Pauline Nicolᵃ

Jean-François Uhlᵇ

Chloé Bertolusᶜ

Christian Vacherᵃ
email: christian.vacher@aphp.fr

Christian Pr

Vacher

The Transverse Facial Artery and the Mandibular Condylar Process: An Anatomic and Radiologic Study

Keywords:

Introduction: In surgical approaches to condylar fractures, there is a risk of damage to the transverse facial artery (TFA) which may in turn account for impaired blood supply to the temporomandibular joint (TMJ). In order to investigate the risk of damage to the TFA, and prevent lesions to this artery resulting from TMJ surgical procedures, we studied the distance between the TFA and the head of the condylar process.

Methodology: A dissection study was conducted on 10 fresh cadavers (20 condylar specimens dissected), involving fifty CT scans of the face with intravenous contrast. Vertical distance from the TFA to the top of the mandibular condyle head and distance from the TFA to the lateral aspect of the mandibular condyle were measured.

Results:

The lateral aspect of the mandibular condyle is vascularized by branches emanating from the superficial temporal artery (STA) and the TFA. The TFA was located 1.84 +/-0.6 cm below the condylar process of the mandible and ran 1.09+/-0.54 mm lateral to the head of the mandibular condyle.

Discussion: In order to spare the TFA in fractures involving the condylar neck, surgical approaches to the condyle should preserve the uppermost 2 cm of the lateral surface of the condyle during dissection. Due to the necessity for periosteal elevation of the lateral surface of the condyle in condylar head fractures, it is possible to spare the TFA, running lateral to the condylar neck, and the medial condylar surface in order to leave the branches that derive from the maxillary artery (MA) intact.

Introduction

Although condylar fractures account for 25% of all mandibular fractures [START_REF] Belli | Surgical evolution in the treatment of mandibular condyle fractures[END_REF] and most of them entail surgery, arterial supply to the mandibular condyle remains a subject of debate [START_REF] Godlewski | Arterial vascularization of the temporomandibular joint[END_REF][START_REF] Funakoshi | Nutrient arteries of the temporomandibular joint: an anatomical and pathologic study[END_REF][START_REF] Wysocki | Vascularization of the mandibular condylar head with respect to intracapsular fractures of the mandible[END_REF][START_REF] Touré | Arterial vascularization of the mandibular condyle and fractures of the condyle[END_REF]. Open reduction and internal fixation (ORIF) surgery appears to be the best treatment for condylar neck fractures in order to improve functional outcomes and prevent complications such as malocclusion [START_REF] Widmark | Open reduction of subcondylar fractures. A study of functional rehabilitation[END_REF][START_REF] Ea | Surgical treatment of adult mandibular condylar fractures provides better outcomes than closed treatment: a systematic review and meta-analysis[END_REF]. However, treatment of condylar head fractures [START_REF] Neff | Position paper from the IBRA Symposium on surgery of the head -the 2 nd International Symposium for condylar fracture osteosynthesis, Marseille, France, 2012[END_REF] by means of either physical therapy or surgery remains controversial [START_REF] Trost | Latest trends in the surgical management of mandibular condyle fractures in France, 2005-2012[END_REF][START_REF] Nogami | Clinical comparison between arthrocentesis and conventional conservative treatment with maxillmandibular fixation for unilateral high condylar fractures[END_REF][START_REF] Merlet | Outcomes of functional treatment versus open reduction and internal fixation of condylar fracture with articular impact: A retrospective study of 83 adults[END_REF]. Following physical therapy, although the normal anatomical structure of the condylar head is not restored, functional outcomes are good in most cases. Following ORIF of condylar process fractures, anatomical outcomes are good in most cases but carry a risk of facial nerve injury and a number of authors have reported condylar resorption [START_REF] Papadacki | Condylar resorption[END_REF][START_REF] Ellis | Treatment of mandibular condylar process fractures: biological considerations[END_REF][START_REF] Choi | Current concept in the mandibular condyle fracture management Part I: Overview of condylar fracture[END_REF]. Where the condylar process was detached from the mandible and extracorporeal fixation was performed, condylar head resorption was more common due to vascular disruption [START_REF] Gupta | Extracorporeal fixation of displaced mandibular condylar fracture: viable option[END_REF][START_REF] Boyne | Free grafting of traumatically disolaced or resected mandibular condyles[END_REF][START_REF] Davis | Free grafting of mandibular condyle fractures: clinical outcomes in 10 consecutive patients[END_REF][START_REF] Mikkonen | Osteotomy -osteosynthesis in displaced condylar fractures[END_REF]. The transverse facial artery (TFA) is considered as part of the arterial supply to the condylar process [START_REF] Cuccia | The arterial blood supply of the temporomandibular joint: an anatomical study and clinical implications[END_REF][START_REF] Yang | Neurovascular structures of the mandible angle and condyle: a comprehensive anatomical review[END_REF], yet there are no accounts of anatomic basis for preservation of the TFA when a preauricular approach to the condylar area is adopted. In order to investigate the risk of damage to the TFA related to a preauricular approach to the mandibular condyle process in condylar head or neck fractures, we examined the arterial supply of the condylar process and the distance between the TFA and the head of the condylar process.

Materials and Methods

Dissection Study

A dissection study was conducted on 10 fresh cadavers (20 condylar specimens dissected) at the Fer à Moulin School of Surgery in Paris, France. The common carotid arteries of the cadavers were injected with colored latex. The dissection technique was standardized: the cervical incision was extended in the preauricular and temporal regions. The platysma was lifted from the sternocleidomastoid muscle to the inferior border of the mandible. The common carotid artery, the carotid bifurcation, and the external carotid artery and its branches were dissected in the carotid and parotid regions. The mandibular condylar neck was transected to show the course of the maxillary artery and its branches. These anatomic components were all harvested en bloc to investigate the arterial blood supply of the condylar process (Fig. 1).

Radiologic Study

Fifty CT scans of the face with intravenous contrast were studied. Only 39 CT scans had sufficient contrast enhancement for the external carotid artery branches to be visible. The sex ratio was 18 females (46%) / 21 males (54%). Mean age was 46.9 years (range 19 to 88 years). The images were acquired between January 2012 and May 2015. Indications for CT scanning were facial cellulitis and pretreatment investigation of oral tumor spread. Three-dimensional reconstructions were obtained using Osirix software. After launching the software and selecting each patient from the database, the contrast-enhanced images were visualized and the facial artery was identified. Intravenous contrast enhancement was considered optimal when the facial artery was visible at the inferior border of the mandible bilaterally. The TFA was traced from the external carotid artery to the condylar process.

Vertical distance from the TFA to the top of the mandibular condyle head in true lateral view was measured (Fig. 2). Mean measurement values for both sides were calculated where the artery was visible on both right and left. Distance from the TFA to the lateral aspect of the mandibular condyle was measured in true axial view (Fig. 3).

Results

Dissection Study

The external carotid artery divided at the condylar neck into the superficial temporal artery which remained posterior to the condyle and the maxillary artery which ran medial to the condylar neck. The maxillary artery, after running adjacent to the medial aspect of the condylar neck, branched into the inferior alveolar artery (IAA) towards the mandibular canal. The maxillary artery and the IAA both contributed branches to the periosteum of the condylar process on its medial aspect. A vascular network was present in the vicinity of the TMJ capsule with multiple perforating vessels. This condylar vascular network was supplied by the maxillary artery and the IAA medially, and by the superficial temporal artery (STA) and TFA laterally. The STA contributed between one to three branches to the lateral aspect of the condyle (Figs. 4 and5) and the TFA contributed one to three branches to the condylar neck. In two cases, the TFA branched off from the bifurcation between the maxillary artery and the STA and in the remaining cases the TFA branched off from the STA. In each case, branches from the STA to the condyle were more distal than the origin of the TFA.

Radiologic Study (Table 1)

The TFA was visible on the right side in 37 patients and on the left side in 32 patients. On the right side the TFA was located at 1.88 +/-0.28 cm, and on the left side at 1.84 +/-0.27 cm. It was located on both sides in 30 patients. In these 30 patients, the TFA was located on both sides 1.84 +/-0.6 cm below the condylar process of the mandible (extreme values: 1.26 cm, 2.54 cm). The TFA ran 1.04 +/-0.56 mm lateral to the condylar process on the right side, and 1.15 +/-0.51 mm on the left side. In the 30 patients in whom the TFA was visible on both sides, it ran 1.09+/-0.54 mm lateral to the head of the mandibular condyle.

Discussion

Dissection demonstrated that the arterial supply of the mandibular condyle originates from a vascular network made up of maxillary and IAA arteries medially, and of the STA and TFA laterally. The TFA runs lateral to the junction between the condylar neck and the condyle in close proximity to its lateral side (1.09 mm) and 1.84 cm from the top of the condyle. In some cases the TFA was impossible to identify on CT imaging due to its small caliber. Distal to the origin of the TFA, one to three branches from the STA participate in arterial supply to the lateral aspect of the head of the condyle. Arterial blood supply to the temporomandibular joint is not completely understood [START_REF] Tagaki | Angiography of the temporomandibular joint. Description of an experimental technique with initial results[END_REF]. Therefore it is impossible to determine the potential consequences of sacrificing lateral arterial supply versus medial arterial supply to the condyle. Ellis and Throckmorton consider, when a preauricular approach is chosen, that entering the capsule of the joint can disrupt the already compromised blood supply to the condyle [START_REF] Ellis | Treatment of mandibular condylar process fractures: biological considerations[END_REF]. In condylar head fracture osteosynthesis, the lateral periosteum of the condyle should be elevated during surgery. Postoperative condylar resorption is more commonly reported in condylar head fractures [START_REF] Lizuka | Severe bone resorption and osteoarthrosis after miniplate fixation of high condylar fractures[END_REF], due to either the fracture itself or to the surgical approach, suggesting that where a preauricular approach is adopted, branches from the STA to the periosteum are unavoidably sacrificed, but preservation of the TFA running lateral to the condylar neck should be paramount wherever possible. In condylar neck fractures, lateral blood supply to the condyle should be preserved [Ellis], even if the TFA runs in close proximity to the condylar neck. According to Godlewski et al, who conducted an anatomic and radiologic study of the TMJ branches arising from the STA, the anterior tympanic and deep temporal arteries were present in all cases. Other branches arising from the TFA, the deep auricular artery and the middle meningeal artery, or sometimes directly from the MA were inconstant [START_REF] Godlewski | Arterial vascularization of the temporomandibular joint[END_REF]. Except for the TFA, all of the arteries supplying blood to the condyle were medial or posterior (STA). Funakoshi describes a branch of the inferior alveolar artery he considered to be the main nutrient artery of the TMJ [START_REF] Funakoshi | Nutrient arteries of the temporomandibular joint: an anatomical and pathologic study[END_REF]. According to Wysocki et al, in most cases the main source of condylar head vascularization is the inferior alveolar artery, but the TMJ capsule receives additional arterial blood supply from the STA, masseteric and external pterygoid arteries [START_REF] Wysocki | Vascularization of the mandibular condylar head with respect to intracapsular fractures of the mandible[END_REF]. In Touré's [START_REF] Touré | Arterial vascularization of the mandibular condyle and fractures of the condyle[END_REF] account of vascularization of the mandibular condyle, the posterior deep temporal artery, the STA, and arterial branches leading to the lateral pterygoid muscle emanating directly from the maxillary artery consistently provide blood supply to the condyle. The STA and masseteric arteries give off inconstant branches to the condyle according to Touré. Touré described an arterial quadrangle around the mandibular condyle made up of the STA posteriorly, the TFA laterally, the MA medially and the masseteric artery ventrally. We are more of the opinion that the mandibular condyle blood supply is composed, as it is in other joints (namely the glenohumeral and coxofemoral joints) of a "lateral circumflex artery" (the TFA) and a "medial circumflex artery" (the MA) giving off branches to the articular capsule in the vicinity of the condylar neck in addition to direct branches to the lateral aspect of the condyle originating from the STA. The STA and the TFA can be damaged during surgery to the condylar area [Yang]. In our study, branches emanating from the TFA were in all cases inferior (more proximal) to branches emanating from the STA. To prevent injury to the TFA in this type of surgical procedure, the position of the TFA at the lateral aspect of the condylar head must be clearly specified. Yang et al consider the TFA branches forwards from the STA approximately 1cm below the zygomatic arch, but any relation between the lateral aspect of the condyle and the TFA has yet to be studied [START_REF] Yang | Neurovascular structures of the mandible angle and condyle: a comprehensive anatomical review[END_REF]. Cuccia et al performed a radiologic study based on CT angiography. They concluded that the vascular supply appeared to come predominantly from the lateral and medial aspects of the condylar head. The arteries depicted as vascularizing the medial side were the inferior alveolar artery, the MA and the middle meningeal artery; the artery vascularizing the retrodiscal tissue was the STA; and the only artery vascularizing the lateral side of the condylar head was the TFA. However this study provided no information on the exact location of the TFA [START_REF] Cuccia | The arterial blood supply of the temporomandibular joint: an anatomical study and clinical implications[END_REF]. A radiologic doppler ultrasound study on the localization of the cutaneous branch of the TFA was performed on 40 healthy female volunteers in anticipation of skin flap surgery in the preauricular area [START_REF] Jacobovicz | Doppler ultrasound localization of the facial transverse artery cutaneous branch[END_REF]. Inferior and lateral distances of the emerging points of the cutaneous branch of the TFA were measured in relation to the lateral eyelid canthus. Mean values were 38 ± 4 mm inferior and 30 ± 4 mm lateral to the lateral canthus. Although this study is important for preservation of the cutaneous branches of the TFA during mobilization of facial skin flaps, it provides no information on vascularization of the mandibular condyle by the TFA. Yang et al, investigated the location of the TFA in relation to the parotid duct. According to Yang, the number of TFAs ranged from one (70.5% of the specimens) to three. The authors investigated the TFA inside the parotid gland but failed to address intraosseous branches leading to the condyle [START_REF] Yang | Topographical anatomy of the transverse cervical artery[END_REF]. Basar et al studied the TFA bilaterally on heads from 20 formalin-fixed cadavers. TFA relationships were determined using 5 anatomical landmarks: (1) the most superior point of the mandibular fossa, (2) the most inferior point of the articular tubercle, (3) the midpoint between the articular tubercle and temporozygomatic suture, (4) the parotid duct, and (5) the maxillary artery. No information was available on the relationship between the TFA and the condylar process of the mandible [START_REF] Basar | Accurate course and relationships of the transverse facial artery in human cadavers[END_REF]. Whetzel and Mathes showed that transection of the TFA occurred during face lift procedures [START_REF] Whetzel | The arterial supply of the face lift flap[END_REF]. According to Whetzel there is a risk of transection of this artery close to its origin when preauricular incisions are performed. In the event of condylar head fracture with substantial displacement, the blood supply emanating from the STA and the inferior alveolar artery is compromised [START_REF] Touré | Arterial vascularization of the mandibular condyle and fractures of the condyle[END_REF], hence it is important to preserve the TFA during surgery to the mandibular condyle. In our study the distance from the TFA to the top of the condyle was inferior to 2cm, and branches from the STA to the head of the condyle were always more distal than the origin of the TFA. When performing surgery on the condyle in condylar neck fractures, to spare the TFA the uppermost 2 cm of the lateral aspect of the condyle should be preserved during dissection. Due to the necessity for periosteal elevation of the lateral surface of the condyle in condylar head fractures, it is possible to preserve the TFA running lateral to the condylar neck and branches arising from the MA.

Figures legends

Fig. 1 .

 1 Fig. 1. Lateral view of right mandibular condyle after injection of colored latex into arteries and en bloc resection of mandibular condyle area (SUP = superior, POST = posterior). The external carotid artery (EC) divides into the superficial temporal artery (STA) and the maxillary artery which is medial to the condylar neck. The transverse facial artery (TFA) contributes two branches to the temporomandibular joint capsule (CB).

Fig. 2 .

 2 Fig. 2. . Lateral CT scan view of mandible (SUP = superior, ANT = anterior). The facial artery (FA) is visible on the lateral aspect of the mandibular corpus. Vertical distance between top of mandibular condyle and transverse facial artery (TFA) was measured.

Fig. 3 .

 3 Fig.3. Axial CT scan view of mandible (ANT = anterior, LAT = lateral) and mastoid process (MAST). The maxillary artery (MA) runs medial to the mandible (MAND); distance (D) between transverse facial artery (TFA) and mandible was measured.

Fig. 4 .

 4 Fig. 4. Lateral view of right mandibular condyle after injection of colored latex into arteries and en bloc resection of mandibular condyle area (SUP = superior, POST = posterior). The superficial temporal artery (STA) contributes one direct branch to the lateral aspect of the mandibular condyle (C), and the transverse facial artery (TFA) runs laterally to the neck of the mandibular condylar process.

Fig. 5 .

 5 Fig. 5. Lateral view of right mandibular condyle after injection of colored latex into arteries and en bloc resection of mandibular condyle area (SUP = superior, POST = posterior). The superficial temporal artery (STA) contributes 3 direct branches to the lateral aspect of the mandibular condyle (C), and the transverse facial artery (TFA) runs downwards lateral to the neck of the mandibular condylar process.

Disclosure of Interest

All authors declare no conflict of interest. CT scanner measures of the vertical distance between the top of the mandibular condyle and the transverse facial artery (TFA) and horizontal distance between the TFA and the mandibular condyle in a population of 39 patients.


Lepelletier
email: didier.lepelletier@chu-nantes.fr

Launay E b , Thomas E c Gras Leguen

Affiliation

to treat Staphylococcus aureus related-catheter bloodstream infection (CR-BSI) in neonates and children? A 8-year period (2010-2017) retrospective analysis in a French University Hospital

INTRODUCTION

Catheter-related-bloodstream infection (CR-BSI) incidence ranges from 0.2 to 11 per 1000 catheter days in neonates and children, and is associated with various clinical symptoms and morbidity [START_REF] Abi Nader | Outcome of home parenteral nutrition in 251 children over a 14-y period: report of a single center[END_REF]. These infections are associated with high morbidity, especially for at-risk patient groups, such as preterm neonates, immunocompromised children, children with renal insufficiency.

The most commonly reported causative pathogens remain coagulase-negative staphylococci and Staphylococcus aureus [START_REF] Fagan | Incidence trends in pathogenspecific central line-associated bloodstream infections in US intensive care units, 1990-2010[END_REF]. The treatment of CR-BSI is based on empiric antibiotherapy (in France mainly with vancomycin, sometimes in association with other antibiotics) with two possible options regarding the catheter: non-conservative treatment (catheter removal <72 hours) or conservative treatment (the catheter is not removed or removed ≥72 hours).

Contrary to the adult patients, withdrawing the catheter is not systematic in neonates and children, mainly because of difficulties in the anatomic site approaches, as well as the risk of new infection onto the new catheter. Conservative treatment is therefore more common in neonates and children than in adults even if local and general complications can occur [START_REF] Carrillo-Marquez | Clinical and molecular epidemiology of Staphylococcus aureus catheter-related bacteremia in children[END_REF].

The aim of this study was to compare the incidence of failure in children with S. aureus CR-BSI with or without conservative treatment, in order to help hospitals and pediatricians to develop specific strategies for S. aureus CR-BSI management.

METHODS

Study design, patients and definitions

We performed a retrospective analysis from a cohort of children hospitalized from January 2010 to December 2017 at the Nantes University Hospital including a 60-bed Neonatal Department with an average of 1,100 admissions per year. We selected all positive S. aureus blood cultures from the laboratory database during the study period among hospitalized neonates and children <18 years old. We collected the following data: Age, sex, gender, type/dates of placement and removal of central venous catheter (CVC), clinical symptoms of CR-BSI, microbiological data related to the S. aureus positive blood cultures, initial and adapted antibiotic therapy, failure associated with the CVC after treatment (relapse or recurrence, outcomes). CR-BSI was included when S. aureus was isolated from the blood culture with standard definition [START_REF] Ekkelenkamp | Bacteremic complications of intravascular catheters colonized with Staphylococcus aureus[END_REF]. Non conservative treatment was defined when the CVC was rapidly removed before 72 hours after the onset CR-BSI. Conservative treatment was defined when the catheter was not removed during the treatment duration or after 72 hours [START_REF] Park | Development of bacteraemia or fungaemia after removal of colonized central venous catheters in patients with negative concomitant blood cultures[END_REF]. Treatment failure was defined as the persistence of positive blood cultures, onset or aggravation of a local infectious complication (abscess, tunnelitis) or systemic complication (thrombosis, endocarditis, sepsis) or relapse (infection with the same S. aureus in the 4 to 12 weeks). Salvage was considered successful if the catheter was still in place after 12 weeks and there was no recurrent bacteremia or CR-BSI death [START_REF] Mermel | Clinical practice guidelines for the diagnosis and management of intravascular catheter-related infection: 2009 Update by the Infectious Diseases Society of America[END_REF].

Statistical analyses

Results were analyzed using STATA V15® software (StataCorp LP, Texas, USA).

Categorical variables were evaluated using the chi-square or Fisher's exact test. Continuous variables were compared using the t test or the Mann-Whitney U test, where appropriate. All tests of significance were two-tailed, and a P values <0.05 were considered statistically significant. Predictive factors for catheter salvage outcome were analyzed by performing a backward stepwise logistic regression analysis.

RESULTS

Patient characteristics

During the 8-years period study, 471 blood cultures positive for S. aureus were extracted from the laboratory database. A given patient, over a given period (several days mainly) could present several positive blood cultures during the same infectious episode. Thus, we identified 225 infectious episodes with S. aureus during the study period. We excluded 155 of S. aureus infectious in patients without CVC. In total, there were 57 CR-BSI among the 70 neonates and children with CVC. The median age of children was 4 years (±5.6). The characteristics of children are presented in Table 1. Blood cultures were positive for at least one other infectious agent in 10 neonates or children (18%), mainly S. epidermidis. Only one strain of S. aureus was methicillin-resistant (MRSA). The use of a preventive antibiotic lock was not common practice for children in this study.

Treatment and failures

Three dates of CVC removal were not available in the medical records. Empiric antibiotic therapy was prescribed within two days for all patients following the onset of infection.

Vancomycin was the most used antibiotic used (72%) , usually in association with other antibiotics (62%). Thirty-three treatments were conservative without CVC removal within 72 hours (61.1%) and 21 treatments were non-conservative with a rapid CVC removal (38.8%) for the infection management. Three (9.1%) and 10 (47.6%) failures were observed in the two groups, respectively (P<0.002). Failures in both groups are detailed in Table 2.

Determination of predictive factors for conservative treatment failures

We analyzed the predictive factors associated with failures after conservative and nonconservative treatment in 54 children. Sepsis within 3 days after the onset infection was the only risk factor identified, independently of the type of treatment (conservative or not) (P=0.02).

DISCUSSION

National guidelines for non-conservative treatment with systematic removal of the CVC within three days for S. aureus CR-BSI in adults are based on different publications showing high rates of treatment failures (>40%) when the CVC is not rapidly removed [START_REF] Kim | Outcomes of Hickman catheter salvage in febrile neutropenic cancer patients with Staphylococcus aureus bacteremia[END_REF]. But no study has been carried out and published in neonates and children in France. The aim of our study was to state if the consequences of pediatric catheterization without systematic removal at the onset of CR-BSI may provide guidelines and confirm those used in adults. The main result of our study is that the incidence of failures occurring after conservative treatment is significantly higher than those after non-conservative treatment in neonates and children. This finding may be essential in helping paediatricians to manage CR-BSI in neonates and children, even if our results should be interpret with cautious according to the small size of our sample, the probable impact of age and the type of CVC. S. aureus CR-BSI are associated with high morbidity, especially for at-risk patients and non-conservative treatment to manage S. aureus CR-BSI should be privileged. Moreover, if catheter removal is one of the main factors to prevent CR-BSI, prevention of CR-BSI should integrate a multidisciplinary bundle of measures involving healthcare professionals who prescribe the CVC insertion and removal, those personnel who insert and maintain CVC, infection control personnel and healthcare managers. The goal of an effective prevention program should be the elimination or drastic decrease of CR-BSI in ICUs [START_REF] Pronovost | An intervention to decrease catheter-related bloodstream infections in the ICU[END_REF]. Although this is challenging, educational trainings have demonstrated success, but sustained elimination requires continued effort.

Most of the 57 neonates and children were young or very young, with high susceptibility to infections. The duration of catheterization was variable, from several days to several months.

In case of long duration of catheterization, CVC are changed during hospitalization to treat them using a non-conservative treatment strategy or to prevent the occurrence of CR-BSI.

We also focused on the conservative strategy of treatment without removal of the catheter or in a time greater than 72 hours. Catheter removal in neonates and children is less systematic, mainly because of the difficulty of the approaches. After identifying 21 infectious episodes with CVC conservation, we studied the modality of therapeutic management, as well as its failure rate and its causes. The initial antibiotic treatment is mainly a dual therapy, combining vancomycin with another antibiotic. This practice follows international recommendations for fast, broad spectrum management. However, the failure rate of conservative treatment was about 50%, compared to only 9% in a rapid removal strategy. The main causes of failure were the persistence of positive blood cultures as well as the occurrence of complications (thromboses, tunnelitis, etc.). We can observe that there is a gap between international recommendations in adults and local practices in pediatric services. This discrepancy was noted due to a more frequent conservative treatment strategy, as well as the non-use of antibiotic lock. We were unable to identify factor associated with failure in conservative group because of the small size of our sample. This is one of the limitations of our study, as those S. aureus CR-BSI are relatively rare events. Another limitation of our study is the lack of information related to the type of CVC in medical records. This information could have been relevant as occurrence of CR-BSI and failures of conservative treatment may be linked to the type of CVC. In conclusion, our study shows that non-conservative treatment with rapid removal of CVC is associated with significant lower failure rate and should be preferred by pediatricians managing S. aureus CR-BSI. Further multicentre researches with large cohort of neonates and children are needed to comfirm our finding and identify the role of host and CVC factors to prevent S. aureus CR-BSI.

Table 1 .

 1 Characteristics of neonates and children with catheter-related bloodstream infection (CR-BSI) (2010-2017)

	Patients

Table 2 .

 2 Characteristics of failures after conservative (N=33) and non-conservative (N=21) treatments for S. aureus CR-BSI* *The date of central venous catheter removal was not available for three children

	Failures	Failures by type of treatment
		Non-conservative	Conservative
		(N=3)	(N=10)
	Persistence of S. aureus positive	-	4
	blood cultures
	Outcomes
	Tunnelitis	-	2
	Thrombophlebitis	-	1
	Local abscess	-	1
	Relapse within 30 days	3	2
	Infection attributable mortality	0	2


Dr Damien Offner
email: doffner@unistra.fr

Lucien Brisset

Anne-Marie Musset

Evaluation of the mechanical cleaning efficacy of dental handpieces

Keywords: sterilization, disinfection, dentistry, safety, cross-infection, washer-disinfector

Objective: Dental handpieces undergo a decontamination process before reutilization. Thorough cleaning is a prerequisite to effective sterilization, to guarantee safety and prevent cross-infections.

The objective of this study was to assess the cleaning efficacy offered by devices dedicated to dental handpieces.

Material and methods

: PIDTests©, which are patented tubes made out of transparent material and designed to replace handpieces in cleaning devices, were artificially stained by Soil Test© (Browne/STERIS). Three cycles were performed with PIDTests© connected to every handpiece adapter in the 4 different machines tested: X-Cid 2© (Micro-Mega) with a total of 9 PIDTests©; iCare+© (NSK) with 9 PIDTests©; DAC Universal© (W&H) with 18 PIDTests©; and BioDA 80© (VR2M) with 24 PIDTests©. A visual evaluation and a biuret reaction test were performed. Results: In 3 of the tested cleaning devices (X-Cid2©, iCare+© and DAC Universal©), all of the PIDTests© showed Soil Test© residues, on the internal and external surfaces indicating cleaning was ineffective. Only the BioDA 80© showed no residual stains on all the PIDTests© and negative biuret reaction test results, making the cleaning effective. Conclusion: Manufacturers should optimize the cleaning device parameters, based on the Sinner circle (grouping compensatory parameters which influence the effectiveness of a cleaning process, such as pressure, temperature, time, detergent concentration), to improve cleaning efficacy and enable dental surgeons to ensure the safety. Although PIDTest© are the only tool to provide visual indications on the cleaning efficacy of washer-disinfectors dedicated to handpieces, manufacturers should continue with the development of improved and validated tools to assess cleaning efficacy.

Introduction

Dental handpieces (HP) are medical devices that are largely used in dental procedures. Utilised in a patient's mouth, they are inevitably soiled and contaminated on their external surface by biological fluids such as blood, saliva, pus, or dentinal smear layer [START_REF] Winter | Failure of non-vacuum steam sterilization process for dental handpieces[END_REF][START_REF] Smith | Microbial contamination of used dental handpieces[END_REF][START_REF] Offner | Cleaning of dental handpieces: a method to test its efficiency, and its evaluation with a washer-disinfector-lubricator-dryer[END_REF]. Moreover, many studies report a phenomenon of backflow when HP stop running [START_REF] Winter | Failure of non-vacuum steam sterilization process for dental handpieces[END_REF][START_REF] Smith | Microbial contamination of used dental handpieces[END_REF][START_REF] Offner | Cleaning of dental handpieces: a method to test its efficiency, and its evaluation with a washer-disinfector-lubricator-dryer[END_REF][START_REF] Petti | Detection of oral streptococci in dental unit water lines after therapy with air turbine handpiece: biological flui retractation more frequent than expected[END_REF][START_REF] Chin | Internal contamination of air-driven low-speed handpieces and attached prophy angles[END_REF][START_REF] Chin | Contamination of handpieces during pulpotomy therapy on primary teeth[END_REF]. Consequently, these devices are also soiled and contaminated on their inner surfaces (narrow air/water manifolds, drive shaft, gears); allowing potential cross-infections [START_REF] Offner | Cleaning of dental handpieces: a method to test its efficiency, and its evaluation with a washer-disinfector-lubricator-dryer[END_REF][START_REF]Summary of infection prevention practices in dental settings: basic expectations for safe care[END_REF][START_REF] Acosta-Gio | Letters to the Editor -Sterilization of dental handpieces[END_REF][START_REF] Lewis | Cross-infections risks associated with current procedures for using highspeed dental handpieces[END_REF][START_REF] Offner | Hygiene management of dental units: speaking about patients' safety[END_REF] and a dangerous microbial quality of the water which runs through the dental unit [START_REF] Petti | Detection of oral streptococci in dental unit water lines after therapy with air turbine handpiece: biological flui retractation more frequent than expected[END_REF][START_REF] Chin | Internal contamination of air-driven low-speed handpieces and attached prophy angles[END_REF][START_REF] Offner | Hygiene management of dental units: speaking about patients' safety[END_REF][START_REF] Weightman | Problems with the decontamination of dental handpieces and other intra-oral dental equipment in hospitals[END_REF]. Indeed, hepatitis B viruses and Staphylococcus aureus have already been found on the inner surfaces of HP [START_REF] Smith | Microbial contamination of used dental handpieces[END_REF][START_REF] Deng | The possibility of hepatitis B virus transmission through dental handpieces[END_REF]. These biofoulings and contaminations mean that, HP are classified as semi-critical reusable medical devices regarding the Spaulding classification. They have to undergo a sterilization process in order to prevent cross-infections and guarantee the safety of care [START_REF] Winter | Failure of non-vacuum steam sterilization process for dental handpieces[END_REF][START_REF] Offner | Cleaning of dental handpieces: a method to test its efficiency, and its evaluation with a washer-disinfector-lubricator-dryer[END_REF][START_REF] Chin | Internal contamination of air-driven low-speed handpieces and attached prophy angles[END_REF][START_REF] Chin | Contamination of handpieces during pulpotomy therapy on primary teeth[END_REF][START_REF] Acosta-Gio | Letters to the Editor -Sterilization of dental handpieces[END_REF][START_REF]Guide de prévention des infections liées aux soins en chirurgie dentaire et en stomatologie[END_REF][START_REF] Herd | The in-vivo contamination of air-driven low-speed handpieces with prophylaxis angles[END_REF][START_REF] Deshpande | Biofouling of surgical power tools during routine use[END_REF][START_REF]Decontamination and reprocessing of medical devices for healthcare facilities[END_REF][START_REF] Pinto | The practice of disinfection of high-speed handpieces with 70% w/v alcohol: an evaluation[END_REF]. To ensure the efficacy of sterilization, the steam must reach the internal cavities and surfaces of HP [START_REF] Winter | Failure of non-vacuum steam sterilization process for dental handpieces[END_REF][START_REF] Offner | Cleaning of dental handpieces: a method to test its efficiency, and its evaluation with a washer-disinfector-lubricator-dryer[END_REF][START_REF] Deshpande | Biofouling of surgical power tools during routine use[END_REF][START_REF] Smith | Survey of the decontamination and maintenance of dental handpieces in general dental practice[END_REF]. A class B steam sterilizer complying with the standard EN 13060 is then required for the vacuum sterilization process [START_REF] Winter | Failure of non-vacuum steam sterilization process for dental handpieces[END_REF]. An unavoidable prerequisite is that HP must have prior thorough cleaning [START_REF]Summary of infection prevention practices in dental settings: basic expectations for safe care[END_REF][START_REF]Guide de prévention des infections liées aux soins en chirurgie dentaire et en stomatologie[END_REF][START_REF] Pinto | The practice of disinfection of high-speed handpieces with 70% w/v alcohol: an evaluation[END_REF][START_REF] Thiveaud | Le lavage: l'étape essentielle en milieu hospitalier[END_REF][START_REF] Wilder | Cleaning of instruments: an absolute requirement for successful reprocessing[END_REF]. According to the standard ISO 15883 part 2 (performance of washer-disinfectors), this cleaning process has to be performed during an internal rotation of HP. Although manufacturers of HP provide instructions for cleaning these devices, there are no validation processes [START_REF] Smith | Survey of the decontamination and maintenance of dental handpieces in general dental practice[END_REF]., Apart from visual assessment which is only feasible on the external surfaces, as reported in standard ISO 15883, there is a methodological gap regarding HP cleaning evaluation [START_REF] Offner | Cleaning of dental handpieces: a method to test its efficiency, and its evaluation with a washer-disinfector-lubricator-dryer[END_REF].

Moreover, there is a lack of information [START_REF] Osegueda-Espinosa | Dentists survey on adverse events during their clinical training[END_REF][START_REF] Röhm-Rodowald | Assessment of decontamination processes: cleaning, disinfection and sterilization in dental practice in Poland in the years 2011-2012[END_REF] and results [START_REF] Winter | Failure of non-vacuum steam sterilization process for dental handpieces[END_REF][START_REF] Offner | Cleaning of dental handpieces: a method to test its efficiency, and its evaluation with a washer-disinfector-lubricator-dryer[END_REF][START_REF] Pinto | The practice of disinfection of high-speed handpieces with 70% w/v alcohol: an evaluation[END_REF] regarding the condition of inner surfaces, and there is a need for tools to facilitate this assessment [START_REF] Offner | Hygiene management of dental units: speaking about patients' safety[END_REF][START_REF] Alfa | Monitoring and improving the effectiveness of cleaning medical and surgical devices[END_REF]. Often, HP are not reprocessed in accordance with recommendations [START_REF] Smith | Survey of the decontamination and maintenance of dental handpieces in general dental practice[END_REF][START_REF]INVS. Analyse du risque infectieux lié à la non-stérilisation entre chaque patient des porte-instruments rotatifs en chirurgie dentaire[END_REF], and mathematical modeling conducted by the national institute of health surveillance (INVS) showed that each year, in France, the poor reprocessing of HP could be responsible for 200 cross-transmissions of hepatitis B, 2 of hepatitis C, and one of HIV [START_REF]INVS. Analyse du risque infectieux lié à la non-stérilisation entre chaque patient des porte-instruments rotatifs en chirurgie dentaire[END_REF]. The practice of disinfection of HP with 70% w/v alcohol appears inadequate to thoroughly clean and disinfect these devices [START_REF] Pinto | The practice of disinfection of high-speed handpieces with 70% w/v alcohol: an evaluation[END_REF]. Moreover, it is not recommended to soak HP in any disinfectant solution [START_REF] Acosta-Gio | Letters to the Editor -Sterilization of dental handpieces[END_REF][START_REF] Dretz-Bourguignon | Infection control techniques in the dental office, Chapter 8 -Instrument recirculation[END_REF], due to corrosion risks, and because air bubbles in inner lumens can reduce the activity of the disinfectant [START_REF] Comident | Guide de traitement des porte-instruments dynamiques avant stérlisation[END_REF]. A daily maintenance regime that follows the manufacturer's instructions also significantly reduces damage to HP [START_REF] Comident | Guide de traitement des porte-instruments dynamiques avant stérlisation[END_REF][START_REF] Angelini | Influence of sterilization on the corrosion resistance of high-speed dental handpieces[END_REF]. architecture, their fragility, and narrow lumens [START_REF] Winter | Failure of non-vacuum steam sterilization process for dental handpieces[END_REF][START_REF] Offner | Cleaning of dental handpieces: a method to test its efficiency, and its evaluation with a washer-disinfector-lubricator-dryer[END_REF][START_REF] Acosta-Gio | Letters to the Editor -Sterilization of dental handpieces[END_REF][START_REF] Weightman | Problems with the decontamination of dental handpieces and other intra-oral dental equipment in hospitals[END_REF][START_REF] Deshpande | Biofouling of surgical power tools during routine use[END_REF]. Novel methods have been proposed to assess the cleaning, but their implementation was too technical to be routinely utilised in hospitals or private practices [START_REF] Offner | Cleaning of dental handpieces: a method to test its efficiency, and its evaluation with a washer-disinfector-lubricator-dryer[END_REF]. However, many manufacturers of cleaning devices advocate that their apparatuses dedicated to HP can ensure adequate cleaning [28][START_REF]Presentation of the DAC Universal© on the W&H website[END_REF][START_REF]Presentation of the X-Cid2© on the Micro-Mega website[END_REF][START_REF]Presentation of the iCare+© on the NSK website[END_REF].

One of the main challenges regarding cleaning HP is in measuring and proving efficacy both for internal and external surfaces. Whilst ISO 15883 describes a number of methods for assessing the surface cleanliness of reusable medical devices, there is no specific procedure for evaluating the efficacy in dental HP. [START_REF] Smith | Survey of the decontamination and maintenance of dental handpieces in general dental practice[END_REF] The control and measurement of cleaning efficacy of internal and external surfaces of HP by different devices on the market is therefore of paramount importance to ensure the quality, safety and consequently the sustainability of dental care.

Material and methods

The objective of our study was to assess the cleaning efficacy of some devices dedicated to the cleaning of dental HP. To perform such an evaluation, we used a new cleaning assessment tool, which has been patented, PIDTest© (VR2m, Saint-Cyr-en-Val, France). The name is derived from the French acronym "PID" (porte-instrument dynamique) meaning dental handpiece. We assessed the cleaning offered by 3 different cleaning devices: X-Cid 2© (Micro-Mega, Besançon, France), iCare+© (NSK, Paris, France), DAC Universal© (W&H, Eckbolsheim, France); and a washer-disinfector: BioDA 80© (VR2M, Saint-Cyr-en-Val, France).

The PIDTest© consists of a tube made out of a transparent material whose closed end presents an orifice of a diameter equal to the normalized diameter (ISO 14457) of a rotary tool (1.6mm). The other end, whose inner lumen diameter is equal to the standard diameter of a HP (ISO 3964), has two lateral vents allowing the correct filling of the device during the cleaning phase. Due to their normalized dimensions, PIDTests© are can be inserted and connected into washer-disinfectors instead of HP during the test cycle (Figure 1).

The internal and external surfaces of PIDTests©, meant to model the internal and external surfaces of a dental HP, were brushed to half-height with a fouling test (Soil Test©, Browne/STERIS, Le Haillan, France) and allowed to dry for 12 hours, which corresponds to the drying time for the Soil Test©. Soil Test© was chosen due to its adaptability and adequacy with biological fouling, equivalent to the soil test described in ISO 15883 part 5 Annex N [START_REF] Offner | Cleaning of dental handpieces: a method to test its efficiency, and its evaluation with a washer-disinfector-lubricator-dryer[END_REF][START_REF] Rochefort | Qualification et requalification des laveurs-désinfecteurs[END_REF]. PIDTests© were then connected to all of the contra-angle adapters of the 4 devices and a clean cycle was performed, in accordance with the manufacturer's recommendations (Figure 2). Each of the four cleaning devices (X-Cid2©, iCare+©, DAC Universal©, BioDA 80©) were tested for 3 cycles (Figure 3). same light conditions). If Soil Test© stains were visible to the naked eye, the cleaning was described as ineffective. If there were no stains, a biuret reaction using swabs (CleanTrace© Surface Test Protein Plus, 3M, Cergy, France) was performed to detect residual proteins. All the surfaces were rigorously rubbed with the swabs, and were then incubated at 55°C for 15 minutes, as specified by the manufacturer.

-If the biuret reaction test was positive (presence of residual proteins), the cleaning was described as ineffective. If the biuret reaction test was negative (absence of residual proteins), the cleaning was described as successful (Figure 4).

Results

Every control test used in this study remained soiled, visible to the naked eye, and the biuret reaction tests were positive for these control tests (Figure 5). PIDTests© detected Soil Test© stains visible to the naked eye, both on their internal and external surfaces following cleaning in X-Cid2©, iCare+©, and DAC Universal© devices making the cleaning ineffective (Table 1) (Figure 5). All of the PIDTests© showed an absence of Soil Test© residues visible to the naked eye, both on the internal and external surfaces following cleaning with BioDA 80©. Biuret reaction tests were negative for all of these PIDTests©, indicating the cleaning effective (Table 1) (Figure 5).

Discussion

Dental HP are reusable medical devices which undergo a sterilization process, their prior cleaning is a crucial step [START_REF] Wilder | Cleaning of instruments: an absolute requirement for successful reprocessing[END_REF][START_REF] Alfa | Monitoring and improving the effectiveness of cleaning medical and surgical devices[END_REF][START_REF] Bagg | Pre-sterilization cleaning of re-usable instruments in general dental practice[END_REF]. PIDTests© are easy to handle tools, designed to simply assess the cleaning efficacy of a HP cleaning device. Nevertheless, there is no publically available manufacturer report which describes the validation for these surrogate devices at this time. Conclusions about this study should therefore be used with caution. Indeed, PIDTests© do not contain internal channels and rotary parts, and their surfaces are smooth and straight, and consequently do not reproduce the complexity of a HP's inner architecture. Thus, a pass result on the surrogate device does not mean that the dental HP has be adequately cleaned, and equally a fail on the surrogate device does not mean that the dental HP been insufficiently cleaned. However, PIDTests© are designed to model the surfaces of HP, and to give some indications about the cleaning efficacy. Since there is no other tool on the market for this purpose [START_REF] Offner | Cleaning of dental handpieces: a method to test its efficiency, and its evaluation with a washer-disinfector-lubricator-dryer[END_REF][START_REF] Smith | Survey of the decontamination and maintenance of dental handpieces in general dental practice[END_REF], these indications could be helpful, even if they are not complete to conclude about the real efficacy of a cleaning device.

The non-complex architecture of a PIDTest© compared to a real HP could be a first step to a cleaning validation, and could be a way to improve cleaning devices which demonstrate a poor cleaning efficacy. Indeed, a machine that is not able to clean a prepared PIDTest© with a simple architecture is unlikely to present better results with a HP. These surrogate devices could be improved in the future by developing further tools mimicking the inside of a HP, potentially using 3D printing techniques and validated materials with equivalent physical properties to HP (drying characteristics, surface adherence, etc.).

In our study, among the four devices we tested, only one (BioDA80©) achieved adequate cleaning of PIDTests© on inner and outer surfaces. There may be several reasons for this. On the one hand, these results could be explained by the non-compliance with the Sinner circle. Indeed, the effectiveness of a cleaning process depends on the Sinner circle's four factors: mechanical action, chemical action, time for action and temperature [START_REF] Adé | Comparison of decontamination efficacy of cleaning solutions on a biological safety cabinet workbench contaminated by cyclophosphamide[END_REF]. If one of these cannot be optimized, its lack needs to be outweighed by an increase in the other factors, and that is the reason it is presented as a circle. Some of the devices we tested only deliver a cold process, that is not counterbalanced with an increase of the pressure (which represents the mechanical action) to clean the devices, or with an increase in the processing time. Indeed, manufacturers highlight the speed of the cleaning cycle while cleaning is not a matter of speed, but of efficacy. Concerning the X-Cid2© for example, although it uses a detergent-disinfectant complying with standards EN 1040, 1275, 14563 and 13727 during its cycle, this parameter was not sufficient to clean PIDTests© and should be coupled with a hot process and/or an increase of the pressure of the cleaning solution. These parameters (pressure, temperature, time, and detergent concentration) should be optimized by manufacturers to offer a better cleaning efficacy. On the other hand, we chose to allow the Soil Test© to dry for 12 hours while standard ISO 15883 part 5 only demands a 2 hours drying time. This certainly represents a harder challenge to the cleaning process than original type tests by the manufacturer. Although the soil is meant to be representative of native soiling which in practice is not meant to be totally dry, we know that in general practice, unfortunately, it is likely that a great amount of HP do not benefit from adequate reprocessing [START_REF] Smith | Survey of the decontamination and maintenance of dental handpieces in general dental practice[END_REF][START_REF]INVS. Analyse du risque infectieux lié à la non-stérilisation entre chaque patient des porte-instruments rotatifs en chirurgie dentaire[END_REF], and an average of only 10% of HP undergo a cleaning process aimed at cleaning their internal surfaces [START_REF] Smith | Survey of the decontamination and maintenance of dental handpieces in general dental practice[END_REF]. Thus, we can easily imagine that some HP are left to air dry during a whole night without having been previously cleaned inside, allowing stains to dry for 12 hours. Moreover, this situation could as well represent an exceptional forgetfulness from the practitioner or his/her dental assistant, and it seems important to be able to show that the consequently dry stains are not permanent and that there is a way to remove them. It should be noted that even if the manufacturer of the Soil Test© advocates a 30 minutes to 2 hours drying time, usual practices in sterilization departments of European hospitals are of at least 12 hours drying time [START_REF]Procédure pour l'utilisation des tests de salissures dans les laveurs-désinfecteurs[END_REF][START_REF] Cavin | Comment tester un detergent en pratique hospitalière[END_REF][START_REF] Reichling | Evaluation de l'efficacité de detergence d'un nouveau détergent pré-désinfectant liquide[END_REF].

Other machines designed to clean HP exist on the market. Some of them, just like the DAC Universal©, do not put HP in rotation during the cycle, and thus are not in accordance neither with recommendations [START_REF]Guide de prévention des infections liées aux soins en chirurgie dentaire et en stomatologie[END_REF] nor with the standard ISO 15883 relative to general performance requirements for washer-disinfectors. Indeed, it has been shown that a lack of internal rotation produces an incomplete clean because fluids cannot reach all the surfaces of HP [START_REF] Offner | Cleaning of dental handpieces: a method to test its efficiency, and its evaluation with a washer-disinfector-lubricator-dryer[END_REF]. Consequently, these devices have not been tested. The DAC Universal© has been tested because of its wide utilization by dental surgeons.

Since PIDTests© are the only tools to provide visual indications about the cleaning efficacy of washer-disinfectors to date, on both external and internal surfaces, these surrogate devices represent an interesting option for the initial qualifications (operational and performance qualifications) of a washer-disinfector required in the standard ISO 15883, but also for routine tests.

However, it is important to keep in mind that as long as there is no documented validation for these tools, PIDTests© can only deliver indications and no opposable results. Therefore, two strategies should be considered in the future : [START_REF] Winter | Failure of non-vacuum steam sterilization process for dental handpieces[END_REF] to validate the PIDTest©, or to develop a more precise tool in the line of the idea of a cost-effective solution to fill the methodological gap that prevents an easy and accurate assessment of the cleaning offered by cleaning devices dedicated to HP [START_REF] Offner | Cleaning of dental handpieces: a method to test its efficiency, and its evaluation with a washer-disinfector-lubricator-dryer[END_REF][START_REF] Offner | Hygiene management of dental units: speaking about patients' safety[END_REF][START_REF] Röhm-Rodowald | Assessment of decontamination processes: cleaning, disinfection and sterilization in dental practice in Poland in the years 2011-2012[END_REF], and

(2) to work on the dental surgeons' behavior regarding hygiene procedures deploying various methods [START_REF] Offner | Evaluation of an ethical method aimed at improving hygiene rules compliance in dental practice[END_REF] in order to use more accurate tests compared to real general practice, for which a 2 hours drying time of the soil test would be sufficient, as described in the standard ISO 15883.

Conclusions

Dental HP are reusable semi-critical medical devices that need to undergo a decontamination process before their reutilization. A thorough clean is an unavoidable prerequisite to an effective sterilization, guaranteeing the safety of care and the prevention of cross-infections. Until now, no simple method had been proposed to evaluate the cleaning process which is offered by washerdisinfectors dedicated to HP without having to destroy HP in order to see their internal surfaces.

PIDTest© seems to be an interesting and easy-to-handle tool to provide further information about this cleaning, although it needs further validation. It provided indications about the cleaning efficacy of three different cleaning devices and one washer-disinfector, in deliberately difficult conditions. Among the X-Cid2©, iCare+©, DAC Universal© and BioDA 80©, only the BioDA 80© met the requirements for the cleaning process, in this study. The general cleaning difficulties offered by devices which are available on the market raises public health issues with a negative impact on the quality, the safety and the sustainability of dental care. Manufacturers should optimize some of their device parameters, according to the Sinner circle (pressure, temperature, time, detergent concentration), to reach a real cleaning efficacy, with development of improved and validated tools to assess the cleaning efficacy of cleaning devices dedicated to HP.

Figure legends :

3

  cycles of the X-Cid2© (3 connections) corresponded to 9 PIDTests©. 3 cycles of the DAC Universal© (6 connections) corresponded to 18 PIDTests©. 3 cycles of the iCare+© (3 connections, plus 1 connection specific to a dental turbine not tested) corresponded to 9 PIDTests©. 3 cycles of the BioDA 80© (8 connections) corresponded to 24 PIDTests©. After each cleaning cycle, the PIDTests© were analyzed according to standard ISO 15883, and compared to a control test corresponding to a PIDTest© which has not been subjected to any cleaning cycle:

Figure 1 :

 1 Figure 1: (A) A PIDTest© and its schematic view. (B) PIDTests© adapted to cleaning devices

Figure 2 :Figure 3 :

 23 Figure 2: (A, B, C) Preparation of PIDTests© with Soil Test©. (D) Prepared PIDTests© let to dry. (E) PIDTests© are soiled on their inner (left) and outer (right) surfaces and (F) connected to the cleaning device

Figure 4 :

 4 Figure 4: Cleaning assessment procedure

Figure 5 :

 5 Figure 5: PIDTests© after the cleaning cycle (T=control test), following manufacturer's recommendations for (A) X-Cid2©, (B) iCare+©, (C) DAC Universal©, and (D) BioDA80© with additional biuret reaction tests

Table I :

 I Results from the cleaning devices

			Visual evaluation	Biuret reaction
	Automaton	Total number of PIDTests©	External	Internal	test	Cleaning
			surface	surface	(if applicable)
	X-Cid2©	9	Soiling (9 tests)	Soiling (9 tests)	Not applicable	Ineffective
	iCare+©	9	Soiling (9 tests)	Soiling (9 tests)	Not applicable	Ineffective
	DAC Universal©	18	Soiling (18 tests)	Soiling (18 tests)	Not applicable	Ineffective
	BioDA 80©	24	No soiling (24 tests)	No soiling (24 tests)	(24 tests) Negative	Effective

Acknowledgment:

The authors would like to thank the company NSK and the company VR2M for having lent respectively the iCare+© and the BioDA 80© we used to perform the tests.

Funding: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Conflict of interest: none


Dr Pauline Jouët
email: pauline.jouet@aphp.fr

MD, Ph D Hôpital Ambroise Paré

Service diététique Nathalie Morel
email: nathalie.morel2@aphp.fr

Keywords: carbohydrates, gluten, diet, irritable bowel syndrome, FODMAPs

FODMAPs is an acronym for Fermentable Oligo-, Di-, Monosaccharides And Polyols, and refers to rapidly fermentable carbohydrates that may be malabsorbed and induce digestive disorders such as abdominal pain, bloating, flatulence and transit disorders. Numerous studies have tested the effect of reducing foods rich in FODMAPs in patients with irritable bowel syndrome, a benign chronic gastrointestinal disease associating abdominal pain and transit disorders (diarrhea, constipation or alternating), and are in favor of a beneficial effect of this diet. The effectiveness of the low FODMAPS diet is unpredictable. This very restrictive diet is difficult to follow, can lead to weight loss, and has been associated with dysbiosis. It is therefore not recommended to follow it in the long term. It may be offered as a second-line treatment if standard dietary recommendations fail in patients sufficiently embarrassed by their symptoms to accept its constraints. It is preferably carried out with the supervision of a dietician trained on this diet because of its complexity and the risk of long-term dietary restrictions. It is usually tested for a period of 4 weeks, followed in case of symptoms improvement by a period of gradual reintroduction of FODMAPS that allows the patient to determine the FODMAPs that cause symptoms regardless of the amount, and those tolerated but at smaller dose than those usually ingested. The patients can thus resume a varied diet with a clear decrease of their symptoms.

Le tableau 1 représente les principaux hydrates de carbone avec une liste non exhaustive des aliments qui en contiennent.

Mécanismes et conséquences de la malabsorption des FODMAPs

Les mécanismes de la malabsorption de ces hydrates de carbone sont variables. Elle peut être due à un défaut de transports à travers l'épithélium (fructose), à un défaut ou à une diminution d'activité d'hydrolases (lactose, fructanes, galactanes) ou encore à des molécules trop larges pour être absorbées par simple diffusion (polyols). Ces hydrates de carbone peuvent entraîner par effet osmotique une augmentation des liquides arrivant dans la lumière intestinale. Lors de leur arrivée dans le colon, ils servent de substrats à la fermentation bactérienne colique, avec une augmentation de production de gaz entraînant une distension de la lumière intestinale, et d'acides gras volatils pouvant modifier la sensibilité viscérale et agir sur la perméabilité et l'état inflammatoire de la paroi intestinale. De plus la fermentation bactérienne peut avoir un effet stimulant sur la motricité intestinale [START_REF] Jouet | Fermentation of starch stimulates propagated contractions in the human colon[END_REF]. Il a été montré chez des patients iléostomisés que la réduction des apports en FODMAPs entraîne une diminution d'au moins 20% des débits de stomie [START_REF] Barrett | Dietary poorly absorbed, short-chain carbohydrates increase delivery of water and fermentable substrates to the proximal colon[END_REF]. L'ingestion de FODMAPs est associée à une augmentation du volume liquidien dans le grêle évalué en IRM (3) et de la production d'hydrogène évaluée par test respiratoire avec peu d'effet sur le volume colique (4). La quantité de FODMAPs dans l'alimentation semble aussi pouvoir moduler la libération d'histamine, un neuromédiateur impliqué dans les mécanismes de la douleur du fait de son action sensibilisatrice sur les neurones sensitifs entériques, et qui est augmenté dans la muqueuse intestinale des patients ayant un SII. L'excrétion urinaire d'histamine est très nettement diminuée (par 8) en cas de régime pauvre en FODMAPs [START_REF] Mcintosh | FODMAPs alter symptoms and the metabolome of patients with IBS: a randomised controlled trial[END_REF]. Le schéma 1 résume les principaux effets physiopathologiques de la malabsorption des FODMAPs. Les FODMAPs peuvent ainsi agir sur la plupart des mécanismes impliqués dans la physiopathologie du SII (voir chapitre 2.1).

Le régime en pratique

Ce régime, dont l'effet a particulièrement été étudié par l'équipe australienne de S. Sheperd et P. Gibson (6), consiste à éliminer dans un premier temps de façon très restrictive tous les hydrates de carbone susceptibles d'être malabsorbés pendant au moins 3 semaines . Il faut noter que la quantité de FODMAPs présente dans le régime « normal » et celui « pauvre » en FODMAPs est très variable d'une étude à l'autre, allant pour le normal de 13 à 27g par jour, et pour le pauvre de 3 à 17g par jour selon les études et les pays où le régime a été testé [START_REF] Harvie | Long-term irritable bowel syndrome symptom control with reintroduction of selected FODMAPs[END_REF][START_REF] Halmos | A diet low in FODMAPs reduces symptoms of irritable bowel syndrome[END_REF][START_REF] Staudacher | Fermentable carbohydrate restriction reduces luminal bifidobacteria and gastrointestinal symptoms in patients with irritable bowel syndrome[END_REF][START_REF] Böhn | Diet low in FODMAPs reduces symptoms of irritable bowel syndrome as well as traditional dietary advice: a randomized controlled trial[END_REF]. Les FODMAPs étant présents dans de très nombreux aliments, la mise en place de ce régime nécessite une prise en charge par une diététicienne formée. Ceci permet d'évaluer dans un premier temps les habitudes alimentaires du patient, qui a parfois une alimentation déséquilibrée, avec des ingesta excessifs en sucre par exemple, ou présente Le SII touche 5% de la population, et est défini selon les critères de ROME IV datant de 2016 par des douleurs abdominales associées à des troubles du transit [START_REF] Lacy | Bowel Disorders[END_REF]. Son diagnostic est clinique, les examens morphologiques étant normaux. Sa physiopathologie est complexe, pouvant impliquer entre autre des anomalies motrices, une hypersensibilité viscérale, une dysbiose (anomalie du microbiote), une inflammation de bas grade, des anomalies des sels biliaires, une augmentation de la perméabilité, des anomalies des contrôles de la douleur au niveau central et/ou des facteurs psychosociaux [START_REF] Spiller | Guidelines on the irritable bowel syndrome: mechanisms and practical management[END_REF]. Le traitement repose le plus souvent sur la prescription de médicaments, mais antispasmodiques et régulateurs du transit en général proposés en première intention peuvent ne pas suffire, et les symptômes peuvent être responsables d'une altération importante de la qualité de vie. Deux tiers des patients font un lien entre l'alimentation et leurs symptômes, excluant d'eux-mêmes certains aliments [START_REF] Shepherd | Dietary Triggers of Abdominal Symptoms in Patients With Irritable Bowel Syndrome: Randomized Placebo-Controlled Evidence[END_REF]. Jusque-là les recommandations diététiques étaient basées sur les effets physiologiques de constituants alimentaires sans études cliniques contrôlées, en limitant certains aliments (choux, haricots blancs, aliments gras, épicés), les boissons gazeuses et sodas, chewing gums et édulcorants se terminant en -ol et en prenant des fibres réparties sur les 3 repas de la journée [START_REF] Böhn | Diet low in FODMAPs reduces symptoms of irritable bowel syndrome as well as traditional dietary advice: a randomized controlled trial[END_REF]. patients SII non coeliaques auparavant améliorés par une alimentation sans gluten. Dans cette étude randomisée en double aveugle et cross over, les patients recevaient dans un premier temps une alimentation pauvre en FODMAPs pendant 2 semaines, puis recevaient en plus du gluten à dose élevée (16g/j) ou faible (2g/j avec 14/j de protéines de lait) ou des protéines de lait sans gluten (16g/j de protéines de lait) pendant une semaine avec une période de wash out d'au moins deux semaines. Les repas étaient fournis aux patients.

Vingt-deux patients ont eu par la suite un rechallenge pendant 3 jours de gluten (16g/j) ou de protéines de lait (16g/j). Tous les patients présentaient une amélioration de leurs symptômes pendant la période de régime pauvre en FODMAPs, et les symptômes s'aggravaient à nouveau de façon similaire à l'introduction de gluten ou de protéines de lait dans les périodes de cross over ou lors du rechallenge de 3 jours. Ceci suggère que les patients s'étant auto-diagnostiqués une intolérance au gluten sont en fait le plus souvent sensibles aux FODMAPs (dont les apports sont également diminués lorsqu'on diminue le gluten) plus qu'au gluten lui-même, la suppression du gluten n'ayant pas d'effet bénéfique supplémentaire sur les symptômes. La réponse au traitement ne semble pas être liée à la sévérité des symptômes ou à des facteurs psychologiques [START_REF] Böhn | Diet low in FODMAPs reduces symptoms of irritable bowel syndrome as well as traditional dietary advice: a randomized controlled trial[END_REF], mais une alimentation habituelle plutôt pauvre en FODMAPs pourrait être un facteur de réponse au régime, les patients pouvant avoir réduit d'euxmêmes leur apport. Les autres facteurs prédictifs de réponse, en dehors de l'adhérence au régime, pourraient être un âge plus élevé, le sexe féminin, un niveau élevé d'éducation, ou encore l'utilisation de livres de cuisine recommandés. Le type de trouble de transit ne semble pas influencer la réponse. L'influence du mode d'informations lors de la mise en place du régime (séance individuelle ou en groupe, diététicienne comparée à un médecin, utilisation de livres de cuisine recommandés) n'a pour l'instant pas été évalué de façon systématique dans des études prospectives.

Par une analyse du microbiote ?

La composition du microbiote fécale pourrait permettre de prédire la réponse au régime pauvre en FODMAPs. Ceci a été suggéré par plusieurs études [START_REF] Valeur | Exploring Gut Microbiota Composition as an Indicator of Clinical Response to Dietary FODMAP Restriction in Patients with Irritable Bowel Syndrome[END_REF][START_REF] Bennet | Multivariate modelling of faecal bacterial profiles of patients with IBS predicts responsiveness to a diet low in FODMAPs[END_REF] comme celle de Bennet et al 2018 [START_REF] Bennet | Multivariate modelling of faecal bacterial profiles of patients with IBS predicts responsiveness to a diet low in FODMAPs[END_REF], qui décrit un profil bactérien particulier chez les patients répondeurs et un index de dysbiose plus élevé chez les non répondeurs. Cependant à l'heure actuelle ces résultats ne peuvent pas être utilisés en pratique et l'analyse du microbiote n'a pas d'utilité en routine en dehors de protocoles de recherche.

1 REGIME

 1 PAUVRE EN FODMAPS, CE QUE DOIVENT SAVOIR LES NUTRITIONISTES LOW FODMAPS DIET, WHAT NUTRITIONIST SHOULD KNOW ABOUT IT FODMAPs est un acronyme pour Fermentable Oligo-, Di-, Mono-saccharides And Polyols, et désigne des hydrates de carbone rapidement fermentescibles susceptibles d'être mal absorbés et d'induire des troubles digestifs à type de douleurs abdominales, ballonnement, flatulence et troubles du transit. De nombreuses études ont testé l'intérêt de réduire dans l'alimentation les aliments riches en FODMAPs chez les patients souffrant du syndrome de l'intestin irritable, pathologie digestive chronique bénigne associant douleurs abdominales et troubles du transit (diarrhée, constipation ou alternance des deux), et sont en faveur d'un effet bénéfique de ce régime. L'efficacité du régime pauvre en FODMAPS est imprévisible. Ce régime très restrictif est difficile à suivre, peut entraîner une perte de poids, et a été associé à une dysbiose. Il n'est donc pas recommandé de le suivre au long cours. Il peut être proposé en deuxième intention en cas d'échec de recommandations diététiques standards chez des patients suffisamment gênés par leurs symptômes pour accepter les contraintes du régime. Il est de préférence effectué avec l'encadrement d'une diététicienne formée à ce régime du fait de sa complexité et du risque de restrictions alimentaires au long cours. Il est en général testé pendant une période de 4 semaines, suivi en cas d'amélioration d'une période de réintroduction progressive des FODMAPS qui permet au patient de déterminer les FODMAPS qui entraînent des symptômes quelle que soit la quantité, et ceux tolérés mais à plus petites doses que celles ingérées habituellement. Les patients peuvent ainsi reprendre une alimentation variée avec une nette diminution de leurs symptômes. Mots clefs : hydrates de carbone, gluten, alimentation, syndrome de l'intestin irritable, FODMAPs. INTRODUCTION FODMAPs est un acronyme anglais pour « Fermentable Oligo-, Di-, Mono-saccharides And Polyols ». Il désigne des hydrates de carbone susceptibles d'être mal absorbés et de provoquer des symptômes digestifs à type de douleurs abdominales, ballonnement, flatulence et troubles du transit. Au début des années 2000, l'équipe australienne de la Monash University a testé l'intérêt d'un régime réduisant l'apport de ces hydrates de carbone chez les patients souffrant du syndrome de l'intestin irritable (SII). Depuis, plusieurs équipes ont confirmé l'intérêt de ce régime dans la prise en charge du SII. Cette mise au point permet de préciser les données récentes concernant ce régime, avec le principe du régime pauvre en FODMAPs, ses indications, son efficacité ainsi que ses limites. 1. Généralités sur le régime pauvre en FODMAPs 1.1. Principe du régime Ce régime repose sur le fait que les symptômes de SII pourraient être en partie secondaires à la malabsorption de certains hydrates de carbone regroupés sous le terme de FODMAPs. Ils incluent des oligosaccharides, (dont les fructanes et les galacto-oligosaccharides), des disaccharides (dont le lactose), des monosaccharides (dont le fructose contenu dans les fruits, le miel, certains sirops, le blé), et les polyols (dont le sorbitol, le xylitol et le mannitol).

  des évictions alimentaires multiples. Ceci permet d'obtenir la meilleure compliance possible, le régime étant très strict et difficile à suivre à court terme et à fortiori à long terme. De ce fait il parait logique en cas d'amélioration des symptômes au décours de la période initiale de tenter de réintroduire des FODMAPs mais peu d'études portent sur les modalités de réintroduction. L'encadrement par une diététicienne pourrait permettre de limiter l'effet nocebo constaté bien souvent lors de la réintroduction d'aliments suivant une période d'éviction afin d'éviter des évictions alimentaires inutiles. On peut proposer une réintroduction par famille de FODMAPs mais ceci n'a pas été validé. Dans l'étude de Harvie et al. (5), la réintroduction d'une quantité importante de FODMAPs semble pouvoir se faire sans nécessairement une rechute notable des symptômes. Ceci pourrait s'expliquer par le fait qu'au décours du régime les patients pourraient arriver à mieux déterminer les aliments qu'ils ne supportent pas du tout, quelle que soit la quantité ingérée, et ceux qu'ils supportent, mais à une quantité moindre. 2. Dans quelles pathologies le régime pauvre en FODMAPS peut-il être proposé ? 2.1. Le SII : 2.1.1. Généralités sur le SII

2. 1 . 2 .

 12 Quelle efficacité du régime pauvre en FODMAPs sur le SII Les arguments en faveur d'une efficacité de ce régime reposent sur plusieurs études, dont une étude australienne de challenge randomisée en simple aveugle (réintroduction en aveugle de fructose, fructanes et/ou de glucose chez des patients améliorés par un régime pauvre en FODMAPs)[START_REF] Shepherd | Dietary Triggers of Abdominal Symptoms in Patients With Irritable Bowel Syndrome: Randomized Placebo-Controlled Evidence[END_REF], et deux études anglaises, l'une comparative non randomisée[START_REF] Staudacher | Comparison of symptom response following advice for a diet low in fermentable carbohydrates (FODMAPs) versus standard dietary advice in patients with irritable bowel syndrome: IBS symptom response to a low FODMAP diet[END_REF], l'autre contrôlée randomisée comparant ce régime pauvre en FODMAPs au régime habituel[START_REF] Staudacher | Fermentable carbohydrate restriction reduces luminal bifidobacteria and gastrointestinal symptoms in patients with irritable bowel syndrome[END_REF]. Plus récemment, dans une étude randomisée en cross over,Halmos et al.(8) ont comparé l'effet d'une alimentation australienne standard à une alimentation pauvre en FODMAPs pendant deux périodes de 21 jours avec une période de Wash out d'au moins 21 jours. Le régime pauvre en FODMAPs entraînait une amélioration du score global de symptômes d'au moins 10mm (échelle visuelle analogique : 0-100mm) chez 70% des patients SII (n=30). Le score global de symptômes, les ballonnements, les flatulences et les douleurs abdominales étaient significativement diminués pendant la période pauvre en FODMAPs en comparaison à l'alimentation standard, et les patients, quel que soit leur type de trouble du transit, étaient plus souvent satisfaits de la consistance de leurs selles. Les volontaires sains (n=8) n'ont pas noté de différence entre les deux régimes. Cette étude constitue donc un argument supplémentaire pour l'efficacité du régime pauvre en FODMAPs, mais portait cependant sur un faible nombre de malades et sur une durée relativement courte, avec un risque de biais lié au cross over, et avec une adhésion au régime facilitée par le fait que les repas étaient fournis aux patients. Enfin, il s'agissait d'une étude en aveugle mais seulement 17% des patients n'avaient pas identifié la période de régime pauvre en FODMAPs. Dans une étude observationnelle de Nouvelle Zélande avec une durée moyenne de suivi de 15,7 mois, le bénéfice du régime apparait après quelques semaines (3,5 semaines en médiane) et semble durable (15). Ce type de régime pourrait aussi diminuer les symptômes de fatigue. Plusieurs études non randomisées suggèrent que le régime pauvre en FODMAPs à un effet plus important que des conseils diététiques standards comme dans une étude anglaise (14) au cours de laquelle les patients étaient significativement plus satisfaits de leur amélioration symptomatique avec le régime pauvre en FODMAPs (n=43) qu'après des conseils standards (n=39), (76% vs 54%, P = 0.038), avec une amélioration significativement plus importante des ballonnements, des douleurs abdominales et des flatulences. L'équipe suédoise de Simren (10) a publié récemment une étude multicentrique randomisée parallèle en simple aveugle comparant chez 75 patients ayant un SII avec des troubles du transit variés l'effet d'un régime pauvre en FODMAPs (n=38) à des conseils diététiques habituels (n=37) suivis pendant 4 semaines. Le score global de sévérité des symptômes, la fréquence des douleurs abdominales, la sévérité de la distension abdominale et l'interférence des symptômes avec la vie quotidienne étaient significativement améliorés par les deux types d'alimentation sans différence d'effet entre les deux régimes. Une réponse définie par une réduction du score de Francis (IBS-SS score, 0-500) ≥ 50 était trouvée chez 50% des patients sous régime pauvre en FODMAPs vs 46% des patients avec conseils diététiques standards (P= 0, 72). Le nombre de selles par jour était significativement diminué dans le groupe pauvre en FODMAPs par rapport à la période basale, et inchangé par les conseils diététiques standards. La consistance des selles n'était modifiée par aucun des deux régimes. Dans cette étude, la quantité de FODMAPs ingérée par les patients n'était pas strictement contrôlée, les repas n'étant pas fournis. Elle reflète cependant les conditions habituelles de mise en place d'un régime pauvre en FODMAPs. Une méta-analyse récente (16) portant sur 596 patients a conclu en faveur d'un effet significativement supérieur du régime pauvre en FODMAPS par rapport aux autres régimes sur les symptômes digestifs (SMD = -0.62; 95% CI = -0.93 to -0.31; P = 0.0001), les douleurs abdominales (SMD = -0.50;95% CI = -0.77 to -0.22; P = 0.008) et la qualité de vie (SMD = 0.36; 95% CI = 0.10-0.62; P = 0.007). L'ensemble de ces données suggère que le régime peut améliorer les symptômes de certains patients SII au moins à court terme, les discordances de résultats pouvant être dues aux modalités de mise en place du régime, et aussi à la population étudiée (sévérité du SII, sous-type de trouble du transit, habitudes alimentaires du pays, quantité de FODMAPs). 2.2. L'intolérance au gluten : 2.2.1. Généralités sur l'intolérance au gluten De nombreux patients essayent de réduire la prise de gluten dans un contexte d'offre croissante de produits sans gluten et du fait de nombreux articles dans la presse suggérant un bénéfice potentiel, certains patients semblant effectivement pouvoir être améliorés en l'absence de maladie coeliaque (17) ou d'allergie au gluten. 2.2.2. Quelle efficacité du régime pauvre en FODMAPs chez les patients se considérant intolérants au gluten Biesierski et al. (17) ont étudié 34 patients SII sans maladie coeliaque qui ont été soulagés par une alimentation sans gluten, et ont comparé dans une étude en double aveugle randomisée contrôlée vs placebo l'effet de l'ajout pendant 6 semaines de gluten ou d'un placebo à une alimentation sans gluten. Le score global de symptômes, les douleurs abdominales, les ballonnements, la satisfaction avec la consistance des selles et la fatigue étaient significativement plus importants pendant la période avec gluten, suggérant un rôle possible de ce dernier dans la genèse des symptômes. La même équipe australienne (18) a comparé l'effet d'un régime pauvre en FODMAPs avec ou sans prise de gluten chez 37

2. 3 .

 3 Les troubles fonctionnels chez les patients ayant une maladie inflammatoire chronique intestinale (MICI) 2.3.1. Généralités sur les MICI La maladie de Crohn et la Recto-colite Hémorragique sont deux pathologies inflammatoires chroniques du tube digestif qui évoluent par poussée et peuvent entraîner douleurs abdominales, diarrhée, rectorragies et amaigrissement. Environ 40% des patients présentent des symptômes digestifs persistants (douleurs abdominales, ballonnement et troubles du transit) au décours des poussées alors que l'inflammation intestinale a disparu, évoquant des troubles fonctionnels secondaires à l'épisode inflammatoire. La prise en charge de ces symptômes, parfois très invalidants pour les patients, n'est pas bien établie. De façon pragmatique, les mêmes traitements que ceux du SII sont utilisés (antispasmodiques, régulateurs du transit, conseils diététiques standards). 2.3.2. Quelle efficacité du régime pauvre en FODMAPS dans les MICI Dans une étude danoise randomisée en ouvert publiée en 2017 (18), 89 patients ayant une MICI et présentant des symptômes fonctionnels ont suivi un régime pauvre en FODMAPS (n=44) ou ont poursuivi leur alimentation habituelle (n=45). Le nombre de patients ayant une amélioration de leurs symptômes était significativement plus important avec le régime pauvre en FODMAPs (81% vs 46%) avec une amélioration significativement plus importante de leur qualité de vie. Dans une méta-analyse portant sur 319 patients MICI dont 96% étaient en rémission (19) ayant suivi un régime pauvre en FODMAPs, ce dernier améliorait significativement les symptômes de diarrhée, ballonnement, douleurs abdominales, fatigue, nausée mais pas de constipation. Il semble donc intéressant de proposer un régime pauvre en FODMAPs aux patients ayant des symptômes digestifs invalidants persistants malgré une MICI en rémission, en cas d'échec d'un traitement de première intention. 3. Peut-on prédire les effets du régime ? 3.1. Par un test respiratoire ? L'absorption de certains FODMAPs comme le fructose a été étudiée en mesurant l'excrétion respiratoire d'H2 après son ingestion. Pour le fructose, une malabsorption est retrouvée chez environ 1/3 des patients SII mais aussi chez des sujets sains, pour certains avec la même fréquence, la prévalence dépendant de la dose de fructose utilisée. Après prise de 50g de fructose, jusqu'à 80% des volontaires ont une augmentation de production d'H2. La corrélation entre une malabsorption et le déclenchement de symptômes par l'hydrate de carbone n'est pas retrouvée systématiquement. Dans une étude prospective récente de Rouen (20), 22% des patients SII avaient une malabsorption après ingestion de 25g de fructose, mais seulement 35% d'entre eux avaient des symptômes d'intolérance, et à l'inverse 28% des patients ayant un test normal présentaient des signes d'intolérance après ingestion. D'autres facteurs peuvent influencer l'apparition de symptômes comme une dysbiose, une hypersensibilité viscérale ou encore une altération de la barrière gastrointestinale 3.2. En fonction des caractéristiques cliniques, d'habitudes alimentaires du patient ou des modalités de prise en charge ?

4 .

 4 Comment mettre en place le régime pauvre en FODMAPS dans des conditions optimales ?Ce régime est complexe à mettre en place, les FODMAPs étant présents dans de nombreux aliments et de plus en plus utilisés par l'industrie agro-alimentaire. Une consultation préalable avec une diététicienne formée à ce type de régime semble préférable, mais les patients peuvent aussi s'aider de supports comme ceux provenant de l'équipe australienne de la Monash University avec un livre et une application en anglais payante pour smartphone, d'autres livres et applications sont également disponibles en français. L'adhérence au régime a été évaluée à l'aide de questionnaires alimentaires et/ou de tests respiratoires. Dans l'étude de Halmos et al.(8) 80% des patients suivaient correctement le régime, mais la plupart des aliments était fournie aux patients pendant l'étude. Dans une étude prospective ouverte où les patients suivaient le régime après une ou deux consultations diététiques, 75% des patients semblaient effectivement y adhérer, 35,6% en permanence en dehors de quelques occasions et seulement 12,2% en permanence (15). Dans l'étude de Maagaard et al. (23) portant sur 131 (73%) SII et 49 (27%) MICI avec un suivi médian de 16 mois (2-80), le régime était correctement suivi dans 16% des cas seulement. 5. Effets à court et à long terme du régime pauvre en FODMAPS ?5.1. A court termeLe régime pauvre en FODMAPs est un régime restrictif. A court terme il a été constaté que les patients tendaient à réduire leurs apports caloriques de 2100 kcal ± 435 à 1658 kcal ± 365 par jour en moyenne[START_REF] Böhn | Diet low in FODMAPs reduces symptoms of irritable bowel syndrome as well as traditional dietary advice: a randomized controlled trial[END_REF], avec un risque de perte de poids.Par ailleurs, il nécessite de faire un tri des aliments chez des patients pouvant avoir des antécédents de troubles du comportement alimentaire. Dans une étude anglaise récente portant sur 233 patients SII, 54 (23%) patients étaient considérés comme à risque de troubles du comportement alimentaire. Les patients à risque adhéraient significativement mieux au régime que ceux n'étant pas à risque (57% vs 35% ; P<0.05)[START_REF] Mari | Adherence with a low-FODMAP diet in irritable bowel syndrome: are eating disorders the missing link?[END_REF]. Ce type de régime pourrait faire aggraver des troubles du comportements alimentaires préexistants.5.2. A long terme5.2.1. Conséquences sur le microbioteA long terme, il pourrait avoir des conséquences sur la flore colique par la restriction d'arrivée dans le côlon de substrats à la fermentation bactérienne. Dans une étude randomisée contrôlée effectuée chez des patients ayant un SII recevant pendant 4 semaines un régime pauvre en FODMAPs ou leur alimentation habituelle, le régime était associé à une diminution de la proportion et de la concentration en Bifidobactéries intraluminales[START_REF] Staudacher | Fermentable carbohydrate restriction reduces luminal bifidobacteria and gastrointestinal symptoms in patients with irritable bowel syndrome[END_REF]. Dans une autre étude australienne[START_REF] Halmos | Diets that differ in their FODMAP content alter the colonic luminal microenvironment[END_REF] randomisée contrôlée en simple aveugle, 27 patients SII et 6 sujets sains ont reçu en cross over pendant deux périodes de 21 j une alimentation différant seulement par son contenu en FODMAPs (3,05g/j vs 23,7/j correspondant aux apports habituels de l'alimentation australienne) avec une période de wash out de 21 j. Après 4 semaines de régime pauvre en FODMAPs, il a été constaté une augmentation du pH fécal, une plus grande diversité microbienne, une diminution de l'abondance totale de bactéries, une augmentation de certains Clostridium producteurs de butyrate et d'Akkermansia muciniphila, et enfin une réduction des Ruminococcus torques. Cette dysbiose pourrait être au moins en partie corrigée par un apport en probiotiques, comme le suggère l'étude de Staudacher et al[START_REF] Staudacher | A Diet Low in FODMAPs Reduces Symptoms in Patients With Irritable Bowel Syndrome and A Probiotic Restores Bifidobacterium Species: A Randomized Controlled Trial[END_REF].

5. 2 . 2 .

 22 Risque de carences Malgré l'absence d'étude sur les éventuelles conséquences nutritionnelles à long terme du régime pauvre en FODMAPs, il existe un risque potentiel de carences nutritionnelles d'après les données de régimes d'exclusion (27). L'exclusion de blé, orge et seigle, comme en cas du régime sans gluten utilisé dans la maladie coeliaque, peut entraîner une diminution des ingesta de fibres, calcium, fer, folates et autres vitamines du groupe B. La suppression du lactose peut entraîner une carence en calcium. Il peut y avoir une diminution des apports en aliments ayant des propriétés anti-oxydantes naturelles, comme la vitamine C, les flavonoïdes, caroténoïdes contenus dans certains FODMAPs (choux fleurs, oignons, ail), ou acide phénolique et anthocyanines présents dans les fruits comme les mûres. CONCLUSIONS Le régime pauvre en FODMAPs semble pouvoir améliorer les symptômes des patients ayant un SII, quel que soit le type de trouble du transit, avec un effet surtout sur les douleurs abdominales, les ballonnements et les flatulences. Son effet a été démontré dans des études pour la plupart effectuées en Australie ou en Angleterre, pays ayant une culture gastronomique différente de la France. La supériorité de ce régime par rapport à des conseils diététiques standards n'est cependant pas bien établie. Les patients ayant déjà d'eux-mêmes réduits leur apport en FODMAPs pourraient être plus susceptibles de répondre, les éventuels autres facteurs prédictifs de réponse au traitement devant encore être précisés. Il est préférable que la mise en place de ce régime soit effectuée à l'aide d'une diététicienne formée à ce type de régime, car il est difficile à appliquer, une adhérence complète au régime étant rarement obtenue. Il pourrait entraîner à court terme une réduction des ingesta avec une perte de poids, et à long terme une modification du microbiote. Son coût pour le patient n'a pas été étudié. Il ne peut pas être actuellement recommandé en première intention en France chez les patients souffrant du SII du fait de sa complexité mais peut être utile chez des patients en cas d'échec de la prise en charge initiale et suffisamment motivés pour le tester. Des études sont nécessaires pour confirmer son efficacité avec nos habitudes gastronomiques françaises, sa supériorité par rapport à des conseils diététiques standards, et mieux déterminer les facteurs prédictifs de réponse.

Figure 1 Figure 1

 11 Figure 1 Principaux mécanismes physiopathologiques pouvant expliquer les symptômes digestifs

  Tableau 1 Principaux aliments contenant des FODMAPs Main Foods containing FODMAPs

		Hydrate de carbone	Aliments
		Fructanes	Blé, oignons, noix de cajou,
	Oligo-saccharides	Galacto-Oligosaccharides	Lentilles, pois chiches, haricots
			blancs, artichauts, échalote..
	Di-saccharides	Lactose	Lait, crème, glace , yaourt
		Fructose	Pommes, poires, mangue,
	Mono-saccharides		pastèque, miel, sirop de mais,
			cerise, asperge
		Sucres d'alcool	Abricots, cerise, nectarines,
	Polyols		champignon, chewing-gum,
			édulcorants de synthèse