Philippe Decq
email: philippe.decq@aphp.fr

David Brauge

Alain Calmat

Helene Cassoudesalle

Patrick Dehail

François Deroche

Alain Frey

Marc Julia

Philippe Le Van

Jehan Lecocq

Criteres Diagnostiques

Cliniques De

L A Commotion

Cerebrale En

Pratique Sportive

: Vers

Claude Mekies

André Monroche

Jérémie Pariente

Romain Rousseau

Benoit Vesselle

Gilles Einsargueix

Philippe Pr

Decq

Mme

Diagnosis clinical criteria of sport related concussion: Toward an operational criteria definition in France

Keywords:

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

Introduction

An expert working group was set up at the initiative of the Ministry of Sports with the objective of harmonizing the management of sport related concussion (SRC) in France. The first step was to establish common diagnostic criteria for this pathology whatever the sport performed, preamble to the establishment of shared management recommendations.

Diagnosis of SRC requires to review the problem of its definition. The term concussion is generally used for mild traumatic brain injury (mTBI) occurring during sports, while in another context, mTBI is preferred. There is still a debate about whether these terms are synonymous or not [START_REF] Mccrory | What is the definition of sports-related concussion: a systematic review[END_REF]. The conditions of the diagnosis are in fact different between sports and other situations. In sports, brain injury is observed during practice and its diagnosis performed usually immediately or the following hours after practice by healthcare professionals in Elite sports or non-healthcare professionals in community level which represents the majority of the cases. At this stage arises the problem of the immediate return to play for the least severe forms which are the most frequent and do not justify emergency procedures and transport to the nearest hospital. Conversely, in other situations of traumatic brain injury, the diagnosis is performed in emergency departments. History relies on what the subject reports, or its relative or first aid. At this stage, the diagnosis is usually of little doubt. The medical attention is rather focused on the screening of potential haemorrhage complications who will require a brain CT scanner to diagnose. The other fundamental difference is that in sports, the event that generates a concussion is observed and the athlete immediately assessed while on arrival at the hospital, it is only reported and the subject is examined several hours after the event. The direct observation of the event and its immediate consequences allows us to describe a precise semiology, the recognition of which leads to an immediate diagnosis, especially if the people present on and around the field are aware of the phenomenon. This may explain why the definition and diagnostic criteria for concussion in sports bring functional complaints to the fore, whereas in hospital, the criteria are rather established on signs of more severe intensity (amnesia, disorientation of several hours…). In both cases however, it is a brain injury that differs perhaps in its severity but requires the same diagnostic clinical criteria to be identified. It seems therefore reasonable to consider the terms concussion and mild brain injury as synonymous with the same diagnostic clinical criteria without considering imaging arguments. It is important to put an end to approximations and to establish reliable and reproducible criteria for diagnosing this first level of severity of brain traumatic injury. Based on this principle, a definition summarizing the definitions of each of these entities (mild brain injury and concussion) is proposed followed by a definition of the clinical criteria for an operational diagnosis of this pathology whatever its context and therefore applicable whatever the sports considered. In the remainder of this document, only the term concussion will be used.

Definition

The commonly used definition of SRC is that established at successive international consensus conferences on this topic, the latest one being held in Berlin in October 2016 [START_REF] Mccrory | 5th International Conference on Concussion in Sport (Berlin)[END_REF]. The most commonly accepted definition of mTBI is that of the American Congress of Rehabilitation Medicine (ACMR) in 1993 [START_REF]Definition of mild traumatic brain injury developed by the Mild Traumatic Brain Injury Committee of the Head Injury Interdisciplinary Special Interest Group of the American Congress of Rehabilitation Medicine[END_REF] as well as that of the WHO Collaborating Center Task Force on Mild Traumatic Brain Injury in 2004 [START_REF] Carroll | WHO Collaborating Centre Task Force on Mild Traumatic Brain Injury. Methodological issues and research recommendations for mild traumatic brain injury: the WHO Collaborating Centre Task Force on Mild Traumatic Brain Injury[END_REF]. Both definitions of mTBI were usefully discussed and weighted, including the interpretation of the diagnostic criteria [START_REF] Levin | Diagnosis, prognosis, and clinical management of mild traumatic brain injury[END_REF][START_REF] Mayer | The spectrum of mild traumatic brain injury[END_REF][START_REF] Menon | Position statement: definition of traumatic brain injury[END_REF][START_REF] Raftery | It is time to give concussion an operational definition: a 3-step process to diagnose (or rule out) concussion within 48 h of injury: World Rugby guideline[END_REF][START_REF] Ruff | NAN Policy and Planning Committee Recommendations for diagnosing a mild traumatic brain injury: a National Academy of Neuropsychology education paper[END_REF]. These three definitions (figure 1) present very similar characteristics which have been been included and thus grouped together in the same definition in 4 points for SRC:

Concussion is a brain injury: 1) caused by a direct or indirect transmission of kinetic energy to the head 2) resulting for an immediate and transient dysfunction of the brain characterized by at least one of the following disorders:

• Brief loss of consciousness (this is a mild brain injury characterized by a Glasgow Coma Scale score greater than 12 to 30 minutes of the event).

• Loss of memory for events immediately before or after the injury, lasting less than 24 hours from the trauma • Altered mental status (confusion, disorientation, unusual or inappropriate behavior) • Neurological signs (convulsions, postural tonic crisis, ataxia, visual disturbance ...) 3) Possibly followed by one or more functional complaints (concussion syndrome) of variable intensity that are of immediate onset but sometimes delayed in the minutes or hours following the injury, with a spontaneous resolution in less than 2 weeks in adults, and in less than a month in the child.

4) The signs and symptoms are not explained by another cause

This definition brings together the criteria usually used in daily hospital practice, based essentially on clinical signs such as amnesia, loss of consciousness or signs of cognitive impairment, with those used in sports where symptoms (the concussion syndrome) are highlighted. As it is the same type of trauma occurring in different situations, the objective of this work was to group these criteria equally in a single definition in order to take advantage of the clinical and scientific data acquired in these different contexts. Hospital practice is essentially focused on screening for complications by performing or not performing a brain CT-scan, while sports allows observation of immediate signs or symptoms never seen in hospital. For instance, the criteria retained for the realization of a scanner help to define the criteria for requesting medical advice without delay during sports practice and conversely, the observation in sports of the immediate clinical semiology improve the clinical criteria retained for the diagnosis of mild brain trauma in hospital practice. This definition emphasizes that concussion is related to the transmission of kinetic energy. Indeed, the head connected by the cervical spine to the thorax, never remains motionless. In direct impacts, the head may initially be in motion and decelerate upon impact, or immobile and accelerate. In the absence of a direct impact (indirect transmission in the case of whiplash), the inertial effects secondary to the rapid displacement of the head are at the origin of the brain injury. Kinetic energy is more accurate than "biomechanical" or "external" force sometimes used [START_REF]Definition of mild traumatic brain injury developed by the Mild Traumatic Brain Injury Committee of the Head Injury Interdisciplinary Special Interest Group of the American Congress of Rehabilitation Medicine[END_REF][START_REF] Carroll | WHO Collaborating Centre Task Force on Mild Traumatic Brain Injury. Methodological issues and research recommendations for mild traumatic brain injury: the WHO Collaborating Centre Task Force on Mild Traumatic Brain Injury[END_REF][START_REF] Menon | Position statement: definition of traumatic brain injury[END_REF] and thus allow us to exclude injury by penetrating agents which constitute another traumatic entity even if in these cases there is also a transmission of kinetic energy to the head that should not be neglected. This definition also adds the concussion syndrome as a potential diagnostic criterion with the difficulty that it may be delayed and could be explained by another cause, in particular a psychological reaction to physical or emotional stress (which may be nevertheless associated with concussion).

At least and for practical reasons, imaging is not part of this definition which remains clinical. Imaging (CT scanner) is needed to screen for potential hemorrhagic complications that transform concussions into complicated concussions [START_REF] Stiell | The Canadian CT head rule for patients with minor injury[END_REF]. Imaging is not performed systematically (only for clinical signs of gravity), and therefore can't constitute as such a diagnostic criterion of concussion. Signs and symptoms of concussion are transient and resolve in less than 15 days in adults and less than one month in children [START_REF] Levin | Diagnosis, prognosis, and clinical management of mild traumatic brain injury[END_REF]. Beyond these delays, it is a persistent concussion syndrome or posttraumatic syndrome [START_REF] Cassidy | Systematic review of self-reported prognosis in adults after mild traumatic brain injury: results of the International Collaboration on Mild Traumatic Brain Injury Prognosis[END_REF]. Numerous studies have shown that predictive factors for the persistence of signs and symptoms more than a month after mild traumatic brain injury were primarily preexisting neuropsychiatric disorders and that this syndrome do not consistently differ from signs and symptoms sometimes observed in patients with acute injury to a body area other than the head (12).

Clinical diagnostic criteria

The concussion clinical diagnostic criteria proposed are based on the 4 points of the definition (figures 2a and 2b): 3.1. Concussion is an injury caused by the direct or indirect transmission of kinetic energy to the head

The transmission of a kinetic energy to the head can be confirmed by the followings:

• The direct transmission of mechanical energy to the head can be observed in a collision with the location and the nature of the impact to the head precisely described. The use of video in sport, especially slow motion, helps to accurately identify the impact. The trace of impact to the head or face (wound, hematoma) could secondarily be observed by physical examination • The indirect transmission to the head can be observed with a rapid and significant head and neck movements or acceleration-deceleration displacements (commonly known as whiplash) • The transmission of energy to the head can sometimes be strongly suspected with a subject immediately carrying one or both hands to the head after a collision • The subject itself and/or its surrounding could also spontaneously report a direct or indirect impact to the head

The observation of the transmission of a kinetic energy to the head is not per se a clinical diagnosis criterion of concussion but it is essential for the interpretation of the signs and symptoms leading to its diagnosis. It is important to emphasize at this point that such a finding leads not only to look for a concussion but also for an associated cervical trauma.

Concussion results in immediate and transient dysfunction of the brain

The dysfunction is immediate with no delay between the event and the disorders occurrence, underlying the importance of being present to be able to observe them. Otherwise, they will be reported with more uncertainty. This point is important as these disorders are transient with a duration ranging from a few seconds to minutes in mild forms. The immediate and transient dysfunction of the brain is characterized by at least one of the following disorders:

3.2.1. Loss of consciousness: The loss of consciousness (LOC) is defined as the loss of awareness of the self and the environment. The subject has his eyes closed, does not execute any simple command and is motionless apart from reflex movements. Its observation confirms the diagnosis of concussion. Contrary to popular belief, LOC is not mandatory for the diagnosis of concussion and is only found in the most severe forms, 15 to 20% of SRC (2). In addition, LOC is brief (a few seconds, very often less than a minute) so that the subject is often conscious and able again to communicate with the first aid. When LOC is secondarily reported by the subject or witnesses, it is often misinterpreted with stupor or even anterograde amnesia and therefore its duration cannot be truly evaluated. Their brevity and difficult recognition by a non-healthcare professional explains why he is important to try to detect observable signs of brief LOC at impact during practice. The clinical diagnostic criterion of LOC can be retained if:

• LOC was noted during a physical examination with a subject who keeps his eyes closed, makes no voluntary movement apart from possible reflex movements and do not execute movement at order (such as shaking hands or opening eyes).

• A complete loss of muscle tone at impact has been observed. This loss of muscle tone can take many forms -Body fall without reflex protection movements: Most often the body falls forward, the face abruptly striking the ground. The subject may also fall backwards. In the latter case, there is no movement of the upper limbs to protect against the fall and the head hits the ground violently.

-Cervical hypotonia characterized by one or more uncontrolled movements of the neck before contact of the head with the ground. Slow motion video analysis is valuable for its detection.

-Sudden fall in sitting position (usually associated with cervical hypotonia) without any delay between impact and fall. The body collapses from the impact in a sitting position and the head does not hit the ground. Better appreciated during video analysis in real speed than in slow motion.

-Projection of the upper limbs from the impact, above the head with hands violently hitting the ground. It is a shoulders hypotonia with no longer control of the upper limbs movement.

• A prolonged immobility on the ground of the subject from the fall was observed.

Immediately from the impact the subject remains totally immobile on the ground for a long time without any voluntary movement (except reflex movements). There is no formal indication of the duration of this immobility but in sport practice, an expert consensus retains a delay of more than 5 seconds, more precisely stated if the video is available. In the context of kinetic energy transmission to the head, complete and prolonged immobility is a good criterion for LOC if no other reason explains it (see point 4 below).

Finally, it is important to stress that concussion is a mild brain injury characterized by a Glasgow- Coma-Scale (GCS) score greater than 12 at 30 minutes from the event from the event 3.2.2. Loss of the memory of the facts preceding or following the trauma, remaining less than 24 hours: This criterion is retained if it is observed that the subject does not remember the facts just after the event (anterograde amnesia) and / or facts that immediately preceded it (retrograde amnesia). It will be necessary to review the subject after 24 hours to ensure the disappearance of memory disorders as they must not exceed 24 hours by definition. In sports, the observed memory troubles last usually only few minutes. It is important to specify that the diagnosis of this criterion depends on the delay from the injury and the way it is investigated: the subject can indeed reconstruct the event according to witnesses or video if available. Questions about the description of the event should be avoided in favor of more factual questions: what is the first memory since or before the event? Behavioral or emotional changes must also not be neglected that can generate authentic amnesic states (9).

Mental status impairment:

The subject does not seem to be in his normal state and has unusual disorders suggestive of brain dysfunction that can take on many aspects. The diagnostic criterion of mental status disorder is retained if the subject:

• Is confused, obsessed: his remarks are unsuited to the situation, he repeatedly repeats the same question (s)

• is dazed, stunned: his gaze is haggard and / or wandering, seemingly not paying attention to the examiner and looking around him for familiar anchor points to reconnect with the present reality

• is disoriented, not fully recognizing his environment and / or the time course of his actions. In practice, this disorder can be assessed by a general orientation score in five simple items, a wrong answer confirming this disorder (figure 3). In team sports practice, the Maddock score is recommended [START_REF] Maddocks | The assessment of orientation following concussion in athletes[END_REF] • Has unusual behavior: the subject is aggressive, irritable, uninhibited or emotional (crying). In sport practice his behavior is abnormal with inappropriate actions in response to a given situation (incorrect or faulty positioning or aptitude to sport practice ...). the subject may spontaneously report being more irritable or nervous

Neurological signs

The neurological signs constituting diagnostic criteria for concussion are as follows (these are the usual signs, the most frequently observed, without pretending to be exhaustive):

• Seizures: brief and repeated involuntary rhythmic muscle contractions, involving one or more limbs, or even the trunk, sometimes associated with abnormal eye movements, are also called concussive seizures. Exceptional but impressive, they hare not related to prognosis or severity. [START_REF] Cassidy | Systematic review of self-reported prognosis in adults after mild traumatic brain injury: results of the International Collaboration on Mild Traumatic Brain Injury Prognosis[END_REF][START_REF] Mccrory | Concussive convulsions. Incidence in sport and treatment recommendations[END_REF] • Postural tonic crisis: Extension of a limb remaining suspended in the air for a few moments before falling back to the ground, which can be accompanied by a tonic neck rotation. It mainly concerns the upper limb or limbs but sometimes also the lower limb or limbs. (15)

• Balance Disorders (Ataxia): Inability to coordinate voluntary muscular movements. Typically, include difficulty standing or standing up from the floor, standing instability that may require support, abnormal walking that may require assistance. The diagnosis of ataxia criterion is retained if the subject: Starts to get up and fall back to the ground often without protection Gets up in several stages by looking at each step his equilibrium. The movement to get up seems "jerky" but is "continuous». Sometimes the subject crawls on the ground before he can get up. it is not a subject that is slow to get up and observes stops between each step from the lying to the upright position.

Has difficulty standing steadily the first second and is forced to step forward or backward to stabilize. This sign is often very transient, but sometimes obvious: the subject seems unable to stand without being supported by one or, most often, two people. In sport practice, this disorder is not to be confused with the habit of the healthcare team accompanying the athlete's exit by surrounding him with an arm.

Has an abnormal initial walk: he begins to walk, appearing to be drawn forward, running after his center of gravity, or, seeming to be drawn backwards, walking on his heels. The instability of walking can also cause a leg crossing or a walk swerving on the side The subject may complain of balance difficulties Visual troubles: The subject complains of a dazzling sensation on impact, a blurred vision, an abnormally colored vision, an amputated field of view, or even a tunnel vision.

He can also complain about double vision. Examination may reveal pupillary abnormalities (anisocoria) or nystagmus in the lateral gaze. 3.3. The cerebral dysfunction is possibly followed by one or more functional complaints (concussion syndrome) of variable intensity that are of immediate onset but sometimes delayed in the minutes or hours following the injury, with a spontaneous resolution in less than 2 weeks in adults, and in less than a month in the child.

Concussion syndrome includes non-specific symptoms classically divided into 4 areas: somatic: headache, dizziness, nausea, vomiting, disturbances of balance and asthenia (fatigue) cognitive: difficulty of concentration, memory disorders, feeling of being slow down, in a fog, confusion, disorientation ... emotional: irritability, emotional lability, anxiety, depressed mood relating to sleep: difficulty falling asleep, drowsiness. The most common symptoms are headache, dizziness, visual and balance troubles, cognitive slowdown, and drowsiness and fatigue [START_REF] Davis | Head injury: triage, assessment, investigation and early management of head injury in children, young people and adults (NICE guideline CG 176)[END_REF]. Although these symptoms are not specific, their unusual presence following the transmission of a kinetic energy to the head, unexplained by another cause, constitutes a diagnostic criterion for concussion. If the subject presents only one symptom without any other criterion, the diagnostic value of the presence of this symptom must be carefully questioned with regard to the antecedents of the subject and the nature of the event.

The collection of symptoms can be usefully achieved by questionnaires most often used to collect symptoms in the day(s) following the traumatic event. The most used are the SCAT (Sport Concussion Assessment Tool) symptom check-list (2) (Figure 4). The Rivermead Post-Concussion Symptoms Questionnaire have been developed more specifically to detect unfavourable evolution (persistant syndrome) (17) (figure 5).

These symptoms not explained by another cause (see below), grouped in a simplified scale into 8 categories for pragmatic reasons, constitute, by the presence of at least one of them immediately after the traumatic event, a diagnostic criterion for concussion. Appearing a few hours apart from the event, or even after a night of rest, they can still constitute a diagnostic criterion for so-called evolutive or delayed clinical expression forms. Nevertheless, if they are isolated (no other signs of brain dysfunction), the clinical interpretation of their presence for diagnostic purposes must be very carefully questioned, looking for all the other reasons that may explain their presence. The simplified symptom checklist is the following:

1. Pressure in head and / or diffuse headache (excluding localized pain at the point of impact) 2. Vertigo and / or dizziness 3. Fatigue and / or unusual low energy 4. Feeling slow down and / or drowsiness 5. Nausea and / or vomiting 6. Sensitivity to light and / or to noise 7. Does not feel well and / or in the fog 8. Difficulty concentrating 3.4. The signs and symptoms are not explained by another cause

The signs and symptoms are not explained by anything other than the transmission of kinetic energy to the head. There are indeed confounding factors such as alcohol, drugs or psychoactive substances. It is also very important to take into account the psychological trauma and the psychological state prior to the event: it may be useful to ask the subject if he was afraid or if he feels stressed or anxious.

Diagnostic difficulties and differential diagnosis

The diagnosis of concussion is sometimes difficult to establish, especially when the subject is seen only in the following day(s) after injury.

If the subject is asymptomatic, the diagnosis is based on the subject declaration, rarely accompanied by a witness of the event. The subject may also not have been aware of his disorders and / or minimize or deny them in order to return to play as soon as possible. It is therefore important to carry out a systematic review of the four points of the proposed definition: mechanism, immediate signs, concussion syndrome, confounding factors, in a retrospective search of the diagnostic criteria.

If the subject is symptomatic, the difficulty lies in establishing the causal link between the symptom(s) and the concussion. The interrogation then focuses on studying the temporal course of complaints (presence since the event, decreasing intensity), their unusual nature and the absence of confounding factors such as a personal or family history of migraines, Attention Deficit Disorder, Hyperactivity Disorder, anxiety (2) …

It is possible at this stage to use different neuropsychological tests such as paper-and-pencil tests (SCAT5) or computerized tests [START_REF] Dessy | Review of Assessment Scales for Diagnosing and Monitoring Sports-related Concussion[END_REF]. The use of these tests for diagnostic purposes must, however, be very cautious, especially in the absence of baseline data from the subject himself. In general, there is only statistical population data with variations to normal without validation with respect to the pathology.

It has also been proposed to use a definite, probable or possible diagnostic classification that can be confusing [START_REF] King | The Rivermead Post Concussion Symptoms Questionnaire: a measure of symptoms commonly experienced after head injury and its reliability[END_REF]. The precautionary principle justifies considering as concussed any subject presenting important doubts about one of the proposed criteria.

If there is no trauma certainty, the presence of symptoms should lead to the search for other neurological diseases, such as spontaneous subarachnoid haemorrhage and ischemic stroke, at the very least.

Concussion and emergency

The head and the neck are subject to the same biomechanical constraints. A concussion must therefore be always considered as a cervical trauma and vice versa. In concussions with consciousness troubles, the neck must be immobilized in extension in order to avoid any secondary cervical spine injury [START_REF] Cheever | Cervical Injury Assessments for Concussion Evaluation: A Review[END_REF][START_REF] Rebbeck | Concussion in combination with Whiplash-associated disorder may be missed in primary care: key recommendations for assessment and management[END_REF] Cerebral concussion is usually a "benign" brain injury which can sometimes be complicated and require further investigations (CT Scanner) or very rarely neurosurgical intervention. Warning signs (Red flags) have been identified justifying the athlete to be immediately and safely removed from participation and evaluated by a physician or licensed healthcare professional who will decide the transportation to a medical facility (figure 6) (2). These signs can also be compared to the criteria used to perform a CT scan for any traumatic brain injury (figure 7) [START_REF] King | The Rivermead Post Concussion Symptoms Questionnaire: a measure of symptoms commonly experienced after head injury and its reliability[END_REF][START_REF] Stiell | Comparison of the Canadian CT Head Rule and the New Orleans Criteria in patients with minor head injury[END_REF]

Conclusion

Accurate definition of reproducible diagnostic criteria for SRC is the prerequisite for the implementation of common rules of its management and should eliminate approximations and uncertainties around his diagnosis. The immediate observation of injured athletes from the impact during sports practice, allows to describe a rich and varied semiology that enriches the clinical diagnostic criteria usually used in hospital practice for mild brain trauma or concussion.

CRITERIA

Dans le contexte de la transmission directe ou indirecte d'une énergie cinétique à la tête, le diagnostic de commotion cérébrale peut être affirmé si au moins l'un des signes ou symptômes suivants, observé ou rapporté, est présent dans les 24 premières heures et non expliqué par une autre cause

Il a été observé (ou rapporté par le sujet ou son entourage) un impact direct à la tête (dont il est possible de décrire la nature et le siège) et/ou un déplacement rapide et de grande amplitude de la tête (Whiplash) et/ou un sujet portant immédiatement ses mains à la tête après une collision et/ou une trace d'impact à la tête (plaie, hématome) Les signes et symptômes surviennent immédiatement après l'impact, sans délai, à l'exception de certains symptômes qui peuvent apparaitre secondairement, dans les minutes ou heures suivantes, en se préoccupant pour les symptômes d'éventuels facteurs confondants : alcool, médicaments, substances psychoactives récréatives, traumatisme psychologique, troubles psychologiques préexistants: il peut être utile de demander au sujet s'il a eu peur ou s'il se sent stressé ou anxieux. ❑ ❑ Dans quel lieu est survenu l'évènement ? Dans quel stade sommes-nous aujourd'hui ? ❑ ❑ Quelle année sommes-nous ?

OUI

À quelle mi-temps sommes-nous ?

❑ ❑ Quel mois sommes-nous ?

Qui a marqué en dernier au cours de ce match ?

❑ ❑ Quel est le jour de la semaine ?

Contre quelle équipe avez-vous joué la semaine dernière / le dernier match ?

❑ ❑ Quelle heure est-il (+/-1 heure) ?

Votre équipe a-t-elle gagné le dernier match ?

❑ ❑ Trouble du comportement

Positionnement ou aptitude à l'action défaillante dans sa pratique sportive []., agressivité inhabituelle [ ]., désinhibition (propos ou action exagérée et inhabituelle), labilité émotionnelle (pleurs inhabituels), se sent anormalement nerveux(se) ou anxieux(se) ❑ ❑ Amnésie, troubles de la mémoire Ne se rappelle pas des faits juste après l'évènement (quel est le premier souvenir depuis l'évènement ?) et/ou des faits avant l'évènement (quel est le dernier souvenir avant l'accident ?). Durée de l'amnésie inférieure à 24h. A des troubles de la mémoire (tests de mémoire défaillants ou difficultés à se rappeler des détails de la vie quotidienne)

❑ ❑ Mal à la tête diffus et/ou tête lourde

Ces symptômes non expliqués par une autre cause constituent, par la présence d'au moins l'un d'entre eux, un critère diagnostique de commotion cérébrale dans les suites immédiates du traumatisme. En apparaissant de façon décalée par rapport à l'évènement de quelques heures, voire après une nuit de repos, ils peuvent encore constituer un critère diagnostique (formes évolutives). Néanmoins, s'ils sont isolés (aucun autre signe de dysfonctionnement cérébral), l'interprétation clinique de leur présence à des fins diagnostique doit être très attentivement questionnée en recherchant toutes les autres raisons pouvant expliquer leur présence.

MOTIFS DE RECOURS MEDICAL SANS DELAI

Mal au cou important -Vision double (diplopie) -Faiblesse ou sensation de picotement/brûlure dans les bras ou les jambes -Mal à la tête important ou croissant -Vomissements (plus d'un épisode) -Convulsions -Détérioration de l'état de conscience -Nervosité, agitation ou agressivité croissantes -Amnésie >30 min -signes de fracture de la base du crâne (écoulement clair par le nez ou l'oreille, hématome derrière l'oreille ou en lunettes) -troubles de la coagulation, traitement anticoagulants ou anti-agrégants -Age > 65 ans After a head injury or accident some people experience symptoms which can cause worry or nuisance. We would like to know if you now suffer from any of the symptoms given below. As many of these symptoms occur normally, we would like you to compare yourself now with before the accident. For each one, please circle the number closest to your answer. Sport related concussion is a traumatic brain injury induced by biomechanical forces. Several common features that may be utilised in clinically defining the nature of a concussive head injury include:

• SRC may be caused either by a direct blow to the head, face, neck or elsewhere on the body with an impulsive force transmitted to the head.

• SRC typically results in the rapid onset of short-lived impairment of neurological function that resolves spontaneously. However, in some cases, signs and symptoms evolve over a number of minutes to hours.

• SRC may result in neuropathological changes, but the acute clinical signs and symptoms largely reflect a functional disturbance rather than a structural injury and, as such, no abnormality is seen on standard structural neuroimaging studies. • In which stadium do we play? • What half-time are we? • Who scored the last points in this match? • Which team did you play last week / previous match? • Did your team win the previous meeting?

0 = Not experienced at all 1 =1 2 3 4 Feelings1 2 3 4 Fatigue1 2 3 4 Being1 2 3 4 Feeling1 2 3 4 Feeling1 2 3 4 Forgetfulness1 2 3 4 Poor1 2 3 4 Taking1 2 3 4

 1444444444 No more of a problem 2 = A mild problem 3 = A moderate problem 4 = A severe problem Compared with before the accident, do you now (i.e., over the last 24 hours) suffer from: Headaches.................................................. 0 of Dizziness ................................. 0 1 2 3 4 Nausea and/or Vomiting ........................... 0 1 2 3 4 Noise Sensitivity, easily upset by loud noise ................ 0 1 2 3 4 Sleep Disturbance ...................................... 0 , tiring more easily ......................... 0 Irritable, easily angered .................. 0 Depressed or Tearful .................... 0 Frustrated or Impatient ................ 0 , poor memory ..................... 0 Concentration .................................... 0 Longer to Think .............................. 0 1 2 3 4 Blurred Vision ............................................. 0 1 2 3 4 Light Sensitivity, easily upset by bright light ................ 0 1 2 3 4 Double Vision ............................................. 0 Restlessness ............................................

Figure 1 :

 1 Figure 1: Definitions of sport related concussion and Mild Traumatic Brain injurySport Related Concussion Mild Traumatic Brain Injury 5 th International consensus conference on Concussion in Sports (2)The American Congress of Rehabilitation Medicine[START_REF]Definition of mild traumatic brain injury developed by the Mild Traumatic Brain Injury Committee of the Head Injury Interdisciplinary Special Interest Group of the American Congress of Rehabilitation Medicine[END_REF]

Table 3 :

 3 Symptoms check-list (2) your symptoms get worse with physical activity? OUI NON Do your symptoms get worse with mental activity? OUI NON

In the context of the direct or indirect transmission of kinetic energy to the head, the diagnosis of concussion may be asserted if at least one of the following signs or symptoms, observed or reported, is present within the first 24 hours and not explained by another cause:

  Any sign of basal skull fracture (clear fluid from the nose or ear, hematoma around the eyes or behind the ear) • Coagulation disorder, Anticoagulant or antiplatelet therapies ...

	YES	NO
	❑	❑ Loss of consciousness
	❑	❑ Convulsions, Tonic posturing
	❑	❑ Balance troubles (ataxia)
	❑	❑ Visual trouble (diplopia, blurred, colored, narrowed vision, nystagmus)
	❑	❑ Other neurologic sign (deficit…)
	❑	❑ Confusion (Confusion (repeats the same question, inappropriate remarks))
	❑	❑	Desorientation One incorrect answer to one of these questionnaires	  ❑ ❑ In which place did the event occur? What venue are we at today? General Questionnaire Maddock's score ❑ ❑ What year are we? Which half is it now? ❑ ❑ What month are we? Who scored last in this match? ❑ ❑ What is the day of the week? What team did you play last week/game?
				❑ ❑ What time is it (within 1 hour) ?	Dis your team win the last game?
	❑	❑ Unsual behavior (inappropriate behavior, aggressiveness, disinhibition, emotional lability)
	❑	❑ Amnesia (anterograde and/or retrograde, difficulties remembering)
	❑	❑ Diffuse headaches and/or Pressure in head
	❑	❑ Dizziness and/or vertigo
	❑	❑ Fatigue, unusual low energy
	❑	❑ Feeling slow down and/or drowsiness
	❑	❑ Nausea and/or vomiting
	❑	❑ Sensitivity to light and/or to noise
	❑	❑ Dont feel right and/or in a fog
	❑	❑ Difficulty concentrating
			CRITERIA REQUIRING MEDICAL ADVICE WITHOUT DELAY
				• Severe neck pain or tenderness
				• Double vision
				• Weakness or tingling/burning in arms or legs
				• Vomiting (more than one episode)
				• Severe or increasing headache
				• Seizure or convulsion
				• Deteriorating conscious state
				• Increasingly restless, agitated or combative
				• Amnesia of more than 30 minutes
	•

• Age over 65 A CONCUSSION MUST BE ALWAYS CONSIDERED ASSOCIATED WITH A CERVICAL TRAUMA UNTIL PROVEN OTHERWISE THE DIAGNOSIS CAN NOT BE EXCLUDED ON THE DAY

OF INJURY Critères diagnostiques cliniques de la commotion cérébrale (Traumatisme cérébral léger) CRITERES INSTRUCTIONS

  La perte de connaissance est le résultat d'un examen clinique où il est constaté que le sujet : 1) a les yeux fermés ; 2) n'obéit à aucun ordre simple ; 3) ne bouge pas en dehors de mouvements réflexes. Indirectement, la perte de connaissance est diagnostiquée dans l'action, lorsqu'est observé une perte du tonus [ ] : chute abrupte du corps sans aucun mouvement pour se protéger vers l'avant, l'arrière ou en position assise ; hypotonie cervicale ou des épaules. Enfin, la suspicion est forte si le sujet est immobile au sol dès la chute sans aucun mouvement volontaire et pendant au moins5 sec [ ].Convulsions : contractions musculaires rythmiques involontaires brèves et répétées, impliquant un ou plusieurs membres [].Crise tonique posturale : Extension d'un membre restant suspendu en l'air quelques instants avant de retomber progressivement au sol, pouvant s'accompagner d'une rotation tonique du cou [ ] Amorce le mouvement de se relever et retombe au sol ; 2) Se relève de façon saccadée en plusieurs étapes en cherchant à chaque étape son équilibre (parfois le sujet rampe à « quatre pattes » avant de pouvoir se relever) ; 3) a du mal à se tenir debout immédiatement de façon stable sans être soutenu ; 4) marche de façon instable

		NON		Sigle [ ] : observable à la vidéo
	❑	❑ Perte de connaissance
	❑	❑ Convulsions, crise tonique
	❑	❑ Trouble visuel
			Tout autre signe neurologique témoignant d'un dysfonctionnement cérébral
	❑	❑ Confusion	Répète la même question, propos non adaptés
		 	Questionnaire général	Questionnaire de Maddock (sports collectifs)	Se trompe et ne reconnait pas un
	❑	❑ Désorientation			lieu, une personne, ou une séquence temporelle d'évènements. Une réponse incorrecte () à l'un de ces
					questionnaires signale une
					désorientation.

❑

❑ Trouble de l'équilibre (ataxie) Le diagnostic de critère d'ataxie [ ] est retenu si le sujet : 1) Vision floue, colorée, champ visuel amputé, vision double, anomalies pupillaires, nystagmus ❑ ❑ Autre signe neurologique (déficit), détail :

EST ASSOCIEE A UN TRAUMATISME CERVICAL JUSQU'A PREUVE DU CONTRAIRE LE DIAGNOSTIC DE COMMOTION CEREBRALE NE PEUT ETRE EXCLU LE JOUR DU TRAUMATISME

	❑	❑ Vertiges et/ou étourdissements
	❑	❑ Fatigue, manque d'énergie inhabituelle
	❑	❑ Sensation d'être ralenti et/ou somnolence
	❑	❑ Nausées et/ou vomissements
	❑	❑ Gêné(e) par la lumière et/ou le bruit
	❑	❑ Ne se sent pas bien et/ou dans le brouillard
	❑	❑ Du mal à se concentrer
	UNE COMMOTION CEREBRALE

Table 2

 2 Orientation ScoreMaddock's Score (13) • In which place did the event occur?• What year are we?• What month are we?• What is the day of the week?• o What time is it (within 1 hour)?

Table 4 :

 4 SCAT 5 Red Flags (2)

	SCAT 5 Red flags
	1. Neck pain or tenderness
	2. Double vision
	3. Weakness or tingling/burning in arms or legs
	4. Vomiting
	5. Severe or increasing headache
	6. Seizure or convulsion
	7. Loss of consciousness
	8. Deteriorating conscious state
	9. Increasingly restless, agitated or combative

Table 5 :

 5 CT scan rules for Mtbi[START_REF] Mccrory | 5th International Conference on Concussion in Sport (Berlin)[END_REF][START_REF] Stiell | Comparison of the Canadian CT Head Rule and the New Orleans Criteria in patients with minor head injury[END_REF][START_REF] Jehlé | comité de pilotage. Minor head injury (Glasgow Coma Score 13 to 15): triage, assessment, investigation and early management of minor head injury in infants, children and adults[END_REF]

	SFMU	Canadian CT Head Rule	New Orleans Criteria
	Risk factors requiring a CT	CT head scan is only required	Computed tomography is
	head scan (*in emergency,	for patients with minor head	required for patients with
	within an hour):	injury with any one of these	minor head injury with any one
	1. Focal neurologic deficit*	findings:	of the following findings. The
	2. Retrograde amnesia (before	High-risk (for neurologic	criteria apply only to patients
	the injury) > 30 minutes	intervention)	who also have a Glasgow
	3. GCS score <15 at 2 hours	1. GCS score <15 at 2 hours	Coma Scale score of 15
	after injury*	after injury	1. Headaches
	4. Loss of consciousness or	2. Suspected open or	2. Vomiting
	amnesia associated with -	depressed skull fracture	3. Older than 60 years old
	one of the following	3. Any sign of basal skull	4. Drug or alcohol intoxication
	traumatic mechanisms:	fracture (hemotympanum,	5. Persistent anterograde
	pedestrian against a	"raccoon" eyes, CSF otorrhea	amnesia (deficits in short-
	vehicle, patient	or rhinorrhea, Battle's sign)	term memory)
	ejected from a vehicle or fall	4. Vomiting ≥ 2	6. Visible trauma above the
	from a height of more than	5. Age ≥ 65	clavicle
	one meter -or an age of over	Medium-risk (for brain injury	7. Seizure
	65 years	on CT scan)
	5. Suspected open or	1. Amnesia before impact > 30
	depressed skull fracture*	minutes
	6. Any sign of basal skull	2. Dangerous mechanism
	fracture (hemotympanum,	(pedestrian struck by motor
	"raccoon" eyes, CSF otorrhea	vehicle, occupant ejected
	or rhinorrhea, Battle's sign) *	from motor vehicle, fall from
	7. Vomiting ≥ 2 in adults*	elevation ≥ 5 ft or 5 stairs)
	8. Post-traumatic Seizure*
	9. Coagulation disorder,
	Anticoagulant or antiplatelet
	therapies ... *

Maria AQALLAL : Direction Générale de la Santé (DGS)


MD Lionel Rebibo

MD Meghane Tricot

MD Jeanne Dembinski

MD Abdennaceur Dhahri

MD Jean-Marc Regimbeau
email: regimbeau.jean-marc@chu-amiens.fr

Professor J.-M Regimbeau

Gastric leak after sleeve gastrectomy: risk factors for poor evolution under conservative management

Keywords: sleeve gastrectomy, gastric leak, double pigtail stent, gastric fistula

Background. Gastric leak (GL) is the most highly feared early postoperative complication after sleeve gastrectomy (SG), with an incidence of 1 to 2%. This complication may require further surgery/endoscopy, with a risk of management failure that may require additional surgery, including total gastrectomy, leading to a risk of mortality of 0 to 9%.

Objectives. Assess the impact of factors that may lead to a poorer evolution of GL.

Setting. University Hospital, France, public practice.

Methods. This was a retrospective, single-center study of a group of patients managed for GL after SG between November 2004 and January 2019 (n = 166). Forty three patients were excluded. The population study was divided into two groups: patients with easy closing of the GL (n=73) and patients with difficult closing of the GL or failure to heal (n=50). Patients were allocated to one of the two groups depending on the time to heal (median time of 84 days). The study's primary efficacy endpoint was to determine the risk factors for a poorer evolution of GL.

Results. Among 123 patients included in this study, 103 patients had undergone primary SG (83.7%). The mean time to the appearance of GL was 15.1 days (1-156). Seventy-four patients underwent a reoperation (60%). The mean number of endoscopies per patient was 2.7

(2-7). The mean time to healing was 89.5 days (18-386). There were eight cases of healing failure (6.5%). Multivariate analysis identified body mass index (>47kg/m 2 ), time to referral (>2 days), and serum pre-albumin level (<0.1g/dl) to be independent risk factors for a poorer evolution of GL.

Conclusion.

Improvement of the nutritional status prior to SG and early referral for GL could reduce the risk of delayed closure or the need for further surgery.

INTRODUCTION

Gastric leak (GL) is only one of the major surgical postoperative complications of sleeve gastrectomy (SG), but it is the most feared. The incidence of GL has decreased over time [START_REF] Demeusy | Current role of staple line reinforcement in 30-day outcomes of primary laparoscopic sleeve gastrectomy: an analysis of MBSAQIP data, 2015-2016 PUF[END_REF] due to improvements in the SG technique and a better knowledge of the mechanisms responsible [START_REF] Iossa | Leaks after laparoscopic sleeve gastrectomy: overview of pathogenesis and risk factors[END_REF] .

GL is a complication that is difficult to manage and may require complex or radical additional surgical procedures for chronic fistula [START_REF] Bruzzi | Open total gastrectomy with Roux-en-Y reconstruction for a chronic fistula after sleeve gastrectomy[END_REF][START_REF] Van De Vrande | Management of chronic proximal fistulas after sleeve gastrectomy by laparoscopic Roux-limb placement[END_REF] . Following SG, there is also a risk of complicated GL, such as gastrobronchial fistula [START_REF] Silva | Gastrobronchial Fistula in Sleeve Gastrectomy and Roux-en-Y Gastric Bypass--A Systematic Review[END_REF] and pseudoaneurysms [START_REF] Rebibo | Gastrointestinal bleeding complication of gastric fistula after sleeve gastrectomy: consider pseudoaneurysms[END_REF] . The reported risk of mortality for GL after SG ranges from 0 to 9%, depending on the series [START_REF] Sakran | Gastric leaks after sleeve gastrectomy: a multicenter experience with 2,834 patients[END_REF][START_REF] Moszkowicz | Sleeve gastrectomy severe complications: is it always a reasonable surgical option?[END_REF][START_REF] Csendes | Management of leaks after laparoscopic sleeve gastrectomy in patients with obesity[END_REF] . The prognosis of GL after SG has gradually improved due to the emergence of new endoscopic techniques, in particular, double pigtail stents (DPSs) [START_REF] Pequignot | Is there a place for pigtail drains in the management of gastric leaks after laparoscopic sleeve gastrectomy?[END_REF][START_REF] Giuliani | Gastric leak after laparoscopic sleeve gastrectomy: management with endoscopic double pigtail drainage. A systematic review[END_REF][START_REF] Nedelcu | Outcome of leaks after sleeve gastrectomy based on a new algorithm adressing leak size and gastric stenosis[END_REF] , an implementation algorithm for surgical and endoscopic management, and, especially, better classification of GL, making it possible to propose revisional surgery to reduce the morbidity risk of GL in certain cases [START_REF] Rebibo | Persistent gastric fistula after sleeve gastrectomy: an analysis of the time between discovery and reoperation[END_REF] .

Although many risk factors for GL after SG have been reported [START_REF] Parikh | Surgical strategies that may decrease leak after laparoscopic sleeve gastrectomy: a systematic review and meta-analysis of 9991 cases[END_REF][START_REF] Alizadeh | Risk Factors for Gastrointestinal Leak after Bariatric Surgery: MBASQIP Analysis[END_REF][START_REF] Berger | The Impact of Different Surgical Techniques on Outcomes in Laparoscopic Sleeve Gastrectomies: The First Report from the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP)[END_REF] , no risk factors for a poorer evolution of GL have been described. This is probably due to the fact that most published studies of post-SG GL have concerned small (n < 65) groups of patients [START_REF] Klimczak | Endoscopic treatment of leaks after laparoscopic sleeve gastrectomy using MEGA esophageal covered stents[END_REF][START_REF] Almadi | Use of Self-Expandable Metal Stents in the Treatment of Leaks Complicating Laparoscopic Sleeve Gastrectomy: A Cohort Study[END_REF][START_REF] Hajj | Fistula Following Laparoscopic Sleeve Gastrectomy: a Proposed Classification and Algorithm for Optimal Management[END_REF] , without standardized management of GL. Currently, few studies with large series have analyzed the results of GL management after SG. We aimed to assess the impact of factors that could lead to a poorer evolution of GL after SG in a large single-center study.

MATERIALS AND METHODS

Population

We performed a retrospective analysis of prospectively gathered data on a group of patients managed for GL after SG (primary and secondary SG) over a 15 year-period (between November 2004 and January 2019). Based on our database, at least seven papers have been published that include at least some of the data of these patients.

Inclusion criteria

Patients included in the study had to meet the following criteria: post-SG GL visualized during an abdominal CT scan, endoscopy, or surgery [START_REF] Rebibo | Persistent gastric fistula after sleeve gastrectomy: an analysis of the time between discovery and reoperation[END_REF] , and a complete set of data during management of the GL.

Exclusion criteria

Patients who underwent bariatric procedures other than SG were excluded from the study. In addition, the first 20 patients of our series were excluded because of the beginning of our experience in managing GL after SG and non-standardized management, as well as patients with GL on a distal part of the SG (because the management of GL in this case is different [20]), patients referred to our center for the management of gastrobronchial fistula and/or chronic GL requiring revisional surgery, patients refereed to our center too long after the diagnosis of GL (≥ 50 days from the diagnosis of GL, because such a long time since the diagnosis could have biased the results), and patients who died prematurely without the possibility of performing endoscopic treatment. However, patients with a GL orifice (measuring more than 2 cm in diameter) and/or stenosis associated with GL were not excluded from our study.

Group selection

The population study was divided into two groups: the first group included patients with easyclosing GL, the "easy" GL (eGL) group, and the second, patients with difficult-closing GL or GL that failed to heal (appearance of a gastropulmonary fistula or pseudo aneurysm), the "hard" GL (hGL) group. Patients were allocated to one of the two groups depending on the time it took the GL to heal from its discovery. According to a previous publication, the median time for a GL to heal from its discovery is 84 days [START_REF] Rebibo | Persistent gastric fistula after sleeve gastrectomy: an analysis of the time between discovery and reoperation[END_REF] . Thus, the eGL group included patients for whom the GL healed before the 85 th day after its discovery, whereas the hGL group included patients for whom the GL healed after the 84 th day following its discovery, as well as patients for whom the GL did not heal or those with complications related to GL.

Definition of GL

The presentation, time to onset, and staple line site of GL were classified according to the modified UK Surgical Infection Study Group definitions [START_REF] Csendes | Conservative management of anastomotic leaks after 557 open gastric bypasses[END_REF][START_REF] Bruce | Systematic review of the definition and measurement of anastomotic leak after gastrointestinal surgery[END_REF] . The patient's clinical presentation was further described in terms of systemic signs of inflammation (tachycardia (> 100 bpm) and hyperthermia (> 38°C)), peritonitis (diffuse abdominal tenderness), pulmonary symptoms (cough and expectoration), and intra-abdominal abscess (localized abdominal tenderness). The time to onset after SG was used to differentiate between early-onset GL (from post-operative day (POD) 1 to 7) and delayed-onset GL (≥ POD 8). The definition for early-vs. delayed-onset GL was decided based on our experience with GL [START_REF] Pequignot | Is there a place for pigtail drains in the management of gastric leaks after laparoscopic sleeve gastrectomy?[END_REF] . We used oralcontrast-enhanced abdominal computed tomography (CT) and/or upper gastrointestinal endoscopy to determine the site of leakage along the staple line.

Management of GL

All cases of post-SG GL were discussed in a multidisciplinary staff meeting that included bariatric surgeons, a radiologist, an endoscopist, and an intensive care physician. This allowed us to develop a protocol for the standardized management of post-SG GL (Figure 1) based on leak-related data and the patient's clinical status [START_REF] Pequignot | Is there a place for pigtail drains in the management of gastric leaks after laparoscopic sleeve gastrectomy?[END_REF][START_REF] Rebibo | Early gastric fistula after laparoscopic sleeve gastrectomy: surgical management[END_REF] .

Management of early-onset or poorly tolerated GLs

Our reoperation procedures for GL have been described in detail elsewhere [START_REF] Rebibo | Early gastric fistula after laparoscopic sleeve gastrectomy: surgical management[END_REF] . For cases of early-onset (≤ POD 7), poorly tolerated GL, open surgery consisted of sample collection for bacteriological and yeast cultures [START_REF] Rebibo | Letter to editor: "Gastric fistula after laparoscopic sleeve gastrectomy: don't forget to treat for Candida[END_REF] , washing of the abdominal cavity, suturing of the orifice of the leak (if possible, and depending on intra-operative local conditions), drainage of the GL (with two drains for post-operative irrigation and drainage), and implementation of a feeding jejunostomy. Laparoscopy was performed for early-onset, well-tolerated GLs.

Management of delayed-onset, well-tolerated GLs and after reoperation Endoscopy was performed by gastroenterologists with extensive experience in the management of post-operative complications.

For cases of GL requiring an immediate reoperation, an oral-contrast-enhanced abdominal CT scan was performed six days after reoperation (to check that the GL was well drained before endoscopy). Endoscopic treatment was performed seven days after reoperation (the day after oral-contrast-enhanced abdominal CT scan). In cases of delayed (POD ˃ 7), well-tolerated GL (not requiring reoperation), endoscopy was performed on the day that the leak was discovered.

Stents, either a CS (Hanarostent ® , Life Partners Europe, Bagnolet, France) or DPS (Zimmon ® Biliary Stent, Cook Ireland Ltd, Limerick, Ireland), depending on the case, were implanted with radiological guidance.

During the study period, we changed our endoscopic procedures for GL treatment. Before 2008, we used CSs. From 2008 onwards, we progressively abandoned CSs in favor of DPSs to drain the GL inside the stomach [START_REF] Pequignot | Is there a place for pigtail drains in the management of gastric leaks after laparoscopic sleeve gastrectomy?[END_REF] . Based on our increasing experience of managing GL, endoscopic treatment sometimes required combining CS and DPS placement for GL associated with stenosis below the leak orifice and/or large gastric leak orifice (measuring over than 2 cm diameter) [START_REF] Rebibo | New endoscopic technique for the treatment of large gastric fistula or gastric stenosis associated with gastric leaks after sleeve gastrectomy[END_REF] . Patients were allowed to drink water after stent implantation and thus wash the GL.

An oral-contrast-enhanced abdominal CT scan was performed three to four weeks after implantation of a CS or six weeks after implantation of a DPS. Endoscopy was performed the day after the abdominal CT scan to remove (if the GL had healed) or change the stent (if the GL had not healed).

Definition of GL healing

In our multidisciplinary staff meeting, healing of a GL was defined as the resumption of oral feeding in the absence of (i) surgical drainage or endoscopic stenting, (ii) flow through a previous surgical drainage path (e.g. a gastrocutaneous fistula), and (iii) collections near the staple line site on an abdominal CT scan (whether contrast-enhanced or not).

Endpoints and data recorded

The primary efficacy endpoint of the study was to determine risk factors for adverse outcomes of GL after SG. Hence, the following data were recorded:

-Patient and preoperative data: age, gender, body mass index (BMI), and comorbidities (diabetes mellitus, hypertension, dyslipidemia, and OSAS).

-Operative data: type of SG performed (history of gastric banding, repeat-SG) and the frequency of SG performed in another institution.

-GL data: time interval between surgery and GL (early-onset GL vs. delayed-onset GL), GL requiring reoperation (at the initial center, at the referral center, or both), time interval between the diagnosis of GL and transfer to the referral center, type of reoperation (laparoscopy and/or laparotomy).

-Endoscopic data: type of GL, type of stent used, alternative used of a different stent, number of endoscopies performed.

-Biological data at the discovery of GL: white blood cell count and C-reactive-protein and serum-creatinine levels.

-Nutrition data: type of nutrition, serum albumin and serum pre-albumin levels at the time of GL diagnosis.

-Hospitalization data: overall length of hospital stay, rate of admission to the intensive care unit (ICU), and length of stay in the ICU.

-Overall management: success rate of GL healing, time to heal, type of GL complication.

Statistical analysis

The patients' baseline characteristics are expressed as the means ± standard deviation (SD) and medians (interquartile range) for continuous data and as numbers (frequency) for categorical data. Intergroup comparisons of quantitative variables were performed using Student's t-test, whereas intergroup comparisons of qualitative variables (including the primary endpoint) were performed using a chi-squared test with Yates' correction, if required.

The threshold for statistical significance was set to p ≤ 0.05.

Risk factors for a poorer evolution of GL after SG were identified using univariate and multivariate analyses with backward stepwise selection. Variables with a p value < 0.15 were included in a multivariable regression model. All statistical analyses were performed using STATA software (Stata/IC 15.1, TX, USA).

RESULTS

Population of the study

During the study period, 166 patients were managed in our institution for GL after the SG procedure. The first 20 patients from this population were excluded, as well as six because they were referred to our institution more than 50 days after the discovery of GL, four for the management of gastro-bronchial fistula, and four for the surgical management of chronic GL requiring revisional surgery. In addition, four were excluded because of incomplete data, four because the GL was repaired using sutures of the GL only, without the need for further endoscopy, and one because of early death (the day of admission) (Figure 2). Finally, our study population included 123 patients, divided between 73 in the eGL group and 50 in the hGL group.

Demographic data (Table 1 & 2)

The mean (range) age of the study population was 37.1 years (19 -68) and the mean BMI 42.7 kg/m 2 (28.7 -62.5). There were 94 women (76.5%). Pre-operative comorbidities were diabetes mellitus in 13% of cases (n = 16), hypertension in 22.8% (n =28), dyslipidemia in 18.7% (n = 23), and obstructive sleep apnea in 23.5% (n = 29). Nineteen patients (15.4%) had a BMI ≥ 50 kg/m 2 . Most (103) patients had undergone primary SG (83.7%), whereas the remainder had undergone revisional SG. The initial surgery was performed in another institution for 65.8% (n = 81). The only significant difference concerning the demographic data between the two groups was the mean BMI, with a lower BMI in the eGL group (42 kg/m 2 vs. 44.4 kg/m 2 , p = 0.02) (Table 1).

Gastric leak data

The mean time to the appearance of post-SG GL was 15.1 days (1 -156).

Clinical data

Fifty-three patients had early-onset GL (43%), whereas the others had delayed-onset GL.

More patients in the hGL group had early-onset GL (54 vs. 35.6%, p = 0.04). The frequency of hypovolemic shock was 19.5% at admission in our institution, with a higher frequency in the hGL group (30 vs. 12.3%, p = 0.02). The rate of ICU admission was similar between the two groups (Table 3).

Biological data

At admission in our institution, the mean white blood cell count was 13,785 (3,900 -32,400), mean C reactive protein 217 (25 -472), mean serum creatinine 67.1 (29-158), mean serum pre-albumin 0.1 (0.03 -0.37), and mean serum albumin 25 (12 -42.7). Patients in the hGL group had higher mean serum creatinine levels and lower normal serum pre-albumin and albumin levels (Table 4).

Surgical management for GL

Seventy-four patients underwent a reoperation (60%), laparoscopic surgery was performed in 46 cases (62.2%), and the fistulous orifice was sutured in 19 (25.6%). Feeding jejunostomy was performed on 63 patients. Eight patients (6.5%) underwent primary radiological drainage as an alternative to surgery. There were significantly fewer reoperations for GL in the eGL group (48 vs. 78%, p < 0.001) and less implementation of feeding jejunostomy as a method for renutrition (41 vs. 66%, p = 0.01) (Table 5).

Among patients referred for the management of GL (n = 81), there were more reoperations in the hGL group (62.8 vs. 34.7%, p = 0.01) and the mean time for referral was higher (7.7 vs. 3 days, p = 0.007) (Table 6).

Endoscopic management

The mean time interval between the diagnosis of GL and first endoscopy was 10.1 days (0 -48). The mean number of endoscopies per patient was 2.7 (2 -7). Most endoscopies showed classical GL (73.2%, n = 90), whereas other endoscopies showed associated gastric stenosis in 5.7% (n = 7) and large GL in 21.1% (n = 26) of patients. Most GLs were treated using a DPS only in 70% of cases (n = 86), whereas the use of a CS only was required in 3.2% of cases and alternative use of CS and DPS in 26.8% of cases (n = 33). The combined use of CS and DPS was required for 18 cases (14.6%).

The mean time interval between the discovery of GL and first endoscopy was longer in the hGL group (14 vs. 7.6 days, p < 0.001). The frequency of classical GL was higher in the eGL group (83.5 vs. 58%, p = 0.002). Finally, more endoscopies were performed for the hGL group, with less use of a DPS only and a greater need for the use of a DPS and CS (Table 7).

Outcomes

The mean duration of hospitalization from the diagnosis of GL was 19.7 days (2 -86). The mean time for the GL to heal was 89.5 days (18-386). There were eight cases of failure to heal (6.5%), including three patients who developed gastro-bronchial fistula (2.4%), requiring revisional surgery, and five (4.0%) who required revisional surgery for chronic GL. There was no mortality in this study population.

Multivariate analysis

All variables with p < 0.15 in the univariate analysis were included in a multivariate analysis.

Multivariate logistic regression modeling identified a BMI > 47 kg/m 2 (OR = 0.90; 95% CI, 0.84-0.97; p = 0.008), time to referral > 2 days (OR = 0.92; 95% CI, 0.86-0.98; p = 0.01), and a serum pre-albumin level < 0.1 g/dl (OR = 1.64; 95% CI, 1.13-2.37; p = 0.04) to be independent risk factors for a poorer evolution of GL after SG (Table 8).

DISCUSSION

This series provides important information, as it was a single-center study with the largest population yet studied, making it possible to not only to show the results of GL management but also to search for risk factors for a poorer evolution of GL. Our mortality rate in the management of GL after SG is low, with a rate of 0.6% (1 of 166). The mean time to the appearance/diagnosis of post-SG GL was 15.1 days in our population. Faced with GL, most patients underwent a reoperation (60%) and the mean number of endoscopies performed for managing GL was 2.7 per patient. Although our series showed good outcomes, with 93.5% of patients cured without the need for revisional surgery, initial management required a length of hospitalization of nearly 20 days and the mean time to heal was 89.5 days, showing that this complication must be taken seriously. Maybe that some patient undergoing reoperation could have rather a radiological drainage rather than a reoperation [START_REF] Corona | Minimally invasive treatment of gastric leak after sleeve gastrectomy[END_REF] , but in our experience radiological drainage is difficult to achieve due to location of the GL.

Our mortality rate was zero, due to our exclusion criteria in this study, versus a mortality rate of 1.2% in one of our previous publications [START_REF] Rebibo | Persistent gastric fistula after sleeve gastrectomy: an analysis of the time between discovery and reoperation[END_REF] . However, despite our good results in terms of mortality rate, it must not be forgotten that GL is a life-threatening complication, with a mortality rate of 9.7% in a recent review of the literature [START_REF] Hughes | Management of Staple Line Leaks Following Sleeve Gastrectomy-a Systematic Review[END_REF] , and that some patients require revisional surgery, as in our series, possibly leading to total gastrectomy and/or splenectomy in some cases [START_REF] Bruzzi | Open total gastrectomy with Roux-en-Y reconstruction for a chronic fistula after sleeve gastrectomy[END_REF] .

Complete healing of GL without the need for revisional surgery was achieved in 93.5% of the cases in our series, with a mean time to heal of 89.5 days (18-386). In their five-year retrospective analysis of 73 cases (2012 to 2017), Bashah et al. [START_REF] Bashah | Management of leak after sleeve gastrectomy: outcomes of 73 cases, treatment algorithm and predictors of resolution[END_REF] reported impressive results, with a mean time to heal of 8.8 weeks and a success rate of endoscopic treatment of 97.1%, with only two patients requiring fistula-jejunostomy. In a previous publication, our mean time to heal was 111 days [START_REF] Rebibo | Persistent gastric fistula after sleeve gastrectomy: an analysis of the time between discovery and reoperation[END_REF] , higher than that for our current series and probably linked to the fact the first series included all patients managed for GL since 2004, whereas we excluded patients managed during our learning curve of managing patients with GL for the current series.

In addition, our management of GL has improved over the years. At the beginning, we used only CSs and then progressively switched to DPSs [START_REF] Pequignot | Is there a place for pigtail drains in the management of gastric leaks after laparoscopic sleeve gastrectomy?[END_REF] . This resulted in better results than those for patients managed using CSs only, as well as better tolerance of this type of prosthesis, along with simpler management, ultimately reducing the initial length of the hospital stay. The eGL group had more patients for whom only DPSs were used than the hGL group (Table 7), although we failed to show a significant difference in our multivariate analysis. Nonetheless, even with DPSs, our goal of 100% resolution, without the need for revisional surgery, was far from being achieved, probably due to the fact that some cases of GL had associated stenosis (or a twist). Thus, although the DPS has become the gold standard for the endoscopic management of GL, it is not effective in certain cases. We therefore developed an endoscopic treatment algorithm based on endoscopic findings, with the objective to provide "à la carte" treatment [START_REF] Rebibo | Persistent gastric fistula after sleeve gastrectomy: an analysis of the time between discovery and reoperation[END_REF] . This probably explains the difference between our results and those on other series evaluating DPS, such as the metanalysis of Giuliani et al. [START_REF] Giuliani | Gastric leak after laparoscopic sleeve gastrectomy: management with endoscopic double pigtail drainage. A systematic review[END_REF] , showing that the overall success rate of endoscopic closure of GL was 83.4% for 681 patients, with a mean time to heal of 118.1 days.

Our large series allowed us to search for risk factors for the poor evolution of conservative management. Univariate analysis identified many risk factors, such as the type of GL (early vs. delayed), hypovolemic shock (Table 3), and certain biological parameters, such as mean serum creatine and lower pre-albumin and albumin levels in the hGL group. This could be explained by the fact that hypovolemic shock required ICU management with increased need for protein. And so, these patients are probably more undernourished than patient without major sepsis explaining lower pre-albumin and albumin levels. Also, most cases of patient with hypovolemic shock concern acute presentation of the GL. These patients had delayed access to endoscopy and thus prolongated abdominal drainage explaining the difficulty of healing a fistula in the process of organization rather than a leak. After multivariate analysis, three statistically significant risk factors for a poorer evolution of GL remained: a BMI > 47 kg/m 2 , a time to referral > 2 days, and a serum pre-albumin level < 0.1 g/dl. These findings are important, as two of these three factors are alterable. The serum pre-albumin concentration can be changed by optimizing the pre-operative nutritional status before SG, as many patients are probably malnourished before bariatric surgery [START_REF] Sharma | Under-Recognizing Malnutrition in Hospitalized Obese Populations: The Real Paradox[END_REF] . Furthermore, the management of GL requires early refeeding, preferentially via an enteral route (nasojejunal tube or feeding jejunostomy). Our series also further strengthens the argument for centralizing the management of complications, as previously demonstrated by Caiaizzo et al. [START_REF] Caiazzo | Impact of Centralized Management of Bariatric Surgery Complications on 90-day Mortality[END_REF] . Our series showed that delayed referral was associated with a poorer evolution of GL. Thus, early referral to expert centers for the management of post-SG complications is critical to reduce morbidity and mortality.

Our study had several limitations, such as the retrospective design, although all other studies published on this topic were also retrospective. The small number of series described in the literature argues for the creation of a national or international database, as there is still insufficient knowledge on the management of GL and most SG surgery concerns young patients, for whom a zero-mortality rate should be an objective. The size of our study population could be considered to be small, but there have been no single-center studies published with as many patients. This is probably why there have been no previous studies to search for risk factors for a poorer evolution of GL after SG. Also, no endoscopic findings were associated with worth outcomes, in particular the occurrence of gastric stenosis or twist associated with GL. This could be due to the fact that probably diagnosis of stenosis or twist were underestimated as most cases concern last cases of our study. Finally, our results were probably influenced by the algorithm-based management specific to our center, probably different to other center and other definition of type of GL [START_REF] Abou Rached | Gastric leaks post sleeve gastrectomy: review of its prevention and management[END_REF] . This is why we decided to exclude patients referred tardively, because the management of such cases in other centers may be different than ours and could have introduced a bias in the interpretation of the results.

CONCLUSION

GL is a difficult complication to manage. We found that a BMI > 47k g/m 2 , a time to referral to a specialized center > 2 days, and a serum pre-albumin level < 0.1g/dl were independent risk factors for a poorer evolution. Two of these three factors are modifiable, suggesting that it may be possible to reduce the morbidity and mortality of GL after SG.

Figure 1 .

 1 Figure 1. Synopsis of the treatment procedures for post-SG GL.

Figure 2 :

 2 Figure 2: Study flow chart.

Table 1 .

 1 Comparison of pre-operative data between the eGL and hGL groups.

	eGL group (n = 73)	hGL group (n = 50)	Total group (n = 123)	p value

Table 2 .

 2 Comparison of the type of surgery and institution that performed the surgery between the eGL and hGL groups.

	eGL group (n = 73) hGL group (n = 50) Total group (n = 123)	p value

Table 3 .

 3 Clinical data at admission in our institution

	eGL group (n = 73) hGL group (n = 50) Total group (n = 123)	p value

Table 4 .

 4 Biological data at admission in our institution for GL after SG.

	eGL group (n = 73)	hGL group (n = 50)	Total group (n = 123)	p value

Table 5 .

 5 Reoperation data and type of renutrition of patients with GL after SG.

	eGL group (n = 73)	hGL group (n = 50) Total group (n = 123)	p value

Table 6 .

 6 Data on patients undergoing SG in another institution

	eGL group (n = 46) hGL group (n = 35)	Total group (n = 81)	p value

Table 7 .

 7 Endoscopic data

	eGL group (n = 73) hGL group (n = 50) Total group (n = 123)	p value

Table 8 .

 8 Results of the multivariate logistic regression model

	Risk factors	Odds ratio	95% confidence interval	p value
	BMI	0.90	0.84 -0.97	0.008
	Delay of diagnosis of GL	1.01	0.98 -1.05	0.46
	Delayed GL	1.05	0.29 -3.79	0.94
	Delay for referral	0.92	0.86 -0.98	0.01
	Hypovolemic shock	0.38	0.12 -1.18	0.09
	Serum pre-albumin level	1.64	1.13 -2.37	0.04
	BMI: body mass index

funding for research and/or publication: No source of funding to declare.