12 weeks	10 weeks	8 weeks
	Time to restart	1.5 months	3 months	2 months
	walking
	Knee range of	0°-150°	0°-165°	0°-155°
	motion (%/Clt)	(94%)	(100%)	(97%)

Funding statement

The authors received no financial support for the research, authorship, and/or publication of this article.

Disclosure of interest

The authors declare that they have no competing interest.

Schernberg: Schernberg classification [START_REF] Schernberg | Classification of fractures of the carpal scaphoid. An anatomoradiologic study of characteristics[END_REF]; Alnot: Alnot classification [START_REF] Alnot | Fractures and non-unions of the proximal pole of the carpal scaphoid bone. Internal fixation by a proximal to distal screw[END_REF]; Lichtman: Lichtman classification [START_REF] Lichtman | Staging and its use in the determination of treatment modalities for Kienbock's disease[END_REF]; preop: pre-operative; postop: post-operative; VAS: visual analog scale; Clt: contralateral; F: flexion; E: extension; RD: radial deviation; UD: ulnar deviation; Grip: hand grip; Kg: kilogram; cm: centimeter; mm: millimeter


M Brumpt

S Alilet

Aubry

T Ceri

A Podda

J Behr

E Brumpt

M Alilet

Posterior interosseous nerve of the elbow at the arcade of Frohse: ultrasound appearance in asymptomatic subjects

Keywords: Ultrasound, Arcade of Frohse, Posterior inter-osseous nerve syndrome, Supinator muscle, Anatomic studies

des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

Introduction

The posterior interosseous nerve (PIN) of the elbow (also called deep branch of radial nerve), is a terminal motor branch of the radial nerve, which is itself a branch of the posterior cord of the brachial plexus with contributions from fifth to eighth cervical nerve roots (distal nerve territory). PIN syndrome is an uncommon peripheral neuropathy [START_REF] Hustead | Nontraumatic, progressive paralysis of the deep radial (posterior interosseous) nerve[END_REF] during which the PIN is usually compressed as it passes between the two heads of the supinator muscle, beneath a fibrous band called the arcade of Frohse. Indeed, this compression site also called the supinator arch, has been described by Frohse and Fränkel and corresponds to a normal fibromuscular structure. Other PIN entrapment sites such as medial edge of the extensor carpi radialis brevis, radial recurrent blood vessels, and inferior margin of the superficial layer of the supinator muscle have been described [START_REF] Chang | Entrapment neuropathy of the posterior interosseous nerve. a complication of rheumatoid arthritis[END_REF][START_REF] Riffaud | Anatomic bases for the compression and neurolysis of the deep branch of the radial nerve in the radial tunnel[END_REF]. PIN syndrome, alternatively named radial tunnel syndrome or supinator syndrome, is clinically characterized by a loss of strength during fingers extension and amyotrophy of posterior muscles of the forearm with the exception of brachioradialis and extensor carpi radialis longus muscles [START_REF] Naam | Radial tunnel syndrome[END_REF]. A deaf pain is generally felt in the dorsoradial aspect of proximal forearm. A partial infringement can affect only the extension of fourth and fifth fingers, which may suggest an ulnar nerve impairment. There is no associated sensory symptom [START_REF] Naam | Radial tunnel syndrome[END_REF]. The diagnosis of PIN syndrome is usually confirmed by a multimodal approach, which includes electromyography and ultrasound or magnetic resonance imaging (MRI).

During the past decade, improvements of high-resolution ultrasound allowed direct visualisation of small nerves [START_REF] Créteur | Sonography of peripheral nerves -First part : upper limb[END_REF] and detection of their shape and echostructure changes as well as extrinsic causes of compression. Ultrasound signs consistent with PIN syndrome are an abnormal swelling of the nerve and an abrupt caliber change at the entrapment site [START_REF] Brasseur | Sonography evaluation of nerve compression in the upper limb[END_REF].

However, in daily practice, a shrinkage of the PIN as it passes beneath the arcade of Frohse is sometimes observed in asymptomatic patients, rising the interest of measuring its diameter.

Studies reporting the role of ultrasound in the diagnosis of PIN syndrome are scarce [START_REF] Bodner | Ultrasonographic appearance of supinator syndrome[END_REF][START_REF] Djurdjevic | High resolution ultrasound in posterior interosseous nerve syndrome[END_REF][START_REF] Kim | Ultrasonographic findings of posterior interosseous nerve syndrome[END_REF][START_REF] Dong | Posterior interosseous nerve of the elbow: normal appearances simulating entrapment[END_REF].

Accordingly, it appears necessary to confirm and determine the normal values of the anteroposterior (AP) diameter of the PIN at this level in order to avoid overdiagnosis of PIN entrapment.

The purpose of this study was to assess the normal values of the AP diameter of the PIN of the elbow as it passes beneath the arcade of Frohse and to search for PIN-diameter differences between the upstream, entry point and downstream of the arcade.

Materials and Methods

Patients

The study was approved by the institutional review board. All patients gave written permission for anonymized use of their medical data for scientific purposes before the ultrasound examination. They were referred by their physician for elbow ultrasound examination and prospectively included between march 2017 and september 2017. Inclusion criteria included an age > 18 years and acceptance for written signed consent. Exclusion criteria included prior elbow surgery and/or any symptom of PIN syndrome.

A total of 30 consecutive patients were included. There were 15 men and 15 women with a mean age of 30.2 ± 5.31 (SD) years (range: 26 -43 years) (Fig. 1). One hundred percent (15/15) of men were right-handers. Fifty-three percent (8/15) of women were right-handers versus 47% (7/15) left-handers women.

Ultrasound protocol

All ultrasound examinations were bilateral according to a standardized protocol using a RS80A Samsung device (Samsung Medison ® ,) equipped with a 18-MhZ superficial linear transducer. Examinations were performed by one radiologist (A.P.) with 4 years of experience in musculoskeletal ultrasound.

Patients were positioned in front of the radiologist, elbow extended in supination on the gurney. The examination began with grayscale B mode ultrasound study of the radial nerve and its division at the elbow fold by sweeping the probe from top to bottom in transverse section. The PIN was first identified on axial images, then longitudinally analysed by turning the probe 90°. Images analysis were done in consensus by two radiologists (A.P. and T.C) to ensure the accuracy of the measurements by using VuePACS ® software (Version 12.1.5.1156, Carestream,). On both arms, the AP diameter of the PIN was measured at three locations in long axis at three different locations including the entry point of the arcade, 5-mm upstream and 5-mm downstream the arcade of Frohse (Fig. 2). The nerve echostructure was also analyzed in terms of echogenicity and fasciculation.

Anatomic study

An anatomic dissection of a 80-year-old woman was performed for anatomoradiological correlation. The upper extremity was dissected in the long axis while limb was maintained in pronation and 30° flexion. Longitudinally from 5cm atop the radio-humeral joint to the middle of the forearm, the fascia of brachio-radialis muscle was dissected and muscle reclined outside, so that direct visualisation of radial nerve between brachio-radialis and brachialis muscles was possible (Fig. 3). Its deep terminal branch, the NIP, crosses dorso-lateraly beneath the arcade of Frohse and enters in the supinator muscle. AP diameter of the NIP was then measured with a micrometer at the same sites on both sides of the arcade of Frohse.

Statistical analysis

The absolute variation in PIN diameter was calculated as the difference between two diameters as follows : ∆ = D1 -D2 (mm). The relative variation (%) in PIN diameter was calculated using the following equation (E1):

E1 % = (D1 -D2) × 100 / D1
Continuous variables were expressed as mean ± standard deviation (SD) and range. A P value < 0.05 was considered statistically significant. Differences in AP diameter of PIN between the three locations were searched for using the paired t-test. The influence of gender and dominance on AP diameter was studied by univariate analysis. Statistical analysis was performed using SAS for Windows version 9.3 (SAS Institute Inc.).

Results

Morphologically, the PIN appeared hypoechoic and monofasciculated in all patients. The mean AP diameters of the PIN on ultrasound were 0.83 ± 0.21 (SD) mm (range: 0.43-1.31 mm), 0.6 ± 0.17 (SD) mm (range: 0.29-1.16 mm) and 0.49 ± 0.13 (SD) mm (range: 0.26-0.86mm) at 5-mm upstream, entry point of the arcade and 5-mm downstream the arcade of Frohse, respectively.

Significant drops in PIN diameter were found between upstream and the arcade (-0.23 mm; 27%; P<0.001), between the arcade and downstream (-0.11 mm; 17%; P<0.001), and between upstream and downstream the arcade (-0.34 mm; 40%; P<0.001).

There were no significant differences in PIN diameter between right and left sides upstream (P=0.257), at the arcade (P=0.45) and downstream (P=0.11). There were no significant effects of the dominance on PIN diameter upstream (P = 0.951), at the arcade (P = 0.941) and downstream ( P = 0.152). There were no significant differences in PIN diameter between men and women (P = 0.417 upstream, P = 0.779 at the arcade and P = 0.369 downstream).

Changes in PIN diameter were also observed macroscopically during anatomic dissection. AP diameter was 0.7 mm upstream, and 0.5 mm at the entry point and downstream the arcade.

Discussion

Our study confirms the physiological drop in AP diameter of PIN when it passes the arcade of Frohse diameter in asymptomatic patients. Our results are consistent with those of two previously published works on this matter (Table 1). Raeburn et al. measured AP and lateral diameters of the PIN on short axis ultrasound images only at two points, 5 mm downstream and 5 mm upstream the arch. They found a significant difference in AP proximal diameter (1.1 mm proximal vs. 0.85 mm distal; P < 0.001) and in lateral diameter (2.6 mm proximal vs.

3.4 mm distal; P < 0.001) [START_REF] Raeburn | Cross-sectional sonographic assessment of the posterior interosseous nerve[END_REF]. There was no difference concerning mean cross-sectionnal area (CSA), measured 0.022 cm² proximally, and 0.023 cm² distally [START_REF] Raeburn | Cross-sectional sonographic assessment of the posterior interosseous nerve[END_REF]. Kim et al. showed a reduction of the AP diameter of the PIN distal to the arcade of Frohse when compared to the measurements at the arcade and proximal to the arcade [START_REF] Kim | Ultrasonographic findings of posterior interosseous nerve syndrome[END_REF]. The AP diameter was 1.0 mm 1 cm proximally, 1.2 mm at the arcade and 0.6 mm 1 cm distally (P < 0.0001). The measure of mean CSA was concordant with the other study, the PIN measured 0.016 cm² proximally, 0.019 cm² at the arcade and 0.018 cm² distally (P = 0.59).

Prospective PIN assessment of AP diameter in long axis at three points makes it possible to be more precise. Indeed, PIN flattening is more important at the entry point of the arcade of Frohse, but continues slowly downstream. The results of anatomic studies corroborate ultrasound results [START_REF] Spinner | Posterior interosseous nerve compression due to an enlarged bicipital bursa confirmed by MRI[END_REF][START_REF] Prasartritha | A study of the posterior interosseous nerve (PIN) and the radial tunnel in 30 Thai cadavers[END_REF]. Spinner et al. [START_REF] Spinner | Posterior interosseous nerve compression due to an enlarged bicipital bursa confirmed by MRI[END_REF] and Prasarthrita and al. [13 dissected upper limbs and described 2 types of arcade of Frohse. One is of membranous type (43%, slim, mobilizable with tweezers) and the other of fibrous type (57%, thick and not mobilizable).

Spinner et al. found fibrous arch in 30% of adults and none in full-term fetuses [START_REF] Spinner | Posterior interosseous nerve compression due to an enlarged bicipital bursa confirmed by MRI[END_REF] and raised the hypothesis that the fibrous arcade was probably secondary acquired in response to repeated rotary movement of the forearm. In all 20 patients with unilateral PIN syndrome operated in Lister's et al. series, the arcade was thickened and fibrous, which also would be a predisposing factor to entrapment [START_REF] Lister | The radial tunnel syndrome[END_REF]. Unfortunately, the difference between membranous and fibrous arcade is only visible during surgery or anatomic dissection, but not with ultrasound. In the 264 cases reported by Quignon and al., the two most frequent etiologies of PIN syndrome were ganglion cyst (19.7%) and a musculo-aponevrotic fibrotic band at the arcade of Frohse (16.7%) [START_REF] Quignon | Posterior interosseous nerve palsy: a series of 18 cases and literature review[END_REF]. Iatrogeny is the cause of 10% of PIN syndromes, most frequently after a repair surgery of the distal tendon of biceps brachii muscle. Quignon and al.

also showed a prevalence of manual profession [START_REF] Quignon | Posterior interosseous nerve palsy: a series of 18 cases and literature review[END_REF], consistent with Spinner et al. hypothesis that repeated mechanical solicitation and anatomic predisposition can lead at an entrapment site.

In our study, dominance has no significant influence on the PIN at the arcade of Frohse. The unsignificant lower diameter at the right side downstream point compared to left side may be linked to inter-individual polymorphism or to the predominance of right-handers in our population (23/30; 77%). There was also no significant effect of gender on the PIN diameter. It contradicts previous results which found CSA of females both proximal and distal to the arcade of Frohse that were statistically lower than that of males on the left side (P < 0.03) [START_REF] Raeburn | Cross-sectional sonographic assessment of the posterior interosseous nerve[END_REF]. These previous results remain unexplained and seem to need to be questioned. The mean AP diameter immediatly proximal to the arcade was significantly greater in patients with PIN syndrome (2 mm) than in volunteers (1.1 mm) [START_REF] Djurdjevic | High resolution ultrasound in posterior interosseous nerve syndrome[END_REF]. There was no overlap between minimum AP pathologic diameter (1.6 mm) and maximum physiological one (1.5 mm). Loss of fascicular structure and increased hypoechogenicity was observed in all patients when PIN enlarged. Similar results were reported by Kim et al. [START_REF] Kim | Ultrasonographic findings of posterior interosseous nerve syndrome[END_REF] These reserchers found a AP diameter of 1.79 mm proximally and 1.02 mm in the controlateral upper limb (P = 0.003), but only 4/10 patients had a PIN syndrome caused by the arcade of Frohse [START_REF] Kim | Ultrasonographic findings of posterior interosseous nerve syndrome[END_REF]. Bodner and al.

described ultrasonography appearence of 4 patients with supinator syndrome [START_REF] Bodner | Ultrasonographic appearance of supinator syndrome[END_REF]. They showed that the nerve was enlarged (mean transverse diameter = 4.2 mm; AP diameter = 3.3 mm) and appeared hypoechoic in association with neovascularization. On the opposite, volunteers had a mean transverse diameter equal to 2.14 mm and an AP diameter equal to 1.31 mm. But these researchers did not compare patients to volunteers nor to the controlateral side [START_REF] Bodner | Ultrasonographic appearance of supinator syndrome[END_REF].

One limitation of our study is that a single experienced radiologist made ultrasound because it may sometimes be difficult to obtain a perfect longitudinal image of this millimetric nervous structure. We may imagine that an oblique image would lead to measurement bias. As a consequence, no reproducibility study of the measurements was made. The rarity of this syndrome made it impossible to compare patients with PIN syndrome to healthy patients in our center, unlike other studies [START_REF] Bodner | Ultrasonographic appearance of supinator syndrome[END_REF][START_REF] Djurdjevic | High resolution ultrasound in posterior interosseous nerve syndrome[END_REF][START_REF] Kim | Ultrasonographic findings of posterior interosseous nerve syndrome[END_REF].

As a conclusion, a disparity in AP diameter of the PIN in the arcade of Frohse is

Figures and tables

  The current role of ultrasound is to provide arguments that corroborate the diagnosis of PIN syndrome, and to seach for possible cause of extrinsic compression. Ultrasound findings in PIN syndrome are an abnormal swelling of the nerve and an abrupt change in its diameter at the entrapment site. A few studies ave assessed the role of ultrasound in the diagnosis of PIN syndrome[START_REF] Bodner | Ultrasonographic appearance of supinator syndrome[END_REF][START_REF] Djurdjevic | High resolution ultrasound in posterior interosseous nerve syndrome[END_REF][START_REF] Kim | Ultrasonographic findings of posterior interosseous nerve syndrome[END_REF][START_REF] Nakamichi | Ultrasonographic findings in isolated neuritis of the posterior interosseous nerve: comparison with normal findings[END_REF]. Djurdjevic et al. compared 15 patients with PIN syndrome confirmed by neurological, clinical examination and electromyography to 20 asymptomatic volunteers[START_REF] Djurdjevic | High resolution ultrasound in posterior interosseous nerve syndrome[END_REF].

Figure 1 .

 1 Figure 1. Flowchart of the study population (n=30).

Figure 2 .

 2 Figure 2. 26-year-old man with no clinical sign of posterior interosseous nerve (PIN) syndrome. B-mode ultrasound longitudinal image shows posterior interosseous nerve as an hypoechoic linear structure that passes between superficial (SS) and deep (DS) heads of the supinator muscle. The antero-posterior diameter of the nerve has been measured at the arcade of Frohse (white arrowheads), then 5 mm upstream and downstream (black arrowheads). BR : brachio-radialis muscle.

Figure 3 .

 3 Figure 3. Anatomic view. The radial nerve (white arrow) divides into a superficial branch (black arrow) and a deep branch, the posterior interosseous nerve (white arrowhead). The latter goes in depth to the arcade of Frohse (black arrowhead), and passes under the superficial head of the supinator muscle (SS). Brachio-radialis muscle (BR) has been reclined.

Table 1 .

 1 Comparison of mean AP diameter of the NIP between our study and previous studies.

physiological and should not be wrongly taken for an entrapment sign when seen in isolation.

Today, correlation to clinical symptoms, electromyography and an ultrasound comparative study of contralateral PIN are still required in symptomatic patients to confirm this diagnosis.

Conflict of interest

The authors have no conflicts of interest to disclose.