External Validation of the Oakland Score for Acute Lower Gastrointestinal Bleeding.

Introduction Acute lower gastrointestinal bleeding (LGIB) presents challenges in emergency settings, with incidence influenced by demographic shifts and anticoagulant usage. The Oakland score aids in risk stratification for safe discharge based on clinical and laboratory parameters. However, external validation remains limited. Methods This study validated the Oakland score in a French cohort of patients with acute LGIB and assessed the discriminatory value of the score using the area under the curve (AUC) and then its sensitivity and specificity. Results A retrospective examination of 343 patient records that satisfied the inclusion criteria showed a median score of 14 points and good discriminatory capacity (area under the receiver operating characteristic (AUROC) curve: 0.83). There was low sensitivity (20.9%) for safe discharge but good specificity (98.5%) when using an 8-point threshold. With a 9-point threshold, the sensitivity was increased to 36.5%, while the specificity remained at 95%. Conclusion Identifying low-risk LGIB patients is accomplished without sacrificing sensitivity by increasing the Oakland score threshold to 9 points. This modification improves patient safety and resource allocation in the emergency room and has been verified by other large series. For wider implementation, additional validation and long-term outcome evaluations are required.

Non-invasive diagnosis and follow-up of primary biliary cholangitis.

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.

Non-invasive diagnosis and follow-up of primary sclerosing cholangitis.

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.

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

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.

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

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.

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

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 (ABCB4) 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. ABCB4 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. ABCB4 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.

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

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.

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

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.

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

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.

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

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 .).

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

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.

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

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.

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

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.

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

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 50th 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.

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

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.

Reference PMHS Sled Tests to Assess Submarining.

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.

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

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.

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

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.