Publications by authors named "Pascal Potier"

34 Publications

NON-INVASIVE DIAGNOSIS AND FOLLOW-UP OF PRIMARY SCLEROSING CHOLANGITIS.

Clin Res Hepatol Gastroenterol 2021 Jul 28:101775. Epub 2021 Jul 28.

Service d'hépato-gastroentérologie, Hôpital Haut-Lévêque, CHU Bordeaux, pessac & INSERM U1053, Université de Bordeaux, Bordeaux.

Primary sclerosing cholangitis (PSC) is a rare and chronic cholestatic liver disease of unknown cause commonly associated with inflammatory bowel disease (IBD) and characterized by progressive obliterative fibro-inflammation of the biliary tree. Although the natural course is highly variable, PSC is often progressive, leading to biliary cirrhosis and its complications. In addition, PSC is a condition harbouring broad neoplastic potential with increased susceptibility for the development of both biliary and colon cancer. As in other chronic liver diseases, non-invasive methods play a major role in the diagnosis and monitoring of PSC. MR cholangiography is the key exam for the diagnosis and has replaced diagnostic endoscopic retrograde cholangiopancreatography (ERCP). A strict and standardised protocol for carrying out MR cholangiography is recommended. Liver stiffness measured by FibroScan® correlates with the degree of liver fibrosis, has a prognostic value and should be repeated during follow-up. Invasive methods still play an important role, especially ERCP which is indicated for therapeutic purposes or for endo-biliary sample collection in suspected cholangiocarcinoma (following discussion in a multidisciplinary team meeting) and total colonoscopy which is recommended at the initial diagnosis of any PSC and annually in patients with IBD.
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http://dx.doi.org/10.1016/j.clinre.2021.101775DOI Listing
July 2021

NON-INVASIVE DIAGNOSIS AND FOLLOW-UP OF PRIMARY BILIARY CHOLANGITIS.

Clin Res Hepatol Gastroenterol 2021 Jul 28:101770. Epub 2021 Jul 28.

Service d'hépato-gastroentérologie, Hôpital Saint Joseph & INSERM UMR 1252 IRD SESSTIM Aix Marseille Université, Marseille.

Primary biliary cholangitis (PBC) is a chronic inflammatory disease of the intra-hepatic bile ducts (1). It is characterised biologically by chronic cholestasis associated with the presence of specific autoantibodies, and histologically by lesions of nonsuppurative destructive cholangitis. If left untreated it can progress to cirrhosis, portal hypertension and liver failure. Diagnosis, staging and follow-up are largely based on non- or minimally-invasive assessment (blood tests, ultrasound, liver stiffness measurement). Histological examination of the liver and upper gastrointestinal endoscopy are sometimes necessary, but their indications remain limited. The purpose of this chapter is to provide the clinicians with what should be known about the non-invasive assessment of PBC and to provide specific recommendations for clinical practice.
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http://dx.doi.org/10.1016/j.clinre.2021.101770DOI Listing
July 2021

Evolution and phenotypic characterization of whole HBV genome in compliant patients experiencing unexplained entecavir treatment failure.

Antiviral Res 2021 08 29;192:105106. Epub 2021 Jun 29.

INSERM U1259, Université de Tours et CHRU de Tours, France; Service de Bactériologie-Virologie-Hygiène, CHRU de Tours, France.

Entecavir treatment failure can be observed in compliant patients despite an absence of detectable resistance mutations by Pol/RT Sanger sequencing. We hypothesized that these unexplained treatment failures could rely on other mechanisms of viral resistance, especially on mutations selected outside of the Pol/RT domain. Partial virological response to entecavir was observed in three patients treated with immunosuppressive drugs, without selection of Pol/RT resistance mutations. Mutations selected in the whole HBV genome during entecavir treatment and potentially associated with resistance were searched for using deep sequencing and characterized using a phenotypic resistance assay. Mutations Q206K (pre-core/core), Q120K (pre-S1/pre-S2, T-cell epitope) and A300E (spacer domain) were selected during entecavir treatment in patient #1 but were not associated with an increased level of resistance to entecavir or an increase in HBV replication capacity. Core promoter mutations T1753G, A1762T and G1764A were present as major mutations before and after treatment in patient #1. HBs Ag immune escape mutations were present as major mutations before and after treatment in patients #2 (sK122R, sT126I, sP127S and sG145R) and #3 (sM133I). We demonstrated that PVR to entecavir does not require selection of any resistance mutation in the whole HBV genome. Our results demonstrate that major mutations can be selected outside of the Pol/RT domain before or during entecavir treatment. These mutations could contribute to entecavir treatment failure by other mechanisms than an increased level of resistance.
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http://dx.doi.org/10.1016/j.antiviral.2021.105106DOI Listing
August 2021

Combination of fibrates with obeticholic acid is able to normalise biochemical liver tests in patients with difficult-to-treat primary biliary cholangitis.

Aliment Pharmacol Ther 2021 05 25;53(10):1138-1146. Epub 2021 Mar 25.

Paris, France.

Background: Obeticholic acid (OCA) and fibrates are second-line therapies for patients with primary biliary cholangitis (PBC) with an inadequate response to ursodeoxycholic acid (UDCA).

Aim: To know whether OCA and fibrates, administered together in combination with UDCA, have additive beneficial effects in patients with difficult-to-treat PBC.

Methods: PBC patients treated for ≥3 months with UDCA, OCA and fibrates (bezafibrate or fenofibrate) due to failure of either second-line therapy were included in a multicentre, uncontrolled retrospective cohort study. Changes in biochemical liver tests and pruritus were analysed using a generalised linear mixed-effect model.

Results: Among 58 patients included, half received OCA as second-line and fibrates as third-line therapy (Group OCA-Fibrate), while the other half had the inverse therapeutic sequence (Group Fibrate-OCA). The mean duration of triple therapy was 11 months (range 3-26). Compared to dual therapy, triple therapy was associated with a significant gain in alkaline phosphatase (ALP) reduction: 22% per first year (95% CI 12%-31%), an effect that was stronger in OCA-Fibrate than in Fibrate-OCA group. Triple therapy was associated with a 3.4 (95% CI 1.4-8.2) odds ratio (OR) of reaching normal ALP and with a significant decrease in gamma-glutamyl transpeptidase (GGT), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin. The ORs of achieving the Paris-2 and Toronto criteria of adequate biochemical response were 6.8 (95% CI 2.8-16.7) and 9.2 (95% CI 3.4-25.1) respectively. Finally, triple therapy significantly improved pruritus in OCA-Fibrate but not in Fibrate-OCA group.

Conclusions: Triple therapy with UDCA, OCA and fibrates is able to normalise biochemical liver tests and improve pruritus in patients with difficult-to-treat PBC.
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http://dx.doi.org/10.1111/apt.16336DOI Listing
May 2021

Low-phospholipid-associated cholelithiasis syndrome: Prevalence, clinical features, and comorbidities.

JHEP Rep 2021 Apr 6;3(2):100201. Epub 2020 Nov 6.

Reference Center for Inflammatory Biliary Diseases and Autoimmune Hepatitis, ERN RARE-LIVER, Saint-Antoine Hospital, Assistance Publique-Hôpitaux de Paris, Sorbonne University, Paris, France.

Background & Aims: Low-phospholipid-associated cholelithiasis (LPAC) syndrome, a rare genetic form of intrahepatic cholelithiasis in adults, is still poorly understood. We report the results of the largest-ever case-control study of patients with LPAC syndrome aiming to assess the prevalence, clinical features, and comorbidities of the disease.

Methods: We included all LPAC cases diagnosed between 2001 and 2016 in 11 French centres. Controls consisted of all patients who underwent a cholecystectomy for common gallstone disease in a single non-academic centre over 1 year. A logistic regression analysis was used to identify the clinical features associated with LPAC syndrome across several patient strata with increasing levels of diagnostic confidence. The ratio between the incident cases of LPAC syndrome and the total number of cholecystectomies for gallstones was used to assess the relative prevalence of the disease.

Results: In this study, 308 cases and 206 controls were included. LPAC syndrome accounted for 0.5-1.9% of all patients admitted with symptomatic gallstone disease. Age at first symptoms <40 years, absence of overweight, persistence of symptoms after cholecystectomy, intrahepatic micro- or macrolithiasis, common bile duct (CBD) lithiasis, and no history of cholecystitis were independently associated with LPAC diagnosis. ATP-binding cassette subfamily B member 4 () variants, present in 46% of cases, were associated with CBD lithiasis, chronic elevation of gamma-glutamyltransferase (GGT), and personal or family history of hepato-biliary cancer.

Conclusions: In this case-control study, LPAC syndrome accounted for approximately 1% of symptomatic cholelithiasis in adults. In addition to pre-established diagnostic criteria, normal weight, CBD lithiasis, and no history of cholecystitis were significantly associated with the syndrome. gene variations in patients with LPAC were associated with CBD lithiasis, chronic cholestasis, and a personal or family history of hepato-biliary cancer.

Lay Summary: In the largest case-control study ever conducted in patients with LPAC syndrome, a rare genetic form of intrahepatic cholelithiasis in young adults, LPAC syndrome was found in approximately 1% of all patients admitted to the hospital for symptomatic gallstones and, in addition to the pre-established characteristics of the syndrome (age at first symptoms <40 years, recurrence of symptoms after cholecystectomy, and/or imaging evidence of intrahepatic microlithiasis), was associated with lower BMI, higher prevalence of common bile duct stones, and lower incidence of acute cholecystitis. gene variants, which were detected in about half of cases, were associated with common bile duct stones and a personal or family history of hepato-biliary cancer.
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http://dx.doi.org/10.1016/j.jhepr.2020.100201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7848766PMC
April 2021

Early liver transplantation for corticosteroid non-responders with acute severe autoimmune hepatitis: The SURFASA score.

J Hepatol 2021 Jun 24;74(6):1325-1334. Epub 2021 Jan 24.

CHRU Lille, Hôpital Claude Huriez, Service des Maladies de l'Appareil Digestif, Lille, France.

Background & Aims: In acute severe autoimmune hepatitis (AS-AIH), the optimal timing for liver transplantation (LT) remains controversial. The objectives of this study were to determine early predictive factors for a non-response to corticosteroids and to propose a score to identify patients in whom LT is urgently indicated.

Methods: This was a retrospective, multicenter study (2009-2016). A diagnosis of AS-AIH was based on: i) Definite or probable AIH based on the simplified IAIHG score; ii) international normalized ratio (INR) ≥1.5 and/or bilirubin >200 μmol/L; iii) No previous history of AIH; iv) Histologically proven AIH. A treatment response was defined as LT-free survival at 90 days. The evolution of variables from corticosteroid initiation (day-D0) to D3 was estimated from: Δ%3 = (D3-D0)/D0.

Results: A total of 128 patients were included, with a median age of 52 (39-62) years; 72% were female. Overall survival reached 88%. One hundred and fifteen (90%) patients received corticosteroids, with a LT-free survival rate of 66% at 90 days. Under multivariate analysis, D0-INR (odds ratio [OR] 6.85; 95% CI 2.23-21.06; p <0.001), Δ%3-INR ≥0.1% (OR 6.97; 95% CI 1.59-30.46; p <0.01) and Δ%3-bilirubin ≥-8% (OR 5.14; 95% CI 1.09-24.28; p <0.04) were predictive of a non-response. The SURFASA score: -6.80+1.92∗(D0-INR)+1.94∗(Δ%3-INR)+1.64∗(Δ%3-bilirubin), created by combining these variables, was highly predictive of LT or death (AUC = 0.93) (88% specificity; 84% sensitivity) with a cut-off point of <-0.9. Below this cut-off, the chance of responding was 75%. With a score higher than 1.75, the risk of dying or being transplanted was between 85% and 100%.

Conclusion: In patients with AS-AIH, INR at the introduction of corticosteroids and the evolution of INR and bilirubin are predictive of LT or death. Within 3 days of initiating corticosteroids, the SURFASA score can identify non-responders who require a referral for LT. This score needs to be validated in a prospective cohort.

Lay Summary: The management of patients with acute severe autoimmune hepatitis is highly challenging, particularly regarding their early referral for liver transplantation. We found that international normalized ratio at the initiation of corticosteroid therapy and the evolution of international normalized ratio and bilirubin values after 3 days of therapy were highly predictive of liver transplantation or death. We are thus proposing a score that combines these variables and identifies patients in whom liver transplantation is urgently required.
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http://dx.doi.org/10.1016/j.jhep.2020.12.033DOI Listing
June 2021

Two cases of yellow urticaria revealing acute lithiasic biliary disease.

Australas J Dermatol 2021 May 20;62(2):e326-e327. Epub 2020 Nov 20.

Department of Dermatology, CHR-Orleans, Orleans, France.

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http://dx.doi.org/10.1111/ajd.13496DOI Listing
May 2021

Assessment of Several THOR Thoracic Injury Criteria based on a New Post Mortem Human Subject Test Series and Recommendations.

Stapp Car Crash J 2019 Nov;63:219-305

CEESAR.

Several studies, available in the literature, were conducted to establish the most relevant criterion for predicting the thoracic injury risk on the THOR dummy. The criteria, such as the maximum deflection or a combination of parameters including the difference between the chest right and left deflections, were all developed based on given samples of Post Mortem Human Subject (PMHS). However, they were not validated against independent data and they are not always consistent with the observations from field data analysis. For this reason, 8 additional PMHS and matching THOR tests were carried out to assess the ability of the criteria to predict risks. Accident investigations showed that a reduction of the belt loads reduces the risk of rib fractures. Two configurations with different levels of force limitation were therefore chosen. A configuration representing an average European vehicle was chosen as a reference. It consists of a 3-point belt with a 3.5 kN and then 2 kN digressive limiter, combined with a 54-liter airbag. For better reproducibility and durability, the tests were performed with a pre-inflated bag and a semi-rigid seat. In this first configuration, the THOR dummy had a maximum resulting deflection of 43 mm. To differentiate the criteria, the second configuration was chosen such that it resulted in about the same deflection on the THOR dummy, but with a 5 kN belt force limitation combined with a lower pressure airbag. To reach this target of 43 mm, the pulse severity was lowered. Some criteria were higher in this second configuration, which allows them to be distinguished from the maximum deflection criterion. Four tests on four PMHS were performed in each configuration. The injury assessments showed that the total number of fractures was almost the same in both configurations, but that the number of separated fractures was greater in the 5 kN configuration. 25% of the subjects sustained AIS >3 injuries related to the number of displaced fractures in the 3.5/2 kN load limitation configuration. The result increased to 75% in the 5kN configuration. In total, 8 PMHS and the matching THOR tests were performed and used to assess the ability of the thoracic criteria to predict rib fractures in 2 types of chest loading configurations. The test results did not allow to conclude on the relevance of the criteria measured on the THOR dummy for the total number of rib fractures identified at autopsy (NFR). However, clearly different assessments for separated rib fractures (NSFR), make it possible to differentiate the criteria. The maximum resultant deflection failed to properly predict separated rib fractures while other criteria that include the left-to-right rib deflection difference did.
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November 2019

Far Side Impact Injury Threshold Recommendations Based on 6 Paired WorldSID / Post-Mortem Human Subjects Tests.

Stapp Car Crash J 2019 Nov;63:127-146

Toyota Motor Corporation (Japan).

Far side has been identified in the literature as a potential cause of numerous injuries and fatalities. Euro NCAP developed a far side test protocol to be performed to assess adult protection. A monitoring phase was undertaken between January 2018 and December 2019, and the far side assessment will become part of the rating for all vehicles launched in 2020 onward. A test buck was developed and 6 paired WorldSID / Post Mortem Human Subjects (PMHS) were subjected to the test protocol proposed by Euro NCAP to contribute to the development of limits. The buck consisted of a rigid seat and a rigid central console covered with 50 mm of Ethafoam TM 180 with a density of 16 kg/m3. The buck was mounted on the sled with an angle of 75° between the X axis of the vehicle and the X axis of the sled. The peak head excursion was compared between PMHS and the WorldSID dummy. It was found reasonably similar. However, the dummy repeatability was found to be poor. Out of 6 tests conducted on 6 PMHS, 2 specimens sustained AIS3 and, 3 specimens AIS2 cervical spine injuries, 3 specimens sustained AIS3, 1 AIS2 and 1 AIS1 thoracic injuries, and 2 specimens sustained AIS2 abdominal injuries. The peak values recorded on the dummy according to the Euro NCAP protocol were compared with the injury assessments of the PMHS tests. In the configuration used, which includes a central console, the hard thorax injury prediction was found to be excellent. For the neck injury prediction, the data were merged with similar results available in the literature and an Injury Risk Curve was proposed as a derivative from the curve published by Mertz et al. (2003) for neck extension.
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November 2019

Budd-Chiari syndrome.

Clin Res Hepatol Gastroenterol 2020 09 2;44(4):420-425. Epub 2020 Apr 2.

French Network for Rare Liver Diseases FILFOIE, Saint-Antoine Hospital, APHP, 184, rue du Faubourg Saint-Antoine, 75012 Paris, France; Department of Gastroenterology and Hepatology, Rangueil Hospital, University Hospital of Toulouse, 1, avenue du Professeur Jean-Poulhès, 31400 Toulouse, France.

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http://dx.doi.org/10.1016/j.clinre.2020.03.015DOI Listing
September 2020

Human Shoulder Response to Lateral Impact in Intermediate Loading Conditions Between High-Velocity, Short-Duration and Low-Velocity, Long-Duration.

Stapp Car Crash J 2018 Nov;62:319-357

Université Paris René Descartes (Paris, France).

The EuroSID-2re (ES-2re) Anthropomorphic Test Device (ATD) commonly known as the crash test dummy is also used in the military domain to assess the risk of injury of armored vehicles occupants from lateral impact. The loading conditions range from low velocity - long duration impacts (4 m/s - 50 ms) similar to the automotive domain, to high velocity - short duration impacts (28 m/s - 3 ms) corresponding to cases where the panel deforms under an explosion. The human shoulder response to lateral impact was investigated at bounds of the loading condition spectrum previously mentioned, and also at intermediate conditions (14 m/s - 9 ms) in previous studies. The aim of the current study is to provide additional insight at the intermediate loading conditions which are not found in the literature. Eight pure lateral shoulder impact tests were performed on Post Mortem Human Subjects (PMHS) using an 8.1 kg rigid impactor at velocities ranging from 3.3 m/s to 8.8 m/s with the duration ranging from 25 ms to 35 ms. The PMHS were instrumented with accelerometers attached to the sternum, and the upper thoracic spine (T1 vertebra). Strain gages were glued onto the right and left clavicles and ribs 2 to 6. The shoulder force was measured at the interface with the impactor and the impact was filmed by high speed cameras (5000 fps) to track the YZ displacements of the impactor, T1 vertebra, and sternum in the laboratory frame. Three shoulders out of the eight sustained AIS 2 injuries which included a clavicle fracture. The impactor forces ranged from 1200 to 4600 N. The PMHS accelerations ranged from 44 to 163 g at the sternum, and from 17 to 60 g at the T1 vertebra. The analysis of the strain gage signals revealed that the clavicle fractures occurred at the beginning of the impact and coincided with a peak force. An estimate of the acromion-to-shoulder compression (Cmax) was computed. It ranged from 0% to 15% for the non-injured shoulders, and from 19% to 28% for the injured shoulders. This new PMHS test series will be used in a future work to develop a shoulder injury criterion for the ES-2re ATD that is relevant for the whole loading conditions spectrum of the military domain.
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November 2018

Reference PMHS Sled Tests to Assess Submarining of the Small Female.

Stapp Car Crash J 2018 Nov;62:93-118

Université René Descartes, Paris.

In the last decade, extensive efforts have been made to understand the physics of submarining and its consequences in terms of abdominal injuries. For that purpose, 27 Post Mortem Human Subject (PMHS) tests were performed in well controlled conditions on a sled and response corridors were provided to assess the biofidelity of dummies or human body models. All these efforts were based on the 50th percentile male. In parallel, efforts were initiated to transfer the understanding of submarining and the prediction criteria to the THOR dummies. Both the biofidelity targets and the criteria were scaled down from the 50th percentile male to the 5th percentile THOR female. The objective of this project was to run a set of reference PMHS tests in order to check the biofidelity of the THOR F05 in terms of submarining. Three series of tests were performed on nine PMHS, the first one was designed to avoid submarining, the second and third ones were designed to result in submarining. In the first configuration, no submarining was observed in 3 cases out of 4 and only one iliac wing fracture occurred in one subject. In the second and third configurations, all subjects but one sustained submarining. In addition, two subjects out of three in the third configuration sustained substantial iliac wing fractures. Nevertheless, all configurations can be represented by at least one or several cases without any pelvis fracture. Corridors were constructed for the external forces and the PMHS kinematics. They are provided in this paper as new experimental references to assess the biofidelity of small female human surrogates in different configurations where submarining did or did not occur.
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November 2018

A Placebo-Controlled Trial of Bezafibrate in Primary Biliary Cholangitis.

N Engl J Med 2018 Jun;378(23):2171-2181

From the Reference Center for Inflammatory Biliary Diseases and Autoimmune Hepatitis, Hepatology and Gastroenterology Department, Saint-Antoine University Hospital, Assistance Publique-Hôpitaux de Paris (APHP) (C.C., O.C., S.L., F.G., R.P.), INSERM Unité Mixte de Recherche (UMR) S938 (C.C., O.C., S.L., R.P.) and the Biochemistry Laboratory (L.H., D.R.), Saint-Antoine University Hospital, APHP, INSERM Unité 1157/UMR 7203, Sorbonne University, the Biochemistry Laboratory, Tenon University Hospital, APHP (G.L.), and the Immunology Laboratory, INSERM UMR S996, Bichat University Hospital, APHP (L.C., S.C.-M.), Paris-Sud University, the Department of Clinical Pharmacology and Clinical Research Platform of the East of Paris, APHP (A.R., F.-H.A., T.S.), and Sorbonne University (T.S.), Paris, the Hepatology and Gastroenterology Department, Rouen University Hospital, Rouen (O.G.), the Hepatology and Gastroenterology Department, Pontchaillou University Hospital, Rennes (A.L.G.), the Hepatology and Gastroenterology Department, University Hospitals of Strasbourg, Institute of Viral and Liver Diseases, INSERM Unité 1110, Laboratory of Excellence HepSYS, University of Strasbourg, Strasbourg (F.H.), the Hepatology and Gastroenterology Department, Claude Huriez University Hospital, Lille (P.M.), the Hepatology and Gastroenterology Department, Orleans Hospital, Orleans (P.P.), the Hepatology and Gastroenterology Department, Dijon Bourgogne University Hospital, Dijon (A.M.), the Hepatology and Gastroenterology Department, University Hospital of Poitiers, Poitiers (C.S.), the Hepatology and Gastroenterology Department, Estaing University Hospital, Clermont-Ferrand (A.A.), the Hepatology and Gastroenterology Department, University Hospital of Limoges, Limoges (M.D.-G.), the Hepatology and Gastroenterology Department, Saint-Eloi University Hospital, Montpellier (D.L.), the Hepatology Department, Beaujon University Hospital, Clichy (O.R.), the Hepatology and Gastroenterology Department, Brabois University Hospital, Nancy (J.-P.B.), the Hepatology and Gastroenterology Department, University Hospital of Angers, Hemodynamics, Interaction, Fibrosis, and Tumor Invasiveness in Hepatic and Digestive Organs Laboratory, Unité Propre de Recherche de l'Enseignement Supérieur 3859, Structures Fédératives de Recherche 4208, Bretagne Loire University, Angers (J.B.), the Hepatology and Gastroenterology Department, Haut-Lévêque University Hospital, Pessac (V.L.), the Hepatology and Gastroenterology Department, Robert Debré University Hospital, Reims (A.H.-B.), the Hepatology and Gastroenterology Department, University Hospital of Amiens, Amiens (E.N.-K.), the Hepatology and Gastroenterology Department, Croix-Rousse University Hospital, Lyon (F.Z.), the Hepatology and Gastroenterology Department, University Hospital of Caen, Caen (I.O.-H.), the Hepatology and Gastroenterology Department, Michallon University Hospital, Grenoble (J.-P.Z.), and the Hepatology and Gastroenterology Department, Jean Verdier University Hospital, Bondy (G.N.) - all in France.

Background: Patients with primary biliary cholangitis who have an inadequate response to therapy with ursodeoxycholic acid are at high risk for disease progression. Fibrates, which are agonists of peroxisome proliferator-activated receptors, in combination with ursodeoxycholic acid, have shown potential benefit in patients with this condition.

Methods: In this 24-month, double-blind, placebo-controlled, phase 3 trial, we randomly assigned 100 patients who had had an inadequate response to ursodeoxycholic acid according to the Paris 2 criteria to receive bezafibrate at a daily dose of 400 mg (50 patients), or placebo (50 patients), in addition to continued treatment with ursodeoxycholic acid. The primary outcome was a complete biochemical response, which was defined as normal levels of total bilirubin, alkaline phosphatase, aminotransferases, and albumin, as well as a normal prothrombin index (a derived measure of prothrombin time), at 24 months.

Results: The primary outcome occurred in 31% of the patients assigned to bezafibrate and in 0% assigned to placebo (difference, 31 percentage points; 95% confidence interval, 10 to 50; P<0.001). Normal levels of alkaline phosphatase were observed in 67% of the patients in the bezafibrate group and in 2% in the placebo group. Results regarding changes in pruritus, fatigue, and noninvasive measures of liver fibrosis, including liver stiffness and Enhanced Liver Fibrosis score, were consistent with the results of the primary outcome. Two patients in each group had complications from end-stage liver disease. The creatinine level increased 5% from baseline in the bezafibrate group and decreased 3% in the placebo group. Myalgia occurred in 20% of the patients in the bezafibrate group and in 10% in the placebo group.

Conclusions: Among patients with primary biliary cholangitis who had had an inadequate response to ursodeoxycholic acid alone, treatment with bezafibrate in addition to ursodeoxycholic acid resulted in a rate of complete biochemical response that was significantly higher than the rate with placebo and ursodeoxycholic acid therapy. (Funded by Programme Hospitalier de Recherche Clinique and Arrow Génériques; BEZURSO ClinicalTrials.gov number, NCT01654731 .).
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http://dx.doi.org/10.1056/NEJMoa1714519DOI Listing
June 2018

New Reference PMHS Tests to Assess Whole-Body Pedestrian Impact Using a Simplified Generic Vehicle Front-End.

Stapp Car Crash J 2017 Nov;61:299-354

Université Paris René Descartes.

This study aims to provide a set of reference post-mortem human subject tests which can be used, with easily reproducible test conditions, for developing and/or validating pedestrian dummies and computational human body models against a road vehicle. An adjustable generic buck was first developed to represent vehicle front-ends. It was composed of four components: two steel cylindrical tubes screwed on rigid supports in V-form represent the bumper and spoiler respectively, a quarter of a steel cylindrical tube represents the bonnet leading edge, and a steel plate represents the bonnet. These components were positioned differently to represent three types of vehicle profile: a sedan, a SUV and a van. Eleven post-mortem human subjects were then impacted laterally in a mid-gait stance by the bucks at 40 km/h: three tests with the sedan, five with the SUV, and three with the van. Kinematics of the subjects were recorded via high speed videos, impact forces between the subjects and the bucks were measured via load cells behind each tube, femur and tibia deformation and fractures were monitored via gauges on these bones. Based on these tests, biofidelity corridors were established in terms of: 1) displacement time history and trajectory of the head, shoulder, T1, T4, T12, sacrum, knee and ankle, 2) impact forces between the subjects and the buck. Injury outcome was established for each PMHS via autopsy. Simplicity of its geometry and use of standard steel tubes and plates for the buck will make it easy to perform future, new post-mortem human subject tests in the same conditions, or to assess dummies or computational human body models using these reference tests.
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November 2017

Investigation of Pelvic Injuries on Eighteen Post Mortem Human Subjects Submitted to Oblique Lateral Impacts.

Stapp Car Crash J 2016 Nov;60:89-134

Université René Descartes, Paris, France.

The aim of this study was to investigate the sacroiliac joint injury mechanism. Two test configurations were selected from full scale car crashes conducted with the WorldSID 50 dummy resulting in high sacroiliac joint loads and low pubic symphysis force, i.e. severe conditions for the sacroiliac joint. The two test conditions were reproduced in laboratory using a 150-155 kg guided probe propelled respectively at 8 m/s and 7.5 m/s and with different shapes and orientations for the plate impacting the pelvis. Nine Post Mortem Human Subject (PMHS) were tested in each of the two configurations (eighteen PMHS in total). In order to get information on the time of fracture, eleven strain gauges were glued on the pelvic bone of each PMHS. Results - In the first configuration, five PMHS out of nine sustained AIS2+ pelvic injuries. All five presented sacroiliac joint injuries associated with pubic area injuries. In the second configuration, four specimens out of nine sustained AIS2+ pelvic injuries. Two of them presented sacroiliac joint fractures associated with pubic area injuries. The other two presented injuries at the pubic area and acetabulum only. The strain gauges signals suggested that the pubic fractures occurred before the sacroiliac joint fractures in the great majority of the cases (five cases out of seven). Conclusions - Even in the oblique impact conditions of the present study, the pubic symphysis area was observed to be the weakest zone of the pelvis and its failure the predominant cause of sacroiliac joint injuries. It was hypothesized that the failure of the pubic rami allowed the hemi-pelvis to rotate inward, and that this closing-book motion induced the failure of the sacroiliac joint.
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November 2016

Reference PMHS Sled Tests to Assess Submarining.

Stapp Car Crash J 2015 Nov;59:203-23

Université René Descartes, Paris.

Sled tests focused on pelvis behavior and submarining can be found in the literature. However, they were performed either with rigid seats or with commercial seats. The objective of this study was to get reference tests to assess the submarining ability of dummies in more realistic conditions than on rigid seat, but still in a repeatable and reproducible setup. For this purpose, a semi-rigid seat was developed, which mimics the behavior of real seats, although it is made of rigid plates and springs that are easy to reproduce and simulate with an FE model. In total, eight PMHS sled tests were performed on this semirigid seat to get data in two different configurations: first in a front seat configuration that was designed to prevent submarining, then in a rear seat configuration with adjusted spring stiffness to generate submarining. All subjects sustained extensive rib fractures from the shoulder belt loading. No pelvis fractures and no submarining were observed in the front seat configuration, but two subjects sustained lumbar vertebrae fractures. In the rear seat configuration, all subjects sustained pelvic fractures and demonstrated submarining. Corridors were constructed for the external forces and the PMHS kinematics. They are provided in this paper as new reference tests to assess the biofidelity of human surrogates in different configurations that either result in submarining or do not. In future, it is intended to analyze further seat and restraint system configurations to be able to define a submarining predictor.
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November 2015

A Comparison of Sacroiliac and Pubic Rami Fracture Occurrences in Oblique Side Impact Tests on Nine Post Mortem Human Subjects.

Stapp Car Crash J 2015 Nov;59:23-52

Université René Descartes (Paris - France).

Unlabelled: The WorldSID dummy can be equipped with both a pubic and a sacroiliac joint (S-I joint) loadcell. Although a pubic force criterion and the associated injury risk curve are currently available and used in regulation (ECE95, FMVSS214), as of today injury mechanisms, injury criteria, and injury assessment reference values are not available for the sacroiliac joint itself. The aim of this study was to investigate the sacroiliac joint injury mechanism. Three configurations were identified from full-scale car crashes conducted with the WorldSID 50th percentile male where the force passing through the pubis in all three tests was approximately 1500 N while the sacroiliac Fy/Mx peak values were 4500 N/50 Nm, 2400 N/130 Nm, and 5300 N/150 Nm, respectively. These tests were reproduced using a 150 kg guided probe impacting Post Mortem Human Subjects (PMHS) at 8 m/s, 5.4 m/s and 7.5 m/s. The shape and the orientation of the impacting face of the probe were selected to match the WorldSID pubic Fy and sacroiliac Fy/Mx loads of the three vehicle test configurations. Three PMHS were tested in each of the three configurations (nine PMHS in total).

Results: In the first PMHS configuration, one specimen sustained an AIS 3 injury and one sustained an AIS 4 injury (an unstable pelvis with complete disruption of the posterior arch, a sacroiliac joint disruption associated with an iliac fracture, and a pubic symphysis separation). In the second configuration, all specimens sustained a fracture of the superior lateral iliac wing (AIS 2). In the third configuration, one specimen sustained a partial disruption of the anterior arch (AIS 2). Based on the data from strain gauges located on the pubic rami and near the sacroiliac joint, the pubic rami fractures were identified as occurring prior to the sacroiliac fractures.

Conclusions: Out of nine impactor tests performed, the PMHS S-I joint injuries were observed to consistently be associated with pelvic anterior arch fractures. In addition, from the injury sequences derived from strain gauges located on the specimen pelvises and on the injury assessments obtained by necropsy, the S-I joint fractures were observed to occur after the anterior arch fractures.
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November 2015

The Effect of Upper Body Mass and Initial Knee Flexion on the Injury Outcome of Post Mortem Human Subject Pedestrian Isolated Legs.

Stapp Car Crash J 2014 Nov;58:197-211

Université René Descartes (Paris - France).

In the ECE 127 Regulation on pedestrian leg protection, as well as in the Euro NCAP test protocol, a legform impactor hits the vehicle at the speed of 40 kph. In these tests, the knee is fully extended and the leg is not coupled to the upper body. However, the typical configuration of a pedestrian impact differs since the knee is flexed during most of the gait cycle and the hip joint applies an unknown force to the femur. This study aimed at investigating the influence of the inertia of the upper body (modelled using an upper body mass fixed at the proximal end of the femur) and the initial knee flexion angle on the lower limb injury outcome. In total, 18 tests were conducted on 18 legs from 9 Post Mortem Human Subjects (PMHS). The principle of these tests was to impact the leg at 40 kph using a sled equipped with 3 crushing steel tubes, the stiffness of which were representative of the front face of a European sedan (bonnet leading edge, bumper and spoiler). The mass of the equipped sled was 74.5 kg. The test matrix was designed to perform 4 tests in 4 configurations combining two upper body masses (either 0 or 3 kg) and two knee angles (0 or 20 degrees) at 40 kph (11 m/s) plus 2 tests at 9 m/s. Autopsies were performed on the lower limbs and an injury assessment was established. The findings of this study were first that the increase of the upper body mass resulted in more severe injuries, second that an initial flexion of the knee, corresponding to its natural position during the gait cycle, decreased the severity of the injuries, and third that based on the injury outcome, a test conducted with no upper body mass and the knee fully extended was as severe as a test conducted with a 3 kg upper body mass and an initial knee flexion of 20°.
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November 2014

Comparison of the Thorax Dynamic Responses of Small Female and Midsize Male Post Mortem Human Subjects in Side and Forward Oblique Impact Tests.

Stapp Car Crash J 2014 Nov;58:103-21

Université René Descartes(Paris V).

Despite the increasing knowledge of the thorax mechanics in impact loadings, the effects of inter-individual differences on the mechanical response are difficult to take into account. For example, the biofidelity corridors for the small female or large male are extrapolated from the midsize male corridors. The present study reports on the results of new tests performed on small female Post Mortem Human Subjects (PMHS), and compares them with test results on midsize male PMHS. Three tests in pure side impact and three tests in forward oblique impact were performed on the thorax of small female specimens. The average weight and stature were 43 kg and 1.58 m for the small female specimens. The initial speed of the impactor was 4.3 m/s. The mass and the diameter of the impactor face were respectively 23.4 kg and 130 mm. The instrumentation and methodology was the same as for the tests published in 2008 by Trosseille et al. on midsize male specimens. The rib cages were instrumented with accelerometers on the T1, T4 and T12 vertebrae, upper and lower sternum, and the ribs were instrumented with up to 110 strain gauges. A force transducer and an accelerometer were mounted on the impactor in order to record the force applied onto the thorax. Targets fixed on vertebrae were tracked using high speed cameras in order to estimate the thoracic deflection. For the six midsize males, the test conditions were exactly the same as for the small female specimens, except for the diameter of the impactor face which was 152 mm. The average weight and stature were 70.3 kg and 1.70 m for the midsize male specimens. The force and thoracic deflection time-histories and the injury assessments are given for each specimen. The thorax force magnitude varied from 1.05 to 1.45 kN and from 1.63 to 2.34 kN, respectively for the small female and midsize male groups. The maximum deflection varied from 51 to 117 mm and from 59 to 81 mm, respectively for the small female and midsize male groups. The maximum forces appeared to be a function of the total body mass for each loading angle.
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November 2014

Hepatogastroenterologists' knowledge of inactive carriers and immunotolerant hepatitis B virus patients in France: results of a practice survey.

Eur J Gastroenterol Hepatol 2015 May;27(5):544-9

aDepartment of Hepatology, Gastroenterology and Digestive Oncology, Regional Hospital, Orléans bDepartment of Hepatology, Gastroenterology and Nutrition, Laennec Hospital, Creil cDepartment of Hepatogastroenterology, Millenium Clinic, Montpellier dDepartment of Hepatogastroenterology, South Paris Region Hospital, Evry eDepartment of Hepatogastroenterology, General Hospital, Hyères fDepartment of Hepatogastroenterology, Palace Clinic, Grasse, France.

Background: Before the 2012 revision of the EASL guidelines for the management of hepatitis B virus infection, we conducted a survey to determine how French nonacademic hepatogastroenterologists defined inactive hepatitis B virus carriers and immunotolerant patients.

Methods: We asked 680 hepatogastroenterologists to complete a simple survey consisting of 11 multiple-choice questions.

Results: The participation rate was 32%. HBeAg positivity was not identified as a key criterion for the diagnosis of immunotolerance by 61.9% of the respondents. A total of 82.5 and 75.9% of the respondents identified repeatedly normal alanine transaminase levels and repeatedly low viremia (<2000 IU/ml), respectively, as relevant criteria for the HBsAg inactive carrier state. The question on the biological monitoring of inactive carriers and immunotolerant patients was answered by 78% of the respondents, 97% of whom considered determinations of α-fetoprotein concentration and viremia every 6 (n=58, 35%) or 12 months (n=105, 63%) to be useful. Overall, 19% of the respondents declared never having treated an immunotolerant patient; 81% reported that they had treated such patients under some circumstances: 73% before immunosuppression or chemotherapy, 54% treated pregnant women in their third trimester when viremia was greater than 7 log IU/ml, 49% treated health professionals to prevent contamination, and 31% before medically assisted procreation.

Conclusion: The definition of 'inactive carrier state' seems to have been well assimilated, but immunotolerance remains poorly understood. Biological monitoring was frequently carried out for inactive carriers and immunotolerant patients, but the diversity of the responses obtained highlights the lack of clear recommendations for the follow-up of these populations.
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http://dx.doi.org/10.1097/MEG.0000000000000306DOI Listing
May 2015

Kinematics and dynamics of the pelvis in the process of submarining using PMHS sled tests.

Stapp Car Crash J 2012 Oct;56:411-42

LAB PSA Peugeot-Citroën Renault, France.

This study focused on a better understanding and characterization of the submarining phenomenon that occurs in frontal crashes when the lap belt slides over the anterior superi or iliac spine. Submarining is the consequence of the pelvis kinematics relative to the lap belt, driven by the equilibrium of forces and moments applied to the pelvis. The study had two primary purposes; the first was to provide new PMHS data in submarining test configurations, the second was to investigate the Hybrid II and Hybrid III dummies biofidelity regarding submarining. Several Post Mortem Human Subject (PMHS) studies have been published on this subject. However, the lack of information about the occupant initial positioning and the use of car seats make it difficult to reconstruct these tests. Furthermore, the two dummies are rarely compared to PMHS in submarining test configurations. A fifteen frontal sled test campaign was carried out on two Anthropomorphic Test Devices (ATDs) and nine PMHS. The test environment was designed to be reproducible. It consisted of a rigid seat, a 2-poi nts shoulder belt and a 2-points lap belt instrumented to record their 3D forces at anchorage. The subjects were instrumented with angular sensors at the sacrum, T1 and T12 levels to record their initial angles. Kinematics was measured at these three levels by means of three accelerometers and angular velocity sensors. A PMHS positioning procedure was developed to ensure repeatability. A pre-test was performed on each subject to characterize its lumbar spine static behavior. All the subjects were CT-scanned from head to toe prior to the test. The campaign was divided into three test configurations leading to different surrogates' interaction with the environment and different kinematics. This resulted in a wider range of behaviors for the dummies evaluation. The deceleration pulse, initial lap belt angle, lap belt slack, seat pan angle and footrest position varied. The Hybrid II and Hybrid III dummies and three PMHS were tested in each configuration. Forces and kinematics time history corridors based on the PMHS responses are provided for each configuration. The dummies' responses are evaluated against these targets. For the first configuration (40 km/h), the peak lap belt tension for both sides was between 3,000 N and 6,385 N for the three PMHS while it was around 4,700 N and 6,200 N in average for Hybrid II and Hybrid III respectively. The maximum pelvic rotation ranged from 41° to 80° for the PMHS and reached approximately 45° for the two dummies. For the other two configurations (50 km/h), the peak lap belt tension varied from 3,660 N to 7,180 N for the PMHS and was between 5,400 N and 6,100 N for Hybrid II and between 7,145 N and 7,900 N for Hybrid III. The maximum pelvic rotation ranged from 43° to 73° for the PMHS, while it reached approximately 54° and 46° for Hybrid II and Hybrid III respectively.
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October 2012

Study of rib fracture mechanisms based on the rib strain profiles in side and forward oblique impact.

Stapp Car Crash J 2011 Nov;55:199-250

CEESAR, Nanterre. France.

Rib fractures constitute a good indication of severity as there are the most frequent type of AIS3+ chest injuries. In 2008, Trosseille et al. showed a promising methodology to exhibit the rib fracture mechanisms, using strain gauges glued on the ribs of Post-Mortem Human Subjects (PMHS) and developing a specific signal analysis. In 2009, they published the results of static airbag tests performed on 50th percentile male PMHS at different distances and angles (pure lateral and 30 degrees forward oblique direction). To complete these already published data, a set of 8 PMHS lateral and oblique impactor tests were performed with the same methodology. The rib cages were instrumented with more than 100 strain gauges on the ribs, cartilage and sternum. A 23.4 kg impactor was propelled at 4.3 or 6.7 m/s. The forces applied onto the PMHS at 4.3 m/s ranged from 1.6 kN to 1.9 kN and the injuries varied from 4 to 13 rib fractures. At 6.7 m/s, the forces applied onto the PMHS ranged from 2.6 kN to 4 kN and the injuries varied from 9 to 16 rib fractures. The results of 24 tests from Trosseille et al. 2008 and 2009 and from the current study were processed in the same way and analyzed together. The time and location of the fractures were determined for each test and a ribcage fracture scenario was defined for each configuration. Strain profile corridors were built for pure lateral and forward oblique impacts, in the case of a rigid impact (impactor) or for an airbag loading. They can be used to assess the human body model biofidelity and the validation of rib fracture mechanisms in these models. Based on these corridors, the effects of the severity, the impact angle and the loading system on rib strain profiles were analyzed and are presented in this paper.
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November 2011

Investigation on occupant ejection in high severity rear impact based on post mortem human subject sled tests.

Stapp Car Crash J 2011 Nov;55:91-115

LAB PSA-Peugeot Citroën Renault, Nanterre, France.

Occupant protection in rear impact involves two competing challenges. On one hand, allowing a deformation of the seat would act as an energy absorber in low severity impacts and would consequently decrease the risk of neck injuries. However, on the other hand, large deformations of the seat may increase the likelihood of occupant ejection in high severity cases. Green et al. 1987 analyzed a total of 919 accidents in Great Britain. They found that occupant ejection resulted in a risk of severe injuries and fatalities between 3.6 and 4.5 times higher than those cases where no ejection was observed. The sample included single front, side and rear impacts as well as multiple impacts and rollover. The rate of belt use in the sample was 50%. While this analysis included all forms of impact scenarios, nevertheless, it highlights the relative injury severity of occupant ejection. Extensive literature search has found no full-scale rear impact tests involving Post Mortem Human Subjects (PMHS) conducted in a laboratory environment and resulting in ejection. This paper describes a total of 10 sled tests conducted on 3 belted PMHS using a simplified seat design composed of rigid plates assembled such that the angular and linear stiffness of the seatback (including the foam) was modeled. The initial angular position and the range of motion of the seatback, the size of the PMHS, the slack length of the seatbelt, the angular stiffness of the seatback, and the use of headrest were varied in the test matrix while the pulse was kept constant (triangular acceleration with a peak of 17 G at 30 ms and a duration of 95 ms). In the test series, the tests were not run randomly but the likelihood of occupant ejection was increased systematically until ejection occurred. PMHS seat ejection was observed only for the 95th percentile, initially positioned with a seatback angle relative to the vertical equal to 22°, a range of seatback angular motion equal to 44° and no headrest. Repeating the test under the same conditions but with the pretentionner fired did not prevent the ejection. In addition, the 50th percentile belted specimen were not observed to sustain rearward seat ejection under realistic conditions including the use of head-rest.
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November 2011

The effect of angle on the chest injury outcome in side loading.

Stapp Car Crash J 2009 Nov;53:403-19

LAB PSA Peugeot Citroën RENAULT.

Thoracic injury criteria and injury risk curves in side impact are based on impactor or sled tests, with rigid or padded surfaces while airbags are very common on current cars. Besides, the loading is generally pure lateral while real crashes or regulations can generate oblique loadings. Oblique tests were found in the literature, but no conclusion was drawn with regard to the effect of the direction on the injury outcome. In order to address these two limitations, a series of 17 side airbag tests were performed on Post Mortem Human Subjects (PMHS) at different severities and angles. The subjects were instrumented with accelerometers on the spine and strain gauges on the ribs. They were loaded by an unfolded airbag at different distances in pure lateral or 30 degrees forward. The airbag forces ranged from 1680 N to 6300 N, the injuries being up to 9 separated fractured ribs. This paper provides the test results in terms of physical parameters and injury outcome of the 17 subjects. Geometrical and physical characteristics of the subjects are described as well as the distribution of injuries as a function of test conditions. Then a statistical analysis is presented which gives the effect of the loading angle on the injury outcome. The results of this study provide useful data for the validation of finite element models in terms of injury prediction, as well as for the development of injury risk curves for side impact dummies.
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November 2009

Investigations on the belt-to-pelvis interaction in case of submarining.

Stapp Car Crash J 2006 Nov;50:53-73

CEESAR (Centre Européen d'Etudes de Sécurité et d'Analyses des Risques), 132 Rue des Suisses, 92000 Nanterre, France.

This study focuses on the phenomenon of lap belt slip on the iliac spines of the pelvis, commonly named "submarining". The first objective was to compare the interaction between the pelvis and the lap belt for both dummies and Post Mortem Human Subjects (PMHS). The second objective was to identify parameters influencing the lap belt hooking by the pelvis. For that purpose, a hydraulic test device was developed in order to impose the tension and kinematics of the lap belt such that they mimic what occurs in frontal car crashes. The pelvis was firmly fixed on the frame of this sub-system test-rig, while the belt anchorages were mobile. Fourteen tests on four Post-Mortem Human Subjects (PMHS) and fifteen tests on the THOR NT, Hybrid III 50th and Hybrid III 95th percentile dummies were carried out. The belt tension was kept constant while a dynamic rotation was imposed on the belt anchorages. The test results show that, in the tests where submarining occurred, the belt angle relative to the pelvis was systematically greater for the pelves of dummies than for those of PMHS. An increase in the belt tension resulted in a greater submarining angle for both dummies and PMHS. The pelvis and abdomen stiffnesses were observed to be similar for the PMHS and the THOR NT dummy while significantly lower for the Hybrid III dummies.
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November 2006

Thoracic Injury Investigation using PMHS in Frontal Airbag Out-of-Position Situations.

Stapp Car Crash J 2005 Nov;49:323-42

Ceesar, 92000, Nanterre, France.

Many studies have reported multiple rib fractures sustained by an Out-of-Position (OOP) driver subjected to a frontal airbag deployment, but the injury mechanisms and thresholds remain unclear. Two successive phases occur during the bag deployment: punch-out loading of the thorax, followed by a membrane effect (Horsch et al. 1990). The aim of this study was to investigate the thoracic injuries generated by each phase separately. Tests of nine post-mortem human surrogates (PMHS) were carried out on a static test bench using a driver side airbag module described by Petit et al. (2003). The steering wheel was replaced by a plate in order to increase the loading generated by the airbag. Three loading configurations were performed: membrane only, punch-out only, and both types combined. The membrane-only tests were performed with the thorax initially positioned at 13, 78 and 128 mm from the plate in order to vary the load magnitude. The punch-out and the combined tests were performed with the thorax initially 8 mm from the module. Accelerometers and angular rate sensors were fixed on the sternum and on the first, fourth, and eighth thoracic vertebrae of the PMHS. Ribs 2 to 6 were instrumented with strain gauges. The reaction force of the bag on the plate was measured using four 2-axis load cells. Results show that both pure punch-out and pure membrane loading can result in thoracic injuries. However, the rib fracture locations seemed to differ from one type of loading to the other. Moreover, for the same initial distance between the airbag module and the thorax, the injuries were more severe in the combined effect tests than in the pure punch-out or pure membrane. The nine PMHS tests formed a matrix allowing validation of a finite element model and further analysis of thoracic injury mechanisms and thresholds.
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November 2005

The effects of axial preload and dorsiflexion on the tolerance of the ankle/subtalar joint to dynamic inversion and eversion.

Stapp Car Crash J 2002 Nov;46:245-65

Center for Applied Biomechanics, University of Virginia.

Forced inversion or eversion of the foot is considered a common mechanism of ankle injury in vehicle crashes. The objective of this study was to model empirically the injury tolerance of the human ankle/subtalar joint to dynamic inversion and eversion under three different loading conditions: neutral flexion with no axial preload, neutral flexion with 2 kN axial preload, and 30 degrees of dorsiflexion with 2 kN axial preload. 44 tests were conducted on cadaveric lower limbs, with injury occurring in 30 specimens. Common injuries included malleolar fractures, osteochondral fractures of the talus, fractures of the lateral process of the talus, and collateral ligament tears, depending on the loading configuration. The time of injury was determined either by the peak ankle moment or by a sudden drop in ankle moment that was accompanied by a burst of acoustic emission. Characteristic moment-angle curves to injury were generated for each loading configuration. Neutrally flexed ankles with no applied axial preload sustained injury at 21 +/- 5 Nm and 38 degrees +/- 8 degrees in inversion, and 47 +/- 21 Nm and 28 degrees +/- 4 degrees in eversion. For ankles tested in neutral flexion with 2 kN of axial preload, inversion failure occurred at 77 +/- 27 Nm and 40 degrees +/- 12 degrees , and eversion failure occurred at 142 +/- 100 Nm and 41 degrees +/- 14 degrees . Ankles dorsiflexed 30 degrees and axially preloaded to 2 kN sustained inversion injury at 62 +/- 31 Nm and 33 degrees +/- 4 degrees , and eversion injury at 140 +/- 53 Nm and 40 degrees +/- 6 degrees . Survival analyses were performed to generate injury risk curves in terms of joint moment and rotation angle.
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November 2002

Abdominal response to high-speed seatbelt loading.

Stapp Car Crash J 2002 Nov;46:71-9

LAB PSA Peugeot-Citroön RENAULT, Nanterre, France.

Unlabelled: This study was conducted to address injury risk due to high-speed loading of the abdomen by a seatbelt during the pretension phase. Indeed, a better coupling of occupants to the structure of the vehicle in frontal impact can be achieved by a strong pretension of the lap belt. However, out of position considerations have to be taken into account in the development of pretension systems. In particular, when the lap belt is on the abdomen instead of the pelvis at the time of pretension, the penetration of the belt into the abdomen should not lead to injuries. Given the sensitivity of pyrotechnic pre-tensioners to the resistance that they encounter, it is important to have an understanding of the behaviors of both human and dummy abdomens in order to evaluate injury risk. These data are indispensable for the evaluation, with dummy tests, of the effects of pre-tensioners on occupants and for the estimation of the levels of injury risk. New experiments were necessary to obtain data on abdomenbehavior in the pretension range of velocity. Six fixed-back cadavers were tested in two configurations: the belt was placed just above the iliac crest and tensed either symmetrically or not from 11 m/s to 23 m/s. Belt forces and kinematics were measured. Autopsies were performed. Tests were duplicated on the THOR dummy.

Results: Load penetration characteristics and injury outcomes are provided and compared to other published data. A spring-damper equivalent model of the abdomen is provided in order to give a means by which to evaluate dummies. The stiffness is 12.9 kN/m and the damping is 765 Ns/m. Static stiffness for the THOR dummy is too high, while the viscous component is four times too low when compared to the tested cadavers.
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November 2002

Laboratory Reconstructions of Real World Frontal Crash Configurations using the Hybrid III and THOR Dummies and PMHS.

Stapp Car Crash J 2002 Nov;46:27-54

Centre Européen d'Etudes de Sécurité et d'Analyse des Risques, Nanterre, France.

Load-limiting belt restraints have been present in French cars since 1995. An accident study showed the greater effectiveness in thorax injury prevention using a 4 kN load limiter belt with an airbag than using a 6 kN load limiter belt without airbag. The criteria for thoracic tolerance used in regulatory testing is the sternal deflection for all restraint types, belt and/or airbag restraint. This criterion does not assess the effectiveness of the restraint 4 kN load limiter belt with airbag observed in accidentology. To improve the understanding of thoracic tolerance, frontal sled crashes were performed using the Hybrid III and THOR dummies and PMHS. The sled configuration and the deceleration law correspond to those observed in the accident study. Restraint conditions evaluated are the 6 kN load-limiting belt and the 4 kN load-limiting belt with an airbag. Loads between the occupant and the sled environment were recorded. Various measurements (including thoracic deflections and head, thorax and pelvis accelerations and angular velocities on the dummies) characterize the dummy and PMHS behavior. PMHS anthropometry and injuries were noted. This study presents the test methodology and the results used to evaluate dummy ability to discriminate both restraint types and dummy measurement ability to be representative of thoracic injury risk for all restraint types. The injury results of the PMHS tests showed the same tendency as the accident study. Some of the criteria proposed in the literature did not show a better protection of the 4 kN load limiter belt with airbag restraint, in particular thoracic deflection maxima for both dummies. The four thoracic deflections measured on the THOR and Hybrid III dummies may allow more accurate analysis of the loading pattern and therefore of injury risk.
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November 2002

[Adenoma of the cardia with atypical cells].

Ann Pathol 2006 Feb;26(1):47-8

Service d'anatomie et cytologie pathologiques, Hôpital de la Source, CHR d'Orléans, BP 6709, 45067 Orléans Cedex 2.

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http://dx.doi.org/10.1016/s0242-6498(06)70663-0DOI Listing
February 2006
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