Intra and Interobserver Reliability and Agreement of Semiquantitative Vertebral Fracture Assessment on Chest Computed Tomography

Objectives

To evaluate the reliability of semiquantitative Vertebral Fracture Assessment (VFA) on chest Computed Tomography (CT).

Methods

Four observers performed VFA twice upon sagittal reconstructions of 50 routine clinical chest CTs. Intra- and interobserver agreement (absolute agreement or 95% Limits of Agreement) and reliability (Cohen''s kappa or intraclass correlation coefficient(ICC)) were calculated for the visual VFA measures (fracture present, worst fracture grade, cumulative fracture grade on patient level) and for percentage height loss of each fractured vertebra compared to the adjacent vertebrae.

Results

Observers classified 24–38% patients as having at least one vertebral fracture, giving rise to kappa''s of 0.73–0.84 (intraobserver) and 0.56–0.81 (interobserver). For worst fracture grade we found good intraobserver (76–88%) and interobserver (74–88%) agreement, and excellent reliability with square-weighted kappa''s of 0.84–0.90 (intraobserver) and 0.84–0.94 (interobserver). For cumulative fracture grade the 95% Limits of Agreement were maximally ±1,99 (intraobserver) and ±2,69 (interobserver) and the reliability (ICC) varied from 0.84–0.94 (intraobserver) and 0.74–0.94 (interobserver). For percentage height-loss on a vertebral level the 95% Limits of Agreement were maximally ±11,75% (intraobserver) and ±12,53% (interobserver). The ICC was 0.59–0.90 (intraobserver) and 0.53–0–82 (interobserver). Further investigation is needed to evaluate the prognostic value of this approach.

Conclusion

In conclusion, these results demonstrate acceptable reproducibility of VFA on CT.     

A Novel Method for Measuring Anterior Segment Area of the Eye on Ultrasound Biomicroscopic Images Using Photoshop

Purpose

To describe a novel method for quantitative measurement of area parameters in ocular anterior segment ultrasound biomicroscopy (UBM) images using Photoshop software and to assess its intraobserver and interobserver reproducibility.

Methods

Twenty healthy volunteers with wide angles and twenty patients with narrow or closed angles were consecutively recruited. UBM images were obtained and analyzed using Photoshop software by two physicians with different-level training on two occasions. Borders of anterior segment structures including cornea, iris, lens, and zonules in the UBM image were semi-automatically defined by the Magnetic Lasso Tool in the Photoshop software according to the pixel contrast and modified by the observers. Anterior chamber area (ACA), posterior chamber area (PCA), iris cross-section area (ICA) and angle recess area (ARA) were drawn and measured. The intraobserver and interobserver reproducibilities of the anterior segment area parameters and scleral spur location were assessed by limits of agreement, coefficient of variation (CV), and intraclass correlation coefficient (ICC).

Results

All of the parameters were successfully measured by Photoshop. The intraobserver and interobserver reproducibilities of ACA, PCA, and ICA were good, with no more than 5% CV and more than 0.95 ICC, while the CVs of ARA were within 20%. The intraobserver and interobserver reproducibilities for defining the spur location were more than 0.97 ICCs. Although the operating times for both observers were less than 3 minutes per image, there was significant difference in the measuring time between two observers with different levels of training (p<0.001).

Conclusion

Measurements of ocular anterior segment areas on UBM images by Photoshop showed good intraobserver and interobserver reproducibilties. The methodology was easy to adopt and effective in measuring.     

Precision and Agreement of Corneal Power Measurements Obtained Using a New Corneal Topographer OphthaTOP

Purpose

To evaluate repeatability and reproducibility of anterior corneal power measurements obtained with a new corneal topographer OphthaTOP (Hummel AG, Germany) and agreement with measurements by a rotating Scheimpflug camera (Pentacam HR, Oculus, Germany) and an automated keratometer (IOLMaster, Carl Zeiss Meditec, Germany).

Methods

The right eyes of 79 healthy subjects were prospectively measured three times with all three devices. Another examiner performed three additional scans with the OphthaTOP in the same session. Within one week, the first examiner repeated the measurements using the OphthaTOP. The flat simulated keratometry (Kf), steep K (Ks), mean K (Km), J₀, and J₄₅ were noted. Repeatability and reproducibility of measurements were assessed by within-subject standard deviation (Sw), repeatability (2.77 Sw), coefficient of variation (CoV), and intraclass correlation coefficient (ICC). Agreement between devices was assessed using 95% limits of agreement (LoA).

Results

Intraobserver repeatability and interobserver and intersession reproducibility of all measured parameters showed a 2.77 Sw of 0.29 diopter or less, a CoV of less than 0.24%, and an ICC of more than 0.906. Statistically significant differences (P<0.001) were found between the parameters analyzed by the three devices, except J₀ and J₄₅. The mean differences between OphthaTOP and the other two devices were small, and the 95% LoA was narrow for all results.

Conclusions

The OphthaTOP showed excellent intraobserver repeatability and interobserver and intersession reproducibility of corneal power measurements. Good agreements with the other two devices in these parameters were found in healthy eyes.     

Diagnosing Nodular Regenerative Hyperplasia of the Liver Is Thwarted by Low Interobserver Agreement

Background and Aims

Nodular regenerative hyperplasia (NRH) of the liver is associated with several diseases and drugs. Clinical symptoms of NRH may vary from absence of symptoms to full-blown (non-cirrhotic) portal hypertension. However, diagnosing NRH is challenging. The objective of this study was to determine inter- and intraobserver agreement on the histopathologic diagnosis of NRH.

Methods

Liver specimens (n=48) previously diagnosed as NRH, were reviewed for the presence of NRH by seven pathologists without prior knowledge of the original diagnosis or clinical background. The majority of the liver specimens were from thiopurine using inflammatory bowel disease patients. Histopathologic features contributing to NRH were also assessed. Criteria for NRH were modified by consensus and subsequently validated. Interobserver agreement was evaluated by using the standard kappa index.

Results

After review, definite NRH, inconclusive NRH and no NRH were found in 35% (23-40%), 21% (13-27%) and 44% (38-56%), respectively (median, IQR). The median interobserver agreement for NRH was poor (κ = 0.20, IQR 0.14-0.28). The intraobserver variability on NRH ranged between 14% and 71%. After modification of the criteria and exclusion of biopsies with technical shortcomings, the interobserver agreement on the diagnosis NRH was fair (κ = 0.45).

Conclusions

The interobserver agreement on the histopathologic diagnosis of NRH was poor, even when assessed by well-experienced liver pathologists. Modification of the criteria of NRH based on consensus effort and exclusion of biopsies of poor quality led to a fairly increased interobserver agreement. The main conclusion of this study is that NRH is a clinicopathologic diagnosis that cannot reliably be based on histopathology alone.     

Assessment of Prosthesis Alignment after Revision Total Knee Arthroplasty Using EOS 2D and 3D Imaging: A Reliability Study

Introduction

A new low-dose X-ray device, called EOS, has been introduced for determining lower-limb alignment in 2D and 3D. Reliability has not yet been assessed when using EOS on lower limbs containing a knee prosthesis. Therefore purpose of this study was to determine intraobserver and interobserver reliability of EOS 2D and 3D knee prosthesis alignment measurements after revision total knee arthroplasty (rTKA).

Methods

Forty anteroposterior and lateral images of 37 rTKA patients were included. Two observers independently performed measurements on these images twice. Varus/valgus angles were measured in 2D (VV2D) and 3D (VV3D). Intraclass correlation coefficients and the Bland and Altman method were used to determine reliability. T-tests were used to test potential differences.

Results

Intraobserver and interobserver reliability were excellent for VV2D and VV3D. No significant difference or bias between the first and second measurements or the two observers was found. A significant mean and absolute difference of respectively 1.00° and 1.61° existed between 2D and 3D measurements.

Conclusions

EOS provides reliable varus/valgus measurements in 2D and 3D for the alignment of the knee joint with a knee prosthesis. However, significant differences exist between varus/valgus measurements in 2D and 3D.     

Development and Validation of Intracranial Thrombus Segmentation on CT Angiography in Patients with Acute Ischemic Stroke

Background and Purpose

Thrombus characterization is increasingly considered important in predicting treatment success for patients with acute ischemic stroke. The lack of intensity contrast between thrombus and surrounding tissue in CT images makes manual delineation a difficult and time consuming task. Our aim was to develop an automated method for thrombus measurement on CT angiography and validate it against manual delineation.

Materials and Methods

Automated thrombus segmentation was achieved using image intensity and a vascular shape prior derived from the segmentation of the contralateral artery. In 53 patients with acute ischemic stroke due to proximal intracranial arterial occlusion, automated length and volume measurements were performed. Accuracy was assessed by comparison with inter-observer variation of manual delineations using intraclass correlation coefficients and Bland–Altman analyses.

Results

The automated method successfully segmented the thrombus for all 53 patients. The intraclass correlation of automated and manual length and volume measurements were 0.89 and 0.84. Bland-Altman analyses yielded a bias (limits of agreement) of −0.4 (−8.8, 7.7) mm and 8 (−126, 141) mm³ for length and volume, respectively. This was comparable to the best interobserver agreement, with an intraclass correlation coefficients of 0.90 and 0.85 and a bias (limits of agreement) of −0.1 (−11.2, 10.9) mm and −17 (−216, 185) mm³.

Conclusions

The method facilitates automated thrombus segmentation for accurate length and volume measurements, is relatively fast and requires minimal user input, while being insensitive to high hematocrit levels and vascular calcifications. Furthermore, it has the potential to assess thrombus characteristics of low-density thrombi.     

Reliability of Corneal Dynamic Scheimpflug Analyser Measurements in Virgin and Post-PRK Eyes

Purpose

To determine the measurement reliability of CorVis ST, a dynamic Scheimpflug analyser, in virgin and post-photorefractive keratectomy (PRK) eyes and compare the results between these two groups.

Methods

Forty virgin eyes and 42 post-PRK eyes underwent CorVis ST measurements performed by two technicians. Repeatability was evaluated by comparing three consecutive measurements by technician A. Reproducibility was determined by comparing the first measurement by technician A with one performed by technician B. Intraobserver and interobserver intraclass correlation coefficients (ICCs) were calculated. Univariate analysis of covariance (ANCOVA) was used to compare measured parameters between virgin and post-PRK eyes.

Results

The intraocular pressure (IOP), central corneal thickness (CCT) and 1_st applanation time demonstrated good intraobserver repeatability and interobserver reproducibility (ICC≧0.90) in virgin and post-PRK eyes. The deformation amplitude showed a good or close to good repeatability and reproducibility in both groups (ICC≧0.88). The CCT correlated positively with 1_st applanation time (r = 0.437 and 0.483, respectively, p<0.05) and negatively with deformation amplitude (r = −0.384 and −0.375, respectively, p<0.05) in both groups. Compared to post-PRK eyes, virgin eyes showed longer 1_st applanation time (7.29±0.21 vs. 6.96±0.17 ms, p<0.05) and lower deformation amplitude (1.06±0.07 vs. 1.17±0.08 mm, p<0.05).

Conclusions

CorVis ST demonstrated reliable measurements for CCT, IOP, and 1_st applanation time, as well as relatively reliable measurement for deformation amplitude in both virgin and post-PRK eyes. There were differences in 1_st applanation time and deformation amplitude between virgin and post-PRK eyes, which may reflect corneal biomechanical changes occurring after the surgery in the latter.     

Precision (Repeatability and Reproducibility) and Agreement of Corneal Power Measurements Obtained by Topcon KR-1W and iTrace

Purpose

To evaluate the repeatability and reproducibility of corneal power measurements obtained by Topcon KR-1W and iTrace, and assess the agreement with measurements obtained by Allegro Topolyzer and IOLMaster.

Methods

The right eyes of 100 normal subjects were prospectively scanned 3 times using all the 4 devices. Another observer performed additional 3 consecutive scans using the Topcon KR-1W and iTrace in the same session. About one week later, the first observer repeated the measurements using the Topcon KR-1W and iTrace. The steep keratometry (Ks), flat keratometry (Kf), mean keratometry (Km), J0 and J45 were analyzed. Repeatability and reproducibility of measurements were evaluated by the within-subject standard deviation (Sw), coefficient of variation (CoV), test-retest repeatability (2.77Sw), and intraclass correlation coefficient (ICC). Agreements between devices were assessed using Bland-Altman analysis and 95% limits of agreement (LoA).

Results

Intraobserver repeatability and interobserver and intersession reproducibility of the Ks, Kf and Km showed a CoV of no more than 0.5%, a 2.77Sw of 0.70 D or less, and an ICC of no less than 0.99. However, J0 and J45 showed poor intraobserver repeatability and interobserver and intersession reproducibility (all ICCs not greater than 0.446). Statistically significant differences existed between Topcon KR-1W and IOLMaster, Topcon KR-1W and iTrace, Topcon KR-1W and Topolyzer, iTrace and Topolyzer, iTrace and IOLMaster for Ks, Kf and Km measurements (all P < 0.05). The mean differences between Topcon KR-1W, iTrace, and the other 2 devices were small. The 95% LoA were approximately 1.0 D to 1.5 D for all measurements.

Conclusions

The Ks, Kf and Km obtained by Topcon KR-1W and iTrace showed excellent intraobserver repeatability and interobserver and intersession reproducibility in normal eyes. The agreement between Topcon KR-1W and Topolyzer, Topcon KR-1W and IOLMaster, iTrace and Topolyzer, iTrace and IOLMaster, Topcon KR-1W and iTrace were not so good, they should not be interchangeable in clinical application. Given that the intraobserver repeatability and interobserver and intersession reproducibility of corneal astigmatism measurements obtained by Topcon KR-1W and iTrace were poor, it should be cautious that Topcon KR-1W and iTrace were applied for the preparation of toric lens implantation.     

Is cardiac CT a reproducible alternative for cardiac MR in adult patients with a systemic right ventricle?

Objective

20 % of patients with a systemic RV are pacemaker dependent, and unsuitable to undergo cardiac magnetic resonance (CMR). Multidetector row computed tomography (MDCT) could provide a reproducible alternative to CMR in these patients. The aim of this study was to compare variability of MDCT with CMR.

Methods

Thirty-five patients with systemic RV underwent either MDCT (n = 15) or CMR (n = 20). Systemic RV volumes and ejection fraction were obtained, and intra- and interobserver variability for both modalities were assessed and compared.

Results

We found the intra- and interobserver variability of volumes and function measurements of the systemic RV obtained with MDCT to be higher compared with those obtained with CMR. However, these differences in variability were not significant, the only exception being the interobserver variability of systemic RV stroke volume.

Conclusions

MDCT provides a reproducible alternative to CMR for volumes and function assessment in patients with a systemic RV.     

High Reproducibility of Histological Characterization by Whole Virtual Slide Quantification; An Example Using Carotid Plaque Specimens

Objective

Tissue biobanks are an important source for discovery and validation studies aiming for new proteins that are causally related with disease development. There is an increasing demand for accurate and reproducible histological characterization, especially for subsequent analysis and interpretation of data in association studies. We assessed reproducibility of one semiquantative and two quantitative methods for histological tissue characterization. We introduce a new automated method for whole digital slide quantification. Carotid atherosclerotic plaques were used to test reproducibility.

Methods

50 atherosclerotic plaques that were obtained during carotid endarterectomy were analysed. For the semiquantitative analysis, 6 different plaque characteristics were scored in categories by two independent observers, and Cohen''s κ was used to test intra- and interobserver reproducibility. The computer-aided method (assessed by two independent observers) and automated method were tested on CD68 (for macrophages) and α smooth muscle actin (for smooth muscle cells) stainings. Agreement for these two methods (done on a continuous scale) was assessed by intraclass correlation coefficients (ICCs).

Results

For the semiquantitative analysis, κ values ranged from 0.55 to 0.69 for interobserver variability, and were slightly higher for intraobserver reproducibility in both observers. The computer-aided method yielded intra- and interobserver ICCs between 0.6 and 0.9. The new automated method performed most optimal regarding reproducibility, with ICCs ranging from 0.92 to 0.97.

Conclusions

The analysis of performance of three methods for histological slide characterization on carotid atherosclerotic plaques showed high precision and agreement in repeated measurements for the automated method for whole digital slide quantification. We suggest that this method can fulfill the need for reproducible histological quantification.     

Progesterone Treatment Shows Benefit in a Pediatric Model of Moderate to Severe Bilateral Brain Injury

Purpose

Controlled cortical impact (CCI) models in adult and aged Sprague-Dawley (SD) rats have been used extensively to study medial prefrontal cortex (mPFC) injury and the effects of post-injury progesterone treatment, but the hormone''s effects after traumatic brain injury (TBI) in juvenile animals have not been determined. In the present proof-of-concept study we investigated whether progesterone had neuroprotective effects in a pediatric model of moderate to severe bilateral brain injury.

Methods

Twenty-eight-day old (PND 28) male Sprague Dawley rats received sham (n = 24) or CCI (n = 47) injury and were given progesterone (4, 8, or 16 mg/kg per 100 g body weight) or vehicle injections on post-injury days (PID) 1–7, subjected to behavioral testing from PID 9–27, and analyzed for lesion size at PID 28.

Results

The 8 and 16 mg/kg doses of progesterone were observed to be most beneficial in reducing the effect of CCI on lesion size and behavior in PND 28 male SD rats.

Conclusion

Our findings suggest that a midline CCI injury to the frontal cortex will reliably produce a moderate TBI comparable to what is seen in the adult male rat and that progesterone can ameliorate the injury-induced deficits.     

Cerebral Blood Volume Analysis in Glioblastomas Using Dynamic Susceptibility Contrast-Enhanced Perfusion MRI: A Comparison of Manual and Semiautomatic Segmentation Methods

Purpose

To compare the reproducibilities of manual and semiautomatic segmentation method for the measurement of normalized cerebral blood volume (nCBV) using dynamic susceptibility contrast-enhanced (DSC) perfusion MR imaging in glioblastomas.

Materials and Methods

Twenty-two patients (11 male, 11 female; 27 tumors) with histologically confirmed glioblastoma (WHO grade IV) were examined with conventional MR imaging and DSC imaging at 3T before surgery or biopsy. Then nCBV (means and standard deviations) in each mass was measured using two DSC MR perfusion analysis methods including manual and semiautomatic segmentation method, in which contrast-enhanced (CE)-T1WI and T2WI were used as structural imaging. Intraobserver and interobserver reproducibility were assessed according to each perfusion analysis method or each structural imaging. Interclass correlation coefficient (ICC), Bland-Altman plot, and coefficient of variation (CV) were used to evaluate reproducibility.

Results

Intraobserver reproducibilities on CE-T1WI and T2WI were ICC of 0.74–0.89 and CV of 20.39–36.83% in manual segmentation method, and ICC of 0.95–0.99 and CV of 8.53–16.19% in semiautomatic segmentation method, repectively. Interobserver reproducibilites on CE-T1WI and T2WI were ICC of 0.86–0.94 and CV of 19.67–35.15% in manual segmentation method, and ICC of 0.74–1.0 and CV of 5.48–49.38% in semiautomatic segmentation method, respectively. Bland-Altman plots showed a good correlation with ICC or CV in each method. The semiautomatic segmentation method showed higher intraobserver and interobserver reproducibilities at CE-T1WI-based study than other methods.

Conclusion

The best reproducibility was found using the semiautomatic segmentation method based on CE-T1WI for structural imaging in the measurement of the nCBV of glioblastomas.     

Incidence and Outcome of Early Acute Kidney Injury in Critically-Ill Trauma Patients

Objective

To determine the incidence and effect on mortality of early acute kidney injury in severely injured trauma patients using the Acute Kidney Injury Network creatinine criteria.

Design

A retrospective cohort study of severely injured trauma patients admitted to the shock trauma intensive care unit.

Setting

Texas Trauma Institute, a state designated level I trauma unit certified by the American College of Surgeons Committee on Trauma.

Patients

901 severely injured trauma patients admitted over a 15 month period to the shock trauma intensive care unit.

Interventions

Retrospective analysis of prospectively collected data abstracted from an electronic trauma database.

Measurements and Main Results

Of 901 eligible patients admitted to the shock trauma intensive care unit after traumatic injury, 54 patients (6%) developed acute kidney injury, of whom 10 (19%) required renal replacement therapy. The 30-day mortality rate for the entire cohort was 83/901 (9.2%). Patients with early acute kidney injury had a mortality rate of 16/54 (29.6%). When corrected for multiple covariates including injury severity scores, the development of early acute kidney injury was associated with a significantly higher risk of death at 30 days with an OR of 3.4 (95% CI 1.6-7.4).

Conclusions

Applying the Acute Kidney Injury Network creatinine criteria in severely injured trauma patients, the incidence of early acute kidney injury was 6%. After correction for injury severity, development of early acute kidney injury was independently associated with significantly higher 30-day mortality.     

Semi-Automatic Quantification of Subsolid Pulmonary Nodules: Comparison with Manual Measurements

Rationale

Accurate measurement of subsolid pulmonary nodules (SSN) is becoming increasingly important in the management of these nodules. SSNs were previously quantified with time-consuming manual measurements. The aim of the present study is to test the feasibility of semi-automatic SSNs measurements and to compare the results to the manual measurements.

Methods

In 33 lung cancer screening participants with 33 SSNs, the nodules were previously quantified by two observers manually. In the present study two observers quantified these nodules by using semi-automated nodule volumetry software. Nodules were quantified for effective diameter, volume and mass. The manual and semi-automatic measurements were compared using Bland-Altman plots and paired T tests. Observer agreement was calculated as an intraclass correlation coefficient. Data are presented as mean (SD).

Results

Semi-automated measurements were feasible in all 33 nodules. Nodule diameter, volume and mass were 11.2 (3.3) mm, 935 (691) ml and 379 (311) milligrams for observer 1 and 11.1 (3.7) mm, 986 (797) ml and 399 (344) milligrams for observer 2, respectively. Agreement between observers and within observer 1 for the semi-automatic measurements was good with an intraclass correlation coefficient >0.89. For observer 1 and observer 2, measured diameter was 8.8% and 10.3% larger (p<0.001), measured volume was 24.3% and 26.5% larger (p<0.001) and measured mass was 10.6% and 12.0% larger (p<0.001) with the semi-automatic program compared to the manual measurements.

Conclusion

Semi-automated measurement of the diameter, volume and mass of SSNs is feasible with good observer agreement. Semi-automated measurement makes quantification of mass and volume feasible in daily practice.     

Dissociation of Regional Activity in Default Mode Network in Medication-Naive,First-Episode Somatization Disorder

Background

Patients with somatization disorder (SD) have altered neural activity in the brain regions of the default mode network (DMN). However, the regional alteration of the DMN in SD remains unknown. The present study was designed to investigate the regional alterations of the DMN in patients with SD at rest.

Methods

Twenty-five first-episode, medication-naive patients with SD and 28 age-, sex-, education- matched healthy controls underwent a resting-state functional magnetic resonance imaging (fMRI) scan. The fractional amplitude of low-frequency fluctuations (fALFF) was applied to analyze the data.

Results

Patients with SD showed a dissociation pattern of resting-state fALFF in the DMN, with increased fALFF in the bilateral superior medial prefrontal cortex (MPFC, BA8, 9) and decreased fALFF in the left precuneus (PCu, BA7). Furthermore, significantly positive correlation was observed between the z values of the voxels within the bilateral superior MPFC and somatization subscale scores of the Symptom Check List (SCL-90) in patients with SD.

Conclusions

Our findings indicate that there is a dissociation pattern of the anterior and posterior DMN in first-episode, treatment-naive patients with SD. The results provide new insight for the importance of the DMN in the pathophysiology of SD.     

Detection of Puumala Hantavirus Antigen in Human Intestine during Acute Hantavirus Infection

Background

Puumala virus (PUUV) is the most important hantavirus species in Central Europe. Nephropathia epidemica (NE), caused by PUUV, is characterized by acute renal injury (AKI) with thrombocytopenia and frequently gastrointestinal symptoms.

Methods

456 patients with serologically and clinically confirmed NE were investigated at time of follow-up in a single clinic. The course of the NE was investigated using medical reports. We identified patients who had endoscopy with intestinal biopsy during acute phase of NE. Histopathological, immunohistochemical and molecular analyses of the biopsies were performed.

Results

Thirteen patients underwent colonoscopy or gastroscopy for abdominal pain, diarrhea, nausea and vomiting during acute phase of NE. Immunohistochemistry (IHC) revealed PUUV nucleocapsid antigen in 11 biopsies from 8 patients; 14 biopsies from 5 patients were negative for PUUV nucleocapsid antigen. IHC localized PUUV nucleocapsid antigen in endothelial cells of capillaries or larger vessels in the lamina propria. Rate of AKI was not higher and severity of AKI was not different in the PUUV-positive compared to the PUUV-negative group. All IHC positive biopsies were positive for PUUV RNA using RT-PCR. Phylogenetic reconstruction revealed clustering of all PUUV strains from this study with viruses previously detected from the South-West of Germany. Long-term outcome was favorable in both groups.

Conclusions

In patients with NE, PUUV nucleocapsid antigen and PUUV RNA was detected frequently in the intestine. This finding could explain frequent GI-symptoms in NE patients, thus demonstration of a more generalized PUUV infection. The RT-PCR was an effective and sensitive method to detect PUUV RNA in FFPE tissues. Therefore, it can be used as a diagnostic and phylogenetic approach also for archival materials. AKI was not more often present in patients with PUUV-positive IHC. This last finding should be investigated in larger numbers of patients with PUUV infection.     

Validation of the French Version of the Child Post-Traumatic Stress Reaction Index: Psychometric Properties in French Speaking School-Aged Children

Background

Although the reliable and valid Child Post-Traumatic Stress Reaction Index (CPTS-RI) is a widely used measure of posttraumatic stress disorder (PTSD) symptoms in children, it has not been validated in French-speaking populations. The present study aims to assess the psychometric properties of the CPTS-RI in three samples of French-speaking school-children.

Methods

Data was obtained from three samples. Sample 1 was composed of 106 children (mean (SD) age = 11.7(0.7), 50% females) victims of an industrial disaster. Sample 2 was composed of 50 children (mean (SD) age = 10.8(2.6), 44% females) who had received an orthopaedic surgical procedure after an accident. Sample 3 was composed of 106 children (mean (SD) age = 11.7(2.2), 44% females) admitted to an emergency department after a road traffic accident. We tested internal consistency using Cronbach''s alpha. We examined test-retest reliability using intraclass correlation coefficient. In order to assess the convergent validity of the French version of the CPTS-RI and the Clinician Administered PTS Scale-Child and Adolescent (CAPS-CA), spearman-correlation coefficient was computed. To verify the validity of the cut-off scores, a ROC curve was constructed which evaluated the sensitivity and specificity of each score compared to the diagnosis with the CAPS-CA. We also used principal components analysis with varimax rotation to study the structure of the French version of the CPTS-RI.

Results

Cronbach''s alpha coefficient was 0.87 for the French version of the CPTS-RI. Two-week test-retest intraclass correlation coefficient (n = 30) was 0.67. The French version of the CPTS-RI was well correlated with the CAPS-CA (r = 0.76, p<0.001). Taking the CAPS-CA as the diagnostic reference, with a diagnostic cut-off of >24 for the CPTS-RI, the sensitivity and specificities were 100% and 62.6%, respectively. The French version of the CPTS-RI demonstrated a three-factor structure.

Conclusions

The CPTS-RI is reliable and valid in French-speaking children.     

The Thermostable Direct Hemolysin from Grimontia hollisae Causes Acute Hepatotoxicity In Vitro and In Vivo

Background

G. hollisae thermostable direct hemolysin (Gh-TDH) is produced by most strains of G. hollisae. This toxin has been reported to be absorbed in the intestines in humans. Secondary liver injury might be caused by venous return of the toxin through the portal system. We aimed to firstly analyze the in vitro and in vivo hepatotoxicity of Gh-TDH.

Methods

Liver cells (primary human non-cancer cell and FL83B mouse cells) were treated and mice (BALB/c) were fed with this toxin to investigate its hepatotoxicity. Morphological examination and cytotoxicity assays using liver cells were also performed. Fluorescein isothiocyanate-conjugated toxin was used to analyze the localization of this protein in liver cells. Mice were subjected to liver function measurements and liver biopsies following toxin treatment and wild-type bacterial infection. PET (positron emission tomography)/CT (computed tomography) images were taken to assess liver metabolism during acute injury and recovery.

Results

The effect of hepatotoxicity was dose and time dependent. Cellular localization showed that the toxin was initially located around the cellular margins and subsequently entered the nucleus. Liver function measurements and liver biopsies of the mice following treatment with toxin or infection with wild-type Grimontia hollisae showed elevated levels of transaminases and damage to the periportal area, respectively. The PET/CT images revealed that the reconstruction of the liver continued for at least one week after exposure to a single dose of the toxin or bacterial infection.

Conclusions

The hepatotoxicity of Gh-TDH was firstly demonstrated. The damage was located in the periportal area of the liver, and the liver became functionally insufficient.